Methodology Newsletter - Summer 2018 by Houston Methodist Professional Publications

METHODOLOGY The Research and Education Newsletter of Houston Methodist

Summer 2018

Houston Methodist Readies 71 Sites for Neuroregenerative Clinical Trials by Gale Smith

A $6 million, five-year clinical trial readiness grant funded by the National Institute of Neurological Disorders and Stroke will be led by Tetsuo Ashizawa, MD, director of the neurosciences research program at Houston Methodist. He will marshal the combined forces of 71 institutions across the globe in establishing the world’s largest cohort of subjects facing the earliest stages of a rare, inherited neurodegenerative disorder, spinocerebellar ataxia. Spinocerebellar ataxia (SCA) is characterized by degeneration of the brain and spinal cord with progressive clumsiness and difficulty balancing, typically leading to total disability and death. It causes loss of neurons in the cerebellum, which controls coordination, and leads to progressive uncontrollable irregularity of hand, speech and eye movement. The degeneration process mimics that of Huntington’s disease, Parkinson’s disease and amyotrophic lateral sclerosis (ALS).

>> CONT. PAGE THREE

“

By leading this global collaboration, we empower researchers to collect data about this rare disease, which otherwise would be unobtainable.

”

– Mauro Ferrari, PhD President & CEO Houston Methodist Research Institute

FROM THE PRESIDENT

Contents

Focused on translation and collaborative by design—this is the driving spirit of the Houston Methodist Research Institute. Our cover story demonstrates how this approach can change the world. Dr. Tetsuo Ashizawa is coordinating an international Spinocerebellar Ataxia clinical trial readiness consortium of over 71 sites in the U.S. and

Cover

Europe—and is expected to continue to expand. These connections

Houston Methodist Readies 71 Sites for Neuroregenerative Clinical Trials..................................... 1

create a network with local, national and international institutions dedicated to advancing treatments for SCA. We also believe that having physicians and scientists working in the

Research Highlights

same physical space fosters a culture of translational collaboration.

History-Making Gift Transforms the Future of Innovation.............................4

In this issue, you will read about the historic philanthropic gift from Paula and Joseph C. “Rusty”

New Blood Pressure Guidelines........6

their new ideas to life in collaboration with scientists.

Tiny, Time-release Beads Fight Infection After Joint Replacement.....8

Read on and you will learn about more collaborations like a study rated as one of the Journal of

Bioengineered “Asteroids”.............10 Type 2 Diabetes Shows Potential to Propagate Similar to Prions.......12 Immunology Team Takes Aim at T-Cells..........................................14 Cultivating the Healing Power of Nature..........................................16 Comparison of Surgeons Favors Females Over Males–Slightly.........18

Walter that cultivates this approach. The visionary gift supports two funds that help physicians bring

Experimental Medicine’s ten most exciting discoveries of 2017. Drs. A. Osama Gaber and Omaima Sabek worked with others in the Texas Medical Center to find unexpected parallels between the genesis of type 2 diabetes and prion diseases. In another neuroscience study, colleagues at the University of California, San Francisco and the National Institute of Neurological Disorders and Stroke worked with Dr. Robert Krencik to create miniature 3-D mini brain models that closely mimic brain microenvironments. I hope you enjoy reading about these collaborations that are advancing research and helping patients live healthier lives. Together we are changing the future of medicine.

Awards & Accolades.............................19

Education News LCME Approves EnMed to Recruit Inaugural Class......................................20 China’s Top Science Advisory Think Tank........................................ 21 Expanding the Reach of Research-Based Education............. 22

Mauro Ferrari, PhD Ernest Cockrell Jr. Presidential Distinguished Chair President and CEO, Houston Methodist Research Institute Director, Institute for Academic Medicine at Houston Methodist Executive Vice President, Houston Methodist Senior Associate Dean and Professor of Medicine Weill Cornell Medical College, New York, NY

Of Interest A Birds-Eye View: Collaboration within the Texas Medical Center....24

Board of Directors • Houston Methodist Research Institute

New Faculty Recruits............................26 Upcoming Events..................................28

Steven D. Arnold

Carrie L. Byington, MD

Antonio M. Gotto Jr., MD, DPhil

Gregory V. Nelson

David C. Baggett, Jr.

Joseph R. "Rod" Canion

Mark A. Houser

Mary Eliza Shaper

John F. Bookout, Jr.

Stephen I. Chazen

Catherine S. Jodeit

Andrew C. von Eschenbach, MD

John F. Bookout, III

Augustine M.K. Choi, MD

Evan H. Katz

Joseph C. "Rusty" Walter, III

Marc L. Boom, MD

John P. Cooke, MD, PhD

Rev. Kenneth R. Levingston

Martha Walton

Timothy Boone, MD, PhD

Dan O. Dinges

Kevin J. Lilly

Elizabeth Wareing

Giorgio Borlenghi

Mauro Ferrari, PhD

Vidal G. Martinez

Judge Ewing Werlein, Jr.

Read more online: issuu.com/instituteforacademicmedicine

>> CONT. FROM PAGE ONE

Over the next five years, Ashizawa and colleagues will establish the world’s largest list of study participants at the earliest disease stages, when they are most likely to benefit from treatment. The study will incorporate MRI biomarkers to detect disease onset and early

“ Colleagues at several U.S.

progression—even in pre-symptomatic individuals.

and European locations are

By consolidating the findings of over 70 institutions,

showing promising results

researchers will collect enough clinical, imaging and

in preclinical research for

biochemical data about this rare disease to allow them to design clinical trials that generate the most

investigational therapies

conclusive results on effective treatment. The multi-site project will include well-established ataxia physicians

focused on SCA1 and SCA3.

and scientists in approximately 20 U.S. locations and two European ataxia consortia comprised of

Now is the time for us to

58 investigators from 23 institutions across Europe.

bring therapies to patients.

