Louisiana Via Research Day Book 2026

2026 Via Research Recognition Day

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2026 Research Recognition Day

ON THE COVER: (left to right) Justin Nguyen, Class of 2026; Savannah Newell, PhD

Via Research Recognition Day Agenda February 27, 2026

Kayla Griffith and Francheska Brzazgon, Class of 2028

7:30–8:30 a.m.

Registration, second floor Coffee service and refreshments, second floor

0.5 CME

8:30–9:00 a.m.

Opening Remarks and Plenary Lecture: “The State of Research at VCOM” Pawel Michalak, PhD and P. Gunnar Brolinson, DO, FAOASM, FAAFP, FACOFP Lecture Hall 2, second floor VIA Learning Management System (VLMS) Update P. Gunnar Brolinson, DO, FAOASM, FAAFP, FACOFP; Fred Rawlins II, DO; Jan Michalak, MA; Heather Price, CSM Lecture Hall 2, second floor

Welcome

0.75 CME

9:00–9:45 a.m.

Welcome to the VCOM Via Research Recognition Day on the VCOM-Louisiana Campus. Each year, the Via Research Recognition Day is a significant event for VCOM that supports the mission of the College to provide medical education and research that prepares globally minded, community-focused physicians and improves the health of those most in need. The Via Research Recognition Day offers a forum for health professionals and scientists in academic institutions, teaching hospitals and practice sites to present and benefit from new research innovations and programs intended to improve the health of all humans. By attending the sessions with guest speakers, participants have the opportunity to learn cutting edge information in the physiological bases of osteopathic manipulative therapy efficacy, new trends in physician-based research networks, and how to develop innovative research projects with high impact for human health. Poster sessions allow participants to learn about the biomedical, clinical, and education-simulation research activities at VCOM-Louisiana and its partner institutions.

Hannah Khairandish, Class of 2028

9:45–10:00 a.m.

Coffee Break

10:00–11:00 a.m.

Keynote Speaker: “Rules of Engagement: Molecular Arms Race Between Host and Viral Genomes”

1.00 CME

Harmit Singh Malik, PhD Lecture Hall 2, second floor

11:00 a.m.–2:00 p.m.

Poster Competition Rooms-107, 129-132, first floor

2:00–3:00 p.m.

Award Ceremony and Final Remarks Lecture Hall 2, second floor

TOTAL: 2.25 CME

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RESEARCH

Contents

Speakers

Program Moderators.................................................................................................................................................................6

Plenary Speaker.........................................................................................................................................................................8

Speaker. .....................................................................................................................................................................................9

Keynote Speaker......................................................................................................................................................................10

Abstracts

Biomedical Research: Section 1.............................................................................................................................................11

Biomedical Research: Section 2.............................................................................................................................................32

Case Studies: Section 1..........................................................................................................................................................40

Case Studies: Section 2..........................................................................................................................................................99

Clinical Research...................................................................................................................................................................116

Community / Public Health....................................................................................................................................................130

changes the world.

Simulation / Education..........................................................................................................................................................143

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Program Moderator

Program Moderator

Supporters

Ray L. Morrison, DO, FACOS, DFACOS Dean, Louisiana Campus VCOM

Pawel Michalak, PhD Associate Dean for Biomedical Affairs & Research, Louisiana Campus VCOM

Ray L. Morrison, DO, FACOS, DFACOS, of Monroe, Louisiana, joined the faculty of the Edward Via College of Osteopathic Medicine (VCOM) as the founding dean for VCOM–Louisiana in July 2018. His subsequent leadership roles at the College have included associate vice president and vice president for College development and advancement in the Louisiana region, dean emeritus, and associate professor of surgery. In April 2025, Dr. Morrison returned to his role as dean for VCOM–Louisiana. Prior to joining VCOM, Dr. Morrison served as assistant dean of clinical education and chair of surgery at Liberty University College of Osteopathic Medicine in Lynchburg, Virginia. He also held the position of assistant professor of surgery in the Department of Rural and Family Practice at the University of North Texas Health Science Center–Texas College of Osteopathic Medicine (UNTHSC/ TCOM) in Fort Worth, Texas.

Dr. Morrison currently serves as speaker of the House of Delegates for the American Osteopathic Association (AOA), a role he has held for 17 years. In addition to his service as speaker, he has contributed to the AOA in numerous leadership capacities, including serving as a member or chair of the Bureau of State Government Affairs, the Constitution and Bylaws Committee, the Committee on Governance and Organizational Structure, and the Bureau of Federal Health Programs. He also serves as vice chair of the Osteopathic Political Action Committee (OPAC). Dr. Morrison is an AOA board-certified surgeon, a Distinguished Fellow of the American College of Osteopathic Surgeons, and a past president of that organization.

Pawel Michalak, PhD, serves as the associate dean for biomedical affairs and research for the VCOM-Louisiana campus. He is also an adjunct faculty member at the Virginia Maryland College of Veterinary Medicine and the University of Haifa in Israel. Michalak served as a professor at the VCOM-Virginia campus, with a focus on comparative genomics, bioinformatics, and One Health, operating as head of the Integrative Genome Analysis Lab (IGAL) at the Center for One Health Research. His team has employed an integrative approach with a variety of molecular, computational, and modeling techniques, including NextGen sequencing, a high-throughput DNA sequencing technology, of entire genomes, epigenomes, and transcriptomes to establish a rigorous understanding of how complexity elaborates from genomes through gene regulatory networks, and how it evolves over generations in response to environmental stress and intragenomic challenges.

Michalak has worked at nine universities in four countries across three continents. He has published his research in one book, with a second currently in preparation. Additionally, Michalak has been credited as a contributor in multiple books, as well as approximately 70 peer-reviewed papers in scientific journals, including “Cell,” “Science,” “Nature,” “Proceedings of the National Academy of Sciences USA” and “Proceedings of the Royal Society.” His research has been cited nearly 2000 times and popularized by various public media outlets.

