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Fourth Annual Research Symposium Program With Abstracts, Office Of Research Affairs, Boonshoft School Of Medicine

Boonshoft School of Medicine Research Symposium

The program booklet is a compilation of abstracts from oral and poster presentations at Wright State University's Fourth Annual Boonshoft School of Medicine Medical Research Symposium held on April 16, 2025.

Short- And Long-Term Effects Of Early Versus Delayed Treatment With Ocrelizumab On Cerebellar Volume Loss In Patients With Rms And Ppms, Douglas L Arnold, Shannon Kolind, Haz-Edine Assemlal, Amit Bar-Or, Matilde Inglese, Ludwig Kappos, Katrin Parmar, Till Sprenger, Anthony Traboulsee, Irene M Vavasour, Jerry S Wolinsky, Corrado Bernasconi, Ulrike Bonati, Stefano Magon, Björn Tackenberg, Laura Gaetano

Faculty, Staff and Student Publications

Background: The cerebellum is a functionally and anatomically complex structure, which, in multiple sclerosis (MS), is affected by focal white/gray matter lesions and by secondary neurodegeneration of afferent/efferent connections to the supratentorial brain and the spinal cord.

Objectives: To assess the efficacy of ocrelizumab compared with interferon β-1a (IFN β-1a)/placebo on cerebellar volume loss and the effect of switching to ocrelizumab on volume change in the Phase III trials in relapsing MS (RMS, OPERA I/II) and in primary progressive MS (PPMS, ORATORIO).

Methods: Cerebellar volume change was computed using paired Jacobian integration and analyzed using a mixed-effect repeated measurement model. …

All Roads That Lead To The Myocardium: Assessment Of Anomalies Of Coronary Artery Course, Ibrahim Khayyat, Silvana Molossi, Ada C Stefanescu Schmidt

Faculty, Staff and Students Publications

No abstract provided.

The Effect Of Kefir Consumption On Gut And Mental Well-Being, Danh Nguyen, Kate Digges, Emerson Morris, Nicole Hinkley-Kellum, Cas Simpson, Dow Mccarty, Erik F. Y. Hom

Neuroscience Research Showcase

(All authors are affiliated with the Department of Biology: Center for Biodiversity and Conservation Research, University of Mississippi)

Members of the Hom Lab are studying the potential benefits of water kefir consumption on Irritable Bowel Syndrome (IBS) symptoms and mental health through Brain-Gut-Microbiota Axis modulation. Water kefir is a probiotic-rich beverage produced by the fermentation of sugar water using symbiotic aggregates of microbes known as water kefir grains (WKGs). WKGs consist of various yeast, lactic acid bacteria, and acetic bacteria bound together through extracellular polysaccharides. Probiotics are defined as foods or supplements that contain live, beneficial microbes that foster well-being …

Analyzing The Neuroprotective Effects Of Phytoestrogens And Aromatase On Male Zebra Finch Cerebellum Post Lesion, Tony Irovic, Grace Thompson, Lainy B. Day

Neuroscience Research Showcase

(All authors are affiliated with Interdisciplinary Studies: Neuroscience, Department of Biology, Interdisciplinary Neuroscience Minor, University of Mississippi)

Introduction:

• Estradiol (E2) & aromatase (AROM) are neuroprotective
• AROM enzymatically converts testosterone (T) into E2
• E2 alters testicular function and increases stroke and cancer risk
• Phytoestrogens, such as genistein (GEN), are plant derived compounds that have a similar chemical structure to E2 and some E2 -like effects
• GEN may possess the neuroprotective effects of E2 while not having the negative effects
• Zebra finch (ZF) brains are highly plastic, and the cerebellum (CB) has low AROM constitutively
• The CB has high levels of estrogen …

Zonal Hepatocellular Responses To Acute Ethanol: Impacts On Mitochondrial Function And Metabolism, Matthew T. Savoca

MUSC Theses and Dissertations

Background: Ethanol (EtOH) consumption causes hepatocellular mitochondrial depolarization (mtDepo) and mitophagy. Here, the Aims were to develop techniques to characterize sublobular hepatocellular metabolism and the distribution of mtDepo and mitophagy after acute EtOH. Methods: Wildtype and GFP-LC3 transgenic mice were treated with EtOH or vehicle and administered the covalently labeling mitochondrial membrane potential (ΔΨ) reporter, MitoTracker Red (MTR), and/or the non-covalent ΔΨ reporter, rhodamine 123 (Rh123), prior to intravital imaging, liver fixation, or hepatocyte isolation. After in vivo MTR, hepatocytes were isolated and sorted. Enrichment in E-cadherin (ECAD) and cytochrome P4502E1 in periportal (PP) and pericentral (PC) hepatocytes, respectively, validated …