Ashizawa, a neurologist in the Houston Methodist Neurological Institute, led the previous NIH-funded study of spinocerebellar ataxias from 2009-2013,

”

– Tetsuo Ashizawa, MD Harriet and Joe B. Foster Distinguished Chair in Neurosciences, Stanley H. Appel Department of Neurology Professor of Neurology Director, Neurosciences Research Program Houston Methodist

and still serves on the Medical Research Advisory Committee of the National Ataxia Foundation. His goal is to bring these investigational therapies to patients within the next several years.

ASHIZAWA U01 CLINICAL TRIAL SITES

North America

Asia

Houston Methodist Africa South America 3

RESEARCH HIGHLIGHTS

History-Making Gift Transforms the

Future of Innovation Houston Methodist has received a rare gift from Paula and Rusty Walter and the Walter Oil & Gas Corporation. The $101 million philanthropic gift—the largest in the institution’s nearly 100-year history—will expand translational research and establish a neurorestoration research program. Through a matching fund that will increase the number of endowed chairs to 100 in recognition of Houston Methodist’s 100-year anniversary in 2019, the total impact of the gift will reach $167 million. What really makes this gift unique is its focused plans for maximum impact: endowed chairs to attract top talent, seed funds to promote collaboration and innovative ideation, and the foundation for a dedicated program in neurorestoration. The first recruit for the neurorestoration program has already joined the Houston Methodist neurosurgery department. Dimitry Sayenko, PhD, a scientist from the University of California, Los Angeles, studies mechanisms to restore neurological control of movement and balance. The gift’s largest component establishes two seed funds, one dedicated to collaborative innovation and the second to expand the Translational Research Initiative. Together they create an entrepreneurial platform for physicians with new ideas they are developing for clinical use, while promoting collaboration between scientists and physicians to design new solutions for clinical challenges that require knowledge from multiple disciplines.

Paula Walter and Rusty Walter

Rusty Walter has unique insight into the value of this research. After suffering a stroke in 2013, he enrolled in two clinical trials at Houston Methodist during his recovery. The experience showed him first-hand how close the field of neurology is to making significant breakthroughs with the right kind of support.

“ As I continue to recover from my stroke, Paula and I thought we could help make

Paula and Joseph C. “Rusty” Walter III Tower

a difference by supporting research through the Walter Neurological Restoration Initiative.”

– Rusty Walter

Rusty has served on the Houston Methodist Board of Directors since 2006. His father, Joseph C. Walter Jr., was a devoted hospital board member for more than 30 years and underwent a lifesaving heart transplant at Houston Methodist. In mid-2018, The Paula and Joseph C. “Rusty” Walter III Tower opens in the Texas Medical Center to provide 366 patient beds and high-tech operating room suites for neurosurgery and cardiovascular surgery, two intensive care floors, six acute care floors and a helipad. This 954,705-square-foot tower will serve Houston Methodist’s growing patient population.

“ The Walters are treasured members of our Houston

Methodist family. This gift will fund some of the world’s best physicians and scientists, bringing important cures and treatments to our

”

patients.

– M arc Boom, MD President and CEO Houston Methodist

RESEARCH HIGHLIGHTS

New Blood Pressure Guidelines: What’s Good for Some May Not Be Best for All by Lisa Merkl

Houston Methodist’s Chief Medical Officer is challenging the new guidelines for hypertension—with the goal of sparing 10 million people from unnecessarily aggressive Robert A. Phillips, MD, PhD, FACC

blood pressure treatments. Among the nation’s leading cardiologists,

The number of Americans under 45 with the

Robert A. Phillips, MD, PhD, collaborated

condition has doubled.

with numerous colleagues to investigate the impact of new guidelines that redefine high blood pressure. Issued in November 2017 by the American Heart Association, American College of Cardiology and nine other professional health organizations, the guidelines classify hypertension as a reading of 130/80 mm Hg, compared to the standard since 1993: 140/90 mm Hg. Under the new tightened rules, 46 percent of U.S. adults are considered hypertensive, up from 32 percent. The new guidelines also recommend treating all hypertensive patients with a risk greater than 10 percent, based on a standardized formula, but without considering a patient’s individual health issues. The change has increased the number of Americans with high blood pressure from 72 million to 103 million, or from 32 percent of adults to 46 percent.

Phillips, an expert in hypertension and cardiovascular disease, is concerned that while patients at higher risk for cardiovascular disease benefit from the stricter guidelines, those with lower risk may face more harm than benefit from the intensive treatment recommendations— potentially causing kidney damage, dizziness, falls and other adverse reactions. He recommends a more patient-centered approach. The new rules were written by a panel of 21 scientists and health experts who reviewed more than 900 published studies. Their call for more aggressive treatment was based largely on data from the Systolic Blood Pressure Intervention Trial, or SPRINT, a large-scale study of more than 9,000 people, sponsored by the National Institutes of Health’s National Heart, Lung and Blood Institute.

