Disease X Vaccine Powered by AI MET HODOLOGY
Houston Methodist Academic Institute
FROM THE PRESIDENT
Welcome to Methodology Magazine.
I continue to be delighted and grateful for the tremendous work we do and the exemplary achievements in academics, research and education. The legacy of what we have achieved in less than 20 years and the advancements we are making for the future of medicine are a testament to our concerted efforts to continually push beyond the status quo and evolve the landscape of medicine.
This issue, “Disease X Powered by AI,” reveals how Houston Methodist researchers are up for the challenge. As urbanization and climate change continue, experts from around the world agree that future outbreaks from dangerous novel viruses (Disease X) are inevitable. A consortium, led by Houston Methodist with the Coalition for Epidemic Preparedness Innovations, is combining cutting-edge artificial intelligence technology with established laboratory techniques to advance the rapid development of future vaccines against Disease X—ideally within 100 days of outbreak.
“Liver Failure Avengers: Weaponizing Lymph Nodes for Battle” marks a first in the world. Our researchers performed a first-in-human miniature liver hepatocyte transplant to change a patient’s lymph nodes into ectopic miniature livers. They discovered that the lymph node can possibly lengthen the life span of a patient with liver failure by replicating the function of healthy liver tissue, thus reversing the signs and symptoms of this disease.
Several stories showcase how researchers are improving chemotherapy efficacy, deprogramming transplant rejection, and how Beta and γ human herpesviruses are responsible for acute infections, multiple forms of cancer, autoimmune disease and birth defects.
In education, the magazine highlights how MITIE at The Bookout Center offers a hands-on clinical training hub for healthcare professionals. Through a collaboration with the Houston Methodist WIC program, MITIE at The Bookout Center hosted its first Maternal and Infant Simulation course focused on improving teamwork during emergencies and teaching how to simulate emergency scenarios at our hospitals for training purposes.
Once again, we celebrated a 100 percent success rate at the annual Match Day. Thirty-four students in the Texas A&M University Engineering Medicine (EnMED) program matched for resident programs throughout the U.S. And for the fifth year, we hosted the annual white coat ceremony for our Class of 2028 EnMED “physicianeers”.
I hope you enjoy this issue of Methodology as you learn more about our ongoing progress in research and education. I continue to be excited about the opportunities that lie ahead as Houston Methodist continues to be instrumental in changing the future of human health.
H. Dirk Sostman, MD, FACR
Ernest Cockrell, Jr. Presidential Distinguished Chair
Emeritus Professor of Radiology, Weill Cornell Medicine
Distinguished Member, Houston Methodist Research Institute
President & CEO, Houston Methodist Academic Institute
Executive Vice President & Chief Academic Officer, Houston Methodist
Disease X Vaccine Powered by AI
By Heather Lander, PhD
As globalization, urbanization and climate change continue, experts agree that future outbreaks of dangerous novel viruses (Disease X) are inevitable. In November 2022, the Coalition for Epidemic Preparedness Innovations (CEPI), published a landmark report, “What Will It Take,” which outlined the paradigm shift needed to speed up vaccine development, and the crucial scientific and technological innovations—including the creation of a vaccine library—that will enable the world to develop new vaccines against future pandemic threats in just 100 days.
Last summer, CEPI and Houston Methodist announced a partnership—and funding of a consortium led by Houston Methodist—to combine cutting-edge artificial intelligence (AI) technology with established laboratory techniques to further the rapid development of future vaccines against Disease X. The Houston Methodist group was awarded $4.98 million to advance the application of AI to analyze the structures of priority viruses from which the next Disease X is likely to emerge. Earlier this year, the award was increased to $34 million over five years.
Led by Jimmy D. Gollihar, PhD, Professor of Pathology and Genomic Medicine and Head of the Antibody Discovery & Accelerated Protein Therapeutics laboratory, the Houston Methodist team joins experts from Argonne National Laboratory (University of Chicago), J. Craig Venter Institute, La Jolla Institute, The University of Texas Medical Branch and The University of Texas at Austin. Initially, the team will focus efforts on paramyxoviruses and arenaviruses, as well as viral families, which include Nipah virus and Lassa virus, respectively.
“We are delighted to have the Houston Methodist Academic Institute be a part of this program, serving our community and the world. Leading this consortium is an amazing undertaking and a testament to the work that Dr. Jimmy Gollihar, his team in pathology and genomic medicine, and many others in our academic institute are doing to help defeat the next pandemic,” said Dirk Sostman, MD, FACR, Ernest Cockrell, Jr. Presidential Distinguished Chair and President and CEO of the Houston Methodist Academic Institute.
The Mission
A critical enabler of the 100 Days Mission is the establishment of a global “vaccine library”—an accessible store of scientific knowledge, data and prototype rapid-response vaccine candidates against selected viruses from the 25 priority virus families.
CEPI’s aim is to store AI-generated, lab-tested and verified antigen designs, developed by the Houston Methodist consortium, in the vaccine library to be quickly used to develop vaccine candidates in the event of an outbreak of a novel pathogenic threat. In this scenario, after sequencing the offending virus, these cataloged antigen designs can be inserted into an appropriate rapid-response vaccine platform to start the production of vaccines for clinical testing.
Gollihar’s group is leading immunogen design, but their work encompasses much more. The team has been developing therapeutic monoclonal antibodies for SARS-CoV-2. As variants of concern emerged, they wanted to determine what those mutations were doing to their monoclonals. So, they developed a mammalian display of viral glycoproteins—called a spike display—to allow researchers to study virus mutations and source code in real time.
“We started using spike display to dissect escape mechanisms and realized it was also an engineering tool. We played around with rational design-based approaches with individual variants and then moved to library approaches where we could use millions of variants in human cells and mammalian cell lines and sort, seek and find out what's binding what. The confluence of AI and directed evolution is outright, but protein engineering is really what allows us to do this rapidly,” said Gollihar.
Battling The Next Pandemic Threat
AI experts from Houston Methodist, The University of Texas at Austin, La Jolla Institute and Argonne National Laboratory will use machine-learning approaches to optimize the design of potential epitopes. The University of Texas Medical Branch will validate their immunogenicity in established preclinical models.
When a new pathogen emerges, vaccine developers could quickly respond by selecting AI-identified epitopes that would have already been validated in preclinical tests, enabling vaccine candidates to be moved quickly into clinical testing. This would provide a significant strategic advantage when battling the next pandemic threat, but Gollihar is looking even further into the future.
“The next generation of models for protein engineering will require data sets that don’t yet exist, so we’re really interested in deep mutational scanning,” noted Gollihar. “Because of our engineering platform, we can now take every amino acid and put it into every single position of a protein and ask: what does that mean to expression, antibody binding or host receptor binding? We’ll learn things we couldn’t otherwise learn. This is the next frontier and we're leading it.”
Jimmy D. Gollihar, PhD
The Team Spike Display
Developing America’s SHIELD
By Heather Lander, PhD
Beta and γ human herpesviruses (HHV)—latently infecting Americans at an annual cost of at least $4 billion—are responsible for acute infections, multiple forms of cancer, autoimmune disease and birth defects.
The β-HHV subfamily includes human cytomegalovirus (CMV) and roseoloviruses. The γ-HHV subfamily includes Epstein-Barr virus (EBV) and Kaposi sarcoma herpesvirus. Of these, EBV and CMV clinically impact the largest proportion of the U.S. population. EBV causes significant disease in adolescents and young adults as the cause of infectious mononucleosis. EBV can later cause lymphomas, gastric and nasopharyngeal cancer—the autoimmune disease multiple sclerosis and lymphoproliferative disease in transplant patients. CMV is a leading cause of congenital birth defects, as in-utero infection can result in permanent hearing loss or more profound neurodevelopmental impairments that disproportionately impact socioeconomically disadvantaged children. Also, CMV infection is linked to educational achievement gaps in disadvantaged populations.