Dixie Tooke-Rawlins, DO, FACOFP President VCOM

John Rocovich, Jr, JD, LLM Chairman VCOM

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Plenary Speaker

Speaker

P. Gunnar Brolinson, DO, FAOASM, FAAFP, FACOFP Vice Provost for Research VCOM

Fred Rawlins, II, DO Senior Associate Dean for Simulation and Technology and Associate Professor for Emergency Medicine VCOM

P. Gunnar Brolinson, DO, FAOASM, FAAFP, FACOFP, is vice provost for research, professor of family and sports medicine at the VCOM and team physician for Virginia Polytechnic Institute and State University. He is an adjunct professor in the Department of Mechanical Engineering at Virginia Tech. He is the fellowship director emeritus of the Primary Care Sports Medicine Fellowship at VCOM and Virginia Tech. He is also a volunteer physician for the United States Olympic Committee and a team physician for the United States ski team and was head team physician for the freestyle ski team at the 2006 Winter Olympic Games in Torino, Italy. He was also named to the medical staff for the 2010 Winter Olympic Games in Vancouver, British Columbia, and was medical director of the USOC performance services center. He obtained his undergraduate training from the University of Missouri at Columbia earning a degree in biology. A 1983 graduate of the Kirksville

College of Osteopathic Medicine, Dr. Brolinson is board certified in family practice and holds a subspecialty certification in sports medicine. Prior to coming to Virginia, he was the co director of the Primary Care Sports Medicine Fellowship training program at The Toledo Hospital in Toledo, Ohio, and team physician for University of Toledo. He has extensive experience in undergraduate and post graduate medical education. Dr. Brolinson has served on the boards of the American Osteopathic Academy of Sports Medicine, the American Medical Society for Sports Medicine and the Midwest Chapter of the American College of Sports Medicine. He is a past president of the American Osteopathic Academy of Sports Medicine. Dr. Brolinson is a fellow of the American Osteopathic Academy of Sports Medicine, the American Academy of Family Practice and the American College of Osteopathic Family Practice. In 1997, he was named outstanding young physician in Ohio by the Ohio State Medical Association.

He is a former associate editor for the Clinical Journal of Sports Medicine and a former member of the editorial board of the “Physician and Sports Medicine.” He is former section editor for Competitive Sports and Pain Management in the journal “Current Sports Medicine Reports.” Dr. Brolinson is a frequent speaker at national sports medicine meetings and often teaches didactic laboratory sessions on the use of osteopathic manipulative therapy for athletic injuries. Dr. Brolinson is a contributing author in the latest edition of “Foundations for Osteopathic Medicine” and he has published several scholarly articles and book chapters in the area of sport and exercise medicine. His research interests have included exercise and immune function, exercise and bone mineral density, mild traumatic brain injury in sports, impact biomechanics, human factors in auto safety, sports performance and manipulation and other health and disease prevention related topics.

Fred Rawlins II, DO, is the senior associate dean of simulation and educational technology, associate professor of emergency medicine at the Virginia Campus of the Edward Via College of Osteopathic Medicine, chief medical officer of Via Learning Management System (VLMS), and chief information officer of Via Voice Recognition Technology (VVrT). He is an attending physician in the Department of Emergency Medicine at West Virginia University. He has been in practice for more than 28 years as an emergency physician. Evaluating cardinal complaints of the undifferentiated patient is synergistic with teaching the pre-clinical medical students. Generating computer algorithms for the evaluation of screening the undifferentiated patients is fundamental to syndromic surveillance. This led to the development of VLMS funded by the Department of Defense. Recently, Dr. Rawlins received a grant to develop voice recognition technology for medical decision making (MDM) called VVrT.

Dr. Rawlins has been actively involved in the world of simulation in his professional career. He earned his private pilot’s license for single and multi-engine land aircraft and has since logged over 5000+ hours of flight on turboprop planes with an instrument rating system. Modeling of aircraft simulation as a training tool contributed to the skillset to apply in medical simulation. In the medical field, he has worked closely with other departments at VCOM to enhance the 1st and 2nd year curriculum by presenting psychomotor cases to medical students that allow them to bring forth their medical knowledge in a hands-on, controlled, learning environment. Expanding this opportunity to other organizations, he has developed standardized patient and manikin-based simulation scenarios unique for aeromedical training certifications.

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Keynote Speaker

Harmit Singh Malik Evolutionary Biologist Fred Hutchinson Cancer Center

Harmit Singh Malik is an evolutionary biologist renowned for uncovering how genetic conflicts and evolutionary “arms races” between genomes shape fundamental cellular processes and host–pathogen interactions. He is a Howard Hughes Medical Institute Investigator and professor in the Basic Sciences Division at Fred Hutchinson Cancer Center in Seattle, where he leads a research program centered on the causes and consequences of genetic conflict. Malik grew up in India and earned his undergraduate degree in chemical engineering from the Indian Institute of Technology Bombay before moving to the United States for graduate school. He completed his PhD in molecular evolutionary biology at the University of Rochester, where his work on retrotransposons showed that these “selfish” genetic elements were already present in ancestral lineages rather than recently acquired like viruses, reshaping prevailing ideas about their origins. He joined Fred Hutch for postdoctoral research on centromeres with Steven Henikoff and

subsequently established his own lab, focusing on how rapidly evolving genetic elements might drive speciation, genome stability, and susceptibility to disease. Malik is best known for helping develop the centromere-drive model, which explains how “selfish” centromeres can bias their transmission during female meiosis and thereby drive the rapid evolution of centromeric DNA and its associated proteins. His lab has been a major force in paleovirology, using viral “fossils” in animal genomes to reconstruct ancient host–virus arms races and to understand why genes involved in chromosome segregation, innate immunity, and mitochondrial biology often evolve unusually quickly. Across these projects, his group uses evolution-guided approaches to identify rapidly evolving genes, link signatures of positive selection to mechanism, and illuminate how conflicts between genes, genomes, and pathogens influence both disease and the origin of new species.