G-Protein-Coupled Estrogen Receptor 1 And Pregnancy Confer Protection Against Hypertension In Older Females, Ravneet Singh, Supaporn Kulthinee, Victoria L Nasci, Elvis A Akwo, Chibundu Juliet Umunna, Rawan N Almutlaq, Oleh M Pochynyuk, Cassianne Robinson-Cohen, Eman Y Gohar

Faculty, Staff and Student Publications

No abstract provided.

Missense Mutation Of Msh6 Leucine 696 Has No Apparent Effect On The Dna Mismatch Repair Process, Razan H. Hammad, Rafia Rashid, Essence Tarrence, Christopher Bolden, Joanna E. Haye-Bertolozzi

XULAneXUS

Lynch Syndrome and Constitutional Mismatch Repair Deficiency are human diseases implicated in mutations of DNA mismatch repair (MMR) genes. This experiment tested a mutation of an MMR gene, MSH6, and evaluated how the mutation affected overall MMR effectiveness. Using the yeast Saccharomyces cerevisiae, we performed the CAN1 forward mutation assay to study msh6-L696F and its implications in the MMR process. We hypothesized that there would be a significant change in molecular function in the Msh6 protein in the presence of this mutation. Bioinformatic tools predicted that this amino acid change would have deleterious effects on MMR function. However, …

Evolution Of The Tumor Immune Landscape During Treatment With Tebentafusp, A T Cell Receptor-Cd3 Bispecific, Joseph Sacco, Peter Kirk, Emma Leach, Alexander Shoushtari, Richard Carvajal, Camille Britton-Rivet, Sophie Khakoo, Laura Collins, Luis De La Cruz-Merino, Zeynep Eroglu, Alexandra Ikeguchi, Paul Nathan, Omid Hamid, Marcus Butler, Sarah Stanhope, Koustubh Ranade, Takami Sato

Department of Medical Oncology Faculty Papers

Metastatic uveal melanoma is an aggressive disease with poor outcome, which is refractory to immune checkpoint inhibitors. A T cell receptor (TCR)-based CD3 bispecific, tebentafusp, delivers clinical benefit in patients with metastatic uveal melanoma. Understanding the molecular basis for the anti-tumor activity of tebentafusp in an indication where checkpoint inhibitors are ineffective could aid in identification of other solid tumor indications where CD3 bispecifics may serve an unmet need. By analyzing tumor biopsies taken prior to treatment, early on-treatment, and at progression (NCT02570308), using RNA sequencing (RNA-seq) and immunohistochemistry (IHC), we show that expression of interferon-related genes in the tumor …

Comprehensive Assessment Of Initial Adaptation Of Extended-Spectrum Β-Lactamase-Positive St131 Escherichia Coli To Carbapenem Exposure, William C Shropshire, Xinhao Song, Jordan Bremer, Seokju Seo, Susana Rodriguez, Selvalakshmi Selvaraj Anand, An Q Dinh, Micah M Bhatti, Anna Konovalova, Cesar A Arias, Awdhesh Kalia, Yousif Shamoo, Samuel A Shelburne

Faculty, Staff and Student Publications

Background: It remains unclear how high-risk Escherichia coli lineages, like sequence type (ST) 131, initially adapt to carbapenem exposure in their progression to carbapenem resistance.

Methods: Carbapenem mutation frequency was measured in multiple subclades of extended-spectrum β-lactamase (ESBL)-positive ST131 clinical isolates using a fluctuation assay followed by whole genome sequencing (WGS) characterization. Genomic, transcriptomic, and porin analyses of the ST131 C2/H30Rx isolate MB1860, under prolonged, increasing carbapenem exposure was performed using 2 experimental evolutionary platforms to measure fast versus slow adaptation.

