ORAL PRESENTATIONS
O-01 Title: Retinal Ganglion Cell Degeneration Linked to Pathogenic Tau Accumulation in Early and Late Stages
of Alzheimer’s Disease
Authors: Edward Robinson1, Miyah R. Davis1, Dieu-Trang Fuchs1 , Yosef Koronyo1 , Elena SalobrarGarcia2, Altan Rentsendorj1, Bhakta P. Gaire1, Rakez Kayed3, Lon S. Schneider4, Keith L. Black1, Alfredo A. Sadun5, Maya Koronyo-Hamaoui1
1Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
2Institute of Ophthalmologic Research Ramón Castroviejo, Complutense University of Madrid, Spain.
3Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch at Galveston, TX, USA
4Alzheimer’s Disease Research Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
5Department of Ophthalmology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA.
Background/Significance: Histological and imaging studies indicate that retinal ganglion cell (RGC) loss occurs in Alzheimer’s disease (AD), potentially contributing to visual and circadian dysfunctions. We previously identified elevated pathogenic tau isoforms, hyperphosphorylated tau at serine 396 (pS396-tau) and tau oligomers (oligo-tau), in the retinas of patients with mild cognitive impairment (MCI, due to AD) and AD dementia compared to cognitively normal (CN) individuals. Whether these tau species localize within RGCs and contribute to neurodegeneration remains unknown.
Methods: Postmortem retinal cross-sections from 25 MCI/AD patients and 16 age- and sex-matched CN controls were examined. Immunofluorescence and Nissl staining were performed using the RGC marker RBPMS alongside antibodies for pS396-tau, T22+ oligo-tau, apoptosis, granulovacuolar degeneration (GVD) bodies, and necroptosis markers. Stereological quantification, RGC morphometry, and spatial distribution analyses were correlated with corresponding brain pathology and cognitive status.
Results: We provide first evidence of pS396-tau and oligo-tau inclusions within RBPMS+ RGCs in MCI and AD retinas. These retinas exhibited a 46–56% reduction in RBPMS+-RGCs and Nissl+ neurons, accompanied by marked soma hypertrophy (10–50%), nuclear displacement, and increased apoptosis (30–50%). CHMP2B+ GVD bodies and pMLKL+ necroptotic markers were prominent in affected RGCs. Tauopathy-laden RGCs were 2.1–3.5-fold more abundant in MCI and AD compared to CN, strongly intercorrelated (r = 0.85, P < 0.0001), and inversely associated with RGC density (r = −0.40 to −0.64, P < 0.05–0.01). Their accumulation correlated with advanced Braak stage (V–VI) and worse cognition (CDR 3, MMSE < 26).
Conclusion and Implications: Abnormal tau isoforms accumulate within RBPMS+ RGCs in MCI and AD, driving substantial RGC loss through apoptotic and GVD-necroptotic mechanisms. These findings implicate retinal tauopathy as a potential early and quantifiable biomarker of AD progression, warranting validation in larger cohorts.
Funding: Studies have been supported by the following NIH/NIA grants: R01 AG055865, R01 AG056478, R41 AG044897, and R01 G075998, by the Hertz Innovation Fund, the Gordon, Jona Goldrich, and Haim Saban Private Foundations. Ray Charles scholar foundation.
O-02
Title: Direct RNA sequencing reveals complex patterns of epi-transcriptomic modification following stroke
Authors: Zulma L. Reyes-Benitez, 1,2 Elham Amini Ph.D., 1 Andrea Pearson1,2, Robert Meller D.Phil.1,2., Michael Frankel, MD.3,4.
1Morehouse School of Medicine, Neuroscience Institute, Atlanta, GA, USA
2Morehouse School of Medicine, Institute of Translational Genomic Medicine, Atlanta, GA, USA
3Grady Hospital, Marcus Stroke & Neuroscience Center, Atlanta, GA, USA
4Emory University School of Medicine, Department of Neurology, Atlanta, GA, USA
Mentor: Robert Meller, D.Phil., Morehouse School of Medicine
Background: In the United States nearly 1 million people suffer a stroke each year. The gold standard treatment for ischemic stroke is currently tPA. For patients to receive this treatment, a distinction between hemorrhagic and ischemic stroke must be made within the therapeutic time window for tPA (4.5 hours following stroke onset). Hemorrhage is identified using CT imaging, diagnostic delays result in only 5% of eligible stroke patients being treated with tPA. Therefore, a biomarker to distinguish hemorrhage from ischemic stroke would have a great effect on population health. In this project, we aim to identify epitranscriptomic biomarkers to distinguish hemorrhagic stroke from other stroke subtypes (specifically 5-methylcytosine (5mC), 6-methyladenosine (m6A), Inosine (I), and Pseudo-Uridine (PsU).