Malik’s contributions have been recognized with many prestigious honors. He received the Presidential Early Career Award for Scientists and Engineers (PECASE), the Vilcek Prize for Creative Promise in Biomedical Science for his work on genetic conflict, and the Eli Lilly and Company Research Award from the American Society for Microbiology. He was appointed an HHMI Investigator, elected to the American Academy of Arts and Sciences and the National Academy of Sciences, and awarded the Genetics Society of America’s Edward Novitski Prize for creative, paradigm-shifting work on chromosome biology and evolution. He has also received the McDougall Mentoring Award at Fred Hutch.Former students and postdocs describe his lab as a place that encourages bold, evolution-guided experiments, interdisciplinary collaborations, and open discussion, and many alumni have gone on to lead independent research programs focused on genetic conflict, viral evolution, and chromosome biology.

Biomedical Research: Section 1

IN THE PHOTO: Kendyl Berry, Class of 2028

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Biomedical Research: Section 1

Biomedical Research: Section 1

Lise-Carla Honore, OMS-II; Kaitlin Wiley, OMS-II; Kasia Michalak, MSc; Maysoon Makhlouf, PhD; Zakaria Abd Elmageed, PhD; Hassan Ebrahim, PhD VCOM-Louisiana 1 THE LABDANE COMMUNIC ACID INDUCES APOPTOTIC CELL DEATH AND ATTENUATES THE PROLIFERATION, MIGRATION, COLONIZATION OF BREAST CANCER CELLS

Francheska Brzazgon, OMS-II; Hannah Khairandish, OMS-II; Kayla Griffith, OMS-II; Rose Pwint, OMS-II; Kasia Michalak, MSc; Zakaria Abd Elmageed, PhD; Hassan Ebrahim, PhD VCOM-Louisiana 2 ANTI-BREAST CANCER POTENTIAL OF NATURAL RESINS: BIOACTIVE DAMMAR FRACTIONS DOWNREGULATE ONCOGENIC C-MET RECEPTOR TYROSINE KINASE IN TRIPLE-NEGATIVE BREAST CANCER (TNBC)

Context: Labdanes are a class of terpenoid natural products and distributed in many plants and some insects. Labdane diterpenes (C20) have been found to exhibit a wide range of biological activities, including neuroprotective, anti-inflammatory and anticancer properties. Communic acid (1R,2R,3S,4R)-labda-8(17),12 diene-15,16-dioic acid) is a naturally occurring labdane diterpene found in different plant species, including those in the Salvia and Tetraclinis genera. Previous studies reported various biological activities of communic acid include antioxidant, anti-inflammatory, anticancer and antimicrobial properties. Breast cancer (BC) is the most diagnosed cancer in women and the second leading cause of cancer related death, behind lung cancer. It is a highly heterogenous disease, characterized by a wide range of subtypes that vary in their biological features, clinical presentation, and response to treatment. Objective and/or Hypothesis: As a part of an ongoing project to discover novel anticancer molecules from natural extracts, we explored the anticancer effects of the diterpene communic acid against multiple breast cancer cell lines.

Methods: MTT assay was conducted to evaluate the effect of communic acid on the growth of BC cells, while scratch assay was used to monitor its antimigratory effect. Furthermore, Western blot was used to evaluate the molecular effects of communic acid against BC cells. Results: Communic acid attenuated the growth, migration, and colonization of BC cells at low µM concentrations. Furthermore, communic acid significantly activated executioner caspases and induced apoptotic cell death of BC cells, as demonstrated by Western blot analysis. Our ongoing research focuses on the discovery of the macromolecular target mediating the anticancer effect of communic acid in BC cells. Conclusions: Communic acid is unique bioactive diterpene potentially inducing apoptotic cell death and attenuating the proliferation and migration, and colonization of multiple BC cells.

Context: Breast cancer (BC) is the most commonly diagnosed cancer in American women and the second leading cause of cancer-related death, behind lung cancer. Approximately, 1 in 8 women in the United States will be diagnosed with BC in her lifetime. Projections for 2025 estimate that 316,950 women will be diagnosed with invasive BC and 42,170 women will die from the disease complications. Triple-negative breast cancer (TNBC) is the most aggressive BC subtype with highest potential for metastasis and recurrence, and it accounts for 10-15% of all BC cases. TNBC is more prevalent in younger women and Black population. Unlike other breast cancer subtypes, TNBC lacks the expression of hormonal receptors (estrogen and progesterone receptors) and the overexpression of HER-2. Chemotherapy remains the mainstay treatment for TNBC, as hormone therapies and HER-2 targeted therapies are inherently ineffective. The development resistance to the current treatments, combined with deleterious adverse effects, warrant the need for the development of novel therapies to manage TNBC. C-Met is a receptor tyrosine kinase that is frequently overexpressed or hyperactivated in TNBC

and is associated with tumor aggressiveness, epithelial-mesenchymal transition (EMT), invasion and metastasis, chemotherapy resistance and poor prognosis. Objective and/or Hypothesis: Herein, we explored the anti-breast cancer potential of dichloromethane extract from Dammar resin (Anthoshorea hypochra) and its purified fractions against TNBC cell lines. Methods: MTT assay was used to evaluate the proliferation of cancerous cells, while scratch assay was used to monitor cell migration. Western blot was used to uncover the potential molecular target mediating the anticancer effect of Dammar resin. Results: The extract and its fractions effectively suppressed the proliferation, migration, invasion, and colonization of TNBC cells at very low µg/ mL concentrations. At the molecular level, bioactive fraction III-76 significantly suppressed the expression of the oncogenic c-Met in a dose-dependent manner, as demonstrated by Western blot and immunofluorescence analyses. Our ongoing research focuses on the dynamics

of c-Met downregulation and its associated downstream signaling pathways.

