Houston Methodist Academic Institute Annual Report 2021 by Houston Methodist Professional Publications

Houston Methodist Academic Institute

BOARD MEMBERS Houston Methodist Academic Institute Judge Ewing Werlein, Jr., Sr. Chair

Martha S. DeBusk

Gregory V. Nelson

John F. Bookout, III, Chair

W. Leslie Doggett

Joe Bob Perkins

Edward R. Allen, III

Antonio M. Gotto, Jr., MD, DPhil

Mary Eliza Shaper

David C. Baggett, Jr.

Edward A. Jones

Suzanne H. Smith

Marc L. Boom, MD

Evan H. Katz

H. Dirk Sostman, MD

Joseph R. “Rod” Canion

Edwin H. Knight

Douglas E. Swanson, Jr.

David T. Chao

Kevin J. Lilly

David M. Underwood, Jr.

Stephen I. Chazen

Steven S. Looke

Amy Waer, MD

Augustine M.K. Choi, MD

Ransom C. Lummis

Joseph C. “Rusty” Walter, III

Ernest D. Cockrell, II

David A. Modesett

Martha S. Walton

Martin S. Craighead

W. Benjamin Moreland

HOUSTON METHODIST ACADEMIC INSTITUTE

Houston Methodist has served as a pillar of the Houston community since it began in 1919 as a small hospital providing medical care during the Spanish Influenza pandemic. When the COVID-19 pandemic arrived 101 years later, it provided many opportunities to appreciate the foresight of our founders, and the resilience, compassion and expertise of our health care providers and staff. Our academic teams worked resolutely throughout the pandemic, contributing to the system-wide COVID-19 response with rapid outcomes studies and clinical trials as well as continuing to make landmark discoveries in each of our Centers of Excellence. This book shares some of the stories that embody our mission to meet the most demanding challenges faced by patients and their physicians. In 2020, our academic community further cemented their position at the center of a global collaborative network that moves medical research from concept to clinical impact and educates healthcare professionals in the latest medical breakthroughs. This year, we partnered with Rice University to launch the Center for Translational Neural Prosthetics and Interfaces, which brings together scientists, clinicians, engineers and surgeons to solve clinical problems with neurostimulation and robotics. 2020 also saw the establishment of the Weill Cornell Graduate School doctoral program in Physiology, Biophysics & Systems Biology at Houston Methodist that builds upon our long-standing academic affiliation with Weill Cornell. None of this work would be possible without the dedication and support of our visionary Houston Methodist Academic Institute board members, generous donors and brilliant faculty. Our work together has established Houston Methodist as a leading academic medical center, and I am honored to be a part of this journey to the future of medicine.

H. Dirk Sostman, MD, FACR Ernest Cockrell, Jr. Presidential Distinguished Chair, Houston Methodist Emeritus Professor of Radiology, Weill Cornell Medicine Distinguished Member, Houston Methodist Research Institute President, Houston Methodist Academic Institute Executive Vice President and Chief Academic Officer, Houston Methodist

FROM THE PRESIDENT

SCIENCE IN SERVICE OF MEDICINE

HOUSTON METHODIST ACADEMIC INSTITUTE 6670 Bertner Ave, Houston, TX 77030

houstonmethodist.org Office of Communications and External Relations | ADMN-EXEC-22-00818 | DO | DH | 04.2021 | 450

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Houston Methodist Academic Institute

ANNUAL METRICS RESEARCH & EDUCATION

Our Commitment to

RESEARCH & EDUCATION

Houston Methodist supports our 742 faculty with a $219.2M annual investment in research and education and a planned investment of $300M over five years for strategic academic initiatives. Investigators also have access to more than $106M in philanthropic funds for research and education and a competitive $15.5M philanthropic fund to support translation of their most promising technologies.

$300M STRATEGIC INITIATIVES $26.7M PRODUCT DEVELOPMENT

$17.7

NIH GRANT FUNDING

$52M EDUCATION

INDUSTRY CONTRACTS

$11.1

OTHER GRANT FUNDING

PHILANTHROPY

ANNUAL EXTRAMURAL FUNDING MILLIONS

$167.2M RESEARCH

$17.8

$23.7

ANNUAL EXTRAMURAL FUNDING: $70.3M

TRANSLATION & DEVELOPMENT to bring new technologies & therapies to patients We bring new scientific discoveries to patients as rapidly as possible through the full cycle of a cure from bench research, to prototyping and production, to clinical trials and FDA approval. Houston Methodist has a $26.7M product development fund to navigate promising technologies through this translational pipeline and facilitate a technology transfer hand off to the market for delivery of safe and effective therapies to patients.

Translational Pipeline $26.7M

TRANSLATIONAL RESEARCH INITIATIVE

200

PRODUCTS IN REGULATORY PIPELINE

LICENSABLE TECHNOLOGIES

523

CLINICAL TRIALS

North America

WORLDWIDE

Collaboration & Leadership p

Global collaboration sources the best expertise for interdisciplinary research and

Houst

education. In 2021, Houston Methodist faculty mentored 1,036 trainees in residence from 68 countries and participated in 6,691 collaborations with peers from 136 countries.

6,691

COLLABORATIONS

1,256

1,722

RESEARCH PROJECTS

PEER-REVIEWED PUBLICATIONS

136

COLLABORATING U.S. STATES

LEARNERS FROM

COUNTRIES

COLLABORATING COUNTRIES

Training the

NEXT GENERATION

of Caregivers & Innovators

Houston Methodist faculty trained 41,809 learners in 2021. Our modern interdisciplinary GME and educational programs have access to advanced resources like the MITIESM virtual hospital and procedural skills labs that support evidence-based practice.

S S

Asia

ton Methodist Africa

South America South America

41,809

LEARNERS

Australia Australia

RESEARCH

399 407

HEALTH CARE PHARMACY ALLIED HEALTH PHYSICIAN NURSING

1,509 303 2,413 8,347 12, 483 14,264

14,869

HOUSTON METHODIST HOSPITALS & INSTITUTES Clinical Care: 8 hospitals and 6 Centers of Excellence Academic Institute: Research Institute and Education Institute Affiliated with Weill Cornell Medicine

HOSPITALS Houston Methodist Hospital

Houston Methodist Sugar Land Hospital

Houston Methodist Baytown Hospital

Houston Methodist West Hospital

Houston Methodist Clear Lake Hospital

Houston Methodist Willowbrook Hospital

Houston Methodist Continuing Care Hospital

Houston Methodist The Woodlands Hospital

CENTERS OF EXCELLENCE Houston Methodist Dr. Mary and Ron Neal Cancer Center Houston Methodist DeBakey Heart & Vascular Center Houston Methodist Lynda K. and David M. Underwood Center for Digestive Disorders Houston Methodist Neurological Institute Houston Methodist Orthopedics & Sports Medicine Houston Methodist J.C. Walter Jr. Transplant Center

DEPARTMENTS

CENTERS & PROGRAMS

Department of Anesthesiology & Critical Care

Ann Kimball and John W. Johnson Center for Cellular Therapeutics

Department of Cardiology

Blanton Eye Institute

Department of Cardiovascular Sciences

CENTERS & PROGRAMS Center for Bioenergetics

Department of Cardiovascular Surgery

Center for Cardiovascular Regeneration

Department of Family Medicine

Center for Critical Care

Department of Medicine

Center for Health & Nature

Department of Nanomedicine

Center for Immunotherapy Research

Stanley H. Appel Department of Neurology

Center for Infectious Diseases Research

Department of Neurosurgery

Center for Musculoskeletal Regeneration

Department of Nursing

Center for Neuroregeneration

Department of Obstetrics and Gynecology

Center for Nursing Research, Education and Practice

Department of Ophthalmology

Center for Outcomes Research

Department of Oral & Maxillofacial Surgery

Center for Rapid Device Translation

Department of Orthopedic Surgery

Center for RNA Therapeutics

Department of Pathology & Genomic Medicine

Center for Translational Neural Prosthetics and Interfaces

Department of Pharmacy

Houston Methodist Institute for Robotics, Imaging and Navigation

Department of Radiation Oncology

Houston Methodist Institute for Technology, Innovation & Education (MITIESM)

Department of Radiology

Immunobiology & Transplant Science Center

Department of Surgery

Immunology Center

Department of Urology

Kenneth R. Peak Brain & Pituitary Treatment Center Nantz National Alzheimer Center Neurosciences Research Program Sherrie and Alan Conover Center for Liver Disease & Transplantation

1.38M

PATIENT ENCOUNTERS

4,737

742

PHYSICIANS

FACULTY

2,110

CREDENTIALED RESEARCHERS

41,809 LEARNERS

PATIENT CARE

2014

2021

Physicians

4,500

4,737

Employees

17,011

27,947

Beds

1,960

2,509

Admissions

82,739

132,874

Outpatient Visits

764,765

1,625,770

RESEARCH

2014

2021

Research Expenditures

$126 M

$167.2M

Extramural Funding

$49.2 M

$70.3M

Faculty

525

742

Credentialed Researchers

1,460

2,110

Clinical Protocols

840

1,387

Peer-Reviewed Publications

1,225

1,722

Collaborations

3,362

6,691

Faculty Academic Activities

1,483

6,136

EDUCATION

2014

2021

Total Learners

25,152

41,809

Trainees in Residence

1,653

1,036

GME Programs

GME Residents & Fellows

245

352

CME Learners

14,719

15,052

MITIESM Learners

6,110

2,907

Research Trainees

399

407

Ranked in 10 Specialties: Cancer Cardiology & Heart Surgery Diabetes & Endocrinology Gastroenterology & GI Surgery Geriatrics Gynecology Neurology & Neurosurgery Orthopedics Pulmonology & Lung Surgery Urology

CRADLE OF TRANSLATION

A vision for integrated research, education and clinical care

From its conception, the Houston Methodist Academic Institute intended to be different than other academic medical centers. Its driving objective is to develop treatments that can be readily adopted into patient care – using its physical connections to the hospital to source ideas for innovations. Our expertise in FDA approval pathways and access to clinical care team expertise reality-tests inventions and streamlines the process of translating laboratory research into clinical impact.