Methods: Whole blood samples were collected from patients at admission (Grady Memorial Hospital, ATL, GA). Following extraction of RNA, 1 ug of RNAwas prepared for direct Sequencing using the Oxford Nanopore workflow (RSK004). Libraries were sequenced on flow cells (P24), for 72h. Read data was aligned to GRCh38 using Dorado and modified bases called. Modkit software was used to extract modified base calls to a bed file, and these data were split by base modification. Data was filtered to only include bases with at least 10x coverage and called present in all samples. For each modification, we determined differential modification rates and corrected for age, sex and race.
Results: Results showed an increase of 5mC and m6A and a decrease in I and PsU RNA modifications. Differential modification of RNA was observed in targets across all chromosomes, some mitochondrial RNAs showed higher levels of differential modification relative to chromosome size. Some RNAs species showed multiple modifications per target RNA. Pathway analysis using cluster profiler suggested modifications occur in RNAs associated with ATP Synthesis, oxidative phosphorylation, and immune system function.
Conclusions and Implications: The large and statistically robust changes observed in our results, suggest RNA modifications may have utility as biomarkers for hemorrhagic stroke diagnosis. Future analysis will include defining stroke biomarkers for ischemic & mimic strokes, as well as how RNA modifications of interest correlate to both gene expression and splicing.
Acknowledgement of Funding:
• This research is supported in part by the following grants: HG012334 , CEGS HG013595, U54 MD007602-33S1, RCMI U54 and NS112422.
O-03 Uncovering Species-Specific Patterns of Antimicrobial Resistance in Klebsiella pneumoniae and Acinetobacter baumannii
Damani Andre¹*, Ali Aslam², Ubong Udoh³, Philip Nwajiobi-Princewill⁴ Muhammed Idris5 Kenneth I. Onyedibe¹
¹Department of Microbiology, Biochemistry & Immunology, Morehouse School of Medicine, Atlanta, GA
²Bioinformatics Core, Morehouse School of Medicine, Atlanta, GA
³ Department of Medical Microbiology and Parasitology, College of Medical Sciences, University of Calabar, Nigeria
⁴National Hospital, Abuja, Nigeria
⁵Infectious Diseases Division, Department of Medicine, Mercer University School of Medicine, Macon, GA
⁶Department of Medicine, Morehouse School of Medicine, Atlanta, GA
Background and Significance: Antimicrobial resistance (AMR) is a growing global health crisis responsible for over one million deaths each year. Klebsiella pneumoniae and Acinetobacter baumannii are critical-priority pathogens due to their resistance to multiple antibiotic classes. Most genomic studies focus on which resistance genes are present, but few analyze how those genes change over time. I hypothesize that Klebsiella pneumoniae and Acinetobacter baumannii exhibit distinct species-specific temporal patterns in antimicrobial resistance gene sequence and amino acid composition.
Methods: Complete genome assemblies for both species were obtained from NCBI RefSeq and GenBank. Each genome was annotated with AMRFinderPlus to identify resistance genes by class, contig ID, and coordinates. Sourmash k-mer profiling was used to determine the presence or absence of mutations in each gene across multiple years. Amino acid composition differences in dominant resistance genes were evaluated by comparing the three most compositionally distinct and sequence rich groups using analysis of variance, while sourmash k-mer profiling was used to assess temporal sequence variation.
Results: A total of 120,000 K. pneumoniae and 50,000 A. baumannii genomes were annotated. Pairwise sequence comparisons revealed variation within the same gene across years, confirming resistance genes are not static. When aggregated by drug class, K. pneumoniae was dominated by β-lactam ARGs, while A. baumannii was dominated by aminoglycoside ARGs. The aminoglycoside-resistant gene aac(6’) showed distinct temporal patterns: K. pneumoniae residues such as leucine, alanine, and glycine remained stable from 2007–2023, whereas A. baumannii displayed fluctuations in asparagine, threonine, and valine between 2010–2018 before stabilizing. These results indicate A. baumannii undergoes greater amino acid plasticity and faster sequence diversification.
Conclusion and Implications: K. pneumoniae and A. baumannii show clear differences in how their resistance genes evolve. K. pneumoniae tends to preserve existing structures, while A. baumannii adapts more rapidly to selective pressures. Understanding these dynamics may guide predictive strategies for tracking and managing antimicrobial resistance.