Conclusions: Resin-derived natural products offer a unique resource for the discovery of novel c-Met-targeted biomolecules for the control of aggressive TNBC.

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Biomedical Research: Section 1

Biomedical Research: Section 1

Taylor Raff, OMS-II; Roya Noorbakhsh, OMS-II; Kayla Griffith, OMS-II, Rose Pwint, OMS-II; Hannah Khairandish, OMS-II; Francheska Brzazgon, OMS-II; Kasia Michalak, MSc; Zakaria Abd Elmageed, PhD; Hassan Ebrahim, PhD VCOM-Louisiana 4 THE NATURAL DITERPENE INCENSOLE ACETATE INTERFERES WITH ONCOGENIC C-MET ACTIVATION IN BREAST CANCER CELLS

Erin Knight, OMS-III 1 ; Krishna Patel; Sophia R. Voth; Chung-Sik Choi, PhD 2 ; Mike T. Lin 2 , PhD; Troy Stevens, PhD 2 ; Melissa Lipsmeyer PhD 1 ; Rebekah Morrow PhD 3 ; K. Adam Morrow PhD 1* ’ and Sarah Voth PhD 1 *Indicates equal contributions 1 Cell Biology and Physiology, VCOM-Louisiana 2 Physiology and Cell Biology, University of South Alabama College of Medicine 3 Microbiology and Immunology, VCOM-Louisiana 3 CYSTATIN C ATTENUATES TRANSMISSIBLE TAU CYTOTOXICITY IN ACUTE LUNG INFECTION

Rationale: Pseudomonas aeruginosa is a common agent of pneumonia induced acute respiratory distress syndrome (ARDS). Virulent respiratory strains of P. aeruginosa utilize a type III secretion system (T3SS) to inject toxins directly into host cells. The T3SS toxin exoenzyme Y (ExoY) is a soluble nucleotidyl cyclase expressed by 90% of clinical strains. ExoY generates unregulated production of cytosolic cyclic nucleotides that induce the hyperphosphorylation of microtubule stabilizing tau. Hyperphosphorylated tau falls from the microtubules promoting cytoskeletal collapse, increased permeability, and the aggregation and release of hyperphosphorylated tau cytotoxins into the extracellular space. Oligomeric tau propagates damage from cell-to-cell and can be passed infectiously from one species to another as a toxic prion. ExoY-elicited tau is often found complexed with lung endothelial-derived amyloid-beta (Aß) converting it into a transmissible cytotoxins as well. Cystatin C (CysC), a ubiquitous cysteine protease that modulates Aß homeostasis, autophagy, and innate defense, is often precipitated with Aß-tau complexes. In these studies, we sought to determine whether

repletion of proteolytically active CysC during ExoY-competent infection would reduce the virulence of ExoY-generated transmissible cytotoxins. Methods: Established rat secondary pulmonary microvascular endothelial cells (PMVECs) were treated with either vehicle control or recombinant active CysC over a range of concentrations (50 ng/ml, 100 ng/ ml, 150 ng/ml) both with and without infection. Confluent monolayers were infected with either the isogenic control strain (ExoYK81M; no cyclase activity) to the virulent ExoY+ lab strain (injects ExoY only) or the ExoY-competent clinical isolate PA808 at a multiplicity of infection of 201 in HBSS. Cell Supernatants, whole cell lysates, and RNA were collected at ~ 5 h post-infection. Supernatants were filter sterilized. Supernatants and lysates were immunoblotted for tau, Aß, CysC, and autophagy proteins SQSTM1 and LC3-I and LC3-II. RT-qPCR was used to assess transcript for each protein. Filter-sterilized supernatants were boiled for 15 min and then iced for 15 min to inactivate non-amyloid proteins prior to transfer to naïve monolayers. Lactate

dehydrogenase (LDH) assays and resazurin assays were utilized to assess cytotoxicity and redox homeostasis, respectively. Results: Treatment of uninfected PMVECs with CysC was not cytotoxic or disruptive to redox homeostasis at any concentration. CysC repletion increased innate immune transcripts and promoted autophagic flux. Treatment of infected PMVECs at even the lowest dose of CysC reduced the release of pathologic tau by 4-fold as compared to untreated cells intoxicated with ExoY. Treatment with 50 ng/ml of CysC during ExoY-competent infection had the most significant impact in reducing amyloid mediated transmissible injury (p < 0.018), while treatment with 100 ng/ml CysC was only slightly less effective (p < 0.0190), and treatment with 150 ng/ml CysC did not significantly reduce transmissible cytotoxicity as compared to untreated ExoY intoxicated cells. Conclusions: Repletion of proteolytically active CysC during ExoY-competent infection is cytoprotective and suppresses the virulence of transmissible cytotoxicity.

Context: Frankincense, also known as olibanum, is an aromatic resin used in

overexpressed in TNBC and is associated with tumor aggressiveness, invasion and metastasis, chemotherapy resistance. Objective and/or Hypothesis: As a part of an ongoing project to discover novel c-Met modulators, we explored the anti-breast cancer potential IA against TNBC cells. Methods: MTT assay was used to evaluate the proliferation of cancerous cells, while scratch assay was used to monitor cell migration. Western blot was used to uncover the potential molecular target mediating the anticancer effect of IA. Results: IA effectively suppressed the proliferation, migration, invasion, and colonization of TNBC cells at low µM concentrations. Furthermore, IA effectively suppressed the phosphorylation (activation) of c-Met in a dose-dependent manner, as demonstrated by Western blot. Furthermore, molecular modeling studies suggested in-pocket binding conformation of IA which is energetically stabilized by interactions with amino acids at the hinge region of the kinase domain. Our ongoing

research focuses on exploring the effect of IA on the downstream signaling pathways of c-Met.