Results: All 13 ESBL-positive ST131 strains selected from a diverse (n = 184) ST131 bacteremia cohort had detectable ertapenem …

Integrated Analysis Of Molecular And Clinical Features Associated With Overall Survival In Melanoma Patients With Brain Metastasis, Swaminathan Kumar, Meredith S Pelster, Merve Hasanov, Renato A Guerrieri, Courtney W Hudgens, Debora A Ledesma, Fuchenchu Wang, Grant M Fischer, Julie M Simon, Lauren E Haydu, Kalman V Katlowitz, Y N Vashisht Gopal, Jennifer L Mcquade, Lawrence N Kwong, Jason T Huse, Alexander J Lazar, Michael T Tetzlaff, Jeffrey E Gershenwald, Aron Y Joon, Ken Chen, Ziyi Li, Prahlad T Ram, Sherise D Ferguson, Michael A Davies

Faculty, Staff and Student Publications

Melanoma brain metastases (MBMs) are diagnosed in up to 60% of metastatic melanoma patients. Previous studies have identified clinical factors that correlate with overall survival (OS) after MBM diagnosis. However, molecular and immune features associated with OS are poorly understood. An improved understanding of the molecular and immune correlates of OS could provide insights into MBM patient outcomes and guide therapeutic development. Thus, we analyzed clinical features and outcomes of 74 melanoma patients who underwent surgical resection (via craniotomy) between 1991 and 2015 at our institution with RNA-seq data generated from their MBMs. The median post-operative OS was 8.6 months …

Single-Cell Analyses Reveal A Functionally Heterogeneous Exhausted Cd8+ T-Cell Subpopulation That Is Correlated With Response To Checkpoint Therapy In Melanoma, Kelly M Mahuron, Osmaan Shahid, Prachi Sao, Clinton Wu, Alexandra M Haugh, Laura A Huppert, Lauren S Levine, Margaret M Lowe, Michael Alvarado, Markee Micu, Katy K Tsai, Melissa Chow, Meromit Singer, Jason M Schenkel, Arlene H Sharpe, Michael D Rosenblum, Kristen E Pauken, Adil I Daud

Faculty, Staff and Student Publications

PD-1 pathway inhibitors have revolutionized cancer therapy. However, most patients do not durably benefit, highlighting the need for biomarkers to stratify patients as responders or nonresponders. Although CD8+ tumor-infiltrating lymphocytes (TIL) have been associated with immune checkpoint therapy response, there is no consensus on which CD8+ TIL subpopulations have the most prognostic value. Preclinical studies have focused on progenitor-like exhausted CD8+ T cells (TPEX) because TPEX proliferate more in response to PD-1 inhibitors than other exhausted T-cell (TEX) subpopulations. However, immune checkpoint inhibitor treatment drives TPEX differentiation into other TEX populations that can mediate antitumor immunity. These data complicate the …

Distinguishing Multisystem Inflammatory Syndrome In Children From Typhus Using Artificial Intelligence: Mis-C Versus Endemic Typhus (Ai-Met), Angela Chun, Abraham Bautista-Castillo, Isabella Osuna, Kristiana Nasto, Flor M Munoz, Gordon E Schutze, Sridevi Devaraj, Eyal Muscal, Marietta M De Guzman, Kristen Sexson Tejtel, Tiphanie P Vogel, Ioannis A Kakadiaris

Faculty, Staff and Students Publications

Background: The pandemic emergent disease multisystem inflammatory syndrome in children (MIS-C) following coronavirus disease-19 infection can mimic endemic typhus. We aimed to use artificial intelligence (AI) to develop a clinical decision support system that accurately distinguishes MIS-C versus endemic typhus (MET).

Methods: Demographic, clinical, and laboratory features rapidly available following presentation were extracted for 133 patients with MIS-C and 87 patients hospitalized due to typhus. An attention module assigned importance to inputs used to create the 2-phase AI-MET. Phase 1 uses 17 features to arrive at a classification manually (MET-17). If the confidence level is not surpassed, 13 additional features …

Volumetric Changes In Cerebellar Transverse Zones: Age And Sex Effects In Health And Neurological Disorders, Farshid Ghiyamihoor, Payam Paymani, Jarrad Perron, Azam Asemi-Rad, Mehdi Marzban, Aashka Mohite, Karen Ardila, Bara Aljada, Asghar Marzban, Mehnosh Toback, Sherif Eltonsy, Ji Hyun Ko, Tabrez J Siddiqui, Christopher J Steele, Jiming Kong, Mario Manto, M Ethan Macdonald, Jason S Gill, Roy V Sillitoe, Fuat Balcı, Iman Beheshti, Hassan Marzban