The America’s SHIELD program application was submitted in response to a funding opportunity posted by the Advanced Research Projects Agency for Health in support of its Antigens Predicted for Broad Viral Efficacy through Computational Experimentation program.
The principal investigator on the award is Erica Ollmann Saphire, PhD, MBA, Professor and President & CEO of the Center for Autoimmunity and Inflammation, Center for Cancer Immunotherapy, Center for Sex-based Differences in the Immune System, and Center for Vaccine Innovation at the La Jolla Institute for Immunology. The Co-PI is Jimmy D. Gollihar, PhD, Professor of Pathology and Genomic Medicine and Head of the Antibody Discovery & Accelerated Protein Therapeutics Laboratory.
Previous HHV vaccine efforts focused on one or more viral glycoproteins or complexes involved in entry, but HHVs have large DNA genomes encoding more than 10 surface glycoproteins and nearly 200 other genes that lack crucial information. The sheer number of possible vaccine antigens made traditional technologies untenable. In addition, it’s still unclear which conformations or combinations of these antigens are needed for robust immunity. The prior focus on neutralization of cell-free virus entry also ignores the needs of the more than 100 million Americans who are latently affected and remain at risk of an HHV-associated disease.
Through the SHIELD program, researchers will develop an integrated sequence-, phylogeny-, structure-, and immunologically-driven computational toolkit for antigen engineering with the potential to transform vaccine development against a myriad of pathogens with the potential to cause cancer. The toolkit will be applied to major public health and economic threats to Americans, the β- and γ-HHV.
HHV
A critical and innovative aspect to our strategy is the targeting of antigens essential to multiple stages of the virus life cycle—beyond initial entry— to also include cell-to-cell spread, immune evasion and the latency and reactivation stages linked to cancer, autoimmune disease and other complications. “ ”
— Jimmy D. Gollihar, PhD
Jerold B. Katz Investigator
Professor, Pathology and Genomic Medicine
By integrating advanced computational models, structural predictions, and immunological data, SHIELD will enable the rapid design and optimization of immunogens against a range of viruses, including those with high mutation rates or novel structures. This comprehensive approach will significantly impact immunogen design and facilitate rapid responses to known and emerging viral threats, potentially transforming vaccine development and therapeutic approaches targeting these dangerous pathogens.
Head, Antibody Discovery & Accelerated Protein Therapeutics Laboratory
Guardians of The Galacardins
Antimicrobial Resistance Looms Large in Health Care
By Heather Lander, PhD
The efficacy of antimicrobials has diminished globally, while development of new antimicrobials is severely lacking. The estimated annual cost to treat infections caused by six multidrug-resistant germs frequently found in U.S. healthcare is more than $4.6 billion. The need for antimicrobial stewardship has become critical. Leading the charge in advocating for and recognizing excellence in antimicrobial stewardship is the Infectious Diseases Society of America (IDSA).
In 2019, IDSA awarded 23 institutions, including Houston Methodist, the designation of Antimicrobial Stewardship Center of Excellence (COE). This COE program prioritizes an institution’s capacity to implement stewardship protocols to enhance infection treatment outcomes and minimize adverse events linked to antimicrobial use.
Houston Methodist’s Antimicrobial Stewardship Program (ASP) includes clinicians, a clinical pharmacist and a medical director assigned to every campus to oversee program goals and initiatives. First-hand experience and routine assessment allow the program to become more effective in real time.
Muhammad Yasser Alsafadi, MD, ASP Medical Director and Assistant Professor of Clinical Medicine, ensures that the program not only meets the minimum requirements, but surpasses them.
Their diligence and hard work are paying off. In 2021, a new protocol allowed pharmacists to independently order a polymerase chain reaction test for Methicillin-resistant Staphylococcus aureus (MRSA). Negative results can allow de-escalation of anti-MRSA therapy, which has significantly reduced the use of anti-MRSA antibiotics.
As an IDSA Center of Excellence, the Houston Methodist Antimicrobial Stewardship Program embodies its mission to solve the toughest problems confronting patients.
Muhammad Yasser Alsafadi, MD
Mobilizing Against Microbes
In 2023, the World Health Organization (WHO) unveiled its Preparedness and Resilience for Emerging Threats Initiative, which provides guidance on response planning for respiratory pathogens.
And though its focus is respiratory pathogens, Tedros Adhanom Ghebreyesus, PhD, WHO Director-General, reiterated that preparedness and response efforts must span sectors, disciplines and pathogens.
With the addition of infectious disease experts—including Eleftherios Mylonakis, MD, PhD, FIDSA, Chair of the Department of Medicine—Houston Methodist is moving to the front lines of emerging infectious disease research.
As a physician-scientist, Mylonakis intends to guide clinical and translational research into a new paradigm
that increases cooperation between disciplines, clinicians, researchers and educators.
“We tend to keep clinical excellence, research and education within discrete silos that are competing for resources, but if we bring them together, we can catalyze their synergy,” said Mylonakis, Charles and Anne Duncan Presidential Distinguished Chair.
Recent events, including the blastomycosis outbreak at the Billerud paper mill in Escanaba, Michigan, demonstrated that fungi are now more of a threat than previously thought.
Mylonakis points out that even before these new threats, there’s been an ongoing, slow-moving, yet dangerous, fungal pandemic caused by Candida auris. “C. auris is very resistant to existing antifungals,” he said. “It is a strong example of a real and present danger from a fungus that seemingly changed its epidemiology and pathogenicity.”
PrEPping for The Future
HIV remains a significant public health problem in the U.S., especially in the South. Pre-exposure prophylaxis (PrEP) is critical in fighting HIV but according to the first-ever study on state-level PrEP use, the South accounted for 52% of HIV diagnoses and only 39% of PrEP users. The imbalance in PrEP use comes down to health disparities exacerbated by barriers to consistent access. While increasing access for underserved communities is crucial, a more practical, low maintenance PrEP regimen would significantly advance equitable PrEP access.
Toward that end, Houston Methodist researchers developed a long-acting, refillable, subcutaneous implant for sustained release of the HIV drug Islatravir, a nucleoside reverse transcriptase translocation inhibitor that is in development for HIV PrEP. "Our goal was to find a fool-proof delivery mechanism that would be easier and more convenient to use," said Lead Investigator Alessandro Grattoni, PhD, Frank J. and Jean Raymond Centennial Endowed Chair and Chair of the Department of Nanomedicine.
In a pre-clinical model, the Islatravir-delivering implants provided protective levels of Islatravir in all animals within 24 hours, with levels remaining consistent for more than 20 months. When challenged with a chimeric simian/human immunodeficiency virus, the implants conferred 100% protection against infection. The implants were well-tolerated throughout the study and there was no reduction in total lymphocytes, CD4+ or CD8+ cells.
Grattoni’s team has shown similar promise in implants for delivering chemotherapeutics in a pancreatic cancer model, so the efficacy in this model wasn’t unexpected. From here, the team will determine the lowest dose needed for continued protection, and whether the implant is effective against sexual and IV transmission of the virus, while they prep for clinical trials. “We hope for clinical testing within three years. If all goes well with human trials, we think the implant could be available within five years,” added Grattoni.
Alessandro Grattoni, PhD
Eleftherios Mylonakis MD, PhD
Liver Failure Avengers: Weaponizing Lymph Nodes for Battle
By Sheryl E. Taylor
They are best described as small, bean-shaped organs.
Think the size of a pea. The power they possess can quite possibly lengthen the lifespan of a patient with liver failure. How? By replicating the function of healthy liver tissue and reversing the signs and symptoms of this disease.
Lymph nodes are found at the convergence of major blood vessels in the body. An adult will have approximately 600-800 nodes—varying by person—located in the neck, armpit, chest, behind the ear, abdomen and groin. These organs are tasked with filtering substances in a person’s lymph fluid (proteins, minerals, nutrients, fats, white blood cells, damaged cells, cancer cells, viruses and/or bacteria).