incense and perfume for spiritual, religious, and meditative purposes. Recent research have shown its utility for the management of inflammation, pain, arthritis and cancer. Incensole acetate (IA) is the main diterpene found in olibanum and can be purified using chromatographic techniques. Breast cancer (BC) is the most diagnosed cancer in women and the second leading cause of cancer death, after lung cancer. Recent statistics estimate that 316,950 women will be diagnosed with invasive BC and 42,170 women will die in 2025. BC is a highly heterogenous disease, characterized by a wide range of subtypes that vary in their biological features, clinical presentation, and response to treatment. Subtypes like hormone receptor-positive, HER2-positive, and triple negative breast cancer (TNBC) exhibit distinct patterns of growth, metastasis, and resistance to therapies. TNBC is the most aggressive subtype with highest potential for metastasis and recurrence. Chemotherapy remains the mainstay therapeutic modality for TNBC, as hormone and HER-2 targeted therapies are ineffective. C-Met is a receptor tyrosine kinase that is

Conclusions: IA is a novel c-Met modulator diterpene amenable for further development as a lead compound for the control of aggressive c-Met-addicted TNBC.

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Biomedical Research: Section 1

Biomedical Research: Section 1

Christian Capers, OMS-III 1 ; David Kang, OMS-III 1 ; Jedidiah, Lim, OMS-III 1 ; Vishveshvar Ramkumar, OMS-III 1 ; Kasia Michalak, MSc 1 ; Maysoon Makhlouf, PhD 1 ; Zakaria Abd Elmageed, PhD 1 ; Hassan Ebrahim, PhD 1 ; Khalid El Sayed, PhD 2 1 VCOM-Louisiana; 2 School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe 5 THE DIBENZOFURAN LICHEN ACID: A NOVEL SCAFFOLD FOR THE CONTROL OF TRIPLE-NEGATIVE BREAST MALIGNANCIES

Carlie Christ, OMS-III 1 *; Sherine Thomas, OMS-III 1 *; Meredith Gwin, PhD 2 ; Samir Gautam, MD; Edward P. Manning, MD 2 ; Melissa Lipsmeyer, PhD 1 , Rebekah Morrow, PhD 3 ; K. Adam Morrow, PhD 1 ; Brant Wagener, MD 4 ; Jean-Francois Pittet, MD 4 ; Tiru Rangasamy, PhD 5 ; Sarah Voth, PhD 1 *Indicates equal contributions 1 Cell Biology and Physiology, VCOM-Louisiana; 2 Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine; 3 Microbiology and Immunology, VCOM-Louisiana; 4 Anesthesiology and Perioperative Medicine, University of Alabama-Birmingham; 5 Pathobiological Science, Louisiana State University School of Veterinary Medicine 6 THE DOSE MAKES THE POISON: OPTIMIZING A MURINE MODEL OF PNEUMONIA INDUCED ACUTE RESPIRATORY DISTRESS DISORDER

Context: Breast cancer (BC) remains the most commonly diagnosed cancer in American women, with over 40,000 deaths projected in 2025. BC encompasses various disease subtypes with distinct biological, clinical and prognostic characteristics. Among these, triple-negative breast cancer (TNBC) is characterized by the lack of positive staining for the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 (HER2). This lack of targetable receptors renders TNBC inherently resistant to the current BC- targeted therapies, resulting in poorer recurrence-free and overall survival rates compared to other BC subtypes. The receptor tyrosine kinase c-Met, a membrane bound receptor activated by hepatocyte growth factor (HGF), plays a crucial role in promoting cell proliferation, survival, motility, and angiogenesis. c-Met is frequently overexpressed or dysregulated in TNBC, making it a compelling therapeutic target. Lichens, a symbiotic association between a fungus (mycobiont) and a photosynthetic partner (photobiont, typically alga or cyanobacterium), serve as a unique resource of the discovery of bioactive compounds.

Objectives and/or Hypothesis: Our previous studies identified the dibenzofuran usnic acid (UA) from Louisiana-grown lichens and developed more than 50 chemically optimized analogs with notable anticancer activity, selectively targeting TNBC cells. This study aims to further investigate the molecular targets of these analogs that are most likely mediating their anticancer mechanism. Methods: Analog U26 was synthesized using Claisen-Schmidt carbon coupling, and its identity was confirmed by NMR and mass spectrometry. Phenotypic screening assays, including cell proliferation, migration and colonization, were implemented to evaluate the anticancer effect of U26 on TNBC cells. Additionally, immunoblotting was utilized to investigate the proteomic profile of TNBC cells treated with U26. Results: U26 was successfully synthesized and demonstrated significant suppression of TNBC cell proliferation, migration and colonization at sub-micromolar levels. Western blot analyses revealed a dose-dependent downregulation of c-Met receptor tyrosine kinase in U26-terated TNBC cells.

Conclusions: Natural products and their analogs continue to serve as valuable resources for discovering novel anticancer biomolecules. The lichen-derived dibenzofuran usnic acid analogs, such as U26, are potential c-Met modulators for TNBC treatment. Further preclinical studies are necessary to validate U26 as a lead compound for therapeutic development.

Results: All mice instilled with either PBS vehicle or 105 or 106 colony forming units (CFU) of ExoY+ or PA808 survived the full 48-hour time course. All mice instilled with 107 CFU of either bacterium died prior to 48-hours. Mice instilled with PA808 lost weight in a dose dependent manner. Those instilled with 107 ExoY+ all gained significant weight with minimal urine output prior to early death. Necropsy revealed massive pulmonary and multi-organ edema in these animals. Histology revealed indices of acute lung injury including infiltration, flooding, and thickened septa, with microthrombi formation in a dose dependent manner with both ExoY+ and PA808 infected animals. Plasma CysC and amyloid burden increased in direct proportion to dose. Conclusions: Infected animals developed pathology ranging from acute lung injury to ARDS in a dose dependent manner. The 106 CFU dose was the most effective for inducing ARDS with both the lab strain ExoY+, and the clinical isolate, PA808, in both male and female mice. This work effectively established a translational model of ARDS for use in future mechanistic studies.