Duncan NRI Faculty and Staff Publications

Cerebellar volumetric changes are intricately linked to aging, with distinct patterns across its transverse zones, the functional subdivisions characterized by unique cytoarchitectural and connectivity profiles. Despite research efforts, the cerebellar aging process in health and neurological disorders remains poorly understood. In this study, we investigated the effects of age and sex on total cerebellum, transverse zone, and lobule volumes using MRI data from over 45,000 participants compiled from six neuroimaging datasets. We also propose a framework for estimating cerebellum age as an indicator of cerebellar health. Significant age‐dependent volume reductions were observed across transverse zones, with the …

Lineage Tracing And Single-Cell Rna Sequencing Reveal A Common Transcriptional State In Breast Cancer Tumor-Initiating Cells Characterized By Ifn/Stat1 Activity, Eric P Souto, Ping Gong, John D Landua, Ramakrishnan Rajaram Srinivasan, Abhinaya Ganesan, Lacey E Dobrolecki, Stephen C Purdy, Xingxin Pan, Michael Zeosky, Anna Chung, S Stephen Yi, Heide L Ford, Michael T Lewis

Faculty, Staff and Students Publications

A tumor cell subpopulation of tumor-initiating cells (TIC) or "cancer stem cells" is associated with therapeutic resistance, as well as both local and distant recurrences. Signal transducer and activator of transcription (STAT) activity is elevated in TICs in claudin-low models of human triple-negative breast cancer, which enables enrichment of TICs using a STAT-responsive reporter. Lineage tracing of TICs as they undergo cell state changes could enable a better understanding of the molecular phenotypes of TIC and uncover strategies to selectively target TICs. In this study, we developed a STAT-responsive lineage-tracing system and used it in conjunction with the original reporter …

Morphogenic, Molecular And Cellular Adaptations For Unidirectional Airflow In The Chicken Lung, Kamryn N Gerner-Mauro, Lisandra Vila Ellis, Guolun Wang, Richa Nayak, Peter Y Lwigale, Ross A Poché, Jichao Chen

Faculty, Staff and Students Publications

Unidirectional airflow in the avian lung enables gas exchange during both inhalation and exhalation. The underlying developmental process and how it deviates from that of the bidirectional mammalian lung are poorly understood. Sampling key developmental stages with multiscale 3D imaging and single-cell transcriptomics, we delineate morphogenic, molecular and cellular features that accommodate the unidirectional airflow in the chicken lung. Primary termini of hyper-elongated branches undergo proximal-short and distal-long fusions, forming parabronchi for air conduction. Through the parabronchial smooth muscle, neoform termini extend radially to form gas-exchanging alveoli. Supporting this radial alveologenesis, branch stalks halt their proximalization, defined by SOX9-SOX2 transition, …

Long-Read Single-Cell Rna Sequencing Enables The Study Of Cancer Subclone-Specific Genotypes And Phenotypes In Chronic Lymphocytic Leukemia, Gage S Black, Xiaomeng Huang, Yi Qiao, Philip Moos, Deepa Sampath, Deborah M Stephens, Jennifer A Woyach, Gabor T Marth

Faculty, Staff and Student Publications

Bruton tyrosine kinase (BTK) inhibitors are effective for the treatment of chronic lymphocytic leukemia (CLL) due to BTK's role in B cell survival and proliferation. Treatment resistance is most commonly caused by the emergence of the hallmark BTKC481S mutation that inhibits drug binding. In this study, we aimed to investigate cancer subclones harboring a BTKC481S mutation and identify cells with co-occurring CLL driver mutations. In addition, we sought to determine whether BTK-mutated subclones exhibit distinct transcriptomic behavior when compared to other cancer subclones. To achieve these goals, we use scBayes, which integrates bulk DNA sequencing and single-cell …

Results Of The Phase I/Ii Study And Preliminary B-Cell Gene Signature Of Combined Inhibition Of Glutamine Metabolism And Egfr In Colorectal Cancer, Kristen K Ciombor, Seong-Woo Bae, Jennifer G Whisenant, Gregory D Ayers, Quanhu Sheng, Todd E Peterson, Gary T Smith, Kangyu Lin, Saikat Chowdhury, Preeti Kanikarla Marie, Alexey Sorokin, Allison S Cohen, Laura W Goff, Dana B Cardin, John Paul Shen, Scott Kopetz, Cathy Eng, Yu Shyr, Jordan Berlin, H Charles Manning

Faculty, Staff and Student Publications

Purpose: EGFR-targeting mAbs are essential for managing rat sarcoma virus wild-type metastatic colorectal cancer (mCRC), but their limited efficacy necessitates exploring immunologic and metabolic factors influencing response. This study evaluated glutamine metabolism targeting with EGFR inhibition to identify response biomarkers in patients with prior anti-EGFR treatment progression.