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CELL ENCAPSULATION Preventing Cell Transplant Rejection

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RNA THERAPEUTICS

Supports National Product Development page

COVID-19 SPOTLIGHTS Social Determinants of Health

CONTENTS President’s Message.............................................................................................................................1 Cycle of a Cure.........................................................................................................................................5

page

VISIONARY GIFTS OF HOPE The Ann Kimball and John W. Johnson Center for Cellular Therapeutics...........................6 The Fondren Food & Health Alliance and The Fondren Inflammation Collaboration.......7 Cockrell Center For Advanced Therapeutics......................................................................................8 Paula and Joseph C. “Rusty” Walter III................................................................................................10 Jerold B. Katz Academy of Translational Research......................................................................12

SPINAL STIMULATION

COVID-19 STUDIES

Enables Paralyzed People to Stand Unassisted COVID-19 Spotlights Social Determinants of Health.................................................................14 Houston Methodist Researchers Step Up and Face the Challenges of COVID-19 Virus......16 Shedding Light on an Unseen Crisis: New Tools Build Health Care Worker Resiliency.....18

FROM DISCOVERY TO CLINIC OUTCOMES RESEARCH reast Cancer Survivors Find a Way to Maintain Healthy Lifestyles and B Lose Weight on Their Phones..................................................................................................................20 Mobile App Improves Joint Replacement Surgery Outcomes...............................................21

RESTORATIVE MEDICINE Houston Methodist and Rice University Launch Center for Translational Neural Prosthetics and Interfaces.........................................................................................................................22

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Non-invasive Spinal Stimulation Enables Paralyzed People to Stand Unassisted............24 Dissolvable Implants Enhance the Body’s Ability to Heal Broken Bones........................26 Cell Encapsulation May Hold the Key to Preventing Cell Transplant Rejection...........28 Revolutionizing the Future of Complex Valve Disease Management.................................30

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NOVEL MONOCLONAL ANTIBODY TREATMENT

PRECISION MEDICINE

CPRIT Funding to Drive New Discoveries in Cancer Therapeutics...........................................32 • An Innovative New Tool to Enable Drug Discovery and Personalized Medicine........32

Halts Tumor Growth in Deadly Cancers

• Devising a Novel Combination Treatment for Aggressive Double-hit Lymphoma..... 33

Building Blocks for

BONE REGENERATION

• Expanding the RNAcore to Encompass the Entire Cycle of a Cure...........................34 S iemens Healthineers and Houston Methodist Imaging Innovation Hub Empowers Researchers to Push Boundaries..................................................................................36 Novel Monoclonal Antibody Treatment Halts Tumor Growth in Deadly Ovarian and Pancreatic Cancers............................................................................................38 Houston Methodist Institute for Technology, Innovation & Education (MITIESM).....................40 • Surgical Technology Developed in MITIESM Gains FDA Approval...............................41 Can Devices Provide A New Treatment Option for Glioblastoma?.....................................42 Houston Methodist Hospital’s New Paula and Joseph C. “Rusty” Walter III Tower Offers the Most Advanced Treatments and Innovations Available......................................43 Neuroimaging Offers New Insights into Neurodegeneration.................................................44

INNOVATIVE EDUCATION LAUNCHING A LEGACY OF LEADING MEDICINE Building a Weill Cornell Graduate School of Medical Sciences Campus at Houston Methodist...................................................................................................................................46 Launching a Legacy of Leading Medicine.........................................................................................46 Engineering Medicine (EnMed)...............................................................................................................47 Neural Control of Organ Degeneration and Regeneration (NeuralCODR) Training Program.......................................................................................................................................................................48 Faculty and Research Development.....................................................................................................49 Graduate Medical Education....................................................................................................................50

CYCLE OF TRANSLATION Research & Education in Service of Medicine Houston Methodist met the challenge of translation early in the design of the Research Institute building. It houses the essential services and technology that support the full cycle of development to efficiently and effectively deliver innovations to the clinic. Translating laboratory innovations into treatments for patients is fraught with challenges. The lack of specialized translational research resources makes it extremely difficult and expensive for most institutions to turn fundamental discoveries into tangible solutions that benefit the public. Their most promising innovations perish in the “Valley of Death” before they reach the clinic. We provide support at every step of the cycle of translation from bridge funding to technical expertise with U.S. Food and Drug Administration (FDA)-approved current good manufacturing practice (cGMP) facilities, good laboratory practice (GLP) facilities and clinical trial operations. The most promising innovations have a lifeline at Houston Methodist.

HOUSTON METHODIST ACADEMIC INSTITUTE | 5

EDUCATION & ADOPTION Throughout our system, we’re building interprofessional education programs that employ the latest

HEALTH CARE DELIVERY SYSTEM

strategies, including simulation, to facilitate the safe and efficient adoption of new technologies as they’re approved for clinical use. Bringing a new innovation from the completion of clinical trials to clinic adoption is very time and resource intensive, needing 10 years and $1 billion, on average.

PATIENT CARE The cycle begins and ends with the care of patients in our hospitals and clinics. Clinicians in our hospitals care for more than 800,000 patients annually, enabling them to identify the most pressing challenges in medicine and provide excellent care.

QUALITY & OUTCOMES A key component of leading medicine is our culture of quality, safety and innovation. As part of the system-wide goals for quality improvement and patient safety, we invest in research and education programs that maximize patient outcomes.

CLINICAL NEEDS Clinicians and researchers form interdisciplinary

DISCOVERY

teams to address their needs and clinical challenges.

DISCOVERY Our teams of clinicians, researchers and collaborators from around the world have access to a full suite of technology to enable the discovery process.

PRECLINICAL VALIDATION Research teams have access to dedicated Translational Research Initiative bridge funds to take the most promising discoveries into preclinical and

CLOSING THE GAP

early-phase clinical development.

cGMP MANUFACTURING The research institute is equipped with FDA cGMP-compliant facilities that produce research and clinical-grade therapeutic materials and custom radiopharmaceuticals for preclinical and first-in-human studies.

GLP PRECLINICAL VALIDATION The GLP facilities at Houston Methodist perform risk, safety and efficacy assessment studies in compliance with current FDA guidelines in preclinical models. Adherence to GLP standards is required for safety studies in order

CLINICAL TRIALS

to move to clinical trials.

CLINICAL TRIALS Teams have access to early phase trial support (pharmacokinetics and pharmacodynamics), and outpatient clinical care and study management services, including research, nursing, regulatory submissions and budget management support for all phases of clinical trials.

Visionary Gifts of Hope

Visionary Gifts of Hope Ushering medical breakthroughs from the lab to the clinic takes many years and millions of dollars. Most promising discoveries are lost in the phase of translation called the “Valley of Death.” To help bridge the Valley of Death and to provide our most promising innovations a lifeline, Houston Methodist is drawing on the transformative power of philanthropy.

THE ANN KIMBALL AND JOHN W. JOHNSON CENTER FOR CELLULAR THERAPEUTICS

With generous support from Ann Kimball and John W. “Johnny” Johnson, Houston Methodist has entered a new era of cellular therapeutics that will expand our growing portfolio of immunotherapeutics and RNA therapeutics. Their cornerstone commitment will build a research program and production facility at Houston Methodist that will allow us to design new therapies rapidly and produce experimental therapeutics on-site. The 5,000-square-foot, state-of-the-art Current Good Manufacturing Practice (cGMP) facility is located in the Houston Methodist Outpatient Center and will open in 2021. Stanley H. Appel, MD, the Peggy and Gary Edwards Distinguished Endowed Chair in ALS Research, Stanley H. Appel Department of Neurology, will lead a multidisciplinary team of researchers dedicated to expanding cell therapy research at Houston Methodist. His regulatory T cell therapy for amyotrophic lateral sclerosis, or ALS, is demonstrating promising results in slowing disease progression in some patients. Appel’s cell therapy for ALS will be manufactured on-site as part of the cell therapy program at the Ann Kimball and John W. Johnson Center for Cellular Therapeutics.

HOUSTON METHODIST ACADEMIC INSTITUTE |

THE FONDREN FOOD & HEALTH ALLIANCE AND THE FONDREN INFLAMMATION COLLABORATION

The first of its kind in the Texas Medical Center,

Ultimately, the Fondren Inflammation Collaborative

Houston and the region, the Fondren Inflammation

will be extended to other disease areas impacted by

Collaborative is creating a singular destination for

inflammation, such as the heart, brain, cancer and

patients to seek normalcy and relief from debilitating

behavioral health. The gift also will fund four endowed

allergy, immunologic, autoimmune and gastrointestinal

chairs to recruit and retain the best minds in the

conditions. The program was made possible when

world, while supporting research, education and

The Fondren Foundation made a generous $15 million

training efforts.

commitment to Houston Methodist. The entire program will be realized in the next decade, helping patients Fondren Foundation who often get passed between doctors and clinics for months or years in search of a proper diagnosis and treatment plan.

The Fondren Foundation’s vision is

The philanthropic gift strengthens and expands two

to close the gap in patient care by

Houston Methodist programs: the new Immunology Center at Houston Methodist and the Food and

building an international destination

Health Alliance within the Lynda K. and David M.

of hope and relief for people with

Underwood Center for Digestive Disorders. The Fondren Inflammation Collaborative will offer patients one-of-a-kind opportunities to participate in clinical trials focused on innovative treatments and therapies for inflammation-triggered conditions.

complex, often intertwined conditions that have underlying inflammatory triggers.

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HOUSTON METHODIST ACADEMIC INSTITUTE

COCKRELL CENTER FOR ADVANCED THERAPEUTICS Since 2009, the Cockrell Foundation has made a generous gift toward an endowment that supports the Cockrell Center for Advanced Therapeutics (CCAT), which opened its Phase I clinical trials unit in 2015 and continues to expand today. The CCAT and Houston Methodist have the expertise to support all phases of clinical trials, beginning with first-in-human trials. The CCAT brings together world-class medical minds and first-class facilities to study novel therapies for various medical conditions, while delivering customized and compassionate care. As part of our deep commitment to developing treatments with ready applicability to human disease, we aim to make a clinical trial available to every person who needs and wants to participate in one. All stages of clinical research operations are supported, and the experts to support all phases of clinical trials are on hand.

Houston Methodist Opens New Facility for Clinical Trials The Houston Methodist Cockrell Center for Advanced Therapeutics supports all phases of clinical research operations. The center provides more than 7,000 square feet of dedicated space across six locations in the greater Houston area, bringing access to the latest investigational treatment options closer to study participants’ homes or workplaces. The center conducts 24-hour pharmacodynamics and pharmacokinetics evaluations, offers early-phase and investigator-initiated trial support services, and provides a centralized clinical trials support office. The Clinical Research Phase 1 Unit caters to early-phase and proof-of-concept clinical trials as well as precision medicine-focused translational research projects.

As the COVID-19 pandemic took hold across the U.S., the center’s resources and expertise played a critical role in the historic efforts to rapidly activate and conduct clinical trials to evaluate potential therapies for COVID-19. The pandemic also underscored the need for dedicated facilities within the center to support infectious disease clinical trials that require specialized services, equipment, training and protocols. This facility is equipped to facilitate outpatient infectious diseases trials and study-mandated follow-up and data collection after discharge.

VISIONARY GIFTS OF HOPE |

Pandemic Propels Need to Develop a Component of the Cockrell Center for Advanced Therapeutics to Administer Clinical Trials for Infectious Diseases Houston Methodist is fortunate to find itself in the very good position of having donors who believe in its mission and wish to provide support. One such donor is Reynolds and Reynolds, an automotive retailing company. Through a personal relationship with Ernest D. Cockrell, II, Reynolds and Reynolds gave a total of $2 million to Houston Methodist, with half of that amount earmarked for the Reynolds and Reynolds Company Infectious Disease Research Unit, a part of the Cockrell Center for Advanced Therapeutics (CCAT), that is housed in the Research Institute. The other half is earmarked for outcomes research. The pandemic made the need to develop a component of CCAT to administer clinical trials for infectious diseases, beginning with COVID-19 patients, even more urgent. These trials require specialized facilities, equipment, training and protocols. This initiative is a component of Houston Methodist’s overall strategy to lead medicine in the prevention and treatment of infectious diseases, which ultimately will lead to the establishment of the Infectious Diseases Center of Excellence. Beyond COVID-19, Houston Methodist will continue with clinical trials under CCAT for the Cancer Center of Excellence, Center for Outcomes Research, Pathology and Genomic Medicine and several others. The Reynolds and Reynolds Company Unit will enable us to conduct clinical research in infectious diseases, which we otherwise would be unable to participate in, for the benefit of the Houston community.