Based on the same data, Phillips and his colleagues

“Classifying patients by degree of future risk might be

performed a secondary analysis and suggest a different

the best way to identify who could benefit most from

strategy that places on medication only a subset of

intensive treatment,” Phillips said. “We developed a

patients with blood pressure between 130/80 and

model using the 10-year cardiovascular disease risk

140/90—those who have at least an 18.2 percent

and found that aggressive treatment of patients with

risk of a cardiovascular event in the coming 10 years,

a risk greater than or equal to 18.2 percent would

according to information doctors plug into a commonly

result in more benefit than harm, while those with

used formula. That formula recommends forestalling

a risk of less than that would fare better under a

medication and instead relying on healthier lifestyles,

standard blood pressure management approach.”

including diet and exercise, to reduce their numbers.

While it’s estimated that 107,500 deaths could be averted annually in the United States by implementing more aggressive treatments, that may be accompanied by other serious, adverse events. This presents clinicians and patients with a dilemma, potentially trading one clinically significant condition for another.

“

– R obert A. Philips, MD, PhD, FACC Chief Medical Officer and Chief Quality Officer Professor of Cardiology, Institute for Academic Medicine Center for Outcomes Research Houston Methodist

Phillips shared his findings in The Journal of the American College of Cardiology. His co-authors include Jiaqiong Xu, PhD, Leif E. Peterson, PhD, MPH, and Ryan M. Arnold, MPH, from Houston Methodist; Joseph A. Diamond, MD, from the Department of Cardiology of Hofstra Northwell School of Medicine in Hempstead, New York; and Adam E. Schussheim, MD, with Cardiac Specialists of Northeast Medical Group at Bridgeport Hospital with Yale New Haven Health in New Haven, Connecticut. Phillips RA, Xu J, Peterson LE, Arnold RM, Diamond JA, Schussheim AE. Impact of cardiovascular risk on the relative benefit and harm of intensive treatment of hypertension. JACC. 2018 April; 71(15):1601-1610.

RESEARCH HIGHLIGHTS

Tiny, Time-Release Beads Fight Infection After Joint Replacement by Hannah Pietsch

More than 1 million people undergo total joint replacements each year, and nearly 10,000 will develop infections. While the risk of infection is present with any surgery, infections after a joint replacement are harder to treat: The metal implants are not connected to the bodyâ&#x20AC;&#x2122;s bloodstream, so the white blood cells sent to fight the infection cannot reach the implant and kill the bacteria.

To reduce this infection risk, a Houston Methodist orthopedic surgeon created small antibiotic beads that are implanted with the new joint to slowly release medicine for several weeks following surgery. Terry Clyburn, MD, developed the antibiotic microspheres that are as small as grains of salt and designed to release enough antibiotics to kill infections for three to six weeksâ&#x20AC;&#x201D;the timeframe when an infection is most likely to develop. Currently, most joint replacement patients are given intravenous antibiotics before and after surgery to help stave off an infection. By coating the implant in the antibiotic microspheres before placing

Terry Clybum, MD, holds a hip replacement implant that has been coated with the antibiotic microspheres that will resist infection over several crucial weeks while the body adjusts to the new joint.

several layers of antibiotics that slowly dissolve as they release the medication on the implant and surrounding tissues, leaving nothing behind in the joint that could lead to future problems for the patient.

”

– Terry A Clyburn, MD Surgeon, Orthopedics and Sports Medicine Houston Methodist

ANNUAL FACTS HOUSTON METHODIST

8 2,165 540,000 $131 M $51.2 M 1,182

it in the patient’s joint, the antibiotics are delivered directly to the surgical site to help prevent bacteria from developing into an infection. In studies to determine the efficacy of the microspheres, Clyburn and his colleagues contaminated two metal implants with staphylococcus aureus bacteria and coated one in the microspheres before inserting them in animal models. Zero infections developed in the model that

“915,817

Hospitals

Operating beds Sq.ft. research space

Research expenditures

Extramural funding

Clinical studies

Patient encounters

22,381

Employees

4,387

Physicians

1,900

Credentialed researchers

received the microspheres. Clyburn, who has been

Dave B, Gonzalez DD, Liu ZB, Li X, Wong H, Granados S, et. al. Role of RPL39

working for 15 years to develop these microspheres,

in Metaplastic Breast Cancer. J Natl Cancer Inst. 2016 Faculty Dec 31;109(6)

is currently seeking FDA approval and hopes to see them used widely in three to five years.

637

29,171 289

Dr. Clyburn developed the microspheres in collaboration with Antonios Mikos, PhD, Louis Calder Professor and Director, Center for Excellence in Tissue Engineering and J.W. Cox Lab, Bioengineering at Rice University, and Catherine Ambrose, PhD, Associate Professor and Director of the Biomechanics, Bone Histomorphometry,

RESEARCH HIGHLIGHTS

“ These microspheres have

Total learners

Trainees-in-residence

GME programs

– Jenny Chang, M.D. Emily Herrmann Chair in Cancer Research & Director, Houston Methodist Cancer Center

and Bone Densitometry Laboratories, Department of Orthopedic Surgery at The University of Texas Health Science Center at Houston.