Patients and methods: We conducted a phase I/II trial in patients with KRAS wild-type mCRC, combining panitumumab (6 mg/kg) and CB-839 (600 mg/kg or 800 mg/kg), hypothesizing that the dual inhibition of glutamine metabolism and MAPK signaling would enhance outcomes. As study correlatives, we investigated the B-cell activation signature "B-score" and glutamine PET …

Germline Pathogenic Drosha Variants Are Linked To Pineoblastoma And Wilms Tumor Predisposition, Peter N Fiorica, Lisa Golmard, Jung Kim, Riyue Bao, Frank Y Lin, Angshumoy Roy, Allison Pribnow, Melissa R Perrino, Julien Masliah-Planchon, Sophie Michalak-Provost, Jennifer Wong, Mathilde Filser, Dominique Stoppa-Lyonnet, Franck Bourdeaut, Afane Brahimi, Olivier Ingster, Giselle Saulnier Sholler, Sarah A Jackson, Mark M Sasaki, Trent Fowler, Anita Ng, Ryan J Corbett, Rebecca S Kaufman, Jeremy S Haley, David J Carey, Kuan-Lin Huang, Sharon J Diskin, Jo Lynne Rokita, Hussam Al-Kateb, Rose B Mcgee, Joshua D Schiffman, Kenneth S Chen, Douglas R Stewart, D Williams Parsons, Sharon E Plon, Kris Ann P Schultz, Kenan Onel

Center for Medical Ethics and Health Policy Staff Publications

Purpose: DROSHA, DGCR8, and DICER1 regulate miRNA biogenesis and are commonly mutated in cancer. Although DGCR8 and DICER1 germline pathogenic variants (GPV) cause autosomal dominant tumor predisposition, no association between DROSHA GPVs and clinical phenotypes has been reported.

Experimental design: After obtaining informed consent, sequencing was performed on germline and tumor samples from all patients. The occurrence of germline DROSHA GPVs was investigated in large pediatric and adult cancer datasets. The population prevalence of DROSHA GPVs was investigated in the UK Biobank and Geisinger DiscovEHR cohorts.

Results: We describe nine children from eight families with heterozygous DROSHA GPVs and a …

Closing The Gaps, And Improving Somatic Structural Variant Analysis And Benchmarking Using Chm13-T2t, Luis F Paulin, Jeremy Fan, Kieran O'Neill, Erin Pleasance, Vanessa L Porter, Steven J M Jones, Fritz J Sedlazeck

Faculty, Staff and Students Publications

The complexities of cancer genomes are becoming more easily interpreted due to advancements in sequencing technologies and improved bioinformatic analysis. Structural variants (SVs) represent an important subset of somatic events in tumors. While the detection of SVs has been markedly improved by the development of long-read sequencing, somatic variant identification and annotation remain challenging. We hypothesized that the use of a completed human reference genome (CHM13-T2T) would improve somatic SV calling. Our findings in a tumor-normal matched benchmark sample and three patient samples show that the CHM13-T2T improves SV detection accuracy compared to GRCh38 with a notable reduction in false-positive …

Unraveling The Hidden Complexity Of Cancer Through Long-Read Sequencing, Qiuhui Li, Ayse G Keskus, Justin Wagner, Michal B Izydorczyk, Winston Timp, Fritz J Sedlazeck, Alison P Klein, Justin M Zook, Mikhail Kolmogorov, Michael C Schatz

Faculty, Staff and Students Publications

Cancer is fundamentally a disease of the genome, characterized by extensive genomic, transcriptomic, and epigenomic alterations. Most current studies predominantly use short-read sequencing, gene panels, or microarrays to explore these alterations; however, these technologies can systematically miss or misrepresent certain types of alterations, especially structural variants, complex rearrangements, and alterations within repetitive regions. Long-read sequencing is rapidly emerging as a transformative technology for cancer research by providing a comprehensive view across the genome, transcriptome, and epigenome, including the ability to detect alterations that previous technologies have overlooked. In this Perspective, we explore the current applications of long-read sequencing for both …

