Methodology-Winter2024

METHODOLOGY

The Research and Education Magazine of Houston Methodist FALL/WINTER 2024

Disease X Vaccine Powered by AI

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

IN THIS ISSUE SPOTLIGHT 2

Disease X Vaccine Powered by AI

4

Developing America’s SHIELD

6

Guardians of The Galacardins

7

Mobilizing Against Microbes

7

PrEPping for The Future

10

8 Liver Failure Avengers: Weaponizing Lymph Nodes for Battle 18 Enhancing Quality of Life Through Human Performance

2

RESEARCH

19

The Best Pitch: Blood Flow Restriction Training

20

Leading The Green Health Care Movement

22

Take A Walk for Your Heart

23

Tipping The Scales Toward Nature

24

Saving Limbs: Combatting Arterial Disease

PULSE

10

What’s Next in Surgical Robotics?

26

Campus News

12

Deprogramming Transplant Rejection

30

Faculty News

14

No Cancer Cells Left Behind

16

A Whole New World

PERSPECTIVE

17 Synchronizing Maternal and Neonatal Emergency Care

32

Guest Column: Aldona J. Spiegel, MD

The Research and Education Magazine of Houston Methodist

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For more Methodology, visit our online edition: read.houstonmethodist.org/methodology

SPOTLIGHT

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.

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The Team

Jimmy D. Gollihar, PhD

Spike Display Led by Jimmy D. Gollihar, PhD,

Gollihar’s group is leading immunogen design, but their

Professor of Pathology and Genomic

work encompasses much more. The team has been developing

Medicine and Head of the Antibody

therapeutic monoclonal antibodies for SARS-CoV-2. As

Discovery & Accelerated Protein

variants of concern emerged, they wanted to determine what

Therapeutics laboratory, the Houston

those mutations were doing to their monoclonals. So, they

Methodist team joins experts from

developed a mammalian display of viral glycoproteins—called

Argonne National Laboratory (University

a spike display—to allow researchers to study virus mutations

of Chicago), J. Craig Venter Institute,

and source code in real time.

La Jolla Institute, The University of Texas Medical Branch and The University of Texas at Austin. Initially, the team

“We started using spike display to dissect escape mechanisms

will focus efforts on paramyxoviruses and arenaviruses,

and realized it was also an engineering tool. We played

as well as viral families, which include Nipah virus and

around with rational design-based approaches with individual

Lassa virus, respectively.

variants and then moved to library approaches where we could use millions of variants in human cells and mammalian

“We are delighted to have the Houston Methodist Academic

cell lines and sort, seek and find out what's binding what.

Institute be a part of this program, serving our community

The confluence of AI and directed evolution is outright,

and the world. Leading this consortium is an amazing

but protein engineering is really what allows us to do this

undertaking and a testament to the work that Dr. Jimmy

rapidly,” said Gollihar.

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,

Battling The Next Pandemic Threat

Ernest Cockrell, Jr. Presidential Distinguished Chair and President and CEO of the Houston Methodist Academic

AI experts from Houston Methodist, The University of Texas

Institute.

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

The Mission A critical enabler of the 100 Days Mission is the establishment

Branch will validate their immunogenicity in established preclinical models.

of a global “vaccine library”—an accessible store of scientific

When a new pathogen emerges, vaccine developers could

knowledge, data and prototype rapid-response vaccine

quickly respond by selecting AI-identified epitopes that

candidates against selected viruses from the 25 priority

would have already been validated in preclinical tests,

virus families.

enabling vaccine candidates to be moved quickly into

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

clinical testing. This would provide a significant strategic advantage when battling the next pandemic threat, but Gollihar is looking even further into the future.

develop vaccine candidates in the event of an outbreak of

“The next generation of models for protein engineering

a novel pathogenic threat. In this scenario, after sequencing

will require data sets that don’t yet exist, so we’re really

the offending virus, these cataloged antigen designs can

interested in deep mutational scanning,” noted Gollihar.

be inserted into an appropriate rapid-response vaccine

“Because of our engineering platform, we can now take

platform to start the production of vaccines for clinical

every amino acid and put it into every single position of

testing.