RESEARCH HIGHLIGHTS

Bioengineered “Asteroids” The Next Frontier for Exploring Neural Connections by Lisa Merkl

The next generation of brain research is underway, with a new model that quickly grows 3-D mini brains from stem cells. The model puts researchers on a fast track to exploring what’s behind diseasecausing mutations and repairing the nervous system after injury or disease of the brain and spinal cord. A team of researchers led by Houston Methodist neuroscientist

of human diseases, such as Alzheimer’s and autism spectrum

Robert Krencik, PhD, is the first to specifically engineer this

disorders.”

type of 3-D mini brain. Their success is partly due to the groups of specialized neurons they study: star-shaped cells known as “astrocytes”—coined “asteroids” by Krencik. Involved in most neural diseases and responsible for maintaining a healthy nervous system, astrocytes are key because they boost the neurons’ ability to communicate by increasing the number and strength of neuronal connections in the brain and spinal cord. “Our system can generate mature astrocytes that interact intimately with neurons to a greater extent than has been done before,” Krencik said. “Unlike other cells in the brain and in the rest of the body, astrocytes have unique properties in humans. They may be partly responsible for the unique cognitive functions of humans and also may underlie aspects

The team’s systematic process for putting together the cells creates a model that more closely resembles the complex interactions within the brain, in contrast with the way cells are broken apart in traditional lab practices. The result is accelerated maturation for both the astrocytes and their surrounding neurons. Krencik foresees using induced pluripotent stem cells, or iPS cells, from any disease or patient to form these mini brains to study the disease process, or to screen therapeutic compounds to aid in the development of drugs. Ultimately, the asteroids may be used to form functional neural circuits that researchers can experimentally manipulate for developing treatments and deciphering what makes diseases tick.

“ Normally, growing these mini brains takes months or years.

Our technique pre-matures the cells separately and then combines them, so within a few weeks they’re able to form mature interactions. The length of time to get to that endpoint for studies is dramatically reduced with our system.

”

– Robert C. Krencik, PhD Assistant Professor Center of Neuroregeneration Department of Neurosurgery Houston Methodist

Krencik, Robert et al. Systematic three-dimensional coculture rapidly recapitulates interactions between human neurons and astrocytes. Stem Cell Reports. 2017 Dec; 9(6):1745-1753. Researchers collaborating with Krencik on this paper include Philip J Horner, Nupur Basu, Caroline Cvetkovic and Saba Barlas with Houston Methodist Research Institute; Michael E Ward with the National Institute of Neurological Disorders and Stroke; and Li Gan, David H Rowitch, Erik M Ullian, Robert Chen, Connor Ludwig, Chao Wang, Kyounghee Seo and Jessy V van Asperen with the University of California, San Francisco. The work was supported by a Paul G. Allen Family Foundation Award, SFARI Award (345471), an NIH National Institute of Mental Health grant (R01MH099595-01), a gift from the That Man May See Foundation, an NIH National Eye Institute Core Grant for Vision Research (EY002162), and a Research to Prevent Blindness Unrestricted Grant.

RESEARCH HIGHLIGHTS

Type 2 Diabetes Shows Potential to

Propagate Similar to Prions by Laura Niles

The word “prion” came to the fore when researchers discovered that certain neurodegenerative diseases—specifically Mad Cow Disease and Creutzfeldt-Jakob disease—were caused by a type of protein, rather than by the usual suspects: a virus or bacteria. Since this revelation in 1982, the unusual ability of prions (short for “proteinaceous infectious particle”) to unfold and effectively damage normal proteins in the brain has been much studied. Now researchers have discovered another type of protein that

clustering prompts even more misfolding. In this way, the

behaves similar to prions—and appears to be linked to the

misfolded IAPP can self-propagate similarly to infectious prions.

infectious spread of type 2 diabetes. Osama Gaber, MD, J.C. Walter Jr. Presidential Distinguished Chair and director

To gain a better understanding of the role IAPP protein plays

of the Houston Methodist J.C. Walter Jr. Transplant Center,

in type 2 diabetes, the researchers seeded pre-formed IAPP

and Omaima Sabek, PhD, are part of the team that investigated

aggregates through a prion-like mechanism in isolated islet

this protein, called “islet amyloid polypeptide” (IAPP).

cultures and also in a transgenic mouse model. They found that when misfolded IAPP was injected into mice expressing

Like prions, the IAPP protein can prompt abnormal folding of

human IAPP, the mice began to express type 2 diabetes-like

normal cellular proteins. When they misfold in certain ways,

symptoms, such as hyperglycemia and impaired glucose

they accumulate, or “aggregate,” in deposits. In turn, this

tolerance. A similar outcome occurred in seeded pancreatic

tissue. Both outcomes suggested that transmission of type 2

such as a high-fat diet. This suggests that the prion-like

diabetes could follow a process of infectious transmission

mechanism plays a key role in spreading the disease from

similar to that of prion diseases.

cell to cell or islet to islet. Further studies are needed to understand the extent to which IAPP aggregation may

Importantly, this study showed that IAPP misfolding—on its

contribute to the spread of diabetes, and its full impact

own—can produce symptoms of type 2 diabetes without

on public health.

being affected by other known processes of the disease,

Protein

Misfolded Protein

Inactive Aggregates of Misfolded Proteins

These findings were published in a paper that was included in Journal of Experimental Medicine’s 10 most exciting discoveries in 2017. Mukherjee A, Morales-Scheihing D, Salvadores N, Moreno-Gonzalez I, Gonzalez C, Taylor-Presse K, Mendez N, Shahnawaz M, Gaber AO, Sabek OM, Fraga DW, Soto C. Induction of IAPP amyloid deposition and associated diabetic abnormalities by a prion-like mechanism. Journal of Experimental Medicine. Sep 2017; 214(9):2591-2610.

RESEARCH HIGHLIGHTS

Immunology Team Takes Aim at T-Cells by Lisa Merkl

T-cells, a type of white blood cell that plays a central role in helping the body fight infection, can be a threat when they “over-protect” the body. For instance, autoimmune diseases occur when T-cells cause the immune system to attack itself. But new discoveries by faculty in the Immunobiology & Transplant Science Center have cracked codes that could make T-cells’ unwanted attacks a thing of the past.