COCKRELL CENTER FOR ADVANCED THERAPEUTICS 1

HOUSTON METHODIST RESEARCH INSTITUTE CCAT - TMC CLINICAL RESEARCH PHASE 1 UNIT - TMC REYNOLDS OUTPATIENT TRIALS CENTER

HOUSTON METHODIST SUGAR LAND HOSPITAL

HOUSTON METHODIST WEST HOSPITAL

HOUSTON METHODIST CONTINUING CARE HOSPITAL

3 4

HIGHLY INFECTIOUS DISEASE UNIT CLINICAL TRIALS CENTER 146

HOUSTON METHODIST PRIMARY CARE GROUP IN PEARLAND

HOUSTON METHODIST THE WOODLANDS HOSPITAL

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HOUSTON METHODIST ACADEMIC INSTITUTE

PAULA AND JOSEPH C. “RUSTY” WALTER III

Translational Research Initiative When Houston Methodist launched the Translational Research Initiative (TRI) in 2014, the aim was twofold: provide vital funding to promising new therapies ready to make the transition from research laboratory to clinical use and capitalize on Houston’s bold entrepreneurial spirit to lead the way toward a new model of medical innovation. TRI exceeded expectations. Houston Methodist is now

The Katz Foundation’s $5 million challenge gift helped

launching its third phase after securing more than

raise another $5 million from community visionaries.

$20 million for translational research projects. The first iteration of TRI, which became known as TRI I when a

Building on the success of TRI I and TRI II, a third

second initiative was created, began with a philanthropic

initiative was established with another matching challenge

matching fund established by Paula and Joseph C.

gift from Paula and Rusty Walter. TRI III’s goal is to create

“Rusty” Walter III.

a $10 million fund much like its predecessors, with one major difference: these funds will focus solely on

The success of TRI I spurred TRI II, which was started

neurology and translational projects, such as neurosurgery,

through the generosity of the Jerold B. Katz Foundation.

stroke recovery or Alzheimer’s disease.

VISIONARY GIFTS OF HOPE |

AnatomicAligner Uses State-of-the-Art Graphics to Help Presurgical Planning Developed by James Xia, MD, PhD, professor of oral and maxillofacial surgery, and Jaime Gateno, DDS, MD, chair of the Department of Oral & Maxillofacial Surgery and professor of oral and maxillofacial surgery, AnatomicAligner, an FDA-approved software program uses information acquired from multiple imaging modalities to simulate jaw surgery. Due to the complex nature of the craniofacial skeleton, corrective surgeries require extensive presurgical planning. The use of state-of-the-art computer graphics and modeling in AnatomicAligner will help reduce unwanted surgical outcomes and procedures.

Before surgery, Lindsay’s bone structure was not symmetrical.

AnatomicAligner software calculated which adjustments were needed to achieve symmetry.

Innovative Magnetic Device Shows Promise for Treating Brain Injury A noninvasive, portable, wireless, affordable, smartphone-compatible magnetic stimulation cap invented by Santosh Helekar, MD, PhD, associate professor of neurosurgery at Houston Methodist and Henning Voss, PhD, associate professor of physics in radiology at Weill Cornell Medical College, uses novel transcranial stimulation technology to modulate neural activity in multiple parts of the brain at the same time, leading to functional recovery following brain injury or dysfunction. When David Chiu, MD, Elizabeth Blanton Wareing Chair in the Eddy Scurlock Stroke Center, and Helekar tested the device in a phase I/IIa clinical trial involving 30 ischemic stroke survivors with motor impairment, the cap increased neural activity near stroke-injured areas of the brain, inducing a trend toward recovery of motor function. The cap is also being tested for other applications, such as improvement of bladder control in multiple sclerosis. The cap technology has been granted four patents by the U.S. Patent and Trademark Office so far, which have been licensed to a startup company called Seraya Medical LLC. A larger multicenter stroke trial and submission for regulatory clearance are being planned.

After two extensive surgeries, Lindsay wore braces for several weeks. With newfound confidence, she began her career at a large corporation.

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HOUSTON METHODIST ACADEMIC INSTITUTE

JEROLD B. KATZ ACADEMY OF TRANSLATIONAL RESEARCH

A substantial commitment from the Jerold B. Katz Foundation established the Jerold B. Katz Academy of Translational Research, which aims to recruit and retain the world’s most promising transformational researchers in health care. According to Evan H. Katz, one of Jerold B. Katz’s sons and the president of the Jerold B. Katz Foundation, the gift is designed to continually seed innovation and facilitate the discovery of improved treatments and medications. A portion of this gift is intended to support the research efforts of eight investigators, of whom three have been announced.

VISIONARY GIFTS OF HOPE |

KATZ INVESTIGATORS Katz Investigators

GIFT IMPACT

Nestor Esnaola, MD, MPH, MBA, FACS Esnaola is the associate director of Cancer Control and Population Science in the Cancer Center, professor of surgery and division head of surgical oncology in the Department of Surgery. He works closely with Cancer Center Director Jenny Chang, MD, to drive efforts in the areas of cancer prevention, community outreach and engagement, cancer health disparities and population science research. He was awarded Katz Foundation funding to evaluate a patientnavigation intervention tool intended to optimize breast cancer care and address outcome disparities in minorities and underserved women. The tool will be tested in a large-scale, community-based, randomized clinical trial.

Khurram Nasir, MD, MPH Nasir is a professor of Cardiology, chief of the Division of Cardiovascular Prevention and Wellness in the DeBakey Heart & Vascular Center and co-director of the Center for Outcomes Research. Nasir was awarded the Katz investigator endowment to support his efforts to develop a systemwide hospital resource for research in the area of cardiovascular disease prevention. This platform will harness the power of big data, innovative computation paradigms and artificial machine intelligence to integrate clinical and research data of patients with cardiovascular disease. By leveraging dashboards and digital solutions like alert systems and automatic prescriptions, Nasir aims to identify gaps in preventative care among high-risk individuals.

Trisha Roy, MD, PhD Assistant professor of Cardiovascular Surgery, vascular surgeon-scientist and Katz investigator, Roy is researching advanced imaging options to improve procedural outcomes for peripheral arterial disease. Current imaging techniques fall short at accurately characterizing arterial lesions, which leads to a “one-size-fits-all” approach to treatment. Roy is developing a peripheral arterial magnetic resonance imaging (MRI) method for evaluating blood vessel blockages that will allow surgeons to precisely tailor surgeries and endovascular procedures to individual patients. By selecting the right treatment for the right patient, Roy hopes to reduce failure rates and make these treatments more successful.

COVID-19 Studies

COVID-19 Spotlights Social Determinants of Health The arrival of the novel SARS-CoV-2 virus had a profound impact on every aspect of Houston Methodist, challenging us to quickly operationalize a new bioinformatics pipeline to better develop best practices for managing COVID-19 patients, prioritize and facilitate COVID-19 research and learn which persons are most impacted by the pandemic and why. The Center for Outcomes Research met this challenge, devising a data repository that obtained real-time data about COVID-19 patients’ sociodemographics, diagnoses, treatments, suitability for enrollment in clinical trials and outcomes.

With CURATOR,

Houston Methodist Experts Gain Deeper Insight into Real-Time COVID-19 Data Trends The rapid global spread of the novel SARS-CoV-2 virus provided an opportunity for Houston Methodist to establish the infrastructure for a learning health-care system that further merges evidence-based medicine and practice-based evidence. When the pandemic arrived, a cross-departmental big-data team led by Farhaan S. Vahidy, PhD, associate director Farhaan S. Vahidy, PhD

of the Center for Outcomes Research, developed the COVID-19 Surveillance and Outcomes Registry, or CURATOR, to roll out processes for collecting, organizing and analyzing real-time data that’s accessible to research and clinical groups across Houston Methodist. CURATOR has proven to be an invaluable resource for advancing research and optimizing patient care as the pandemic evolves.

“

Houston Methodist’s big-data infrastructure and data engineering teams proved to be highly agile and adaptable, which made it possible to establish a robust COVID-19 analytics pipeline in literally weeks. The ability to generate and implement scientific evidence was phenomenal. We consider ourselves battle tested and have confidence in our capacity to respond quickly in the midst of a global pandemic, with the majority of the teams working remotely.

”

– Farhaan S. Vahidy, PhD Coneway Family Centennial Endowed Directorship in Quality and Outcomes Associate Director and Associate Professor, Center for Outcomes Research Associate Professor, Neurological Institute Houston Methodist

HOUSTON METHODIST ACADEMIC INSTITUTE | 15

Research

COVID-19 Highlights How the Virus Has Impacted People Differently, Depending on Specific Social Determinants

CURATOR Identifies Differences Between Those Most Impacted During the First and Second COVID-19 Surges

The increase in COVID-19 cases and scrutiny of racial

CURATOR’s bioinformatics repository made it possible

inequality throughout the spring and summer of 2020 has

for researchers to make evidence-based comparisons

made people more aware of underlying race and ethnic

between Houston’s first COVID-19 surge from March 13 –

health-care disparities. Fairly early in the pandemic, most

May 15 and the second surge from May 15 – July 7, 2020,

reports showed higher rates of severe COVID-19 cases

that began two weeks after the statewide phased business

and fatalities among minority racial groups across major

reopening program began. Analyzing the electronic

U.S. metropolitan areas. However, Houston Methodist was

health records of hospitalized COVID-19 patients

one of the first to provide systematically analyzed robust

revealed a demographic shift between the first and

insights on the racial/ethnic differences for COVID-19

second COVID-19 surges.

infection by harnessing CURATOR.

Chief Physician Executive & Specialty Physician Group

Analysis of COVID-19 test results and sociodemographic

CEO Robert Phillips MD, PhD, and Farhaan S. Vahidy, PhD,

data from across the exceptionally ethnically diverse

and their team revealed that patients being admitted during

Greater Houston area revealed that people who identified

the second surge had shifted toward a younger, largely

as non-Hispanic Black or of Hispanic ethnicity were

Hispanic and lower socioeconomic patient population

almost twice as likely to test positive for COVID-19 than

who had lower rates of comorbidities, intensive care unit

non-Hispanic whites. Vahidy and his colleagues identified

admissions, and in-hospital mortality than the patients seen

possible mechanisms of these racial disparities within

during the first surge. These findings were published in

the data including lower socioeconomic status, higher

the Journal of the American Medical Association.

comorbidity burden and residence in higher population

These findings likely reflect how the phased return to work

density areas that may not permit adequate social

impacted which people were becoming infected. While

distancing. These data were published in BMJ Open.

many people with desk jobs were able to work from home,

As the pandemic evolves, emerging information on the

people who work in retail, transportation and hospitality

link between COVID-19 infection and various sociodemo-

service industries, many of whom are Hispanic, interacted

graphic factors will continue to enhance our understanding

with the public directly. These findings provided helpful

of targeted risks for contracting and preventing infectious

guidance for preparing and managing the next COVID-19

diseases, enabling Houston Methodist to provide better

surge during the fall of 2020 both locally at Houston

care for all members of our community.

Methodist and for health systems across the country.

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HOUSTON METHODIST ACADEMIC INSTITUTE

Houston Methodist Researchers Step Up and Face the Challenges of the COVID-19 Virus When the COVID-19 pandemic arrived, although the scientific and medical communities had limited information about how to treat people infected with the novel virus, Houston Methodist was well positioned to meet the urgent need for diagnostics, treatments, vaccines and critical medical technologies. Throughout the pandemic, our research groups continued their studies without interruption. In fact, Houston Methodist researchers submitted 32 more funding proposals during 2020 than they did the previous year. Many investigators quickly pivoted their research focus to COVID-19-related challenges by participating in more than 50 preclinical studies and clinical trials that resulted in more than 170 COVID-19-related published journal articles and 16,000 media placements.

Houston Methodist Leads the Way in Treating COVID-19 Patients with Innovative Therapies that Boost the Recovery Process Houston Methodist was the first academic medical center in the nation to receive FDA approval to treat critically ill COVID-19 patients with convalescent plasma therapy — a plasma transfusion from a recovered individual that contains antibodies against the virus. Although some other organizations had suboptimal results with this treatment, our patients benefited from it because we carefully analyzed and optimized our processes to select the patient populations that would be the optimal candidates. Other institutions treated broad populations much less likely to respond to Houston Methodist’s type of treatment. Eric Salazar, MD, PhD

James M. Musser, MD, PhD

In anticipation of the FDA issuing regulatory guidelines, assistant professor in the Department of Pathology and Genomic Medicine, Eric Salazar, MD, PhD, and James M. Musser, MD, PhD, Fondren Presidential Distinguished Chair, developed the therapy protocol. They were the first group in the nation to publish data demonstrating that the therapy is safe and effective. Their work rapidly resulted in five high-profile, peer-reviewed publications on convalescent plasma donors and recipients.