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.”

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SPOTLIGHT

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)

The America’s SHIELD program application was submitted in

and roseoloviruses. The γ-HHV subfamily includes Epstein-Barr

response to a funding opportunity posted by the Advanced

virus (EBV) and Kaposi sarcoma herpesvirus. Of these, EBV

Research Projects Agency for Health in support of its Antigens

and CMV clinically impact the largest proportion of the U.S.

Predicted for Broad Viral Efficacy through Computational

population. EBV causes significant disease in adolescents

Experimentation program.

and young adults as the cause of infectious mononucleosis.

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EBV can later cause lymphomas, gastric and nasopharyngeal

The principal investigator on the award is Erica Ollmann Saphire,

cancer—the autoimmune disease multiple sclerosis and

PhD, MBA, Professor and President & CEO of the Center

lymphoproliferative disease in transplant patients. CMV is a

for Autoimmunity and Inflammation, Center for Cancer

leading cause of congenital birth defects, as in-utero infection

Immunotherapy, Center for Sex-based Differences in the

can result in permanent hearing loss or more profound

Immune System, and Center for Vaccine Innovation at the

neurodevelopmental impairments that disproportionately

La Jolla Institute for Immunology. The Co-PI is Jimmy D. Gollihar,

impact socioeconomically disadvantaged children. Also,

PhD, Professor of Pathology and Genomic Medicine and

CMV infection is linked to educational achievement gaps

Head of the Antibody Discovery & Accelerated Protein

in disadvantaged populations.

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

HHV

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.

“

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.

”

By integrating advanced computational models, structural predictions, and immunological data, SHIELD will enable the rapid design and optimization of immunogens against

— Jimmy D. Gollihar, PhD Jerold B. Katz Investigator Professor, Pathology and Genomic Medicine Head, Antibody Discovery & Accelerated Protein Therapeutics Laboratory

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.

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SPOTLIGHT

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 Muhammad Yasser Alsafadi, MD

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mission to solve the toughest problems confronting patients.

Mobilizing Against Microbes In 2023, the World Health Organization (WHO) unveiled

that increases cooperation between disciplines, clinicians,

its Preparedness and Resilience for Emerging Threats

researchers and educators.

Initiative, which provides guidance on response planning “We tend to keep clinical excellence, research and education

for respiratory pathogens.

within discrete silos that are competing for resources, but And though its focus is respiratory pathogens, Tedros

if we bring them together, we can catalyze their synergy,”

Adhanom Ghebreyesus, PhD, WHO Director-General,

said Mylonakis, Charles and Anne Duncan Presidential

reiterated that preparedness and response efforts

Distinguished Chair.

must span sectors, disciplines and pathogens.

Recent events, including the blastomycosis outbreak at With the addition of infectious

the Billerud paper mill in Escanaba, Michigan, demonstrated

disease experts—including Eleftherios

that fungi are now more of a threat than previously thought.

Mylonakis, MD, PhD, FIDSA, Chair of

Eleftherios Mylonakis MD, PhD

the Department of Medicine—Houston

Mylonakis points out that even before these new threats,

Methodist is moving to the front lines of

there’s been an ongoing, slow-moving, yet dangerous,

emerging infectious disease research.

fungal pandemic caused by Candida auris. “C. auris is

As a physician-scientist, Mylonakis

very resistant to existing antifungals,” he said. “It is a strong

intends to guide clinical and transla-

example of a real and present danger from a fungus that

tional research into a new paradigm

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.

Alessandro Grattoni, PhD

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.

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SPOTLIGHT

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

in a single year; however, more than 1,700 patients die annually

by person—located in the neck, armpit,

while on a liver transplant waitlist.

chest, behind the ear, abdomen and Constance M. Mobley MD, PhD, FACS

groin. These organs are tasked with

The team has dosed three patients, who are currently on a

filtering substances in a person’s lymph

transplant waitlist, using their lymph nodes as living bioreactors

fluid (proteins, minerals, nutrients, fats,

to regenerate an ectopic organ. The selected patients must

white blood cells, damaged cells,

have a Model for End-Stage Liver Disease score that is greater

cancer cells, viruses and/or bacteria).