Understanding Autoimmunity May Transform Transplants Over-protective T-cells are the culprits when it comes to autoimmune diseases and transplant rejection. To understand the mechanisms involved, a team led by Wenhao Chen, PhD, in the Immunobiology & Transplant Wenhao Chen, PhD

Science Center, identified a

“

How to therapeutically inhibit IRF4 is the Nobel-prize winning question. If we can find a way to inhibit IRF4 as desired in activated T-cells, then I think most autoimmune diseases and transplant rejection will be solved.

critical switch that controls T-cell function—and dysfunction. And they have discovered a pathway to target it.

– Wenhao Chen, PhD Assistant Professor, Transplant Immunology in Surgery Houston Methodist

The team began systematically deleting different molecules in T-cells, which led to identifying a crucial

Now the team is aiming to inhibit only T-cells that have

molecule for controlling gene expression: the transcription

already been exposed to antigens, without activating

factor IRF4.

the so-called “naïve T-cells”—those that have never seen antigens and therefore produce no or little IRF4.

“When we delete IRF4 in T-cells they become

The team’s initial studies are promising. By inhibiting

dysfunctional,” Chen said. “However, you need them

IRF4 expression for 30 days, the typical time required

to remain functional to control infection. If we can

for transplant patients to remain infection free, they

find an IRF4 inhibitor, then those issues would be

see hope for prolonging patients’ tolerance of

solved—that’s big.”

transplanted organs.

”

Insight into Super-Enhancers Brings a Breath of Fresh Air The Journal of Experimental

When healthy, the lungs' inner lining, made of

Medicine, one of medicine’s

epithelial cells that keep their surface moist, secretes

oldest journals, recently

mucin to protect the airways. But mucin causes

published a study that explains

damage when it’s over-produced.

what causes the lungs’ airways

Xian C. Li, MD, PhD

to close during asthma attacks.

Li and his team discovered that T-cells, which aim

Written by Xian C. Li, MD, PhD,

to fight foreign toxins, communicate with mucin-

and his team at Houston

producing cells in the lungs by secreting a small

Methodist's Immunobiology &

protein called interleukin 9 (IL-9). The hyperactive

Transplant Science Center, the breakthrough study

T-cells also express a molecule called OX40, which

is leading them to develop a class of drugs that

organizes super-enhancers—regions of DNA that

offers hope for treatment that is radically different

control which genes become active—and cause

from the steroids currently used and could change

T-cells to over-produce IL-9.

the lives of 300 million asthma sufferers worldwide. Li’s team is using chemical inhibitors to find a new Asthma’s small airways and blocked airflow are

way to stop this assembly of IL-9 gene super-

caused by overproduction of mucin, a sticky protein

enhancers to prevent the production of IL-9. With

secreted by the mucous membranes in the lungs.

new possibilities for treatment, asthmatic patients can start breathing a little easier.

essence, OX40 presses the gas peddle in T helper cells, “ Inaccelerating the production of IL-9 through a powerful molecular machinery of super-enhancers that regulate gene expression. – Xian C. Li, MD, PhD

”

Professor, Transplant Immunology in Surgery Director, Immunobiology & Transplant Science Center Houston Methodist

Xiao X, Fan Y, Li J, Zhang X, Lou X, Dou Y, Shi X, Lan P, Xiao Y, Minze L, Li XC. Guidance of super-enhancers in regulation of IL-9 induction and airway inflammation. J E M. 2018 Feb; 215(2):559-574. This study was funded by two National Institutes of Health R01 grants (R01AI129906 and R01AI106200). Wu J, Zhang H, Shi X, Xiao X, Fan Y, Minze L, Wang J, Ghobrial R, Xia J, Sciammas R, Li XC, Chen W. Ablation of Transcription Factor IRF4 Promotes Transplant Acceptance by Driving Allogenic CD4+ T Cell Dysfunction. Immunity. 2017 Dec; 47(6):1114-1128.

RESEARCH HIGHLIGHTS

Cultivating the

Healing Power of Nature Everyone agrees that nature has the power to heal. But ask how it heals—and answers are in short supply.

The need to find answers grew out of Laura

environmental and occupational health

Bush’s passion for the land of Texas and the

sciences at the University of Washington

outdoors. While serving as First Lady, she

School of Public Health. He presented the

championed preservation of natural spaces

current evidence linking exposure to nature

and heritage by serving as Honorary Chair of

to lower blood pressure, improved recovery

the National Park Foundation and helping to

from surgery, better birth outcomes, lowered

found Preserve America. When she left the

need for pain management, and lower rates

White House, she was determined to continue

of specific conditions related to diabetes,

advancing conservation and connecting

weight, eyesight, allergies, cancer and

people to the great outdoors.

autoimmune disorders. The symposium also

In 2011, she founded Texan by Nature to spur conservation in her home state with Leaders of the three founding organizations announced the Center for Health & Nature on May 2: President & CEO Marc Boom, MD, of Houston Methodist, Founder Laura Bush of Texan by Nature, and Chancellor John Sharp of Texas A&M University System.

public and private partnerships. Four years later, she saw an opportunity to tap another great Texas resource, the Texas Medical

underlying biological mechanisms, exposure science and implementation science—all requiring rigorous, randomized, controlled studies of what interventions work.

Center, to explore how nature positively

Seeing the need for more research, Texan by

impacts health.