Houston Methodist researchers are now in a Phase 2a Clinical Trial—Safety, Tolerability, and Efficacy of Hepatocyte Transplantation into Periduodenal Lymph Nodes Among Subjects With End-Stage Liver Disease. Houston Methodist is one of two study sites partnering with LyGenesis, Inc. Boston’s Tufts Medical Center is the other participating site.
Under the leadership of Constance Mobley, MD, PhD, FACS, researchers have successfully performed a first-in-human miniature liver hepatocyte transplant to change a patient’s lymph nodes into ectopic miniature livers.
Since enrolling the first patient, Mobley’s team has been inundated with people asking to participate in this study, from as far as Europe to Australia and across the U.S. According to the United Network for Organ Sharing, more than 10,000 liver transplants were performed in 2023—the most ever
in a single year; however, more than 1,700 patients die annually while on a liver transplant waitlist.
The team has dosed three patients, who are currently on a transplant waitlist, using their lymph nodes as living bioreactors to regenerate an ectopic organ. The selected patients must have a Model for End-Stage Liver Disease score that is greater than 10, but less than 25 at the time they are enrolled in the study. The goal is to have a total of 12 patients for the study, which began in 2022.
Mobley’s colleague, Sunil Dacha, MD, MBBS, performs an endoscopic ultrasound to locate the lymph nodes in the periportal area. Patients who are experiencing end-stage liver disease tend to have enlarged lymph nodes in the area between the stomach, liver and duodenum. Once Dacha locates a lymph node in that area, he endoscopically injects that lymph node with the liver cells.
“The procedure is simple; however, the difficulty lies in identifying the nodes around the liver due to their size—one centimeter or less. They are not easy to find, but with meticulous examination, we’ve been able to successfully perform three procedures,” said Dacha, Associate Professor of Clinical Medicine. “All three patients have done well. What we are doing is a unique thing. Only at Houston Methodist in the world.”
Constance M. Mobley MD, PhD, FACS
“
What’s
so exciting about this study is that these types of studies have never been performed in patients. We are the first hospital in the world to successfully inject these cells into a human. We always hear that Houston Methodist is leading medicine; in this instance, we actually are the first in the world to accomplish this goal.
”
The first stage of this study is to meet the FDA requirements of safety, tolerance and efficacy.
“With our initial patient cohort, we want to ensure that their lymph nodes are functioning like livers,” said Mobley. “Our primary endpoint is safety and tolerability.”
Presently, Mobley’s team is monitoring their three patients for a year to note any changes in their baseline liver function with the hope that their liver is becoming healthier.
If this first-in-class allogeneic regenerative cell therapy obtains FDA approval, it would enable one donated liver to treat dozens of end-stage liver disease patients, which could vastly affect the organ supply and demand imbalance for patients suffering from liver failure.
“There are so many patients waiting, and many die waiting,” she said. “There’s such a great need for the success of this study because there aren’t enough organs for the number of patients who are in need. Once we are successful in this study, the number of patients who we will be able to treat and save from liver disease will be immeasurable.”
Mobley also noted how this can be a game changer when treating patients with liver failure who may have additional underlying conditions that can be a barrier to receiving a liver transplant.
“Ultimately, my hope is that using liver cells will allow us to rescue patients who are extremely sick and can’t tolerate surgery,” Mobley said. “Theoretically, we could get so good at this that maybe patients wouldn’t need liver transplants, which would be incredible.”
–
Constance M. Mobley, MD, PhD, FACS
Associate Director, Liver Transplantation
J.C. Walter Jr. Transplant Center
What’s Next in Surgical Robotics? Creating the Framework for Evaluating New Technologies
By Callie Rainosek Wren, MS
Surgical robots have the potential to transform the surgical technology landscape.
However, compared to other types of medical devices, surgical technologies, including robots and AI, are historically underevaluated before implementation.
Assessment after the technology is implemented is also lacking. This innovation without evaluation can lead to catastrophic consequences for health care and society.
“That’s why it’s critical to develop an evaluation framework for these new surgical technologies before and after they’ve been approved for use—a current knowledge gap in the field,” explained
Pedro T. Ramirez, MD, FACOG.
As Chair of the Department of Obstetrics and Gynecology, Ramirez knows that new technology doesn’t always equate to the best outcomes for patients.
“Unfortunately, there hasn't been a formal entity that has provided guidance on how to evaluate and incorporate new technology, specifically robots and AI, into surgery,” Ramirez explained. “So, I joined the IDEAL Collaboration to help implement a robotics colloquium to address this need.”
Founded in 2007-2008 at Balliol College, University of Oxford, the IDEAL Collaboration is comprised of a group of research methodologists and surgeons with a common goal of improving surgical innovation research. While the group has already established an IDEAL Framework to evaluate surgical innovation and devices, the nature of surgical robots and AI pose new questions and concerns that go beyond the IDEAL Framework and the boundaries of classical evidence-based medicine.
“We felt that robotics needed its own evaluation framework because it is a technology that is growing quickly and being integrated so fast,” Ramirez noted. “We need to become more critical of robotic technology as it is introduced to the field, especially when AI is involved and there’s potential for increasing device autonomy.”
Pedro T. Ramirez MD, FACOG
In the near future, I think surgical robots could perform entire procedures. “ ”
–
Pedro T. Ramirez, MD, FACOG Chair, Department of Obstetrics & Gynecology
Using the existing IDEAL Framework as guidance, Ramirez and a team of diverse experts—surgeons, engineers, economists, patient representatives and social scientists— began developing the IDEAL Robotics Colloquium in 2022.
Dividing into panels, these experts participated in a series of virtual discussions focusing on key concerns regarding surgical robotics.
Through these discussions, significant questions emerged.
What is the patient consent process and legal implications if a surgical robot performs the majority of a surgery? If surgical robots gain autonomy due to AI, will surgeons begin questioning their own intuition? If so, what are the implications of this?
“We’re moving toward a technology where the surgeon can potentially be on autopilot or standby,” Ramirez said.
“These types of advancements come with ramifications if the technology is not evaluated and used properly.”
Taking these concerns into account, Ramirez and his team published the IDEAL Robotics Colloquium in Nature Medicine in 2024. This new framework outlines recommendations for surgical robot evaluation during development, comparative study and clinical monitoring. It also provides practical recommendations for developers, clinicians, patients and health care systems while considering multiple perspectives, including economics, surgical training, human factors, ethics, patient perspectives and sustainability.
Ramirez’s next goal is to raise more awareness of the IDEAL Robotics Colloquium among surgeons and manufacturers to shape how we use surgical robots in the future.
Deprogramming Transplant Rejection
By Heather Lander, PhD
In 1945, a young Army surgeon named Joseph Edward Murray suspected that a soldier’s successful skin graft was due to the impact of the young man’s severe burn injuries on his immune system. He was convinced that regulating the immune response would make organ transplants possible. Murray was right, and 45 years later, he received the Nobel Prize in Physiology or Medicine for his work on organ transplantation.
Today, a Houston Methodist team of researchers, led by Wenhao Chen, PhD, Associate Professor of Transplant Immunology in Surgery, has further advanced the field with the identification of a troublesome subset of CD4+ T cells that may be a more effective therapeutic target for preventing transplant rejection in patients.
Transplanted tissues and organs are recognized as “other” by our immune systems, thus, triggering an immune response that results in physiological rejection of the tissue. To prevent this, physicians must modulate immunity, so the foreign object is tolerated.
The molecular pathways leading to T-cell activation have been extensively studied, but the mechanisms modulating subsequent CD4+ T-cell effector programs leading to transplant rejection are not fully understood.
To gain deeper insight into the role of CD4+ T cells in transplant rejection, Chen’s study utilized single-cell RNA sequencing to analyze the CD4+ T cell response in transplantation scenarios. Published recently in Nature Immunology, the results indicate the presence of stemlike CD4+ T cells in transplant recipients, as well as the stem-like program directing the CD4+ T cell response in models of transplantation.