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,

Houston Methodist researchers are now in a Phase 2a

which began in 2022.

Clinical Trial—Safety, Tolerability, and Efficacy of Hepatocyte Transplantation into Periduodenal Lymph Nodes Among

Mobley’s colleague, Sunil Dacha, MD, MBBS, performs an

Subjects With End-Stage Liver Disease. Houston Methodist

endoscopic ultrasound to locate the lymph nodes in the

is one of two study sites partnering with LyGenesis, Inc.

periportal area. Patients who are experiencing end-stage

Boston’s Tufts Medical Center is the other participating site.

liver disease tend to have enlarged lymph nodes in the area between the stomach, liver and duodenum. Once Dacha

Under the leadership of Constance Mobley, MD, PhD, FACS,

locates a lymph node in that area, he endoscopically injects

researchers have successfully performed a first-in-human

that lymph node with the liver cells.

miniature liver hepatocyte transplant to change a patient’s lymph nodes into ectopic miniature livers.

“The procedure is simple; however, the difficulty lies in identifying the nodes around the liver due to their size—one centimeter or

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Since enrolling the first patient, Mobley’s team has been

less. They are not easy to find, but with meticulous examination,

inundated with people asking to participate in this study, from

we’ve been able to successfully perform three procedures,”

as far as Europe to Australia and across the U.S. According

said Dacha, Associate Professor of Clinical Medicine. “All three

to the United Network for Organ Sharing, more than 10,000

patients have done well. What we are doing is a unique thing.

liver transplants were performed in 2023—the most ever

Only at Houston Methodist in the world.”

“

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.

”

– Constance M. Mobley, MD, PhD, FACS Associate Director, Liver Transplantation J.C. Walter Jr. Transplant Center

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.”

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RESEARCH

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

“Unfortunately, there hasn't been a formal entity that has

technology landscape.

provided guidance on how to evaluate and incorporate new technology, specifically robots and AI, into surgery,” Ramirez

However, compared to other types of medical devices,

explained. “So, I joined the IDEAL Collaboration to help

surgical technologies, including robots and AI, are historically

implement a robotics colloquium to address this need.”

underevaluated before implementation.

Founded in 2007-2008 at Balliol College, University of Oxford, Assessment after the technology is implemented is also

the IDEAL Collaboration is comprised of a group of research

lacking. This innovation without evaluation can lead to

methodologists and surgeons with a common goal of improving

catastrophic consequences for health care and society.

surgical innovation research. While the group has already

“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

Pedro T. Ramirez MD, FACOG

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.

knowledge gap in the field,” explained

“We felt that robotics needed its own evaluation framework

Pedro T. Ramirez, MD, FACOG.

because it is a technology that is growing quickly and being

As Chair of the Department of Obstetrics and Gynecology, Ramirez knows that new technology doesn’t always equate to the best outcomes for patients.

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established an IDEAL Framework to evaluate surgical innovation

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.”

the near future, I think surgical robots could perform “ Inentire procedures. ” – Pedro T. Ramirez, MD, FACOG Chair, Department of Obstetrics & Gynecology

Using the existing IDEAL Framework as guidance, Ramirez

“These types of advancements come with ramifications

and a team of diverse experts—surgeons, engineers,

if the technology is not evaluated and used properly.”

economists, patient representatives and social scientists— began developing the IDEAL Robotics Colloquium in 2022.

Taking these concerns into account, Ramirez and his team published the IDEAL Robotics Colloquium in

Dividing into panels, these experts participated in a series

Nature Medicine in 2024. This new framework outlines

of virtual discussions focusing on key concerns regarding

recommendations for surgical robot evaluation during

surgical robotics.

development, comparative study and clinical monitoring.

It also provides practical recommendations for

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

developers, clinicians, patients and health care systems while considering multiple perspectives, including economics, surgical training, human factors, ethics, patient perspectives and sustainability.

begin questioning their own intuition? If so, what are the

Ramirez’s next goal is to raise more awareness of the

implications of this?