“

There is so much to be learned about this disease while it’s occurring. If an infusion of convalescent serum can help save the life of a critically ill patient, then applying the full resources of our blood bank, our expert faculty and our academic medical center is incredibly worthwhile and important to do.

”

– Marc L. Boom, MD President and Chief Executive Officer Ella Fondren and Josie Roberts Presidential Distinguished Centennial Chair Houston Methodist

COVID-19 STUDIES |

Research

Houston Methodist’s Participation in Clinical Trials for Innovative COVID-19 Treatments Has Aided Many Patients’ Recoveries antibody, or mAb, therapies contain synthetic versions of the

Houston Methodist Played a Key Role in Establishing Remdesivir as a Standard of Care for Treating COVID-19

proteins made by the immune system to neutralize the virus.

In mid-March of 2020, Houston

The mAbs are designed to bind to key sites on the virus

Methodist became the only clinical

molecule to prevent it from attaching to and infecting

trial site in Houston and the fifth site in the nation

human cells.

to join the two global phase III clinical trials evaluating

Considered the next evolution of plasma therapy, monoclonal

A team of experts at Houston Methodist, led by Salazar, began participating in the clinical trials in hospitalized patients determining the safety and effectiveness of the combination mAb therapy from Regeneron containing two neutralizing mAbs called casirivimab and imdevimab in July 2020. Current data from the Regeneron REGN-COV2 trial show that trial participants receiving the experimental therapy had a lower

Gilead Sciences antiviral drug Remdesivir in patients hospitalized with moderate or severe COVID-19 infections. Originally developed to treat Ebola, Remdesivir blocks the SARS-CoV-2 virus’s ability to quickly replicate throughout the body, neutralizing the deadly inflammatory cascade that leads to respiratory failure and dependence on a ventilator.

risk of death or need for mechanical ventilation than those

The Houston Methodist clinical study led by Katherine

in the placebo group.

Perez, PharmD, assistant professor of allied health sciences,

Houston Methodist is also actively involved in the clinical studies investigating how well Eli Lilly’s bamlanivimab, a mAb therapy similar to Regeneron’s cocktail, safely and effectively prevents mild COVID-19 infections from becoming more serious. Clinical trial lead Howard Huang, MD, interim chief, division of pulmonary, critical care and sleep medicine, and his teams are administering a single intravenous infusion of the drug to patients who have recently received a positive COVID-19 test and show mild to moderate symptoms in the hopes of intervening before patients have a chance to develop more serious symptoms, thereby reducing COVID-19-related hospitalizations and emergency department visits. Huang and his team are also involved in similar studies of the Regeneron mAbs in patients with mild to moderate symptoms. In November, the FDA issued an emergency use authorization for both the Regeneron and Eli Lilly therapies for treating mild to moderate COVID-19 infections in patients who are at high risk of becoming dangerously ill. The quick progression from beginning investigational clinical studies on newly developed drugs to having the ability to treat patients not involved in a study is a prime example of translational research in action.

Department of Pharmacy, Department of Pathology and Genomic Medicine and Kevin Grimes, MD, assistant professor of clinical medicine, Department of Medicine, found that participants with COVID-19 responded quickly to the investigational drug and recovered more quickly than their control counterparts. The final report from the global trial leadership confirmed that Remdesivir shortens the time to recovery in adults hospitalized with COVID-19, which paved the way for Remdesivir to become the first antiviral treatment approved by the FDA for COVID-19.

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HOUSTON METHODIST ACADEMIC INSTITUTE

Shedding Light on an Unseen Crisis:

New Tools Build Health-Care Worker Resiliency COVID-19 has brought the issue of health-care provider fatigue to the forefront of national conversation, but experts at Houston Methodist have been studying it for many years

Faisal N. Masud, MD

Farzan Sasangohar, PhD

During the initial COVID-19

are inherently prone to bias. To better maintain objectivity,

surge in Houston, a team

Sasangohar, Masud and their teams employed wearable

of researchers led by

technology to provide quantitative measurements of

Faisal N. Masud, MD,

stress and anxiety levels in ICU workers. Participating

Mary A. and M. Samuel

ICU staff were observed while wearing eye-tracking

Daffin, Sr. Centennial Chair

glasses with a built-in camera that recorded exactly

in Anesthesia and Critical Care and Farzan Sasangohar, PhD,

what the wearer was seeing and hearing in real time.

assistant professor of outcomes research, published a paper

The information collected from this device was paired

in Anesthesia & Analgesia discussing factors that contribute

with heart rate data and self-reported observations

to provider fatigue and burnout in intensive care units (ICUs)

to provide a more complete picture of stress triggers

during the pandemic. The article, which remained in Altmetric’s

and reactions.

top 99th percentile of publications for months, was one of the first to propose specific policy recommendations for organizational readiness, resilience and disaster mitigation — many of which were already in place at Houston Methodist. Most studies investigating burnout, including the

“Nothing like this has ever been done before in an ICU setting,” said Sasangohar. “The use of wearable technology combined with artificial intelligence could set the benchmark for future research on stress and burnout.”

aforementioned, rely on self-reporting measures that

New wearable technology developed by Faisal N. Masud, MD, and Farzan Sasangohar, PhD, provides quantitative measurements of stress and anxiety levels in ICU workers. These devices will provide objective data in self-reporting measures.

COVID-19 STUDIES |

While data analyses are still ongoing, the research team is using the preliminary results to explore potential mitigation strategies, including measures to limit or eliminate environmental, task-related and technological sources of stress that contribute to burnout among ICU personnel. The next phase of this study is to utilize wearable technology to compare burnout among health-care providers in COVID-19 ICUs with those in non-COVID-19 ICUs. Masud, who is also the medical director of critical care at Houston Methodist Hospital, has been passionate about finding transformational solutions to support the mental well-being of intensive care personnel. “The wearable technology study could provide the evidence-based solutions we need to fill the knowledge gap in health care provider stress and burnout,” he said. “COVID-19 and its far-reaching psychological implications have brought a greater sense of urgency to our work.”

FROM DISCOVERY TO CLINIC

Outcomes Research Roberta Schwartz, PhD, chief innovation officer of Houston Methodist Hospital, led an observational study of patients and concluded that the use of mobile health technology (mHealth) has shown significant improvement in clinical outcomes among patients. The investigators found that patients who used mHealth technology averaged shorter hospital stays and lower post-surgical readmission rates. Breast cancer patients often gain weight during treatment, and that is a concern because obesity is a factor in the recurrence of the cancer. The Methodist Hospital Cancer Health Application, or the MOCHA app, was developed by Stephen T.C. Wong, PhD, and his informatics development team to help cancer patients make healthy lifestyle choices. A pilot study showed that 56% of enrolled patients who used the app lost an average of 3.5 pounds and that frequency of app use was positively linked with weight loss.

Breast Cancer Survivors Find a Way to

Maintain Healthy Lifestyles and Lose Weight on Their Phones Breast cancer treatment often leads to unintentional weight gain, which is concerning because obesity is associated with an increased risk of breast cancer recurrence and a higher rate of hospital readmissions. Renee Stubbins, PhD

Stephen T.C. Wong, PhD

While weight management tools are among the most frequently accessed health apps, most are not tailored to the specific needs of cancer survivors. Stephen T.C. Wong, PhD, John S. Dunn Presidential Distinguished Chair in Biomedical Engineering, and his informatics development team designed a mobile app called the Methodist Hospital Cancer Health Application, or MOCHA, to be an interactive resource that helps post-treatment cancer survivors to make healthy lifestyle choices, including weight loss. A four-week pilot study of the MOCHA app revealed that 56% of enrolled patients lost an average of 3.5 pounds and that frequency of app use was positively linked with weight loss. The complete results are available in the journal JCO Clinical Cancer Informatics. The next phase of this study will involve 12 weeks of intervention and one year of follow-up. While the app is currently accessible only to study participants, the goal is to broaden its use and focus on changing long-term behaviors to reduce health issues most common in cancer survivors.

“

Maintaining a healthy weight is difficult enough for the average person, let alone for breast cancer survivors. With MOCHA, we can track multiple patients at once, identify those who need additional support or intervention and communicate with them via real-time messaging to help them stay motivated. This is a tremendous improvement from the typical six-month clinic visit schedule for breast cancer survivors, between which patients can lose motivation and experience weight gain.

– R enee Stubbins, PhD Assistant Clinical Member Houston Methodist

”

HOUSTON METHODIST ACADEMIC INSTITUTE |

Mobile App Improves Joint Replacement Surgery Outcomes With close to 90% of the U.S. population having access to mobile devices, mobile health (mHealth) technology could transform how health care is delivered. Despite widespread recognition of its potential, there is limited evidence supporting the effectiveness of mHealth technology in a health care setting. In an observational study published in the journal JMIR mHealth and uHealth, Houston Methodist investigators, led by Roberta Schwartz, PhD, chief innovation officer of Houston Methodist Hospital, show that effective use of patient-facing mHealth technology can significantly improve both clinical and patient-centered Roberta Schwartz, PhD

Stephen Incavo, MD

Courtenay R. Bruce, JD, MA

care outcomes.

The study compared the outcomes of 2,059 patients who underwent a total hip or knee replacement by orthopedic surgeons who used mHealth technology with 2,554 similar patients of nonparticipating surgeons for a year. In the mHealth group, the patients received one text or email message per day, some of which required responses while others were only informational, for 20 days before and 30 days following the joint replacement. “In our study, we observed a significant improvement in clinical outcomes among patients who used mHealth technology,” said senior author Courtenay R. Bruce, JD, MA, associate professor of medicine. “The participating group had a significantly shorter average hospital stay and lower post-surgical hospital readmission rates compared with the nonparticipating group. In addition, the participating group also had better patient-centered care outcomes such as patient engagement, experience and satisfaction.” According to Bruce, a more engaged patient is a better informed and more empowered patient. And this ultimately translates to improved outcomes.

“

We now know that mHealth technology is not only effective but significantly enhances patient outcomes. This is particularly important in the context of the rapidly evolving COVID-19 pandemic that has made mHealth services an integral part of patient care. The results of this study were so encouraging that what started as a small pilot program in a few hospital departments has rapidly expanded to include 50 different therapeutic areas, benefiting more than 300,000 patients.

”

– R oberta Schwartz, PhD Executive Vice President Chief Innovation Officer Houston Methodist

FROM DISCOVERY TO CLINIC

Restorative Medicine Houston Methodist remains at the cutting edge of regenerative medicine by developing a range of medical and biotherapeutic products that help restore the functionality of impaired organs and tissues. These restorative solutions address challenges, including protecting transplanted tissues from rejection, restoring sensorimotor function in people with neuromuscular disorders and repairing broken bones.