More specifically, they found stem-like CD4+ T cells that recognize transplant antigens that can differentiate into
effector cells that attack transplanted organs. Their data indicated that naïve alloantigen-specific CD4+ T cells develop first into TCF1-hi effector precursor T (TEP) cells and then into TCF1–CXCR6+ effector cells. However, the effector cells lose their ability to proliferate and fail to reject allografts upon adoptive transfer into new recipients. Conversely, the TCF1-hi CD4+ TEP cells can self-renew and differentiate into effector cells, thereby representing the stem-like CD4+ T cells in transplantation scenarios.
Crucially, the rejection of allografts is dependent on continuous replenishment of TCF1–CXCR6+ effectors from TCF1-hi CD4+ TEP cells. Moreover, the sustainability of the CD4+ TEP cell population is largely dependent on TCF1, while differentiation into effector cells requires other factors, including the transcription factor IRF4 and the glycolytic enzyme LDHA. In fact, IRF4 or LDHA deletion in T cells resulted in transplant acceptance.
These results provide robust evidence for a stem-like program that controls the self-renewal and effector differentiation abilities of CD4+ TEP cells. Because the stem-like CD4+ T cells continually replenish the effector cell pool, they may be the more effective therapeutic target for preventing transplant rejection and in other T cell-related immunotherapies.
This revelation about the true ‘troublemaker’ within the CD4+ T cell population is just the tip of the iceberg. I hope that our findings garner widespread attention, motivating both researchers and patients to recognize the significance of targeting these ‘troublemakers.’ “ ”
Wenhao Chen, PhD
– Wenhao Chen, PhD Associate Professor, Transplant Immunology in Surgery J.C Walter Jr. Transplant Center
No Cancer Cells Left Behind Improving Chemotherapeutic
By Abanti Chattopadhyay, PhD
Efficacy
Chemotherapy often removes the bulk of cancerous tumors while sparing a few residual tumor cells. These cells can become a recurring tumor months or years after the primary tumor is vanquished.
The rapamycin (mTOR) pathway has traditionally been an attractive cancer therapeutic target since mTOR dysfunction leads to tumorigenesis.
The mTOR signaling network is evolutionarily conserved and regulates several basic biological and physiological processes including cell survival, growth, metabolism, aging, regeneration, protein synthesis, autophagy, inflammation and homeostasis. mTOR (a serine/threonine kinase) functions as a hub that integrates many intracellular and environmental signals.
The FDA has only approved a few mTOR inhibitors for controlling late-stage tumor expansion in specific cancers.
The reason is that out of 500 clinical trials using mTOR inhibitors, few have demonstrated clinical benefit.
Yulin Li, MD, PhD, Assistant Professor of Immunotherapy in Medicine, demonstrated in a research study published in Nature Communications that mTOR inhibition promotes the development of a chemoresistant “persister” state, potentially contributing to tumor recurrence. His findings challenge the long-held paradigm that mTOR is an ideal therapeutic target and point towards novel therapeutic strategies to prevent tumor recurrence in cancer patients.
Li and his team performed a genome-wide CRISPR knock-out screen in a murine pancreatic cell line using gemcitabine and selinexor (two genotoxic chemotherapeutic
Yulin Li, MD, PhD
“ ”
The use of mTOR inhibitors can be counterproductive in the context of chemotherapy, which may explain the general lack of efficacy of mTOR inhibitors in cancer clinical trials and argues against their widespread use in combination with DNA damage-inducing agents. In this light, stimulation of mTOR signaling, but not its inhibition, may be the strategy of choice to reduce residual tumors and improve chemotherapeutic efficacy.
agents). The screen identified the mTOR signaling pathway as a crucial determinant of chemosensitivity. Specifically, Li concluded that mTOR suppression in tumor cells leads to a drug-tolerant and chemoresistant persister population with a reversible phenotype.
The persister tumor population exhibits a senescence phenotype whose survival is dependent on autophagy and G2/M cell cycle arrest. The persister cells also showed multifaceted survival mechanisms based on a small molecule screen performed by Li. Interestingly, the mTOR inhibitor rapamycin has demonstrated to prolong lifespan in various model organisms and mammals.
mTOR inhibition is not the best strategy for chemotherapy since it leads to tumor persisters that may lead to tumor recurrence. On the other hand, mTOR activation enhances chemosensitivity and improves survival in various human cancers. A growing body of research supports this conclusion. For instance, germline and somatic mutations in cancer patients that lead to mTOR activation also cause heightened sensitivity to DNA damage-inducing cancer therapies.
“We observed that mTOR suppression promotes the induction of persisters in various cancer cells undergoing chemotherapy and dampens therapeutic efficacy,” noted Li. “Similarly, others have shown that mTOR inhibition is chemoprotective in leukemia cells.”
– Yulin Li, MD, PhD Assistant Professor, Immunotherapy in Medicine
A Whole New World Hands-on Clinical Training Hub for Health Care Professionals
By Heather Lander, PhD
MITIE at The Bookout Center has long been known as a hands-on clinical training hub for health care professionals seeking to enhance their procedural skills and acquire new expertise.
MITIE’s simulation, imaging, audiovisual and virtual reality capabilities create a comprehensive training system. Its new app—MITIEverse™—is a groundbreaking initiative in healthcare education, training and innovation for medical and scientific learners. Developed in collaboration with FundamentalVR, this app offers a wealth of resources and experiences.
“Our new app provides a community where anybody, anywhere, can plug in and get access to world class biomedical educational resources. It extends MITIE’s renowned hands-on education and training to a virtual audience,” said Stuart J. Corr, PhD, Director of Innovation Engineering and inventor of the MITIEverse™.
Within the MITIEverse™, users gain access to hands-on practice opportunities, remote guidance from seasoned clinicians and more. The app immerses users in customizable showcase rooms, lifelike surgical simulations and lectures delivered by experts from Houston Methodist and partners worldwide.
One of the standout features is the DeBakey Heart & Vascular Center's showcase room, where users can observe actual surgeries performed by faculty and engage with 3D human models for a deeper understanding. Alan B. Lumsden, MD,
Walter W. Fondren III Distinguished Chair and Chair, Department of Cardiovascular Surgery, believes that the MITIEverse™ represents a paradigm shift in health care education and training.
“It essentially democratizes access to health care educators and innovators by breaking down physical barriers. There’s no need to travel thousands of miles to attend a conference when you can patch into the MITIEverse™,” noted Lumsden, Professor, Cardiovascular Surgery.
MITIEverse™users can expect to:
• Interact with world-renowned surgeons and health care providers.
• Sit in a virtual auditorium where medical professionals from around the globe can deliver presentations to an unlimited live audience.
• Gain insights into complex surgical procedures through case study videos and anatomical 3D models.
• Participate in interactive hands-on training modules.
• Use virtual study spaces for collaborative learning with interactive models, whiteboards and other educational tools.
• Network with medical device and digital health companies to explore emerging technologies.
The app is currently invitation-only as development continues. “We're focused on use-case development and publishing. One possibility under consideration is utilizing the app to train health care professionals to perform intubations in difficult scenarios, using 3D modeling of various airway pathologies,” said Corr.
Stuart J. Corr, PhD
Synchronizing Maternal and Neonatal Emergency Care
By Callie Rainosek Wren, MS
When Randolph H. Steadman, MD, MS, was allocated educational funds for frontline staff to train at MITIE at The Bookout Center, Stephanie S. Bruce, MD, MAS, FACOG, and physician champion for the Houston Methodist Women and Infants Council (WIC), jumped at the opportunity.
Through collaboration with WIC, Steadman led MITIE at The Bookout Center’s first Maternal and Infant Simulation Instructor course. Attended by health care staff from all seven of Houston Methodist’s birthing hospitals, the course focused on improving teamwork during emergencies and teaching how to simulate emergency scenarios for training purposes.