Methods: All animal experiments were approved by the Louisiana School of Veterinary Medicine IACUC. Clinical strain PA808 was isolated from the bronchoalveolar lavage fluid of a patient diagnosed with a monomicrobial nosocomial pneumonia by clinical collaborators at University of Alabama Birmingham. Male and female 10-week-old wildtype C57BL/6J mice were anesthetized with isofluorane (1-3%). Animals were instilled with 40 ul of either sterile PBS vehicle or different concentrations (105, 106, 107 bacteria) of ExoY+ or PA808 via intratracheal cut down. Methacrylate was used to repair the wound and a single injection of buprenorphine XR was used for pain management. Body temperature was maintained during recovery and their diet was fortified with NutraGel to encourage recovery. Weight and urine were collected prior to infection and every 24 h afterward. At 48-hours post-infection, surviving mice were sacrificed. Urine was collected via cystocentesis, blood was collected via cardiac puncture, and the lungs, kidneys, and liver were collected for histology and RT-qPCR. Plasma and urine levels of protein, CysC, albumin, and creatinine were measured with ELISA. Amyloid and tau levels were determined with immunoblotting and thioflavin T.

Rationale: Acute respiratory distress syndrome (ARDS) is characterized by pulmonary edema, refractory hypoxemia, and a mortality rate of ~ 45%. Coagulopathy and acute kidney injury frequently complicate ARDS pathology. Pseudomonas aeruginosa infection is a leading cause of ARDS particularly strains armed with a type III secretion system (T3SS) to inject toxins directly into host cells. Roughly 90% of clinical strains utilize exoenzyme Y (ExoY) in their T3SS arsenal. ExoY is an edema factor that aggressively disrupts endothelial barrier integrity and converts cytoprotective endothelial amyloids into cytotoxic prions. In the absence of ExoY intoxication endothelial amyloids including amyloid-beta (Aß) increase both the innate resistance and resilience of the pulmonary endothelial barrier during infection. Infection elicited tau disrupts the innate function of endothelial amyloids and promotes the dissemination of tau and Aß cytotoxins to promote secondary end-organ damage. However, the mechanisms responsible remain poorly resolved and studies to date have only utilized isogenic lab strains of P. aeruginosa. Here, we utilized a novel clinical isolate of ExoY-competent P. aeruginosa to establish a translationally relevant mouse model of pneumonia induced ARDS for use in future mechanistic studies.

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Biomedical Research: Section 1

Biomedical Research: Section 1

Hana Khalifa, OMS-II; Alessandra, Martinez, OMS-II; Kasia Michalak, MSc; Zakaria Abd Elmageed, PhD; Hassan Ebrahim, PhD VCOM-Louisiana 7 THE NATURAL DITERPENE CAFESTOL ATTENUATES THE PROLIFERATION, MIGRATION, COLONIZATION OF BREAST CANCER CELLS THROUGH MODULATING MTOR

David Solis, OMS-III; Dinesh Aryal, PhD VCOM-Louisiana 8 IMPACT OF GATA3, PIK3CA, AND TP53 MUTATIONS ON ENDOCRINE THERAPY RESPONSE (TAMOXIFEN VS FULVESTRANT VS LETROZOLE) IN HR+ INVASIVE DUTAL BREAST CARCINOMA USING MSK-CHORD CBIOPORTAL DATA

Context: Green coffee has been studied for its potential health benefits, particularly its role in cancer treatment and prevention. It harbor a diverse range of bioactive ingredients including fatty acids, terpenes and phenolics. Cafestol is a diterpene compound (C20) found in unroasted coffee beans, and it has gained attention due to its potential health effects, including anti-inflammatory and antioxidant effects. Breast cancer (BC) is the most diagnosed cancer in women and the second leading cause of cancer death, behind lung cancer. BC is a highly heterogenous disease, characterized by a wide range of subtypes that vary in their biological features, clinical presentation, and response to treatment. mTOR (mechanistic target of rapamycin) is a key regulator of many cellular processes, including growth, proliferation, metabolism, and survival. It’s a part of the complex mTOR signaling pathway, which integrates signals from growth factors, nutrients, energy status, and cellular stress. mTOR plays a crucial role in regulating the growth of breast cancer cells, and its dysregulation can contribute to cancer progression, metastasis, and resistance to treatment.

Objective and/or Hypothesis: As a part of an ongoing project to discover novel anticancer molecules of natural origin, we explored anticancer effects of cafestol against breast cancer cells of different phenotypic characteristics. Methods: MTT assay was conducted to evaluate the growth of BC cells, while wound healing assay was used to monitor cell migration. Western blot was used to uncover the potential molecular target mediating the anticancer effect of cafestol. Results: Bioassay-guided fractionation of coffee beans extract lead to the identification of cafestol as potential anticancer diterpene against multiple breast cancer cells. Cafestol effectively attenuated the growth, migration, and colonization of BC cells at low µM concentrations. Furthermore, cafestol significantly inhibited mTOR kinase in a dose-dependent manner, as demonstrated by Western blot. Furthermore, molecular modeling studies suggested a potential low-energy binding conformation of cafestol at the mTOR kinase pocket, stabilized by

interactions with key amino acids at C-terminal lobe of the kinase domain.