Houston Methodist and Rice University Launch

Center for Translational Neural Prosthetics and Interfaces

Gavin W. Britz, MD

Behnaam Aazhang, PhD

Neurosurgery’s history of

of Electrical and Computer Engineering, who also directs

cutting diseases out of

the neuroengineering initiative. “Several core members,

the brain is morphing into

myself included, have existing collaborations with our

a future in which implanting

colleagues at Houston Methodist in the area of neural

technology into the brain

prosthetics. The creation of the Center for Translational

may help restore function,

Neural Prosthetics and Interfaces is an exciting development

movement, cognition and memory after patients suffer strokes, spinal cord injuries and other neurological disorders. Rice University and Houston Methodist have forged a partnership to launch the Center for Translational Neural Prosthetics and Interfaces, a collaboration that brings together scientists, clinicians, engineers and surgeons to solve clinical problems with neurorobotics.

toward achieving our common goals.” The physical space for the center’s operation includes more than 25,000 square feet of Rice Neuroengineering Initiative laboratories and experimental spaces in the university’s BioScience Research Collaborative, as well as an extensive build-out underway at Houston Methodist’s West Pavilion location that’s expected to be completed late in 2021.

“This will be an accelerator for discovery. This center will

The Houston Methodist facility will include operating rooms

be a human laboratory where all of us — neurosurgeons,

and a human laboratory where ongoing patient/volunteer

neuroengineers, neurobiologists — can work together to

diagnosis and assessment, device fabrication and testing

solve biomedical problems in the brain and spinal cord.

and education and training opportunities are planned.

And it’s a collaboration that can finally offer some hope and options for the millions of people worldwide who suffer from brain diseases and injuries,” said center Co-Director Gavin W. Britz, MD, Candy and Tom Knudson Distinguished Centennial Chair in Neurosurgery at Houston Methodist. Houston Methodist neurosurgeons, seven engineers from the Rice Neuroengineering Initiative and additional physicians and faculty from both institutions form the center’s core team. The center also plans to hire additional engineers who will have joint appointments at Houston Methodist and Rice. Key focus areas include spinal cord injury, memory and epilepsy studies, and cortical motor/sensation conditions.

“This partnership is a perfect blend of talent,” said Rice’s Marcia O’Malley, PhD, a core member of the new center. “We will be able to design studies to test the efficacy of inventions and therapies and rely on patients and volunteers who want to help us test our ideas. The possibilities are limitless.” Houston Methodist neurobiologist Philip J. Horner, PhD, describes the lab as “a merging of wetware with hardware,” where robotics, computers, electronic arrays and other technology — the hardware — is incorporated into the human brain or spinal cord — the wetware. The centerpiece of this working laboratory is a zero-gravity harness connected

“The Rice Neuroengineering Initiative was formed with

to a walking track with cameras and sensors to record

this type of partnership in mind,” said center Co-Director

feedback, brain activity and other data.

Behnaam Aazhang, PhD, Rice’s J.S. Abercrombie Professor

HOUSTON METHODIST ACADEMIC INSTITUTE |

Center Collaborations Collaborations already are underway between the two institutions, which sit across Main Street from one another in the Texas Medical Center. Among them are the following: • Houston Methodist’s Dimitry Sayenko, MD, PhD, assistant

• Britz and Center Co-Director Behnaam Aazhang, PhD,

professor of neurosurgery, and O’Malley, Rice’s Thomas

Rice’s J.S. Abercrombie Professor of Electrical and

Michael Panos Family Professor in Mechanical Engineering,

Computer Engineering, and Taiyun Chi, PhD, assistant

will head the first pilot project involving the merging of

professor of electrical and computer engineering at Rice,

two technologies to restore hand function following a

are collaborating on the detection of mild traumatic brain

spinal cord injury or stroke. O’Malley will pair the upper

injuries (mTBI) from multimodal observations and on

limb exoskeleton she invented with Sayenko’s noninvasive

alleviating mTBI using neuromodulations. This project is

stimulator designed to wake up the spinal cord. Together,

of particular interest to the U.S. Department of Defense.

they hope these technologies will help patients achieve a more extensive recovery — and at a faster pace. • Britz, a neurosurgeon, and Lan Luan, PhD, Rice assistant

Center for Translational Neural Prosthetics & Interfaces

professor of electrical and computer engineering, are collaborating on a study to measure the neurovascular response following a subarachnoid hemorrhage, a life-threatening stroke caused by bleeding just outside the brain.

NEUROSTIMULATION THERAPY

SEND SIGNAL

ROBOTICS & BRAIN COMPUTER INTERFACE

ACQUIRE SIGNAL

PROCESS & DECODE PROCESS & DECODE MUSCLE CONTROL

DEVICE CONTROL

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HOUSTON METHODIST ACADEMIC INSTITUTE

Noninvasive Spinal Stimulation

Enables Paralyzed People to Stand Unassisted Dimitry Sayenko MD, PhD, assistant professor of neurosurgery, and his colleagues in the Neuromodulation & Recovery Lab are developing ways to promote mobility in people who have sustained a spinal cord injury.

Regaining the ability to control a full

Dimitry Sayenko MD, PhD

minimal external assistance applied to the knees or hips, using

weight-bearing standing posture without

their hands for upper-body balance as needed. The quality of

assistance from weight-supporting

their balance control improved with continued training. When

devices or other people is a key goal

the participants shifted their weight while standing, high levels

for someone who is paralyzed. Not only

of leg muscle activity emerged that depended on the amount

does this ability provide a greater level

of muscle loading.

of physical independence and mobility, maintaining balance when standing is the foundation for regaining the ability

These findings suggest that the noninvasive stimulation therapy

to walk, including stepping with assistance from robotic

can modulate the spinal circuitry into a physiological state that

devices being developed at Houston Methodist and

enables sensory inputs during weight-bearing to serve as a

other places.

primary source of neural control to maintain externally unassisted upright posture and balance.

In a well-controlled clinical study published in the Journal of Neurotrauma, people with spinal cord injuries who could

Sayenko recently began collaborating with Niche Biomedical to

not stand unassisted received noninvasive transcutaneous

initiate a sponsored clinical trial evaluating the effects of spinal

electrical spinal cord stimulation via electrodes placed on

stimulation on upper limb function in individuals with spinal cord

the spinal column three days per week for a month.

injuries. Niche Biomedical is a multidisciplinary bioelectronics medical device company focused on developing neuromodulatory

Following this treatment, all the participants could maintain

technologies to address chronic conditions that have previously

an upright standing position either independently or with

defied conventional medical treatment.

RESTORATIVE MEDICINE |

“

Our clinical research program focuses on central nervous system plasticity throughout the course of motor learning and regaining lost sensorimotor function. We are especially interested in exploring the strategies for regaining functionality during self-assisted standing and stepping, as well as for improving control of motor and autonomic functions.

”

– D imitry Sayenko MD, PhD Assistant Professor, Neurosurgery Houston Methodist

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HOUSTON METHODIST ACADEMIC INSTITUTE

Dissolvable Implants Enhance the Body’s

Ability to Heal Broken Bones The Houston Methodist Center for Musculoskeletal Regeneration recognizes that the human body has an incredible capacity for healing and develops biomimetic implantables to augment these processes.

Center Director and Assistant Professor of Orthopedic Surgery Francesca Taraballi, PhD, and her colleagues have demonstrated that all regenerative processes Francesca Taraballi, PhD

Bradley K. Weiner, MD

depend on a complex dialogue among different types of cells.

They have developed a collagen-based scaffold device called 3 Zonal Membrane (3ZM), which is currently in cGMP production, that enhances the structure and composition of growing bones to quickly repair complex fractures that would usually result in high infection rates, slow/incomplete healing or amputation.

RESTORATIVE MEDICINE |

3ZM Steps in Healing Process

In preclinical models, 3ZM guided immune, stem and bone membrane cells that remodeled the area into functional bone. Within six weeks, the fracture healed and the implanted

3ZM Steps in Healing Process

materials were absorbed by the body, leaving the bone strong. 3 Zonal Membrane (3ZM) is cut and shaped The center was awarded $6 million by the U.S. Department of

to fit the defect site and then sutured to the

Defense under the leadership of Bradley Weiner, MD, professor

surrounding periosteum. The process requires

of clinical orthopedic surgery, to complete preclinical cGMP

only one operation and no additional growth

assessment of 3ZM technology for a pre-Investigational Device

factors. After four to six weeks, the bone is

Exemption regulatory consultation with the Food and Drug

fully healed, and the 3ZM is absorbed.

Administration. The center leaders have worked with industry partners and regulatory experts and policymakers to identify an accelerated path to clinical application.

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HOUSTON METHODIST ACADEMIC INSTITUTE

Cell Encapsulation May Hold the Key to

Preventing Cell Transplant Rejection Cell transplantation is a promising option for the management of endocrine disorders such as type I diabetes and testosterone deficiency, but risk of rejection by the recipient’s immune system and the resulting life-long dependency on immunosuppressive drugs has been a major obstacle to long-term success.

Alessandro Grattoni, PhD

A. Osama Gaber, MD

In order to protect transplanted

NICHE is implanted just under the skin, permitting easy

cells and improve cell viability,

access for replenishing transplanted cells or drugs when

several research groups

needed. The researchers utilized 3D printing technology

have tried encapsulating

to create the NICHE platform as it allows easy customization

the cells within a capsule

based on cell type and rapid, cost-effective scalability.

that acts as a physical

barrier. However, issues with inadequate blood supply and

In a preclinical study published in Biomaterials, Grattoni

oxygen permeability within the capsule have limited their

and his team successfully used NICHE to transplant

ability to support the transplanted cells.

testosterone-producing testicular Leydig cells, offering a potential new treatment option for testosterone

A Houston Methodist research team of nanomedicine and

deficiency. The NICHE platform effectively established

cell transplant experts led by Alessandro Grattoni, PhD,

blood supply within the capsule and achieved sustained

Frank J. and Jean Raymond Centennial Chair, and chair

immunosuppressant delivery. Promisingly, the transplanted

and professor of nanomedicine, has developed a novel

cells remained viable for the length of the study. Building

encapsulation platform for transplanted cells termed

upon their work with Leydig cells, the team is evaluating

neovascularized implantable cell homing and encapsulation,

the efficacy of pancreatic islet cell transplantation using

or NICHE, that directly addresses these limitations.

NICHE in preclinical diabetes models.

“

Unlike other encapsulation platforms, NICHE successfully integrates blood supply, oxygenation and localized immunosuppressant drug delivery into one device. This has significantly improved cell viability, while avoiding the adverse effects of systemic immunosupression. – A lessandro Grattoni, PhD Chair and Professor of Nanomedicine, Frank J. and Jean Raymond Centennial Chair Houston Methodist

”

RESTORATIVE MEDICINE |

“

These findings are a culmination of a long history of collaboration in cellular transplantation research at Houston Methodist and should expedite the translation of cell encapsulation technology from the lab to the clinic, delivering more effective treatment options to patients with conditions like type I diabetes.

”

– A . Osama Gaber, MD, FACS, FAST John F., Jr. and Carolyn Bookout Presidential Distinguished Chair in Surgery Chair, Department of Surgery Houston Methodist

MSCs

MSCs C

Immunosuppressant

Endocrine Cells

Nanoporous Membrane Credit: Biomaterials Fig. 1. NICHE deployment strategy. (A) Mesenchymal Stem Cells (MSCs) hydrogel-filled NICHE is implanted in a subcutaneous pocket to stimulate vascularization. (B) Prevascularization phase, with blood vessel formation across the cell reservoir. (C) Transcutaneous loading of immunosuppressant into NICHE drug reservoir using loading and venting needles. Needles are advanced into the NICHE drug reservoir through self-sealing silicon ports. Upon drug loading, the venting needle permits flushing of the reservoir and removal of entrapped air or liquid. (D) Transcutaneous transplantation of cells into the vascularized and immunosuppressed cell reservoir using a needle connected to a cell-loaded syringe.