“We want to make sure every nurse and doctor in our system is comfortable managing maternal and neonatal emergencies,” Bruce emphasized.
Ultimately, this course will contribute to the standardization and improvement of maternal and neonatal care systemwide a goal that dates back to 2016 when Texas implemented level of care designations for maternal and neonatal care.
“We received a lot of feedback that staff didn 't want to learn virtually,” explained WIC member Sharon Patagoc, MSN RN, Senior Program Manager, Women Services in the Department of Quality and Patient Safety. “They really wanted to learn in a hands-on environment. This became an important consideration that led us toward simulation trainings.”
It was during the process of deciding how to accomplish these simulation trainings when Steadman offered the opportunity for frontline staff to train at MITIE at The Bookout Center—which proved to be a milestone opportunity for WIC to meet its maternal and neonatal training goals. In addition to learning how to work more effectively as a team and how to simulate their own training
scenarios, participants were able to identify irregularities in how each hospital responds to emergencies. For example, color-coded emergency supply carts and code calls were not standardized systemwide, which could delay care in a critical situation. These discrepancies were high on the agenda during WIC’s strategic planning meeting in early 2024.
As WIC works to standardize these discrepancies, staff continue to expand their skills through Steadman’s half-day refresher courses and simulation training conferences.
WIC members, who helped organize these trainings, are adamant that Steadman’s leadership was the key to their success and are looking forward to addressing further educational needs.
“Running these drills allows us to know what skills and education we need to work and improve upon. Other types of learning platforms, such as virtual learning, can leave knowledge gaps,” explained Cristina Martin, MSN, RN, WIC Chairman and Director of the Childbirth Center at Houston Methodist Sugar Land Hospital.
“We’re going to see better outcomes for our patients and better teamwork within our nurses and health care staff,” Patagoc said. “Those who train together, stay together.”
Randolph H. Steadman MD, MS
Stephanie S. Bruce, MD, MAS, FACOG
Enhancing Quality of Life Through Human Performance
By Heather Lander, PhD
Houston Methodist and Rice University have joined forces to create a premier center where clinicians, faculty and university students work side by side with student-athletes, trainers and coaches to advance research and education in human performance.
The Houston Methodist-Rice University Center for Human Performance facilitates joint research, clinical care initiatives and educational activities in exercise science, injury prevention and rehabilitation. Located in Rice University’s Tudor Fieldhouse, the 6,000-square-foot center houses gold-standard equipment that can be used for research designed to maximize athletic performance, prevent injury and aid in recovery following surgery, injury and other stressors from physical challenges.
Enhancing performance means optimizing results, whereas the study of human performance applies to much more than sports. The center will benefit Houston Methodist patients, older adults, performing artists, people with disabilities, surgical patients—anyone who needs to function better and improve their quality of life through a combination of physical activity, nutrition, sleep and other aspects.
With advanced technologies, the center evaluates human performance metrics such as aerobic capacity, muscular strength, agility, biomechanics and body composition. Available technologies include 3D motion capture, force platforms, metabolic, cardiovascular and aerobic performance testing, electromyography technologies as well as DEXA bone density and body composition imaging.
The center’s vision is to attract new faculty, provide student research and internship possibilities and create opportunities for interdisciplinary collaborations with peers in biomechanics, neuroscience, psychology, robotics, wearable technologies, data sciences, biosciences and other disciplines. Additionally, the center will also offer an environment where high-impact findings can be efficiently translated from a concept to an application on the field or in the clinic.
The Best Pitch: Blood Flow Restriction Training
By Abanti Chattopadhyay, PhD
Blood Flow Restriction Training Therapy is an up-and-coming training tool method that allows athletes to work out smarter, not harder. Essentially, the technique involves an athlete wearing a tourniquet-style cuff on the upper arm or thigh while lifting lighter weights to build muscle mass. The tourniquet prevents blood flow out of the area, which makes the body think that the athlete is exercising harder than he or she actually is.
Bradley S. Lambert, PhD, Assistant Professor of Orthopedic Surgery, performed a randomized clinical trial in which he tested the efficacy of BFR-LIX (low-load resistance exercise) on the shoulder when added to standard offseason training in Division IA collegiate baseball pitchers. This study received grant support from Major League Baseball and Delfi Medical Innovations.
Lambert assessed if BFR combined with LIX would enhance training-induced increases in shoulder-region lean mass, rotator cuff strength and endurance. The results suggested that BFR-LIX training when combined with a collegiate off-season program can boost increases in shoulder-region lean mass and rotator cuff strength and endurance. This approach may promote favorable outcomes and prevent injuries in baseball pitching athletes. The details of this study were published in the Journal of Shoulder and Elbow Surgery
The scapulohumeral muscles, which connect the scapula to the humerus, are particularly important in overhead throwing athletes such as baseball pitchers. These muscles play a key
role in the advanced coordination and strength needed for pitching. Therefore, a great deal of off- and in-season training focuses on strengthening these muscles, which are also prone to injury, especially if subjected to high-intensity and high-load resistance training (HIX).
The purpose of the rotator cuff is to block blood flow across the occlusion site via compression. Specifically, occlusion reduces arterial blood flow from the heart to the limb and prevents venous return with a typical 40-80% arterial limb occlusion pressure. Combining BFR and LIX produces results similar to HIX with less risk of over-training and injuries.
In this randomized trial, 28 baseball pitchers were classified into two groups: one with BFR and the other without BFR. Both groups performed shoulder LIX along with off-season training. The results indicated that when compared to rotator cuff training alone, BFR-LIX combined with rotator cuff training led to increases in upper extremity lean mass. Essentially, BFR provided a novel stimulus leading to additional muscle mass gain.
“Our findings provide support for future research investigating the efficacy of blood flow restriction for preventative in-season shoulder training. The results also provide a rationale for future research on the efficacy of blood flow restriction augmented rehabilitation after operative and non-operative injuries in overhead throwing athletes,” said Lambert. “Future investigations should seek to determine the optimal combination of exercise selection, training frequency, blood flow restriction occlusion duration and timing within a sports training program that may provide the greatest benefit for different types of overhead throwing for athletes.”
Bradley S. Lambert, PhD
Leading The Green Health Care Movement
By Callie Rainosek Wren, MS
When thinking of sustainability, recycling, conservation and reducing, the carbon footprint may come to mind. But what does sustainability mean for Houston Methodist?
“Aligning with our I CARE Values, sustainability means conserving resources to protect the environment while continuing to provide high-quality patient care,” explained Jason Fischer, MBA, System Director of Sustainability. Established in 2023, the Office of Sustainability supports system-wide sustainability efforts led through employee and community engagement; introspective analyses; actionable roadmaps; and non-profit, industry and governmental partnerships.
Although the office is relatively new, its faculty and staff have initiated several research and operations-focused projects to conserve energy and resources.
One such example, Faisal N. Masud, MD, FCCP, FCCM, Medical Director of the Center for Critical Care, collaborates with the Office of Sustainability to lead various Green ICU Initiatives. Masud’s team is part of the Society of Critical Care Medicine’s National Task Force on Green ICUs. These projects
have attracted partners across the Texas Medical Center, leading to one of the nation’s first collaborative and systematic approaches to health care sustainability goals.
These efforts are paramount, as health care accounts for 10% of the nation’s greenhouse gas emissions. ICUs are considered carbon “hot spots,” emitting enough daily greenhouse gas emissions to rival driving a car 62.14 million miles. Medical waste is another concern. Caring for a single ICU patient can result in as many as 108 disposable gloves, 57 compresses, 34 infusion bags, 16 articles of disposable clothing and 8 bed liners per day.