Background: Impact of PIK3CA, TP53, and GATA3 Mutations on Endocrine Therapy Response in Hormone Receptor–Positive Invasive Ductal Breast Carcinoma Background: Hormone receptor–positive (HR+) breast cancer accounts for the majority of breast cancer diagnoses and is primarily treated with endocrine therapy. Despite improved outcomes, intrinsic and acquired resistance to endocrine agents remains a major clinical challenge. Genomic alterations, particularly in PIK3CA, TP53, and GATA3, are common in HR+ disease and have been shown to influence estrogen receptor signaling and therapeutic response. However, comparative survival outcomes across different endocrine therapies stratified by mutation status remain poorly defined. Objective: To determine whether mutations in PIK3CA, TP53, or GATA3 are associated with differential overall survival outcomes among HR+ invasive ductal carcinoma patients treated with tamoxifen, letrozole, or fulvestrant.

accessed through cBioPortal. The cohort included 2,557 patients with HR+ invasive ductal breast carcinoma. Patients were stratified by mutation status (PIK3CA, TP53, GATA3) and by endocrine therapy type (tamoxifen, letrozole, or fulvestrant monotherapy). Overall survival was analyzed using Kaplan–Meier methods, with comparisons assessed by log-rank testing. Overlapping treatment cases were excluded to maintain mutually exclusive therapy groups. Statistical significance was defined as p < 0.05. Results: Across the entire cohort, mutation status significantly predicted overall survival (p = 2.37 × 10 -3 ), with TP53 mutations associated with the poorest outcomes. In the tamoxifen treated cohort, GATA3 mutations conferred the most favorable survival, while TP53 mutations were associated with inferior outcomes (p = 2.77 × 10 - ³). Among letrozole-treated patients, PIK3CA mutations were associated with the highest survival probabilities, followed by GATA3, with TP53 remaining the poorest prognostic marker (p = 3.46 × 10 -3 ). In the fulvestrant cohort, GATA3-mutant tumors demonstrated superior survival, while TP53 mutations again predicted poor outcomes (p = 1.83 × 10 -3 ).

Conclusions: Mutations in PIK3CA, TP53, and GATA3 are associated with distinct survival patterns across endocrine therapy types in HR+ breast cancer. TP53 mutations consistently predict poor outcomes, while GATA3 and PIK3CA mutations are associated with more favorable survival, with therapy-specific differences observed. These findings support the integration of genomic profiling into endocrine therapy selection to improve personalized treatment strategies in HR+ breast cancer.

Conclusions: Cafestol is a novel mTOR modulator amenable for further development as a lead compound for the control of breast malignancies.

Methods: A retrospective analysis was conducted using the MSK-CHORD dataset

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2026 Research Recognition Day

Biomedical Research: Section 1

Biomedical Research: Section 1

Julie Do, OMS-I; Ryan Vergara, OMS-III; Hunter Santogrossi, OMS-III; Dinesh Aryal, PhD VCOM-Louisiana 10 HEME OXYGENASE-1–DEPENDENT ACTIVATION OF TUBULAR NA + /H + EXCHANGER 3 UNDERLIES HYPERTENSION DURING CHRONIC METABOLIC ACIDOSIS

Erin Vasquez, OMS-III; Anne B. Remorca, OMS-III; Sabeen Wazir, OMS-III; Kasia Michalak, MSc; Stephen DiGiuseppe, PhD VCOM-Louisiana 9 POXVIRUSES REPROGRAM WNT/ ß -CATENIN SIGNALING THROUGH GSK-3 ß TO PROMOTE INFECTION

Background: Poxviruses such as mpox are re-emerging pathogens that pose a burden of disease. The glycogen synthase kinase-3ß (GSK-3ß) - ß-catenin axis regulates cell growth, Wnt signaling, and immune modulation. When GSK-3ß activity is reduced, ß-catenin escapes degradation and enters the nucleus to drive transcription of TCF/LEF target genes. Many viruses exploit this pathway by disrupting the destruction complex, stabilizing ß-catenin to enhance replication. However, our data reveals that poxviruses exhibit the opposite strategy. Vaccinia virus (VacV), a prototypic poxvirus, increases phosphorylated ß-catenin and accelerates its degradation. Notably, ß-catenin is critical to Wnt signaling, the pathway that contributes to the antiviral response; we reasoned that poxviruses target ß-catenin to suppress immunity. Hypothesis: We hypothesize that poxviruses utilize host GSK-3ß kinase to tag ß-catenin for degradation, inhibit Wnt signaling, and dampen the antiviral response to enhance replication.

of infection and time points, then measured viral titers and protein levels. Parallel cultures received selective GSK-3ß kinase inhibitors. We quantified total and phosphorylated ß-catenin by western blot and assessed viral proteins D8 and A14 by immunoblotting. Plaque assays determined the effect of GSK-3ß inhibition on replication. Results: Inhibition of GSK-3ß reversed infection-induced changes total ß-catenin increased, phosphorylated ß-catenin decreased, IRF3 was phosphorylated, and viral proteins and plaque formation were decreased. Conclusions: These results indicate poxviruses rely on GSK-3ß kinase activity to tag ß-catenin for degradation, suppress Wnt/ß-catenin signaling, and evade host antiviral defenses. Furthermore, this data identifies GSK-3ß as a potential therapeutic target.

Context: Heme oxygenase-1 (HO-1) produced in the kidney has recently been implicated in chronic metabolic acidosis (CMA), which itself has been associated with hypertension in murine models. However, the direct effects of CMA mediated through renal HO-1 on pressure natriuresis, and renal vascular function remain poorly understood. This study examined renal HO-1 expression during CMA and evaluated its influence on proximal tubular Na + /H + exchanger 3 (NHE3) expression and renal vasculature. Objective: To determine whether HO-1– dependent upregulation of renal tubular NHE3 promotes sodium retention and hypertension in a rat model of chronic metabolic acidosis. Methods: Male Sprague–Dawley rats (150–320 g) were assigned to four groups (n = 5/group) (I) Control, (II) CMA, (III) CMA + δ -aminolevulinic acid (DALA; HO-1 inducer), and (IV) CMA + zinc protoporphyrin IX (ZnPP; HO-1 inhibitor). CMA was induced using 0.28 M ammonium chloride for 8 weeks in Groups II–IV, with corresponding HO-1 modulation in Groups III and IV. Renal HO-1 concentrations in microdialysis samples, proximal tubular NHE3 expression, serum &

urine-sodium concentrations and renal blood flow (RBF) is measured.