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HOUSTON METHODIST ACADEMIC INSTITUTE

Revolutionizing the Future of

Complex Valve Disease Management Replacing a faulty aortic valve once required open-heart surgery, which can pose significant risks for patients who are older or have certain comorbidities. The advent of minimally invasive transcatheter aortic valve replacement, or TAVR, where the replacement valve is inserted via a small incision in the groin or chest, has opened much-needed treatment options for these patients.

RESTORATIVE MEDICINE |

“Momentous breakthroughs don’t happen often in medicine. TAVR is certainly one of the most exciting developments in recent times,” said Michael J. Reardon, MD, Allison Family Distinguished Chair of Cardiovascular Research in the Department of Cardiovascular Surgery. “The Houston Methodist DeBakey Heart & Vascular Center’s valve clinic team has been at the very forefront of this pioneering innovation in minimally invasive surgery, making Houston Methodist one of the most experienced TAVR sites in the nation.” Under the leadership of Reardon and his cardiology partner Lois and Carl Davis Centennial Chair Neal Kleiman, MD, the TAVR program has contributed to hundreds of publications in recent years and has played a key role in shaping this new field.

TAVR was initially approved by the U.S. Food and Drug Administration (FDA) for use in patients with an intermediate or high risk of death or major complications during open-heart surgery. In August 2019, the FDA expanded approval to low-risk patients based on outcomes from two landmark clinical trials; Reardon was the national principal investigator for one of the trials. It confirmed that TAVR was a safe and effective treatment option for low-risk patients and was associated with shorter hospital stays, improved qualityof-life scores and a significantly lower rate of all-cause mortality or disabling stroke compared to traditional surgery. The complete findings are published in The New England Journal of Medicine.

“

TAVR is a force of positive disruption that is completely redefining the scope of valve replacement surgery. With the expanded indication, TAVR will be a game-changer for low-risk patients who are seeking to avoid the risks and longer recovery associated with surgery.

”

– Michael J. Reardon, MD Allison Family Distinguished Chair of Cardiovascular Research Department of Cardiovascular Surgery Professor of Cardiovascular Surgery Houston Methodist

FROM DISCOVERY TO CLINIC

Precision Medicine At Houston Methodist, we develop cutting-edge medical treatments and employ advanced technology platforms and programs to translate innovations into therapies and diagnostics that can be tailored to individual patient needs.

CPRIT Funding to Drive New Discoveries in Cancer Therapeutics Three Houston Methodist researchers have received funding from the Cancer Prevention and Research Institute of Texas (CPRIT) to address critical gaps in cancer research and therapeutics. CPRIT awarded Houston Methodist $4 million to further the RNAcore’s evolution from a research and clinical-grade RNA provider to the only academic group in the U.S. to provide integrated RNA therapeutics services that span from the conception of an idea to commercialization.

An Innovative New Tool to Enable Drug Discovery and Personalized Medicine A High-Impact/High-Risk Award from CPRIT is facilitating the development of a novel organoid platform – a mini-brain model that mimics glioblastoma, one of the deadliest forms of brain cancer. With a new High-Impact/High-Risk Award from CPRIT, Robert C. Krencik, PhD, assistant professor of neurosurgery, is developing a reproducible and physiologically accurate model of human glioblastoma by incorporating patientspecific glioblastoma stem cells within 3D spheres of human neural cells. This model can be utilized as a tool to screen drugs and test the effectiveness of potential treatment options for glioblastoma and other brain cancers. Using glioblastoma stem cells from individual patients will also enable a personalized approach to treatment selection.

“

This platform will not only serve as an important tool for drug discovery and personalized medicine, it will also enhance our understanding of cell interactions within the glioblastoma microenvironment.

”

– R obert C. Krencik, PhD Assistant Professor, Neurosurgery Houston Methodist

HOUSTON METHODIST ACADEMIC INSTITUTE |

Devising a Novel Combination Treatment for Aggressive Double-hit Lymphoma Assistant Professor of Immunotherapy in Oncology, Yulin Li, MD, PhD, received CPRIT funding to investigate the therapeutic efficacy of a new combination therapy for treating the aggressive double-hit lymphoma, or DHL cancer. DHL simultaneously activates multiple cancer-causing oncogenes, making it very difficult to treat with frontline chemotherapy. While inactivating oncogenes with targeted therapy effectively kills tumor cells, this effect is limited by relapse and treatment resistance. In contrast, immunotherapies can provide a long-term survival benefit but are less effective with DHL because of reduced expression of the common anticancer immunotherapy, CD20. Li believes that combining the treatment approaches in a targeted therapy that suppresses oncogenes together with anti-CD20 immunotherapy holds great promise.

“

If successful, this approach may lead to a new paradigm of coupling targeted suppression of multiple oncogenes with simultaneous engagement of the immune system.

”

– Y ulin Li, MD, PhD Assistant Professor of Immunotherapy in Oncology Houston Methodist

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HOUSTON METHODIST ACADEMIC INSTITUTE

Expanding the RNAcore to Encompass the Entire Cycle of Translation The RNAcore began as a core group for the National Heart, Lung and Blood Institute Progenitor Cell Biology Consortium, producing high-fidelity research and clinical-grade RNA, including mRNA, modified mRNA and noncoding RNA, for the support of fundamental research and clinical applications. In 2015, the Houston Methodist RNAcore was awarded

Fast-forward six years, and RNA therapeutics are on the tip

$4.8 million from the Cancer Prevention and Research

of everyone’s tongue. The development of mRNA vaccines

Institute of Texas (CPRIT) to expand the small RNAcore

against COVID-19 brought worldwide attention to the

supporting basic research and RNA construct development.

transformative potential of RNA-based therapeutics.

At the time, the RNAcore was the first academic entity in Texas to generate the new class of drugs known as RNA therapeutics. The grant funded support of the development and generation of RNA therapeutics, particularly for cancer immunology.

In 2020, CPRIT awarded Houston Methodist with an additional $4 million to expand the RNAcore into a state-of-the-art comprehensive RNA therapeutics facility that further enables academic and biotechnology groups to translate their ideas and innovations into therapies by providing services in

PRECISION MEDICINE |

development, manufacturing, quality control and preclinical and early-stage clinical testing of RNA drugs. The RNAcore’s industry partner VGXI has licensed their manufacturing processes to scale-up for late-stage trials and commercialization. The CPRIT funding helps the RNAcore to accelerate the drug discovery process for RNA therapeutics by significantly reducing the time needed to bring potential new treatments from bench to bedside. Under the leadership of John P. Cooke, MD, PhD, Joseph C. “Rusty” Walter and Carole Walter Looke Presidential Distinguished Chair in Cardiovascular Disease Research, and principal investigator of the CPRIT grant, the RNAcore has supported the development of several RNA-based

There are many biotech companies and academic institutes

therapies, including an mRNA vaccine for metastatic

that can quickly develop these therapies, but most lack the

melanoma cancer treatment. Promising preclinical data

means to translate their product into the clinic. Researchers

showing dose-dependent antitumor activity with the vaccine

at Houston Methodist have built critical infrastructure to

led to the creation of a spin-off company focused on mRNA-

support the democratization of mRNA therapeutics. This

based vaccine products for cancer. Daniel L. Kiss, PhD,

program is a single-entry point for the development of RNA

assistant professor of cardiovascular sciences, working

therapy candidates into transformative drugs and might be

with the RNAcore, has generated circular RNAs to block

the only program of this sort in an academic center.

the activity of overexpressed microRNAs in breast cancer.

“

Though the concept of using RNA-targeting for therapeutic purposes has been around for a while, clinical potential is only just being realized, an example being the COVID-19 mRNA vaccines. With CPRIT funding, the RNAcore will help accelerate the drug discovery process for RNA therapeutics by significantly reducing the time needed to bring potential new treatments from bench to bedside.

”

In 2020, under the leadership of John P. Cooke, MD, PhD, and principal investigator of the CPRIT grant, CPRIT awarded Houston Methodist with an additional $4 million to expand the RNAcore into a state-of-the-art comprehensive RNA therapeutics facility.

– John P. Cooke, MD, PhD Joseph C. “Rusty” Walter and Carole Walter Looke Presidential Distinguished Chair in Cardiovascular Disease Research Chair, Department of Cardiovascular Sciences Professor of Cardiovascular Sciences Houston Methodist

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HOUSTON METHODIST ACADEMIC INSTITUTE

Siemens Healthineers and Houston Methodist

Imaging Innovation Hub Empowers Researchers to Push Boundaries

The Houston Methodist Translational Imaging Center provides clinicians and researchers across the Texas Medical Center with access to advanced, high-performance imaging equipment to create a direct translational environment for innovation. Access to such high-throughput multimodality tools in a translational research setting is seen in very few centers in the world.

PRECISION MEDICINE |

Diego Martin, MD, PhD

Through a Siemens Healthineers and

examinations. These procedures use radiation and contrast

Houston Methodist multiyear consortium

load that pose a risk of renal failure and contrast reactions

agreement, the Research Institute is home

apart from the risks of cumulative radiation. Although the widely

to one of the world’s most powerful

available 3T clinical MRI can circumvent these undesirable

magnetic resonance imaging (MRI)

effects, it has its own limitations. The 7T clinical MRI scanner

machines – the Siemens 7 Tesla (7T)

may provide a good alternative as its superior spatial resolution

MAGNETOM Terra, which is the first 7T MRI of its kind

and shortened T1 relaxation time of stationary tissue results

in Texas and the first 7T MRI scanner approved for clinical use in the U.S. This agreement also emphasizes an interventional imaging partnership that allows clinicians and researchers to collaborate on developing new technologies for robotic- and image-guided navigation. The higher spatial resolution and improved contrast capabilities of the 7T MRI is being harnessed in clinical studies to more accurately localize the lesions that may 7T MRI Brain Scan

be responsible for seizures in epileptic patients with focal cortical dysplasia, the most common cause of medically

in superior contrast to blood than current 3T clinical MRI and

refractory epilepsy in children and the third most common

thereby may prominently display the lumen of the aneurysm

cause of medically intractable seizures in adults. For epilepsy

and the parent vessel. Experienced endovascular neurosurgeons

patients who are good candidates for surgery, equipping

and neuro-interventional radiologists plan to compare magnetic

the surgeon with more detailed information on the lesion

resonance angiographic images with clinical standard CT

sites has the potential to significantly improve surgical

angiographic or digital subtraction angiographic acquisitions

outcomes. Houston Methodist’s collaboration with Siemens is also enabling safer, more autonomous imaging with intracardiac echocardiography, or ICE, which allows physicians to focus their efforts and time on delivering therapy rather than

3T MRI Brain Scan

to determine when the 7T provides a significant advantage.

“

The array of advanced imaging technologies at the Research Institute Translational

dividing their attention with acquiring images. The use of

Imaging Center, the partnership with Siemens

robotic- and AI-assisted ICE imaging may provide simple

Healthineers and the strong interdisciplinary

and intuitive procedural navigation. C. Huie Lin, MD, PhD, assistant professor of cardiology, is leading an effort to

collaborations within our organization are

introduce image-based control for semi-autonomous

all major reasons for my excitement in the

robotic ICE imaging and to optimize the physician-robot

opportunity to join and help lead our efforts

interface.

to make imaging sciences a centerpiece of

The 7T is also allowing physicians to better monitor patients

innovation. The 7T Terra whole-body MRI, in

with small cerebral aneurysms over time and tailor their

addition to our other MRI research systems,

course of treatment as needed. Traditionally, follow-up for such patients is conducted with computed tomography

our advanced radiopharmacy GMP lab,

(CT) angiographic or digital subtraction angiographic

cyclotron, PET facilities and our imaging scientists are vital building blocks that support development of a world-class

A ribbon-cutting ceremony to celebrate the new imaging center and its capabilities was held on June 26, 2019. Leaders from Houston Methodist, Siemens and across the Texas Medical Center enjoyed tours and demonstrations of the most advanced, high-performance equipment for imaging research and innovation.

translational research center. – Diego R. Martin, MD, PhD Professor and Chair, Department of Radiology Houston Methodist

”

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HOUSTON METHODIST ACADEMIC INSTITUTE

Novel Monoclonal Antibody Treatment

Halts Tumor Growth in Deadly Ovarian and Pancreatic Cancers A research collaboration between Houston Methodist and The University of Texas MD Anderson Cancer Center has identified a promising new antibody therapy for late-stage ovarian and pancreatic cancers. Termed “silent killers,” these cancers often go undetected until it is are too late to treat.