Nature board member and nature enthusiast

On September 12, 2016, Texan by Nature and Houston Methodist convened a diverse audience for a one-day symposium on a shared interest: the influence of nature on health. The state of the field was reviewed by keynote speaker Howard Frumkin, DRPH, MPH, MD, former dean and professor of

clarified the gaps in our understanding of the

Cynthia Pickett-Stevenson convened leaders from Houston Methodist, Texas A&M University and Texan by Nature to develop evidencebased and actionable recommendations for incorporating nature into public policy, clinical care and wellness plans. They had a plan in place by fall 2017 to establish the tripartite Center for Health & Nature.

We’ve only just begun to understand the depth of the connection between health and nature through scientific research….The question is not if nature provides those health benefits

“

but how it delivers those benefits.

– Laura Bush Founder, Texan by Nature

To support the center’s plans to promote healthy green space, Texas A&M University’s Landscape Architecture Department held a competition to select an evidence-based design of healing gardens in urban settings. Laura Bush is featured with winners Phillip Hammond (1st place), Leticia Meza (3rd place) and Claudia Pool (2nd place).

The Center was announced on May 2, 2018, by Laura Bush, Houston Methodist President & CEO Marc Boom, MD, and Texas A&M Chancellor John Sharp. The Center will conduct science

Vision for the

Center for Health & Nature

and provide guidelines for using nature-based interventions, initially under the guidance of interim director, Bita Kash, PhD. Kash is the director of the joint Center for Outcomes Research for Houston Methodist and Texas A&M. As part of the announcement, Texas A&M landscape architecture students presented designs for healing gardens at Houston Methodist Hospital.

• Catalyze health & nature research

VISION

• Drive innovation in health care

The new center is currently creating a $2.5 million Health & Nature Innovation Fund to support

• Guide conservation and public health policy

projects that develop evidence-based applications of nature to health and wellness. Current randomized and controlled pilot projects focus on stress, clinician burnout and heart health. One project will identify protocols for reducing physician and nurse burnout with greenspace exposure in the workplace. Another will measure the ability of natural environments to lower blood pressure and reduce stress levels in cardiology patient waiting rooms. The results of pilot projects and new research ideas in related fields will be presented at the second annual Health & Nature Research Symposium in 2019.

For information about contributing to the Center for Health & Nature, contact Houston Methodist Hospital Foundation at 832.667.5838. For general information, please contact Domenica Delgado at ddelgado@houstonmethodist.org or 346.238.0152.

RESEARCH HIGHLIGHTS

Comparison of Surgeons Favors Females Over Males–Slightly by Laura Niles

In the past few years, the 2017 March for Women and the Time’s Up Legal Defense Fund have drawn attention to the advancement of women, bringing increased scrutiny on the equality of women in all disciplines, including medicine.

longstanding stigma around female surgeons in the OR

Although patients of female surgeons were only four percent

may be the source of gender disparities that persist in both

less likely to die, the study garnered a good deal of attention.

number of female surgeons in the field and their pay.

It was picked up by Time magazine, and The New Yorker’s

A timely study published in late 2017 by Raj Satkunasivam, MD, assistant professor in the Department of Urology, compared surgical outcomes between males and females and found a

Health, Medicine & the Body Issue featured an animated cover of four female surgeons, which served as the impetus for the #ILookLikeASurgeon social media campaign.

small but statistically significant edge in favor of female surgeons. After controlling for age and experience, Satkunasivam and colleagues found that patients of female surgeons had lower rates of 30-day mortality.

Wallis, CJ, Ravi, B, Coburn, N, Nam, RK, Detsky, AS, Satkunasivam, R. Comparison of postoperative outcomes among patients treated by male and female surgeons: a population based matched cohort study. BMJ 2017;359:j4366.

AWARDS & ACCOLADES

Timothy Boone, MD, PhD, receives Victor A. Politano Award for outstanding research Timothy B. Boone, MD, PhD, chair of the Department of Urology at Houston Methodist Hospital, was awarded the American Urological Association 2018 Victor A. Politano Award for excellent clinical research and educational efforts in neurourology and neuroscience, including urodynamics, female pelvic medicine and spinal cord injury.

Robert Phillips, MD, PhD, FACC, to serve on AMA Medical Education National Advisory Panel Robert A. Phillips, MD, PhD, FACC, was invited by the American Medical Association (AMA) to serve as a member of the newly created AMA Medical Education National Advisory Panel. The 15-member panel will focus on Graduate Medical Education and will include representation from the Accreditation Council for Graduate Medical Education (ACGME), National Board of Medical Examiners, Veterans Administration and other health system leaders. Phillips is Chief Medical Officer and Chief Quality Officer, Houston Methodist, and professor of Cardiology, Institute for Academic Medicine.

Stephen Wong, PhD, elected IEEE Fellow Stephen T. Wong, PhD, the John S. Dunn, Sr. Presidential Distinguished Chair in Biomedical Engineering and professor of Systems Medicine & Bioengineering at Houston Methodist Research Institute, was elected IEEE Fellow for leadership in drug discovery, systems biology, bioinformatics, and health analytics. The IEEE is the largest technical professional organization in the world, with 400,000 members worldwide.

Janice Zimmerman, MD, MACP, MCCM, elected President of the World Federation of Societies of Intensive and Critical Care Medicine Janice Zimmerman, MD, MACP, MCCM, head of the Division of Critical Care Medicine and Program Director of the Pulmonary and Critical Care Fellowship at Houston Methodist, was elected President of the World Federation of Societies of Intensive and Critical Care Medicine. The Federation has a membership of over 80 national scientific societies with a combined individual membership of over 80,000 intensive and critical care practitioners throughout the world.