Despite these statistics, Green ICUs are in their infancy in the U.S. Masud and Green ICU colleagues recently published an article in Critical Care that outlines these knowledge gaps as well as the state of global health care sustainability efforts. The article also shares experiences from Houston Methodist’s Green ICU Initiative and proposed a three-step pathway to overcome challenges to Green ICUs, such as cost, employee education and availability of resources.
Faisal N. Masud MD, FCCP, FCCM
“Multiple ICU units across Houston Methodist are examining strategies to reduce the amount of unused supply waste. We found that just one of our ICUs used 1,464,262 medical supplies in a six-month period— so reducing waste is an important priority,” explained Masud, Mary A. and M. Samuel Daffin, Sr., Centennial Chair in Anesthesia and Critical Care.
Further, the systemwide virtual ICU program, created during the COVID-19 pandemic, continues to show potential for low-carbon emissions. These enhanced facilities allow for remote patient consultations, virtual family visits, tele-rounding and reduction in staff commuting—all innovations that reduce travel-associated carbon emissions without compromising patient safety and quality of care.
Beyond the ICU, planet-friendly practices have been instituted in other areas of the hospital, including the operating rooms, which are also considered carbon “hot spots.” Sustainable interventions include the elimination of desflurane to reduce emissions from anesthesia gases, one of the largest contributors to health care emissions. Additional Office of Sustainability projects include sustainability-focused continuing education programs, solar panel installation on the Josie Roberts Administration Building’s parking garage, an EV charging station implementation study with Evolve Houston, the Healing Gardens of Houston Methodist are envisioned as a rooftop garden at the new Centennial Tower, and an employee discount for Moonshot Compost home services through HR benefits.
For instance, the Houston Methodist Academic Institute is reducing water with pressurized valves, recycling pipette boxes, ensuring hood vents are closed when not in use and using equipment stoplights to reduce energy consumption. The supply chain workgroup is making environmentally preferred purchases, using reusables and renewables and planning for zero waste.
Houston Methodist also continues to engage the community through sustainability fairs, community gardens and I CARE in Action volunteer projects. All these initiatives, new or ongoing, require strategic collaboration among faculty and staff to protect the planet while keeping safety, quality, service and innovation at the core of patient care.
Take A Walk for Your Heart
By Erin Graham
Walking in the great outdoors can do wonders for you, they say.
Now, researchers at the Center for Health and Nature have a study to prove that it’s true. The study, which examined the health benefits of the Bayou Greenways for Houstonians, found that residents living in zip codes with a greenway trail had a lower likelihood of being admitted to the hospital for certain health conditions compared to those living in zip codes without a trail. There was a 93% reduction in obesity-related admissions, a 77% reduction in heart disease admissions, and a 71% reduction in heart attack admissions among residents who lived within a 10-minute walk of the Bayou Greenways trail system. Researchers want to conduct further studies to understand the relationship between walking trails and overall health. Their next step is to survey individuals who use the trail system.
Tipping The Scales Toward Nature
By Erin Graham
Spending time in nature has its benefits, especially for our mental and physical health.
A recent study published in BMC Psychology, “Development and Validation of Self-efficacy and Intention Measures for Spending Time in Nature,” developed and evaluated the reliability and validity of self-efficacy and intention measure for time spent in nature (TSN) as it relates to improvement in psychological well-being and health. Self-efficacy and intentions are shown to be strong predictors of health behavior.
Jay Maddock, PhD, FAAHB, Director, Center for Health and Nature and Professor in the Department of Environmental and Occupational Health at Texas A&M University’s School of Public Health, led a 14-member team to embark on a nine-phase procedure. This team—comprised of researchers and practitioners in various investigative fields—created, refined and tested scales to measure factors related to TSN, highlighting the collaborative nature of this research. They developed TSN self-efficacy and intention scales using a sequential nine-step procedure: identification of the domain and item generation; content validity; pre-testing of questions; sampling and survey administration; item reduction; extraction of factors; tests of dimensionality; tests of reliability; and tests of validity.
The first phase identified self-efficacy and intentions as the factors to be measured by the scales. A person’s intentions as well as their self-efficacy, which is their belief that they can attain a goal, are strong predictors of positive health behaviors including physical health. These are the first scales created to quantify the impact of these factors on TSN.
Phases two and three refined phase one factors with pre-tested survey questions administered to a nationwide sample of more than 2,000 adults. Phases five through nine used data analytics to eliminate items showing extreme characteristics and to test the dimensionality, reliability and validity of the scales.
More time spent in nature correlated with both self-efficacy and intentions, indicating more time spent in nature should be a goal for improving TSN. However, the age of the respondents showed a more negative result, which may indicate the limited mobility or safety concerns of the respondents. Males had higher self-efficacy than female respondents. Additional research has shown that women are less likely to participate in recreational activities in nature.
“We’re working on developing a whole suite of measures,” Maddock said. “Once those are complete, we want to
Jay Maddock PhD, FAAHB
Saving Limbs: Combatting Arterial Disease
By Abanti Chattopadhyay, PhD
Affecting more than 236 million people worldwide, peripheral arterial disease (PAD) is a chronic, circulatory condition that is caused by an atherosclerotic plaque build-up inside arteries that leads to a blood-flow blockage to the limbs.
PAD increases the risk of stroke, cardiovascular death, myocardial infarction, coronary artery disease and cerebrovascular disease. Managing PAD includes pharmacological treatments and revascularization of blood vessels. Percutaneous vascular intervention (PVI) is a minimally invasive procedure to unblock occluded arteries. However, in cases of impenetrable plaques, PVI has led to worsened secondary bypass outcomes and amputation.
People in the United States aged 40 and older—6.5 million —have PAD. It is more common in the legs than arms. PAD blockages result from the build-up of fatty deposits or plaque and can be hard (calcium and dense collagen) or soft. Appropriate interventional strategies for blood flow restoration are critical to prevent amputation and death.
Trisha Roy, MD, PhD, FRCSC, Assistant Professor of Cardiovascular Surgery, published a case report in the Methodist DeBakey Cardiovascular Journal 2023 to illustrate the importance of Magnetic Resonance Imaging (MRI) histology in PVI planning to minimize unwanted patient outcomes. This report discusses the case of a 64-year-old female patient with critical limb ischemia (CLI) who underwent an above-knee amputation because of a failed PVI attempt to recanalize the limb.
The CLI patient’s right foot had worsening rest pain, non-healing wounds and ulcers and an impenetrable
Trisha Roy MD, PhD, FRCSC
plaque in the popliteal artery. Failed PVI attempts were followed by failed bypass attempts, eventually requiring an above-knee amputation. According to the Amputee Coalition, about 185,000 amputations occur in the U.S. each year. Nearly 54% of limb loss cases are due to diabetes and PAD.
Using ultrashort echo time (UTE) and T2-weighted (T2W) sequences, MRI histology can be used to determine if blockages are hard or soft. This offers a good predictive value of not only identifying patients who are at a high risk of failing the endovascular intervention, but also predicting whether their lesions would require more adjunctive devices.
“
PAD is a real epidemic, and it is growing along with diabetes and renal failure. Our understanding of PAD is quite poor and the imaging techniques that we use have been the same for decades. So, having the ability to be more advanced with how we're diagnosing PAD, and tailoring our treatment can help patient outcomes, particularly because there's a big spectrum to what the blockages can be made of.
Assistant Professor, Cardiovascular Surgery
”
There are a couple of anatomic scores for PAD that indicate if a lesion or patient will be better served by endovascular treatment or open bypass. These scores are based on length and degree of stenosis. However, these do not provide any details about what the occlusion is made of. Soft lesions (whether long or short) can be recanalized using endovascular procedures whereas hard lesions are impenetrable.
With the advent of new sophisticated MRI scanners, researchers now have access to refined methods because of the availability of a wide array of sequences (in addition to UTE and T2W) and material equipment.