IDEAL Robotics Colloquium among surgeons and

“We’re moving toward a technology where the surgeon can potentially be on autopilot or standby,” Ramirez said.

manufacturers to shape how we use surgical robots in the future.

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RESEARCH

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.

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Wenhao Chen, PhD

Transplanted tissues and organs are

effector cells that attack transplanted organs. Their data

recognized as “other” by our immune

indicated that naïve alloantigen-specific CD4+ T cells develop

systems, thus, triggering an immune

first into TCF1-hi effector precursor T (TEP) cells and then

response that results in physiological

into TCF1–CXCR6+ effector cells. However, the effector

rejection of the tissue. To prevent this,

cells lose their ability to proliferate and fail to reject allografts

physicians must modulate immunity,

upon adoptive transfer into new recipients. Conversely, the

so the foreign object is tolerated.

TCF1-hi CD4+ TEP cells can self-renew and differentiate into effector cells, thereby representing the stem-like

The molecular pathways leading to

CD4+ T cells in transplantation scenarios.

T-cell activation have been extensively studied, but the mechanisms modulating subsequent CD4+ T-cell effector

Crucially, the rejection of allografts is dependent on continuous

programs leading to transplant rejection are not fully

replenishment of TCF1–CXCR6+ effectors from TCF1-hi

understood.

CD4+ TEP cells. Moreover, the sustainability of the CD4+

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 stem-

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.

like CD4+ T cells in transplant recipients, as well as the

These results provide robust evidence for a stem-like program

stem-like program directing the CD4+ T cell response

that controls the self-renewal and effector differentiation

in models of transplantation.

abilities of CD4+ TEP cells. Because the stem-like CD4+ T cells continually replenish the effector cell pool, they may be

More specifically, they found stem-like CD4+ T cells that

the more effective therapeutic target for preventing transplant

recognize transplant antigens that can differentiate into

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 Associate Professor, Transplant Immunology in Surgery J.C Walter Jr. Transplant Center

” 13

RESEARCH

No Cancer Cells Left Behind Improving Chemotherapeutic Efficacy

By Abanti Chattopadhyay, PhD

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

The reason is that out of 500 clinical trials using mTOR

traditionally been an attractive cancer

inhibitors, few have demonstrated clinical benefit.

therapeutic target since mTOR

Yulin Li, MD, PhD

dysfunction leads to tumorigenesis.

Yulin Li, MD, PhD, Assistant Professor of Immunotherapy

The mTOR signaling network is

in Medicine, demonstrated in a research study published

evolutionarily conserved and regulates

in Nature Communications that mTOR inhibition promotes

several basic biological and physiological

the development of a chemoresistant “persister” state,

processes including cell survival,

potentially contributing to tumor recurrence. His findings

growth, metabolism, aging, regeneration,

challenge the long-held paradigm that mTOR is an ideal

protein synthesis, autophagy, inflammation and homeostasis.

therapeutic target and point towards novel therapeutic

mTOR (a serine/threonine kinase) functions as a hub that

strategies to prevent tumor recurrence in cancer patients.

integrates many intracellular and environmental signals.

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Li and his team performed a genome-wide CRISPR

The FDA has only approved a few mTOR inhibitors for

knock-out screen in a murine pancreatic cell line using

controlling late-stage tumor expansion in specific cancers.

gemcitabine and selinexor (two genotoxic chemotherapeutic

“

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.

”

– Yulin Li, MD, PhD Assistant Professor, Immunotherapy in Medicine

agents). The screen identified the mTOR signaling

mTOR inhibition is not the best strategy for chemotherapy

pathway as a crucial determinant of chemosensitivity.

since it leads to tumor persisters that may lead to tumor

Specifically, Li concluded that mTOR suppression in

recurrence. On the other hand, mTOR activation enhances

tumor cells leads to a drug-tolerant and chemoresistant

chemosensitivity and improves survival in various human

persister population with a reversible phenotype.

cancers. A growing body of research supports this

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

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.

small molecule screen performed by Li. Interestingly,

“We observed that mTOR suppression promotes the

the mTOR inhibitor rapamycin has demonstrated

induction of persisters in various cancer cells undergoing

to prolong lifespan in various model organisms and

chemotherapy and dampens therapeutic efficacy,”

mammals.

noted Li. “Similarly, others have shown that mTOR inhibition is chemoprotective in leukemia cells.”