EDUCATION NEWS

LCME Approves EnMed

to Recruit Inaugural Class of

Physician Engineers

by Gale Smith

Poised to become the largest engineering-based medical degree program in the nation, Engineering Medicine is the nation’s first and only program to confer a doctorate of medicine and master’s in engineering in four years. The innovative track was included in the Liaison Committee on

Methodist Hospital. The curriculum’s case-based format will

Medical Education (LCME) accreditation of Texas A&M College

integrate medicine and engineering content to develop and

of Medicine’s MD program. The approval in April allows EnMed

improve student’s clinical reasoning and problem-solving skills

to matriculate students in July of 2019 and begin coursework

through real-world examples. During the program, every EnMed

on the Houston campus.

student will be required to design an innovation with ready clinical application.

The program is a result of the partnership between the Texas A&M Colleges of Engineering and of Medicine, and Houston

“ EnMed will be a signature program for the Texas A&M College of Medicine and will serve the state by offering unique training that will advance health care technologies and ultimately the health of Texans.

”

– Carrie L. Byington, MD Vice Chancellor for Health Services, The Texas A&M University System Senior Vice President, Texas A&M Health Science Center Dean, Texas A&M College of Medicine

Houston Methodist Research Institute Member Inducted into

China’s Top Science Advisory Think Tank by Maitreyi Muralidhar

Yuliang Zhao, PhD, a full affiliate member of the Houston Methodist Research Institute, was inducted into the Academic Divisions of the prestigious Chinese Academy of Sciences in November 2017. China’s highest academic recognition in science and technology, this lifelong honor is bestowed on individuals who are leaders in their fields. As the founder and director of the Key Laboratory for Biomedical Effects on Nanomaterials and Nanosafety at the Chinese Academy of Sciences (CAS) in Beijing, Zhao leads a globally renowned research program that is developing novel cancer therapies using low toxicity nanoparticles. Under Zhao’s leadership, Yuliang Zhao, PhD, and Joy Wolfram, PhD

this laboratory has become a prominent hub for nanomaterial safety research, and collaborates with international regulatory and government agencies, including

the National Institutes of Health and the U.S. Food and Drug Administration. A scientist with a big global footprint, Zhao has served as an expert on nanosafety committees of organizations like the European Commission and the United Nations Environmental Program. Zhao has had a close association with the Houston Methodist Research Institute since 2010. Collaborating with the Department of Nanomedicine, Zhao and the CAS have offered a joint graduate student exchange program. One of its earliest students, Joy Wolfram, PhD, pursued her graduate course work and part of her thesis research in China under the mentorship of Zhao. Wolfram describes Zhao as an excellent mentor who leads by example and a remarkable human being. She credits Zhao’s generous hospitality and thoughtfulness for making her transition to China as smooth as possible. Now an Assistant Professor of Medicine at the Mayo Clinic in Jacksonville, Florida, Wolfram says the exchange program benefitted her immensely, as it helped her pursue research and train with both Zhao and Mauro Ferrari, PhD, considered one of the founders of nanomedicine. Zhao was elected to the CAS Division of Chemistry for his outstanding scientific contributions to nanoscience, particularly nanotoxicology. Elected members play key roles in advancing science and technology programs and leveraging science for socioeconomic progress. With close to 500 peer-reviewed publications, Zhao is one of the most prolific and highly cited researchers in the field.

Zhao, PhD, is not only a dear friend and collaborator, but also a cherished “ Yuliang member of the Houston Methodist Research Institute team. A prolific researcher who has made innumerable contributions to nanotechnology and nanomedicine, Zhao is truly one of the most respected leaders in this field. I cannot think of a more deserving recipient of this honor.

”

– Mauro Ferrari, PhD President & CEO Houston Methodist Research Institute

EDUCATION NEWS

Expanding the Reach of

Research-Based Education The Institute for Academic Medicine offers opportunities for learners at all levels, from inquisitive high-schoolers to doctoral students on the opposite side of the globe. Education builds bridges for sharing knowledge and processes that ultimately will bring the best innovative minds and medicine to our patients.

MCTM Alums Win TMC Hackathon Lourdes Chacon and Marco Garza—both graduates of the Master in Clinical Translation Management (MCTM) program—were winners of the 2018 TMC Biodesign Hackathon. They were joined by Ulysses Guillermo, a former intern from Monterrey Tech.

Summer Program Attracts 73 Interns The Houston heat isn’t stopping 73 determined students from participating in the 14th consecutive year of Houston Methodist’s Summer Research Internship Program. They come from across the

Their team, GastroLoop, won second place and $1,000 for its 360-degree

U.S. for the opportunity to work with,

feeding tube designed to prevent dislodgement and clogging. Of more

and learn from, top scientists who serve

than 200 applicants, only 75 hackers were invited to participate in the

as mentors. The program includes 46

3rd annual event, held April 22 at the TMC Innovation Institute. The

students who are undergraduates, and

MCTM program is a collaboration between The University of St. Thomas

another 27 who are a mix of medical

Cameron School of Business and Houston Methodist, designed to

students, MD/PhD graduate students and

bridge the gap between science and business and support biomedical

high school students. A committee selects

entrepreneurship.

the high-achieving students based on their GPA, essay and letters of recommendation. Faculty mentors specialize in a broad spectrum of research areas, including biomedical informatics and systems medicine, cancer, computational surgery, cardiovascular sciences, immunobiology and inflammation, nanomedicine, neurosciences, regenerative medicine and surgery.