Results: CMA significantly increased renal HO-1 levels and mean arterial pressure (MAP) compared with controls. However, HO-1 induction in the kidney appeared independent of circulating HO-1, as renal HO-1 levels did not differ between Groups III and IV. RBF remained unchanged across all groups, indicating an absence of renovascular hypertension. NHE3 expression is elevated in the CMA group and is significantly reduced in the HO-1 inhibited group (IV), consistent with impaired pressure natriuresis. Conclusions: Overall, these results lead to the findings that, renal HO-1 modulates proximal tubular NHE3 expression to maintain basal blood pressure and contributes to hypertension under chronic acidotic conditions.

Funding: This work was funded through Delta CRP grant (1032432).

Method: Normal human dermal fibroblasts were infected with VacV at varying multiplicities

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2026 Research Recognition Day

Biomedical Research: Section 1

Biomedical Research: Section 1

Melanie K Johnson 1 ; Fei Peng 1 ; Tai Ngo 2 ; Felix Zhou 2 ; Asal Saeid 1 ; Blake Schwitterman 1 ; Angad Kumar 1 ; Valli Annamalai 1 ; Saurav Bhattacharya 1 ; Hazel Borges 2 ; Qionghua Shen 2 ; Kevin Dean 2 ; Ravikanth Maddipati 1 1 Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center; 2 Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center 12 ACINAR CELL PLASTICITY DRIVES ACINAR-TO-DUCTAL METAPLASIA IN PANCREATITIS REVEALED BY 3D IMAGING AND AI ANALYSIS

Areeba Imran, OMS-II; Kendyl Berry, OMS-II; Kyrillos Guirguis, OMS-II; Kasia Michalak, MSc; Maysoon Makhlouf, PhD; Hassan Ebrahim, PhD; Zakaria Y. Abd Elmageed, PhD VCOM-Louisiana 11 PIMAVANSERIN CURTAILS TUMOR SPREAD AND SHRINKS CASTRATION RESISTANT PROSTATE CANCER

Background: Prostate cancer (PCa) that progresses despite standard androgen deprivation therapy remains a major clinical challenge, as resistance inevitably develops in many patients. Repurposing atypical antipsychotics for metastatic castration resistant prostate cancer (mCRPC) offers an innovative and promising therapeutic avenue. Growing evidence indicates that some antipsychotic drugs exhibit anticancer activity. This study investigated whether the atypical antipsychotic pimavanserin (PV) can suppress cell proliferation and migration in vitro and reduce tumor burden in a preclinical mouse model. Methods: The anticancer efficacy of PV was assessed in two mCRPC PC-3M and CWR-R1ca cell lines. Cytotoxicity assay was conducted to determine the half-maximal inhibitory concentration (IC 50 ) in these cell lines. Clonogenic, wound-healing, and transwell migration assays evaluated the impact of PV on cell proliferation and motility. Additionally, a nude mouse mCRPC xenograft model was employed to investigate the effects of this antipsychotic agent on xenografted tumors.

Results: PV demonstrated a significant reduction in cell colony-formation. It also inhibited mCRPC cell migration confirmed by scratch and Boyden chamber assays. The treatment of mice with PV (10 mg/kg/ day, intraperitoneal) for three weeks resulted in a 57.6% reduction in xenografted tumor volume (p<0.001) compared to control group, underscoring their therapeutic potential in treating mCRPC. Conclusion: This study highlights the potential of repurposing PV as a promising strategy for treating mCRPC. PV demonstrated notable anticancer effects by inhibiting cell proliferation, migration, and tumor growth in a mouse model. These results identify PV as a strong candidate for continued research. Ongoing work will aim to clarify the molecular mechanisms driving its antitumor activity, both as a standalone treatment and in combination with existing therapeutic options.

Context: Pancreatitis is a recurrent inflammatory disease of the pancreas that can lead to chronic dysfunction and increase the risk of pancreatic cancer. A central feature of this process is acinar-to-ductal metaplasia (ADM), in which differentiated acinar cells adopt ductal like characteristics in response to injury. Objective: While ADM is recognized as an early and potentially reversible stage in pancreatic disease, the cellular dynamics underlying this transition- including the incidence of metaplastic conversion at the single-acinar level, temporal progression, proliferative adaptations, and morphometric alterations- have yet to be systematically defined. Methods: To investigate these processes, we employed a Cre-LoxP-based lineage tracing approach in mice subjected to cerulein-induced acute pancreatitis. Entire pancreatic tissues were rendered optically transparent via benzyl alcohol/benzyl benzoate (BABB) clearing and imaged using light sheet fluorescence microscopy, enabling volumetric interrogation of intact tissue. Image datasets were analyzed with U-Segment3D, a 2D-to-3D segmentation

algorithm trained to discriminate acinar and ductal phenotypes to generate pixel-based instance cell masks. Results: Preliminary analyses indicate a progressive increase in acinar cells acquiring ductal-like phenotypes over time in mice subjected to cerulein-induced acute pancreatitis. Early observations suggest that ADM cells may undergo proliferation and morphologic remodeling, and some lineage-traced acinar cells that appear to revert retain partial ductal signatures. Comprehensive analyses across all acini, time points, and spatial contexts are ongoing to fully quantify these dynamics. Conclusions: Our approach establishes a scalable platform integrating lineage tracing, tissue clearing, 3D imaging, and AI-driven analytics to characterize ADM and provide a foundation for quantitative studies of cellular plasticity in pancreatitis.

Keywords: mCRPC, pimavanserin, cell proliferation and migration, xenograft tumors

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2026 Research Recognition Day