O-04
Title: Perceived Causes of Fertility Challenges and Utilization of Infertility Treatment
Modalities: Insights from U.S. Black Women
Authors: Isabel Morgan, PhD, MSPH1; Christine Tucker, PhD, MPH2 Aunchalee E.L. Palmquist, PhD, MA, IBCLC3, Stephanie Baker, PhD, MS, PT4, Larissa Jennings Mayo-Wilson, PhD, MHS2, Chantel L. Martin, PhD2, Natalie D. Hernandez, PhD, MPH1, Lasha S. Clarke, PhD, MPH1
1Morehouse School of Medicine Center for Maternal Health Equity; 2University of North Carolina at Chapel Hill Gillings School of Global Public Health; 3Duke University Global Institute of Health; 4Elon University Department of Public Health Studies
Mentor: Lasha Clarke, PhD, MPH, Morehouse School of Medicine
Background/Significance: Black women are underrepresented among infertility clinic patient populations, despite having the greatest prevalence of infertility. Prior research has focused on access to care based on assumptions regarding how Black women conceptualize infertility and perceive the usefulness of biomedical interventions. The purpose of this study was to explore what Black women themselves perceive as the causes of their fertility challenges and to examine the treatment modalities they use to address infertility
Methods: The study included 40 Black women ages 18-45 years, with a history of fertility challenges, recruited from medical practices and online fertility support groups, who participated in the Fertility Equity Study between 2021-2023. Participants completed a demographic survey, and up to two semi-structured interviews to discuss their fertility journeys and perceived causes of infertility. We used a thematic analytic approach to examine participant perceptions of infertility causes. Frequencies and percentages were calculated for each commonly reported cause of fertility challenges and for treatment modalities used.
Results: Most participants were 35-45 years, married or cohabitating, and had advanced educational degrees (e.g., PhD), with household incomes >$100,000, and some or full health insurance coverage with fertility benefits. Black women described five common perceived causes of their fertility challenges: 1) reproductive health conditions (n=27; e.g., fibroids); 2) age (n=7); 3) unknown causes (n=6); 4) structural conditions (n=4; e.g., medical neglect); and 5) stress (n=4). Thirty-two participants (78.0%) had initiated medically assisted reproduction (MAR), including medicated timed intercourse, intrauterine insemination, or in vitro fertilization. Nearly half of participants (n=19) only used MAR, while one-third (n=13) had used both MAR and holistic approaches (e.g., acupuncture, herbal teas). None of the participants who only used holistic approaches attributed their fertility challenges to reproductive health conditions.
Conclusions and Implications: While reproductive health conditions were the predominant perceived cause, nearly half of participants leveraged holistic approaches to address their fertility challenges, including those that also used MAR. These findings may inform how reproductive medicine specialists counsel Black women about their fertility challenges and underscore the importance of acknowledging and integrating the diverse ways patients engage both biomedical and holistic treatments in their fertility journeys.
Acknowledgement of Funding: This research is supported by funding from Ferring Pharmaceuticals.
Authors: Ertha Sefu Omba, M.S., MP.H 1, Naomi Coles, M.S.2, Mari Chiles B.S.3, Jazmine Baylor, M.S.4, Berlandon Saint Julien, M.S.5
1 2 3 4 5
Morehouse School of Medicine Doctor of Medicine Program
Mentor: Ervin Christopher, MD, Morehouse School of Medicine, Director of Operations H.E.A.L Clinic
Background/Significance: Student-run free clinics (SRFCs) are vital in providing care to underserved populations while training future healthcare professionals. Despite their impact, SRFCs have faced recurring challenges with sustainability, resource allocation, and care continuity. We hypothesize that the development of a student-centered, evidence-based quality improvement (QI) framework emphasizing structured operations, interdisciplinary collaboration, and sustainable funding will enhance clinic efficiency and educational outcomes. Therefore, the purpose of this analysis was to examine 1) key operational challenges, 2) success factors, and 3) sustainability strategies to inform the development of a comprehensive QI model for SRFCs.
Methods: A structured literature review was conducted using peer-reviewed articles, national organizational reports, and published clinic evaluations identified through PubMed, Google Scholar, and organizational repositories focused on student-run clinics. An initial search identified 118 articles. After screening and exclusion of non–student-run clinic models, opinion-only articles, duplicates, and studies lacking operational or sustainability outcomes, 32 articles published between 2005 and 2024 were included. Recurring themes were qualitatively analyzed and organized into three domains: operational challenges, success factors, and evidence-informed interventions, which were used to develop a studentcentered QI framework.
Results: Analysis identified five major, recurring challenges across SRFCs: inconsistent volunteer staffing, limited and unstable funding sources, fragmented care coordination, insufficient health outcomes tracking, and gaps in interdisciplinary collaboration. Clinics with strong academic affiliations, faculty oversight, and curricular integration demonstrated improved continuity of care, expanded service scope, and greater operational stability. Based on these findings, the proposed QI framework includes structured volunteer recruitment and training models, diversified and sustainable funding strategies, standardized follow-up and outcome tracking systems, and intentional interprofessional engagement initiatives.
Conclusion/Implications: This student-led QI initiative introduces an adaptive and evidence-based framework to enhance the operational effectiveness and sustainability of SFRCs. By addressing persistent systemic challenges and empowering student leadership, the model aims to equip SRFCs with actionable tools to enhance healthcare delivery, advance interprofessional collaboration and uphold their educational mission of student-run care. Future work should evaluate implementation outcomes across diverse clinic settings to assess impact on patient care, learner outcomes, and long-term clinic sustainability.
Acknowledgment of Funding: This research was supported in part by the Johnson & Johnson/ National Medical Fellowship Alliance for Inclusion in Medicine Scholarship.