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RESEARCH

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

Walter W. Fondren III Distinguished Chair and Chair,

hands-on clinical training hub for health care professionals

Department of Cardiovascular Surgery, believes that

seeking to enhance their procedural skills and acquire new

the MITIEverse™ represents a paradigm shift in health

expertise.

care education and training.

MITIE’s simulation, imaging, audiovisual

“It essentially democratizes access to health care educators

and virtual reality capabilities create a

and innovators by breaking down physical barriers. There’s

comprehensive training system. Its new

no need to travel thousands of miles to attend a conference

app—MITIEverse™—is a groundbreaking

when you can patch into the MITIEverse™,” noted Lumsden,

initiative in healthcare education, training

Professor, Cardiovascular Surgery.

and innovation for medical and scientific learners. Developed in collaboration with Stuart J. Corr, PhD

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

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.

worldwide.

The app is currently invitation-only as development continues.

16

One of the standout features is the DeBakey Heart & Vascular

“We're focused on use-case development and publishing.

Center's showcase room, where users can observe actual

One possibility under consideration is utilizing the app to train

surgeries performed by faculty and engage with 3D human

health care professionals to perform intubations in difficult scenarios,

models for a deeper understanding. Alan B. Lumsden, MD,

using 3D modeling of various airway pathologies,” said Corr.

Synchronizing Maternal and Neonatal Emergency Care

By Callie Rainosek Wren, MS

When Randolph H. Steadman, MD, MS, was allocated

scenarios, participants were able to identify irregularities

educational funds for frontline staff to train at MITIE at

in how each hospital responds to emergencies. For example,

the Bookout Center, Stephanie S. Bruce, MD, MAS,

color-coded emergency supply carts and code calls were

FACOG, and physician champion for the Houston Methodist

not standardized systemwide, which could delay care in

Women and Infants Council (WIC), jumped at the opportunity.

a critical situation. These discrepancies were high on the agenda during WIC’s strategic planning meeting in

Through collaboration with WIC,

early 2024.

Steadman led MITIE at the Bookout Center’s first Maternal and Infant

As WIC works to standardize these discrepancies, staff

Simulation Instructor course. Attended

continue to expand their skills through Steadman’s half-day

by health care staff from all seven of

refresher courses and simulation training conferences.

Houston Methodist’s birthing hospitals, the course focused on improving Randolph H. Steadman MD, MS

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

Stephanie S. Bruce, MD, MAS, FACOG

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.

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.”

“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

17

RESEARCH

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.

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The Best Pitch: Blood Flow Restriction Training

By Abanti Chattopadhyay, PhD

Blood Flow Restriction Training Therapy is an up-and-coming

role in the advanced coordination and strength needed for

training tool method that allows athletes to work out smarter,

pitching. Therefore, a great deal of off- and in-season training

not harder. Essentially, the technique involves an athlete

focuses on strengthening these muscles, which are also

wearing a tourniquet-style cuff on the upper arm or thigh

prone to injury, especially if subjected to high-intensity and

while lifting lighter weights to build muscle mass. The tourniquet

high-load resistance training (HIX).

prevents blood flow out of the area, which makes the body think that the athlete is exercising harder than he or she actually is.

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

Bradley S. Lambert, PhD, Assistant Professor of Orthopedic

prevents venous return with a typical 40-80% arterial limb

Surgery, performed a randomized clinical trial in which he

occlusion pressure. Combining BFR and LIX produces results

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 Bradley S. Lambert, PhD

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.

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

The scapulohumeral muscles, which connect the scapula to

duration and timing within a sports training program that may

the humerus, are particularly important in overhead throwing

provide the greatest benefit for different types of overhead

athletes such as baseball pitchers. These muscles play a key

throwing for athletes.”