“MRI histology is a good tool to shed light on what these blockages are composed of and thereby predict endovascular failure. Right now, our outcomes are quite poor and we're having to intervene on these patients again and again, each time more futile than the last,” noted Roy. “We hope that by being able to image and understand what we're treating, we will have a better understanding of how to treat individual patients so that they have the best possible outcomes.”
This work was supported by the Jerold B. Katz Foundation (Katz Academy of Translational Research).
Nearly 54% of limb loss cases are due to diabetes and PAD.
– Trisha Roy, MD, PhD, FRCSC
Jerold B. Katz Investigator
CAMPUS NEWS
Match Day 2024: 100% Match Success
The Office of Graduate Medical Education hosted its annual Match Day event celebrating 34 students who matched in the Texas A&M University’s EnMed program, with 18 remaining in Texas. These students were among the hundreds of medical students in the Houston area matched to resident training programs across the U.S.
Snapshot of Matches: 2024-2025 Incoming Residents
• 60 U.S. Graduates (80%)
• 8 from Texas (50%)
• 22 from other U.S. medical schools
• 15 International Graduates (20%)
• 3 Urology positions in the American Urological Association Match (EnMed; University of Minnesota School of Medicine; University of South Carolina School of Medicine)
Center for Innovation @ The Ion
Houston's new innovation corridor, The Ion, brings entrepreneurial, corporate and academic communities into collaborative spaces and programs to develop new ideas. Houston Methodist was the first health care institution to become a tenant of The Ion. The development included the interior build-out of approximately 924 square feet of open space on The Ion's lower level. The space includes collaboration spaces and a flexible health care showroom environment to serve as the community outreach hub for the Houston Methodist Center for Innovation.
EnMed Class of 2028
The Texas A&M University School of Engineering Medicine (EnMed) hosted its annual White Coat Ceremony. This notable event featured EnMed students receiving their first white coat—a rite of passage signifying their transition into the medical community. Founded in 2019, the EnMed program is a collaboration between Texas A&M’s School of Engineering Medicine and Houston Methodist to transform health care through the development and training of “physicianeers,” the creation of medical technologies and translational research. The EnMed physicianeer is an innovative problem-solving doctor uniquely qualified to address some of health care’s greatest challenges. These graduates receive a Medical Doctorate and Master of Engineering degree focused on the design and implementation of impactful medical technologies through a revolutionary curriculum.
It’s
a FACT: Johnson Center Earns CAP Accreditation
The Ann Kimball and John W. Johnson Center for Cellular Therapeutics received its first accreditation from the College of American Pathologists (CAP) and the Foundation for the Accreditation of Cellular Therapy (FACT). CAP accreditation ensures Houston Methodist’s Johnson Center is in accordance with the latest best practices in the field of laboratory medicine worldwide—from accuracy and quality of test results—making the center one of the only cell therapy facilities in the Texas
Medical Center to perform its own quality tests and offer these services to other facilities. The Centers for Medicare and Medicaid Services (CMS) has granted the CAP Laboratory Accreditation Program deeming authority, allowing CAP inspection instead of a CMS inspection. FACT accreditation is the threshold for excellence in cell therapy, informing patients, health insurance companies and governments that the Johnson Center is dedicated to the highest quality patient care and safety.
With FACT recognition, the Johnson Center can store commercial CAR T-cell products, such as Yescarta® and Kymriah®, for ease of use in Houston Methodist patients with blood cancers.
U.S. News & World Report utilizes FACT accreditation in its annual ranking of best U.S. hospitals.
Photo: Ann Kimball and John W. Johnson Center for Cellular Therapeutics Steering Committee: Patrick McCulloch, MD; John P. Cooke, MD, PhD; Jenny Chang, MD; Eamonn Quigley, MD; Stanley H. Appel, MD; and Osama Gaber, MD
Expanding Medical Education in The Woodlands
Thanks to a $10 million anonymous commitment to expand academic medical education in The Woodlands, Houston Methodist The Woodlands Hospital is the recipient of the largest gift to any regional hospital within the Houston Methodist system. It’s also the first instance in which a Texas Medical Center (TMC) institution will sponsor an academic medical program in one of the community hospitals where patients can seek specialty care typically only offered in the TMC.
This 36-month ACGME-accredited Internal Medicine Residency Program will allow residents to rotate through various core and elective rotations in the outpatient and inpatient setting and
participate in a longitudinal continuity clinic. The program also broadens options for advancing scholarly activity with Houston Methodist faculty and staff who will be part of training these residents and fellows to bring highly specialized offerings to the north side of Houston.
Proposed future fellowships include Cardiovascular Diseases, Orthopedic Surgery, Pulmonary Critical Care and Sports Medicine.
Houston Methodist’s academic medical program includes more than 350 residents and fellows, receiving training in various specialties. Many of these physicians-in-training often rotate to one of Houston Methodist’s eight hospitals in Greater Houston.
Progress Through Partnership
$4 Million Multi-Institutional Commercialization Hub
The Gulf Coast Consortia and their partner institutions, including the Houston Methodist Research Institute, Texas A&M University Health Science Center, The University of Texas Medical Branch, Texas Southern University (TSU), Baylor College of Medicine, The University of Texas MD Anderson Cancer Center, Rice University, University of Houston and The University of Texas Health Sciences Center-Houston, were awarded a four-year, $4 million cooperative research agreement from the National Institutes of Health (NIH) to establish the Gulf Coast Consortium Research Evaluation and Commercialization Hub (GCC-REACH).
This multi-institutional commercialization hub will support the development and commercialization of transformative health care treatments based on research discoveries. Within the GCC-REACH, academic entrepreneurs work closely with life science experts and biotech executives to develop milestones to rapidly validate the commercial value of their discoveries. They also assist entrepreneurs in strategic planning for management and operations, and provide vetted resources and support to achieve value-added commercialization inflection points.
The GCC is an ideal organization to be leading this hub. According to its site, the “GCC delivers important advances in bioscience research and training by empowering individuals to go beyond the limitations of any single institution, discipline or degree program.” Located in Houston’s Texas Medical Center, GCC is one of the largest inter-institutional cooperatives in the world, integrating the strengths of its member institutions to build interdisciplinary collaborative research teams and training programs in biological sciences at their intersection with the computational, chemical, mathematical and physical sciences. GCC provides a unique, cutting-edge collaborative training environment and research infrastructure beyond the capability of any single institution.
Over the next four years, the GCC-REACH will train academic entrepreneurs and scientists within GCC member institutions, TSU and regional research institutions to navigate the process of successfully commercializing their novel discoveries. The consortium aims to launch as many as 60 early-stage biomedical companies that will attract venture investments and additional grant funding.
Joint Symposium Weaves Bioengineering Seamlessly with Cardiovascular Nanomedicine
For the first time, Houston Methodist hosted a combined symposium featuring the George and Angelina Kostas Research Center for Cardiovascular Nanomedicine Symposium and the 8th Annual National Institutes of Health Progenitor Cell and Translational Medicine in Cardiovascular Bioengineering Symposium. The hybrid event brought together the world’s top cardiovascular scientists and bioengineers to exchange ideas on innovative developments in translational cardiovascular nanotechnology and bioengineering. The event showcased 54 speakers, 70 poster presentations and a panel discussion on the Future of Cardiovascular Nano-Therapeutics.
John Cooke, MD, PhD, Joseph C. “Rusty” Walter and Carole Walter Looke Presidential Distinguished Chair in Cardiovascular Disease Research; Director, Center for Cardiovascular Regeneration
Inaugural Symposium Highlights Neuroprosthetics and Neural Restoration
Houston Methodist and Rice University’s new joint Center for Neural Systems Restoration hosted its inaugural symposium, NeuroSystems: From Circuits to Restoration. This two-day event featured 24 world-renowned scientists to spotlight recent advances in the understanding of neural circuits, brain states and pioneering technologies while providing a platform to showcase the current state of the field and charting future research directions. The symposium's key focus included the translation of these insights into innovative treatments for neurological disorders, promising a significant impact on the field of neuroscience and beyond.