Stephen T.C. Wong, PhD, from Houston Methodist Dr. Mary and Ron Neal Cancer Center, and Samuel Mok, PhD, from The University of Texas MD Anderson Cancer Center, are collaborating to create an antibody as a new type of immunotherapy.

PRECISION MEDICINE |

For any tumor, its surrounding environment plays a crucial role

antibody 130A that successfully blocked MFAP5 in preclinical

in promoting growth and progression. Tumor microenvironment

models of ovarian and pancreatic cancer. Developed and

is composed of different types of cells and proteins, each of

patented by Wong and Mok, the antibody prevented the

which influences cancer cell growth, migration and differentiation.

formation of new blood vessels within the tumor, thereby cutting off the support needed for tumor growth and

A group of researchers led by Stephen T.C. Wong, PhD, from

proliferation. It also enhanced the bioavailability and

Houston Methodist Dr. Mary and Ron Neal Cancer Center,

effectiveness of other chemotherapy drugs and inhibited

and Samuel Mok, PhD, from The University of Texas MD

tumor growth as well as progression. Most importantly,

Anderson Cancer Center, identified a protein called MFAP5,

treatment with the MFAP5-targeting antibody curbed tumor

which was elevated in the tumor microenvironment of both

progression without producing noticeable toxic effects.

ovarian and pancreatic cancers. They also showed that MFAP5

Co-corresponding authors Wong and Mok published their

plays a crucial role in promoting metastasis of these cancers,

findings in the journal Clinical Cancer Research.

stimulating blood vessel formation within the tumor and enhancing cancer cells’ resistance to chemotherapy drugs. This made

“The lack of side effects can be attributed to the fact that

MFAP5 a promising therapeutic target for treating ovarian

MFAP5 is expressed at very low levels in normal cells

and pancreatic cancers.

compared to cells in the tumor microenvironment, which makes this therapy highly targeted,” said Wong.

To test if blocking MFAP5 produced a desirable anticancer effect, Wong and colleagues devised a new monoclonal

After demonstrating the efficacy of their monoclonal antibody in preclinical models, the team’s next step will be to design an anti-MFAP5 antibody that can be used in human studies. According to Wong, this work requires the seamless convergence of expertise across varied disciplines such as biological science, computational science and engineering, making this a truly multidisciplinary effort.

Wong and Mok created the antibody to block the action of the MFAP5 protein, secreted by the cells that surround and support ovarian and pancreatic tumor cells.

“

Finding an effective targeted treatment for two of the most lethal cancers is like the holy grail of cancer research. This translational discovery has raised the prospect of developing a treatment for late-stage ovarian and pancreatic cancers.

”

– S tephen T.C. Wong, PhD John S. Dunn Presidential Distinguished Chair in Biomedical Engineering Professor of Computer Science and Bioengineering in Oncology Cancer Center Houston Methodist

Houston Methodist Institute for Technology, Innovation & Education (MITIE ) SM

Over the past decade, the Houston Methodist Institute for Technology, Innovation & Education has become one of the most advanced simulation education and clinical research facilities in the world. At MITIE, our experts can

development within the research core, confirm efficacy

continually refine their skills

within a simulated clinical environment and disseminate

and acquire new expertise

to practicing physicians within the training area and

to perform at optimal levels

MedPresence Suite.

as well as advance new innovations and develop

Under the new leadership of Alan Lumsden, MD, Walter W.

the metrics required to define procedural competence in a

Fondren III Presidential Distinguished Chair, DeBakey Heart

hands-on simulated clinical care environment. The integrative

& Vascular Center, MITIE is closely working with experts

design of the institute’s research and training spaces enables

throughout the organization to further align Houston Methodist’s

our experts to effectively collaborate within MITIE throughout

research and education efforts with the Centers of Excellence

the entire progression of technological or procedural

in a venture that will synergistically expand all of our programs.

Alan B. Lumsden, MD Randolph H. Steadman, MD

PRECISION MEDICINE |

MITIE has become an incubator for innovative ideas and technological advances that offers an extensive array of resources for training, research and device development. MITIESM Simulation Center offers a procedural and clinical environment for simulation in education and research. The Institute for Robotics, Imaging and Navigation connects conceptualization to rapid prototyping related to robotics to transform ideas into products and processes.

“

Houston Methodist is a clinical powerhouse. Aligning our education and research efforts with our Centers of Excellence allows us to share these clinical strengths. We are building relationships with collaborators and experts that create a powerful synergy as we continually expand.

The Center for Rapid Device Translation connects industry with subject matter experts in clinical and translational medicine to collaborate on preclinical device development and good laboratory practice on the path to FDA approval.

“

– Alan B. Lumsden, MD Walter W. Fondren III Presidential Distinguished Chair, DeBakey Heart & Vascular Center Professor and Chair, Department of Cardiovascular Surgery Houston Methodist

Surgical Technology Developed in MITIESM Gains FDA Approval MITIE played an integral role in the development of a new device called StimSite that creatively solves an issue confronted by surgeons during the three million procedures in the U.S. annually that involve making incisions near the ureters. StimSite was devised by Albert Huang, MD, a former Houston Methodist surgical resident and research fellow and current founder and CEO of Allotrope Medical and TMCx entrepreneur in residence. The device provides general, ob/gyn and colorectal surgeons with an elegant tool to help locate and avoid the ureters. After years of planning, prototyping and testing, Huang’s device received FDA clearance in November 2020. When the StimSite device generates a specifically calibrated current in the lower abdomen, the famously difficult-to-locate ureters are the only structures in the vicinity containing the smooth muscle needed to respond to electrical stimulation. The rhythmic movement of the stimulated ureters makes it much quicker and easier for surgeons to locate and avoid the ureters when performing surgical procedures in the region. Huang began the clinical pilot studies on StimSite by training ob/gyn surgeons from a private practice to use the device at MITIE.

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HOUSTON METHODIST ACADEMIC INSTITUTE

Can Devices Provide A

New Treatment Option for Glioblastoma? Experts at the Houston Methodist Kenneth R. Peak Brain & Pituitary Tumor Treatment Center are developing new glioblastoma multiforme (GBM) treatment options, including an innovative technology that provides anticancer therapy through a wearable device.

David S. Baskin, MD

Santosh Helekar, MD, PhD

GBM is the most common

On a cellular level, they demonstrated that when OMFs are

and aggressive form

applied in a defined pattern at a certain range of frequencies,

of brain cancer. After

they disrupt electron flows in the mitochondrial electron

40 years of research,

transport chain that drives cellular fuel production. This

median survival with

disruption leads to the generation of reactive oxygen species,

aggressive treatment

triggering a cascade of cellular events that leads to cancer

has only improved from 9 to 15 months and the quality

cell apoptosis. Compared with normal cells of the same tissue

of life during this time is often poor.

type, cancer cells have critically high levels of reactive oxygen species at baseline that are poised to trigger apoptosis if

A team of researchers has developed a new method of

further increased.

generating an oscillating magnetic field (OMF) that eradicates cancer cells via a wearable device. These studies were made

With this information, the investigators further optimized the

possible by the prior invention of a wearable miniaturized

stimulus parameters of OMF stimulation and confirmed safety

multifocal transcranial magnetic stimulator by Santosh

and efficacy in a humanized preclinical model of GBM. They

Helekar, MD, PhD, associate professor of neurosurgery, and

then modified the Helekar-Voss Transcranial Permanent

Henning Voss, associate professor of physics in radiology at

Magnet Stimulator device to construct a wearable prototype

Weill Cornell Medical College. The device uses microstimulators,

for humans called an Oncomagnetic device along with the

called oncoscillators, that rotate strong neodymium permanent

associated hardware, software and mobile applications.

magnets-devised patterns. Helekar and his colleagues have produced selective anticancer effects in patient-derived GBM and breast cancer cells in culture without damaging cultured normal cells.

“

We believe that our current investigations may help to establish Oncomagnetics as a GBM treatment that does not have the limitations of chemotherapeutic agents. Given that various cancerous cell types are susceptible to apoptosis by OMF-induced accentuation of reactive oxygen species, we hope to modulate our nascent OMF treatment to target other cancers.

”

– D avid S. Baskin, MD Kenneth R. Peak Presidential Distinguished Chair & Program Director, Neurosurgery Residency, Department of Neurosurgery Professor, Neurosurgery Houston Methodist

PRECISION MEDICINE | 43 PRECISION MEDICINE | 43

Houston Methodist Hospital’s New Paula and Joseph C. “Rusty” Walter III Tower Offers the

Most Advanced Treatments and Innovations Available

Houston Methodist’s Paula and Joseph C. “Rusty” Walter III Tower is home to sophisticated neurological and cardiovascular surgical suites specially designed for highly technical and minimally invasive image-guided procedures. Through the Siemens consortium, the Walter Tower and MITIESM have been outfitted with triple hybrid surgical suites that integrate robotic-assisted technology with the most advanced computed tomography (CT), angiography and magnetic resonance imaging technology available as well as a dual CT and positron emission tomography scanner that can illuminate specific biochemical processes in order to provide precise, efficient and safe surgeries for our patients and advance our clinical research endeavors.

New Virtual Intensive Care Unit Simultaneously Improves Patient Care and Bed Capacity The virtual ICU system has provided a great advantage to health-care providers during the COVID-19 pandemic as it reduces the amount of direct patient interaction needed, thereby limiting PPE use and potential exposure to pathogens. At the same time, the virtual ICU system increases the number of patients that can be cared for simultaneously and empowers clinical staff to provide earlier interventions. The virtual ICU provides continuous intensivist coverage for Houston Methodist’s 300+ ICU beds, offering additional support to bedside ICU teams. The virtual unit’s operations The coronavirus pandemic has escalated a digital

center is equipped with specialized software that captures

transformation within intensive care units (ICUs) where

and analyzes real-time clinical data to calculate each

remote monitoring technologies enable professionals to

patient’s stability or risk of deterioration, allowing the team

more efficiently and safely manage their patients.

to anticipate events and act quickly. Each of the ICU rooms is equipped with a virtual alert button so that the bedside

When the pandemic began, Houston Methodist accelerated

team can immediately alert the remote intensivist and

the timeline for completing ongoing virtual ICU programming

nurses. The patient rooms also contain two-way audiovisual

and construction. In March of 2020, we launched a

technologies for unobtrusive observation or communication

comprehensive virtual ICU system that utilizes specifically

between the patient, bedside team and virtual team.

tailored remote clinical surveillance and data analytics

Houston Methodist has also deployed tablets for health-

platforms as well as interactive video conferencing.

care providers to perform “virtual rounds” on patients.

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HOUSTON METHODIST ACADEMIC INSTITUTE

Neuroimaging Offers

New Insights into Neurodegeneration

PRECISION MEDICINE |

At a time when most efforts to combat Alzheimer’s disease were focused on amyloid protein, Joseph C. Masdeu, MD, PhD, Graham Family Distinguished Chair for Neurological Sciences and director of the Nantz National Alzheimer Center at the Houston Methodist Neurological Institute found evidence that Alzheimer’s development was associated with an abnormal folded tau protein derived from the normal tau proteins that neurons use to form the white matter highways that facilitate communication among the brain’s various networks.