19

RESEARCH

Leading The Green Health Care Movement

By Callie Rainosek Wren, MS

When thinking of sustainability, recycling, conservation

have attracted partners across the Texas Medical

and reducing, the carbon footprint may come to mind.

Center, leading to one of the nation’s first collaborative

But what does sustainability mean for Houston Methodist?

and systematic approaches to health care sustainability

“Aligning with our I CARE Values, sustainability means conserving resources to protect the environment while

These efforts are paramount, as health care accounts for

continuing to provide high-quality patient care,” explained

10% of the nation’s greenhouse gas emissions. ICUs are

Jason Fischer, MBA, System Director of Sustainability.

considered carbon “hot spots,” emitting enough daily

Established in 2023, the Office of Sustainability supports

greenhouse gas emissions to rival driving a car 62.14 million

system-wide sustainability efforts led through employee

miles. Medical waste is another concern. Caring for a single

and community engagement; introspective analyses;

ICU patient can result in as many as 108 disposable gloves,

actionable roadmaps; and non-profit, industry and

57 compresses, 34 infusion bags, 16 articles of disposable

governmental partnerships.

clothing and 8 bed liners per day.

Although the office is relatively new, its faculty and staff

Despite these statistics, Green ICUs are in their infancy

have initiated several research and operations-focused

in the U.S. Masud and Green ICU colleagues recently

projects to conserve energy and resources.

published an article in Critical Care that outlines these

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 Faisal N. Masud MD, FCCP, FCCM

20

goals.

Medicine’s National Task Force on Green ICUs. These projects

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.

“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

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

important priority,” explained

is reducing water with pressurized valves, recycling

Masud, Mary A. and M. Samuel

not in use and using equipment stoplights to reduce

Daffin, Sr., Centennial Chair in

making environmentally preferred purchases, using

Anesthesia and Critical Care.

pipette boxes, ensuring hood vents are closed when energy consumption. The supply chain workgroup is reusables and renewables and planning for zero waste.

Houston Methodist also continues to engage the community through sustainability fairs, community

Further, the systemwide virtual ICU program, created

gardens and I CARE in Action volunteer projects.

during the COVID-19 pandemic, continues to show

All these initiatives, new or ongoing, require strategic

potential for low-carbon emissions. These enhanced

collaboration among faculty and staff to protect the

facilities allow for remote patient consultations, virtual family

planet while keeping safety, quality, service and

visits, tele-rounding and reduction in staff commuting—all

innovation at the core of patient care.

innovations that reduce travel-associated carbon emissions without compromising patient safety and quality of care.

21 5

RESEARCH

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.

22

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

Phases two and three refined phase one factors with

and Validation of Self-efficacy and Intention Measures for

pre-tested survey questions administered to a nationwide

Spending Time in Nature,” developed and evaluated the

sample of more than 2,000 adults. Phases five through

reliability and validity of self-efficacy and intention measure

nine used data analytics to eliminate items showing extreme

for time spent in nature (TSN) as it relates to improvement in

characteristics and to test the dimensionality, reliability

psychological well-being and health. Self-efficacy and intentions

and validity of the scales.

are shown to be strong predictors of health behavior.

More time spent in nature correlated with both self-efficacy

Jay Maddock PhD, FAAHB

Jay Maddock, PhD, FAAHB, Director,

and intentions, indicating more time spent in nature should

Center for Health and Nature and

be a goal for improving TSN. However, the age of the

Professor in the Department of

respondents showed a more negative result, which may

Environmental and Occupational Health

indicate the limited mobility or safety concerns of the

at Texas A&M University’s School of

respondents. Males had higher self-efficacy than female

Public Health, led a 14-member team

respondents. Additional research has shown that women

to embark on a nine-phase procedure.

are less likely to participate in recreational activities

This team—comprised of researchers

in nature.

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

“We’re working on developing a whole suite of measures,” Maddock said. “Once those are complete, we want to develop theory-based interventions to increase time spent in nature.”

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.