Update On Cancer And Central Nervous System Tumor Surveillance In Pediatric Nf2-, Smarcb1-, And Lztr1-Related Schwannomatosis, Melissa R Perrino, Marjolijn C J Jongmans, Gail E Tomlinson, Mary-Louise C Greer, Sarah R Scollon, Sarah G Mitchell, Jordan R Hansford, Kris Ann P Schultz, Wendy K Kohlmann, Jennifer M Kalish, Suzanne P Macfarland, Anirban Das, Kara N Maxwell, Stefan M Pfister, Rosanna Weksberg, Orli Michaeli, Uri Tabori, Gina M Ney, Philip J Lupo, Jack J Brzezinski, Douglas R Stewart, Emma R Woodward, Christian P Kratz

Faculty, Staff and Students Publications

Schwannomatosis (SWN) is a distinct cancer predisposition syndrome caused by germline pathogenic variants in the genes NF2, SMARCB1, or LZTR1. There is a significant clinical overlap between these syndromes with the hallmark of increased risk for cranial, spinal, and peripheral schwannomas. Neurofibromatosis type 2 was recently renamed as NF2-related SWN and is the most common SWN syndrome, with increased risk for bilateral vestibular schwannomas, intradermal schwannomas, meningiomas, and less commonly, ependymoma. SMARCB1-related SWN is a familial SWN syndrome associated with peripheral and spinal schwannomas and an increased risk for meningiomas and malignant peripheral nerve sheath tumors, even in the absence …

A Hitchhiker’S Guide To Long-Read Genomic Analysis, Medhat Mahmoud, Daniel P Agustinho, Fritz J Sedlazeck

Faculty, Staff and Students Publications

Over the past decade, long-read sequencing has evolved into a pivotal technology for uncovering the hidden and complex regions of the genome. Significant cost efficiency, scalability, and accuracy advancements have driven this evolution. Concurrently, novel analytical methods have emerged to harness the full potential of long reads. These advancements have enabled milestones such as the first fully completed human genome, enhanced identification and understanding of complex genomic variants, and deeper insights into the interplay between epigenetics and genomic variation. This mini-review provides a comprehensive overview of the latest developments in long-read DNA sequencing analysis, encompassing reference-based and de novo assembly …

Proteogenomic Characterization Of Non-Functional Pancreatic Neuroendocrine Tumors Unravels Clinically Relevant Subgroups, Shunrong Ji, Lihua Cao, Jing Gao, Yang Du, Zeng Ye, Xin Lou, Fen Liu, Yehan Zhang, Junfeng Xu, Xiaohan Shi, Huan Wang, Penghao Li, Yikai Li, Hongxu Chen, Zhicheng Yang, Suizhi Gao, Wuhu Zhang, Dan Huang, Shujuan Ni, Miaoyan Wei, Fei Wang, Yan Wang, Tian Ding, Desheng Jing, Guixiong Fan, Zhiyun Gong, Renquan Lu, Yi Qin, Jie Chen, Xiaowu Xu, Pei Wang, Bing Zhang, Li Ding, Ana I Robles, Henry Rodriguez, David K Chang, Ralph H Hruban, Dong Gao, Daming Gao, Gang Jin, Hu Zhou, Jianmin Wu, Xianjun Yu

Faculty, Staff and Students Publications

The majority of neuroendocrine neoplasms in pancreas are non-functional pancreatic neuroendocrine tumors (NF-PanNETs), which exhibit a high occurrence of distant metastases with limited therapeutic options. Here, we perform a comprehensive molecular characterization of 108 NF-PanNETs through integrative analysis of genomic, transcriptomic, proteomic, and phosphoproteomic profiles. Proteogenomic analysis provides functional insights into the genomic driver alterations of NF-PanNETs, revealing a potential mediator of MEN1 alterations using Men1-conditional knockout mice. Machine-learning-based modeling uncovers a three-protein signature as an independent prognostic factor, which is validated by an independent external cohort. Proteomic and phosphoproteomic-based stratification identifies four subtypes with distinct molecular characteristics, immune microenvironments, …

Somatodendritic Orientation Determines Tdcs-Induced Neuromodulation Of Purkinje Cell Activity In Awake Mice, Carlos A Sánchez-León, Guillermo Sánchez-Garrido Campos, Marta Fernández, Álvaro Sánchez-López, Javier F Medina, Javier Márquez-Ruiz