Valentin Dragoi, PhD, Rosemary and Daniel J. Harrison III Presidential Distinguished Chair in Neuroprosthetics; Scientific Director, Center for Neural Systems Restoration
Katz Investigators Named for Translational Research FACULTY NEWS
The Jerold B. Katz Academy of Translational Research was established with a commitment of $8 million from the Jerold B. Katz Foundation. The Katz Academy aims to recruit and retain the world’s most promising transformational researchers in health care. Katz Investigators hold their $1 million endowed position for five years. After the five-year appointment term, Katz Investigators retain the title. Three new faculty members have joined to the Jerold B. Katz Investigator Academy:
Sadeer Al-Kindi, MD, Jerold B. Katz
Investigator and Associate Professor of Medicine, serves as a preventative and imaging cardiologist at the DeBakey Heart & Vascular Center, where he is associate director for the Division of Cardiovascular Prevention and Wellness. He also focuses on environmental determinants of cardiovascular disease, social determinants of health, cardiometabolic disease and advanced cardiovascular imaging.
Matthew D. Cykowski, MD, Jerold B. Katz Investigator and Associate Professor of Pathology and Genomic Medicine, Stanley H. Appel Department of Neurology, is currently focused on defining the role of Sox9 in the pathogenesis of Alzheimer's disease and age-related TDP-43 neuropathology using disease-driving mechanisms to guide classification.
Jimmy D. Gollihar, PhD, Jerold B. Katz
Investigator, Professor of Pathology and Genomic Medicine and Head of the Antibody Discovery & Accelerated Protein Therapeutics Laboratory, and his team have contributed to the genomic surveillance and characterization of SARS-CoV-2, B-cell repertoire mining for neutralization and protection assays, and the engineering of enzymes intended for mRNA vaccine manufacturing.
A New Pathway for PAH
Pulmonologist Zeenat Safdar, MD MS, FACP, FCCP, ATSF, Director of the Houston Methodist Lung Center, Director of the Hypertension Program and Professor of Medicine, is involved with a series of clinical trials that led to the recent FDA approval of the novel compound, sotatercept—the first pulmonary arterial hypertension (PAH) medicine. The clinical trial began with a Phase 2 study, PULSAR, followed by Phase 3, STELLAR, and now phase 4 open label study, SOTERIA. According to Safdar, “It’s been more than a decade since the last time a new pathway was identified and proven beneficial for our patients.” Presently, there are at least 14 medications on the market to treat PAH, which basically target three pathways (endothelin, prostacyclin, nitric oxide). “This new pathway has the potential to add background therapy for these patients, allowing us to modify the disease process itself,” Safdar noted.
VenoStent’s Phase III Trial Hopes to Make Dialysis More Reliable
Eric Peden, MD, J.C. “Rusty” Walter III Centennial Chair, DeBakey Heart & Vascular Center and Associate Professor, Cardiovascular Surgery, is the national primary investigator (PI) of the Phase III, 15-site clinical trial of VenoStent. This device aims to improve the usability and durability of arteriovenous fistula for more reliable dialysis. This phase of the trial began in 2024. The device is wrapped around the dialysis access site where the artery and vein join to provide additional structural support, extending the life of the port. The wrap is made from a material absorbed by the vascular walls. The VenoStent is a 3D-printed polymer that bioabsorbs into the vascular tissue in 100 days. Peden’s Houston Methodist collaborators include Christof Karmonik, PhD, Research Professor of Radiology, who helped design and deploy the VenoStent technology in a controlled setting; and 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, Director, Center for Cardiovascular Regeneration, and Medical Director, Center for RNA Therapeutics, who brought academic expertise with grant submission documentation. As the national PI, Houston Methodist is the lead on all resulting academic publications and has the ability to make podium/keynote presentations at conferences on patient outcomes. The clinical trial is scheduled for completion in 2027.
New Endowed Faculty
The Houston Methodist Endowed Positions and Awards Committee announced the following faculty:
Stephen J. Incavo, MD, PhD, Professor, Clinical Orthopedic Surgery, has been named the inaugural Henrietta and Terence Hall Distinguished New Century Chair in Orthopedics.
Comron Saifi, MD, Associate Professor, Orthopedic Surgery, has been named the inaugural C. James and Carole Walter Looke Chair in Orthopedic Spine Surgery.
Aldona J. Spiegel, MD, Chief, Division of Surgical Innovation and Professor, Clinical Plastic Surgery has been named the inaugural John F., Jr. and Carolyn Bookout Chair in Surgical Innovation and Technology.
Kyuson Yun, PhD, Associate Professor, Neurology, has been named the inaugural Houston Methodist Chair in Neurodegenerative Disease Research.
Photo: VenoStent
The Future of Surgical Device Innovations: Shaping Tomorrow's Health Care
We stand on the cusp of a transformative era for surgical device innovation.
Advancements in technology are revolutionizing the foundation of surgical practices. As a plastic reconstructive surgeon and an innovator, I have witnessed firsthand the profound impact these innovations have on patient care, outcomes and overall healthcare efficiency.
Three-dimensional printing technology has been one of the most exciting developments in surgical practices. This technology has become a vital tool in complex surgical procedures, allowing for the creation of customized, patient-specific implants and prosthetics, which will set new standards in the personalization of devices available for surgical procedures.
Another innovation is the use of robotic-assisted surgery. Robotic systems, such as the da Vinci Surgical System, have been around for years, but recent advancements are making these technologies more accessible and versatile. New systems also enhance the surgeon's precision, dexterity and control, allowing for fine-tuning microsurgical procedures for lymphatic surgery and supermicrosurgery. Integrating artificial intelligence (AI) and machine learning with robotic systems is poised to further elevate capabilities by offering predictive analytics and real-time decision support during surgeries.
AI is also making significant strides in surgical device innovations. AI algorithms can analyze data to identify patterns and predict surgical outcomes, which is beneficial in preoperative planning and intraoperative decision-making. AI-powered imaging systems can highlight critical structures, such as nerves and blood vessels, reducing the risk of accidental damage during surgery.
Biosensors are another area where innovation is driving change. Wearable biosensors can provide real-time data that can be crucial during and after surgery, which represents a leap forward in patient safety and postoperative care.
Smart surgical instruments are enhancing the precision and effectiveness of procedures. These instruments are equipped with features that provide real-time feedback. Smart scalpels can measure tissue density and adjust their cutting force, minimizing damage to surrounding tissues. Similarly, smart sutures can monitor wound healing and alert medical professionals if there are signs of infection or improper healing.
The convergence of these technologies will continue to push the boundaries. These innovations are enhancing the capabilities of surgeons, improving patient outcomes and transforming health care delivery. As an innovator, it is both an exciting and humbling experience to be part of this journey.
The future of surgical device innovations is bright. By embracing and integrating these technologies, we are paving the way for a more precise, personalized and patient-centric era in surgery. Continuing collaboration between surgeons, engineers and researchers will undoubtedly lead to more groundbreaking advancements, shaping the future of health care for generations to come.
– Aldona J. Spiegel, MD John F., Jr. and Carolyn Bookout Chair in Surgical Innovation and Technology Chief, Division of Surgical Innovation Professor, Clinical Plastic Surgery
METHODOLOGY
The Research and Education Magazine of Houston Methodist
Editorial Director
Jennifer Walker
Editor-in-Chief
Sheryl E. Taylor
Creative Lead & Design
Doris T. Huang
Photographer
Jose Hernandez
Editors
Erin Graham
Donna Ostermayer, PhD
Contributing Writers
Abanti Chattopadhyay, PhD
Heather Lander, PhD
Aldona J. Spiegel, MD
Callie Rainosek Wren, MS
Houston Methodist Academic Institute Office of Communications & External Relations news@houstonmethodist.org
More Methodology read.houstonmethodist.org/methodology
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