23

RESEARCH

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,

Trisha Roy, MD, PhD, FRCSC,

myocardial infarction, coronary artery disease and

Assistant Professor of Cardiovascular

cerebrovascular disease. Managing PAD includes

Surgery, published a case report

pharmacological treatments and revascularization of

in the Methodist DeBakey

blood vessels. Percutaneous vascular intervention (PVI) is

Cardiovascular Journal 2023 to

a minimally invasive procedure to unblock occluded arteries.

illustrate the importance of Magnetic

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)

24

Resonance Imaging (MRI) histology Trisha Roy MD, PhD, FRCSC

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.

or soft. Appropriate interventional strategies for blood flow

The CLI patient’s right foot had worsening rest pain,

restoration are critical to prevent amputation and death.

non-healing wounds and ulcers and an impenetrable

“

plaque in the popliteal artery. Failed PVI attempts were

Using ultrashort echo time (UTE) and T2-weighted (T2W)

followed by failed bypass attempts, eventually requiring

sequences, MRI histology can be used to determine if

an above-knee amputation. According to the Amputee

blockages are hard or soft. This offers a good predictive

Coalition, about 185,000 amputations occur in the U.S.

value of not only identifying patients who are at a high risk

each year. Nearly 54% of limb loss cases are due to

of failing the endovascular intervention, but also predicting

diabetes and PAD.

whether their lesions would require more adjunctive devices.

PAD is a real epidemic, and it is

There are a couple of anatomic scores for PAD that indicate if a lesion or patient will be better served by endovascular

growing along with diabetes and

treatment or open bypass. These scores are based on length

renal failure. Our understanding

details about what the occlusion is made of. Soft lesions

and degree of stenosis. However, these do not provide any (whether long or short) can be recanalized using endovascular

of PAD is quite poor and the imaging techniques that we use have been the same for decades.

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

So, having the ability to be

to UTE and T2W) and material equipment.

more advanced with how we're

“MRI histology is a good tool to shed light on what these

diagnosing PAD, and tailoring

blockages are composed of and thereby predict endovascular

our treatment can help patient

failure. Right now, our outcomes are quite poor and we're

outcomes, particularly because

time more futile than the last,” noted Roy. “We hope that

there's a big spectrum to what the blockages can be made of.

– Trisha

Roy, MD, PhD, FRCSC Jerold B. Katz Investigator Assistant Professor, Cardiovascular Surgery

having to intervene on these patients again and again, each 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.

25

CAMPUS NEWS

PULSE

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.

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

Snapshot of Matches: 2024-2025 Incoming Residents

build-out of approximately 924 square

• 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)

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.

26

It’s a FACT: Johnson Center Earns CAP Accreditation The Ann Kimball and John W.

Medical Center to perform its

Johnson Center for Cellular

own quality tests and offer these

Therapeutics received its first

services to other facilities. The

accreditation from the College

Centers for Medicare and Medicaid

of American Pathologists (CAP)

Services (CMS) has granted the

and the Foundation for the

CAP Laboratory Accreditation

Accreditation of Cellular Therapy

Program deeming authority,

(FACT). CAP accreditation

allowing CAP inspection instead

ensures Houston Methodist’s

of a CMS inspection. FACT

Johnson Center is in accordance

accreditation is the threshold for

and Kymriah®, for ease of

with the latest best practices in

excellence in cell therapy, informing

the field of laboratory medicine

patients, health insurance companies

use in Houston Methodist

worldwide—from accuracy and

and governments that the Johnson

patients with blood cancers.

quality of test results—making

Center is dedicated to the highest

the center one of the only cell

quality patient care and safety.

U.S. News & World Report

therapy facilities in the Texas

With FACT recognition, the Johnson Center can store commercial CAR T-cell products, such as Yescarta®

utilizes FACT accreditation in its annual ranking of

Photo: Ann Kimball and John W. Johnson Center for Cellular Therapeutics Steering Committee:

best U.S. hospitals.

