Louisiana Via Research Day Book 2026

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