Faculty, Staff and Students Publications

Transcranial direct-current stimulation (tDCS) of the cerebellum is a promising non-invasive neuromodulatory technique being proposed for the treatment of neurological and neuropsychiatric disorders. However, there is a lack of knowledge about how externally applied currents affect neuronal spiking activity in cerebellar circuits in vivo. We investigated how Cb-tDCS affects the firing rate of Purkinje cells (PC) and non-PC in the mouse cerebellar cortex to understand the underlying mechanisms behind the polarity-dependent modulation of neuronal activity induced by tDCS. Mice (n=9) were prepared for the chronic recording of local field potentials (LFPs) to assess the actual electric field gradient imposed by …

Integrating Short-Read And Long-Read Single-Cell Rna Sequencing For Comprehensive Transcriptome Profiling In Mouse Retina, Meng Wang, Yumei Li, Jun Wang, Soo Hwan Oh, Yexuan Cao, Rui Chen

Faculty, Staff and Students Publications

The vast majority of protein-coding genes in the human genome produce multiple mRNA isoforms through alternative splicing, significantly enhancing the complexity of the transcriptome and proteome. To establish an efficient method for characterizing transcript isoforms within tissue samples, we conducted a systematic comparison between single-cell long-read and conventional short-read RNA sequencing techniques. The transcriptome of approximately 30,000 mouse retina cells was profiled using 1.54 billion Illumina short reads and 1.40 billion Oxford Nanopore Technologies long reads. Consequently, we identify 44,325 transcript isoforms, with a notable 38% previously uncharacterized and 17% expressed exclusively in distinct cellular subclasses. We observe that long-read …

Spreading Depolarization And Seizures: End Of The Beginning, Or Beginning Of The End?, Isamu Aiba, Jeffrey L Noebels

Faculty, Staff and Students Publications

Like Janus, the Roman god of beginnings, transitions, and endings, spreading depolarizations (SDs) can be depicted with two faces: one looking backward, waving a symbolic farewell to the end of a cortical seizure; the other forward looking, opening a darker door for a fatal wave in the brainstem that ends life. There is good agreement on the distinct electrical nature of both events, but neither role is yet proven in patients. SD is a slow-moving wave of cellular depolarization that steadily silences neuronal networks and depresses EEG amplitude, whereas seizures represent fast, intermittent synchronization of neural networks with highly variable …

Region-Specific Roles Of Oviductal Motile Cilia In Oocyte/Embryo Transport And Fertility†, Deirdre M Scully, Tian Xia, Guzel R Musina, Michaela A Mccown, Kohei Umezu, Bonnie K Kircher, Richard R Behringer, Irina V Larina

Faculty, Staff and Students Publications

The physiological and clinical importance of motile cilia in reproduction is well recognized; however, the specific role they play in transport through the oviduct and how ciliopathies lead to subfertility and infertility are still unclear. The contribution of cilia beating, fluid flow, and smooth muscle contraction to overall progressive transport within the oviduct remains under debate. Therefore, we investigated the role of cilia in the oviduct transport of preimplantation eggs/embryos using a combination of genetic and advanced imaging approaches. We show that the region of the oviduct where cumulus-oocyte complex circling occurs, around the time of fertilization, is correlated with …

The Effects Of Estradiol And Genistein On Cerebellar Neuroprotection In Zebra Finches, Grace Thompson, Tony Irovic, Lainy B. Day

Neuroscience Research Showcase

Poster presented at Annual Neuroscience Showcase University of Mississippi related to neuroprotection of genistein and estradiol post-brain lesion.

Investigating The Effects Of Sex And Estrous Cycle On The Incubation Of Cue-Induced Oxycodone Craving, Bhumiben Pradipkumar Patel

Theses and Dissertations

The overprescription and misuse of opioids like oxycodone has played a significant role in the ongoing opioid crisis. While effective painkillers, drugs like oxycodone are also reinforcing and often misused. While sex and ovarian hormones can impact the analgesic effects of these drugs, the impact of these factors on oxycodone reinforcement are not fully understood. This relationship between ovarian hormones and opioid reward is further complicated by the fact that opioid use can disrupt ovarian hormone levels and produce reproductive cycle irregularities. Using a rat model of drug craving and relapse vulnerability, we found that chronic oxycodone exposure produced reproductive …