Patrick McCulloch, MD; John P. Cooke, MD, PhD; Jenny Chang, MD; Eamonn Quigley, MD; Stanley H. Appel, MD; and Osama Gaber, MD

27

PULSE

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

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.

largest gift to any regional hospital within the Houston Methodist

Proposed future fellowships include Cardiovascular Diseases,

system. It’s also the first instance in which a Texas Medical

Orthopedic Surgery, Pulmonary Critical Care and Sports

Center (TMC) institution will sponsor an academic medical

Medicine.

program in one of the community hospitals where patients can seek specialty care typically only offered in the TMC.

Houston Methodist’s academic medical program includes more than 350 residents and fellows, receiving training in

This 36-month ACGME-accredited Internal Medicine Residency

various specialties. Many of these physicians-in-training

Program will allow residents to rotate through various core and

often rotate to one of Houston Methodist’s eight hospitals

elective rotations in the outpatient and inpatient setting and

in Greater Houston.

Progress Through Partnership $4 Million Multi-Institutional Commercialization Hub The Gulf Coast Consortia and their partner institutions, including

The GCC is an ideal organization to be leading this hub.

the Houston Methodist Research Institute, Texas A&M University

According to its site, the “GCC delivers important advances

Health Science Center, The University of Texas Medical Branch,

in bioscience research and training by empowering individuals

Texas Southern University (TSU), Baylor College of Medicine,

to go beyond the limitations of any single institution, discipline or

The University of Texas MD Anderson Cancer Center, Rice

degree program.” Located in Houston’s Texas Medical Center,

University, University of Houston and The University of Texas

GCC is one of the largest inter-institutional cooperatives in the

Health Sciences Center-Houston, were awarded a four-year,

world, integrating the strengths of its member institutions to

$4 million cooperative research agreement from the National

build interdisciplinary collaborative research teams and training

Institutes of Health (NIH) to establish the Gulf Coast Consortium

programs in biological sciences at their intersection with the

Research Evaluation and Commercialization Hub (GCC-REACH).

computational, chemical, mathematical and physical sciences.

GCC provides a unique, cutting-edge collaborative training

This multi-institutional commercialization hub will support the

environment and research infrastructure beyond the capability

development and commercialization of transformative health

of any single institution.

care treatments based on research discoveries. Within the

28

GCC-REACH, academic entrepreneurs work closely with life

Over the next four years, the GCC-REACH will train academic

science experts and biotech executives to develop milestones

entrepreneurs and scientists within GCC member institutions,

to rapidly validate the commercial value of their discoveries.

TSU and regional research institutions to navigate the process

They also assist entrepreneurs in strategic planning for

of successfully commercializing their novel discoveries. The

management and operations, and provide vetted resources

consortium aims to launch as many as 60 early-stage biomedical

and support to achieve value-added commercialization

companies that will attract venture investments and additional

inflection points.

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

29

FACULTY NEWS

PULSE

Katz Investigators Named for Translational Research 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.

A New Pathway for PAH Pulmonologist Zeenat Safdar, MD MS,

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.

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,

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.

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.

30

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

Photo: VenoStent

in 2024. The device is wrapped around the dialysis access site where the artery and vein join to provide

“Rusty” Walter and Carole Walter Looke Presidential Distinguished

additional structural support, extending the life of the

Chair in Cardiovascular Disease Research, Chair, Department of

port. The wrap is made from a material absorbed by

Cardiovascular Sciences, Professor of Cardiovascular Sciences,

the vascular walls. The VenoStent is a 3D-printed

Director, Center for Cardiovascular Regeneration, and Medical

polymer that bioabsorbs into the vascular tissue in

Director, Center for RNA Therapeutics, who brought academic

100 days. Peden’s Houston Methodist collaborators

expertise with grant submission documentation. As the national

include Christof Karmonik, PhD, Research

PI, Houston Methodist is the lead on all resulting academic

Professor of Radiology, who helped design and

publications and has the ability to make podium/keynote

deploy the VenoStent technology in a controlled

presentations at conferences on patient outcomes. The clinical

setting; and John P. Cooke, MD, PhD, Joseph C.

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.

31

PERSPECTIVE

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 32

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

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HMAIMAGAZINE-018 | 12.2024 | 1300

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