Progressive Care Residency for RN’s

Far-Reaching Doctorate in Research

Houston Methodist Center for Nursing

Innovative research knows no boundaries. And to build bridges across cultures and continents, the Institute for Academic Medicine partners with universities, both national and international, to attract the brightest and best to MD/PhD programs in the heart of Houston. Laura Pandolfi, PhD

Research, Education and Practice has developed a new progressive care residency program to fill a gap that many programs overlook—training nurses who work on progressive care or intermediate care (IMU) units. Since moving to a system approach, the Nurse Residency Program’s trainers assessed their transition-to-practice classes, given within eight to 10 weeks of hire. They identified a definite gap when it came to progressive care and have since developed the new curriculum. Now in its second year, The Progressive Care Residency Program has expanded to include tenured nurses,

One of our widely traveled success stories features Laura Pandolfi, PhD,

with classes held separately to accommodate

who worked on her thesis in collaboration with Houston Methodist and the

different learning curves.

Chinese Academy of Sciences in Beijing, China. Her research focused on developing biomaterials for tissue engineering applications, working with mentor

*contributed by Kelli Gifford, Leaders in Nursing, Spring 2018

Ennio Tasciotti, PhD, director of the Center for Musculoskeletal Regeneration. Upon completion of her PhD in materials science and engineering in 2016, Pandolfi was selected as one of six Fresenius Kabi Global trainees from a pool of over 700 international candidates—and was assigned to Hong Kong operations. Pandolfi, now Manager of Business Development and Key Accounts for Fresenius Kabi in Germany, oversees development of product pipeline capacity in the European market. She received her master’s degree in nuclear physics from the University of Trieste in Italy.

Match 2018 Welcomes 91 Houston Methodist’s Office of Graduate Medical Education enjoyed a successful Match in 2018, filling a total of 91 positions. In March 2018, it announced the 62 residents matched through the National Residency

Germany USA

Houston

Italy

Matching Program (NRMP) Main Match.

Beijing CHINA

Hong Kong

An additional 18 positions Matched in the NRMP Specialties Match (fellowship program), held during the preceding year, and 11 positions were filled through San Francisco Match and American Urological Association. Of all incoming residents, a total of 32 are medical students from Texas schools, including six from Texas A&M University.

OF INTEREST

A Birds-Eye View:

Recent Collaboration within the Texas Medical Center The Texas Medical Center is the largest medical complex in the world with more than 10 million patient encounters per year. As a founding member, Houston Methodist is an active partner that shares the TMC vision for Houston to drive the next generation of life science and medical innovation through inter-institutional collaboration. From TMC-wide consortia to independent research collaborations, Houston Methodist creates a translational node in the TMC network of discovery and advanced medicine. Here is a quick look at recent initiatives already underway with our medical center partners.

The Center for Immunotherapeutic Transport Oncophysics (CITO) hosted “The Physics of Cancer Immunotherapy,” its Spring Symposium, on May 3. Investigators and collaborators came from institutions that are part of the CITO network, including TMC member MD Anderson Cancer Center, as well as Dana-Farber Cancer Institute, Mayo Clinic, Moffit Cancer Center and UT Southwestern Medical Center. CITO is a multidisciplinary research team led by Mauro Ferrari, PhD, and supported by the National Cancer Institute. Mauro Ferrari, PhD, president and CEO, Houston Methodist Research Institute, served on a panel to discuss the critical role of federal funding in the TMC during a visit from U.S. Representative John Culberson in April. He was joined on the panel by Marshall Hicks, MD, interim president for The University of Texas MD Anderson Cancer Center, Thomas Kent, MD, professor and associate dean for the Texas A&M University Engineering Medical School, and John Hancock, MD, chair of Integrative Biology and Pharmacology and vice-dean of research and executive director of the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases.

The Center for Outcomes Research is Houston Methodist’s partnership with Texas A&M University School of Public Health. It drives fundamental improvements in outcomes for patients treated in acute-care settings and throughout their care. Key areas of research include health services research, health economics, industrial and systems engineering, and health care. Read about one of its newest initiatives, the Center for Health & Nature, on page 16.

The Summer Research Internship Program

The collaboration on antibiotic microspheres

is entering its 14th year of pairing 73 high-achieving students

connects Terry Clyburn, MD, of Houston Methodist, Antonios

with leading scientists who can foster their interest in medical

Mikos, PhD, of Rice University, and Catherine Ambrose, PhD,

research. Of the 46 students who are undergraduates,

of the University of Texas Health Science Center (UTHealth).

37 come from institutions with affiliations in the Texas Medical

Together, they are conducting clinical trials that will bring the tiny,

Center, including Rice University, Baylor University and Prairie

time-release beads that fight infection after joint replacement into

View Texas A&M University. Read more on page 22.

wider use within three to five years. Read more on page 8.

The TEXAS Project: Leveraging Data to Prevent Readmissions in the TMC, was one of four research projects in the inaugural Grant Program in Collaborative Health

The study on “Induction of IAPP amyloid deposition and associated diabetic abnormalities by a prion-like mechanism” was a high impact

Policy Research, funded by the TMC’s Health Policy Institute.

collaboration between researchers at McGovern Medical School

Robert A. Phillips, MD, PhD, FACC, Executive Vice President,

at UTHealth, led by Claudio Soto, PhD, and Houston Methodist

Chief Medical Officer & Chief Quality Officer at Houston Methodist,

Research Institute. Their paper was named among Journal of

collaborated with researchers from University of Texas MD Anderson

Experimental Medicine’s 10 most exciting discoveries in 2017.

Cancer Center, Texas A&M University Health Science Center,