With the use of magnetic

These findings, published in Neurology, suggest that tau, rather than amyloid, is the critical factor in the development

resonance imaging (MRI)

of neurodegenerative disorders.

combined with 18F-FDG,

Masdeu was the first to demonstrate in vivo that abnormal

F-flortaucipir and 18F-AV-1451

positron emission tomography (PET), Masdeu’s group was the

tau proteins spread throughout human brain networks using white matter tracts. The Journal of Nuclear Medicine study combined MRI and 18F-flortaucipir PET to study tau protein behavior in a tau-dependent progressive neurodegenerative disorder that affects the languagerelated syntactic neural network. In the study participants,

first to report that brain areas

tau accumulation likely began in the anterior frontal node

with abnormal tau protein

lobe. The arcuate fasciculus white matter tract connecting

deposits had decreased

node, corresponding to a loss of neurons in the anterior node.

metabolism, a sign of low

This discovery reveals a window of opportunity for treatment,

and travelled to the spatially separate posterior temporal these regions was most affected near the anterior frontal

because to jump from neuron to neuron, tau appears

regional activity. The tau accumulations form the neurofibrillary tangles seen in Alzheimer’s disease and other neurodegenerative disorders.

to become extracellular – and possibly amenable to immunotherapy using antibodies that target this abnormal protein to hamper the spread, thereby preserving neural networks. Three clinical trials are underway at the Nantz National Alzheimer Center using anti-tau antibodies from Abbvie, Biogen and Eli Lilly.

INNOVATIVE EDUCATION

Launching a Legacy of Leading Medicine Houston Methodist is committed to building transformative education experiences at the intersections and gaps between disciplines through health science and medical education programs. Houston Methodist is not degree-granting; rather, we forge academic partnerships that bring in measurable results today and offer greater opportunities for tomorrow. Our residencies, fellowships, research doctoral program and continuing education programs in medicine, research, nursing and pharmacy attract more than 41,344 learners from around the world each year.

Building a Weill Cornell Graduate School of Medical Sciences Campus at Houston Methodist The Weill Cornell Graduate School of Medical Sciences (WCGS) has expanded its PhD program to an additional campus at Houston Methodist Academic Institute, the research and education arm of Houston Methodist Hospital in the Texas Medical Center. This is a new enhancement, building upon the John P. Cooke, MD, PhD

Barbara L. Hempstead, MD, PhD

16-year academic affiliation between Weill Cornell Medicine and Houston Methodist to train the next generation of physicians and scientists.

WCGS faculty at the New York campus will provide the didactic curriculum via remote learning with mentoring by WCGS faculty at the Houston campus. The thesis research will be performed at the Houston Methodist Academic Institute, under the direction of WCGS faculty located at both the Houston and NYC campuses. Graduate students and WCGS faculty based in Houston will visit New York City for program retreats and graduate school events. In turn, graduate students and faculty based in New York City can benefit from Houston-based faculty expertise and state-ofthe-art facilities and technology at the Houston Methodist Academic Institute. This collaboration will enhance the experience of students and faculty at both locations, promote scientific interactions and add diversity to the student body.

HOUSTON METHODIST ACADEMIC INSTITUTE |

Engineering Medicine (EnMed) The Nation’s First Training Program at the Convergence of Medicine and Engineering In August of 2019, Texas A&M University and Houston Methodist launched the EnMed program to instill a new generation of “physicianeers” with the skills to create innovative technological solutions that can transform patient care.

The EnMed program integrates medical education and research focused on innovation and entrepreneurship to empower future professionals with the clinical skills needed to diagnose and treat patients along with the engineering mindset to solve problems, invent new technologies and rapidly move these innovative ideas to practice inpatient care.

The EnMed program is housed in an 18-story office building acquired and renovated by Texas A&M. The building will be the focal point of the future Texas A&M Innovation Plaza, a 5-acre campus currently being constructed. The students have access to a simulation center, which occupies an entire floor, a makerspace so students can print 3D models for prototypes. Most of their didactic training will be in this building, but all wet anatomy labs happen at the Houston Methodist campus.

The 34 students who entered the EnMed program in 2020 came from a variety of educational backgrounds, including biological systems engineering, chemical engineering, material physics, mechanical engineering and mathematics. Many of these students are ready to embark on capstone projects, which are two-year mentored projects involving innovative research and technology development that directly address clinical or biomedical challenges. These projects will be conducted at Houston Methodist.

HOUSTON METHODIST ACADEMIC INSTITUTE

Neural Control of Organ Degeneration and Regeneration (NeuralCODR) Training Program

The training program can be distinguished from traditional physiology or neuroscience programs by its strategic focus on the interface between regeneration/disease organ model systems and functional neuroanatomy and physiology. NeuralCODR was conceived by Philip Horner, PhD, and a team of expert faculty from across several Texas Medical Center institutions with a rich history of research training, clinical modelling and education, including Rice University, University of Houston, The University of Texas MD Anderson Cancer Center, The University of Texas Health Science Center at Houston and Baylor College of Medicine.

opment vel De ools al nd T a

d an g in

Ne ur

The 2020 NeuralCODR Fellows

NEURALCODR FELLOWS

The NeuralCODR training program is an interdisciplinary training program at the intersection of neurophysiology and organ engineering/modeling that investigates how the central nervous system communicates with other organ systems.

Neural Innerv Organ Eng atio ine n er

Caroline Cvetkovic, PhD For her NeuralCODR fellowship in the lab of Robert Krencik, PhD, Cvetkovic is investigating the relationship between astrocytes and neurons in the brain. She is developing human stem-cell derived 3D neural tissue cultures to gain deeper insights into neuronal development and degeneration that could someday lead to regenerative clinical therapies.

Betsy Salazar As a NeuralCODR fellow under the guidance of Alvaro Munoz, PhD, and Timothy Boone, MD, PhD, Salazar is investigating the impact of therapeutic drugs on functional recovery following spinal cord injury in rodent models. She is specifically interested in assessing motor function recovery using behavioral tests as well as assessing the impact that treatments have at the cellular level.

d N an r Pe e r v o u s S y s t e m orde ri p s h e ra l O rgan Di

48 |

INNOVATIVE EDUCATION |

Faculty and Research Development Houston Methodist bolsters academic productivity throughout our researchers’ careers with a full complement of individually tailored resources that includes one-on-one professional development guidance, cohorted courses and customized workshops. Our experienced development team provides services essential to developing strategic academic priorities and securing extramural funding, including matching our experts with appropriate funding opportunities and providing planning and writing support for grant proposals, manuscripts, outcomes/big-data protocols Dorothy Lewis, PhD

Salim Allana, MD

and other academic publications.

In 2020, two new courses open to both trainees and faculty were launched via videoconferencing. The recorded sessions are currently available on the Academic Institute’s website. A seminar series Key Elements of Clinical Research details essential elements of planning and conducting clinical research including clinical trial design, working with industry, project presentation and grantsmanship. The Concept to Commercialization seminar lays the foundation for translating key laboratory discoveries to clinical uses that improve patient lives. It provides a practical and efficient process for researchers to bring their innovations to the market.

125

Grant applications were submitted through Academic Affairs 95 through Faculty Development and 30 through Research Development

577

Mentorships hours

50 |

HOUSTON METHODIST ACADEMIC INSTITUTE

Graduate Medical Education Houston Methodist provides an academic health-care environment that promotes comprehensive learning opportunities for more than 41,000 medical students and physicians each year through medical student rotations, residency and fellowship programs, MITIESM procedural skills training and continuing education courses. Our 920 medical students work with inpatient teams and one-on-one with subspecialists during rotations in general surgery, family medicine, internal medicine, orthopedic surgery and obstetrics and gynecology. Houston Methodist has 336 residents and fellows placed within 45 programs accredited by the Accreditation Council for Graduate Medical Education (ACGME) and nine Graduate Medical Education Committee-sponsored fellowships. On Match Day in March 2020, 60 medical students from around the world officially became incoming residents at Houston Methodist for the 2020-2021 academic year. Of the new group of residents, 32 hailed from U.S. News & World Report-ranked medical schools.

336

RESIDENTS/FELLOWS

GRADUATE MEDICAL EDUCATION PROGRAMS

ACGME ACCREDITED

NON-ACGME ACCREDITED

INNOVATIVE EDUCATION |

Mayo Clinic

Cleveland Clinic

Massachusetts General Hospital NYU Langone Mount Sinai UPMC Mercy University of Pennsylvania

UCSF Medical Center Stanford Hospital

Keck Hospital of USC UCLA Medical Center Mayo Clinic

Our residents and fellows join Houston Methodist from throughout the U.S., and go on to prestigious fellowship opportunities at institutions including Mayo Clinic, Cleveland Clinic, and Massachusetts General Hospital.

Houston Methodist Academic Institute The Houston Methodist Academic Institute oversees the Research Institute and Education Institute, including 775 faculty and 41,344 learners. The Academic Institute aligns our research and education initiatives in service to the clinical mission, providing solutions that answer the call for new technologies and skills our clinicians need for patient care. The Houston Methodist Research Institute supports research programs and infrastructure that enable faculty across the system to bring new scientific discoveries to patients as rapidly as possible through the full cycle of a cure from conceptual bench research, to prototyping and development, to clinical trials and FDA approval. The Institute supports more than 1,470 clinical research protocols and $64.1 million in extramurally funded translational research programs. The Houston Methodist Education Institute coordinates our primary academic affiliation with Weill Cornell Medicine and joint programs, including the EnMed engineering medicine program with Texas A&M University. The Institute also oversees continuing medical education and graduate medical education and supports more than 3,355 trainees in residence for medical, nursing, allied health and research education programs.

Houston Methodist Academic Institute 6670 Bertner Avenue, Houston, TX 77030 | 713.790.3333 | houstonmethodist.org

Houston Methodist Academic Institute | houstonmethodist.org

Houston Methodist Academic Institute Annual Report 2021

Articles inside

Faculty and Research Development

Graduate Medical Education

Engineering Medicine (EnMed

Neural Control of Organ Degeneration and Regeneration (NeuralCODR) Training Program

Houston Methodist Hospital’s New Paula and Joseph C. “Rusty” Walter III Tower Offers the Most Advanced Treatments and Innovations Available

Can Devices Provide A New Treatment Option for Glioblastoma?

Houston Methodist Institute for Technology, Innovation & Education (MITIESM

Novel Monoclonal Antibody Treatment Halts Tumor Growth in Deadly Ovarian and Pancreatic Cancers

Siemens Healthineers and Houston Methodist Imaging Innovation Hub Empowers Researchers to Push Boundaries

Expanding the RNAcore to Encompass the Entire Cycle of a Cure

Dissolvable Implants Enhance the Body’s Ability to Heal Broken Bones

Devising a Novel Combination Treatment for Aggressive Double-hit Lymphoma

Non-invasive Spinal Stimulation Enables Paralyzed People to Stand Unassisted

Houston Methodist and Rice University Launch Center for Translational Neural Prosthetics and Interfaces

Breast Cancer Survivors Find a Way to Maintain Healthy Lifestyles and Lose Weight on Their Phones

The Ann Kimball and John W. Johnson Center for Cellular Therapeutics

COVID-19 Spotlights Social Determinants of Health

Mobile App Improves Joint Replacement Surgery Outcomes

Paula and Joseph C. “Rusty” Walter III

Jerold B. Katz Academy of Translational Research

Houston Methodist Researchers Step Up and Face the Challenges of COVID-19 Virus

The Fondren Food & Health Alliance and The Fondren Inflammation Collaboration