Translational Science Oral Session III: Hematology/Oncology, Rheumatology/Immunology and Neurology

Tuesday, April 15, 2025
3:30 pm - 4:45 pm

CYTOTOXIC AND PRO-INFLAMMATORY EFFECTS OF MICROPLASTICS AND MICROCYSTIN TOXIN ON HUMAN AIRWAY EPITHELIAL CELLS (Environmental Factors Affecting Health) Upasana Shrestha, BS, The University of Toledo
Harmful algal blooms (HABS) release potent cyanotoxins into water bodies, posing serious threats to human and animal health due to their toxic effects on vital organs, including liver, kidneys, and lungs. Lake Erie HABs are dominated by microcystin (MC) -producing cyanobacteria, with microcystin-leucine arginine (MC-LR) being one of the most prevalent and toxic variants. In addition to health risks posed by MC, there is a growing concern about nano- and microplastic (NP and MP) in and around water bodies. Humans can be exposed to MCs and MPs through ingestion, skin contact, and inhalation. While most research have focused on oral exposure, emerging evidence highlights dangers of inhaling MCs and MPs, both of which can cause lung injury. Furthermore, aerosols contaminated with these contaminants can travel over 30 km from affected areas, potentially exposing large population to inhalation risks. Using a fully differentiated 3D human airway epithelial model, we have previously shown that short-term exposure to NP-containing aerosols induced differential secretion of cytokine and chemokine proteins with significant reductions in levels of IL-21, IL-15, IL-2, CXCL10, and TGFβ. This combined reduction in these cytokines could result in a dampened immune response, potentially affecting the long-term ability of the airway epithelium to cope with environmental stressors like HAB aerosol exposure.

NORTRIPTYLINE: A REPURPOSABLE ADJUVANT TO CHEMOTHERAPY IN GROUP 3 MEDULLOBLASTOMA THAT TRIGGERS APOPTOSIS BY INDUCING MITOCHONDRIAL DYSFUNCTION (Hematology and Oncology / Bone Marrow Transplant)
David Doss, Creighton University School of Medicine
Medulloblastoma (MB) is the most common malignant pediatric brain tumor, with Group 3 (G3MB) representing 25% of cases and demonstrating the most aggressive clinical course. G3MB is characterized by poor 5-year survival rates (< 50%), high recurrence, and limited efficacy of current multimodal treatments, which include surgery, craniospinal irradiation, and chemotherapy. While subgroup-specific therapies have shown promise in other MB subtypes, the therapeutic landscape for G3MB remains sparse, necessitating novel approaches to improve outcomes.

TARGETING THE ABCB7/GPX4 AXIS USING ARTESUNATE POTENTIATES CISPLATIN RESPONSE IN PEDIATRIC GROUP 3 MEDULLOBLASTOMAS BY TRIGGERING FERROPTOSIS (Neurology)
Ranjana K. Kanchan, PhD, University of Nebraska Medical Center
Medulloblastomas are the leading cause of cancer-related mortality in childhood. Group 3 medulloblastomas (G3MB) are the most aggressive MB tumors, with 5-year survival < 50%. A poor understanding of mechanisms driving aggressiveness contribute to a lack of novel therapies for this subgroup. We have isolated ferroptosis evasion as a powerful mechanism that drives aggressiveness in G3MBs. Ferroptosis is a form of cell death triggered by iron overload. Inhibiting the deregulated iron transporter ABCB7 in G3MBs triggers ferroptosis in vitro. It dually inhibits the principal regulator of ferroptosis, GPX4. Artesunate is an FDA-approved, antimalarial drug, whose mechanism of cytotoxicity in Plasmodium is through inducing iron overload.

SOCIOECONOMIC AND DEMOGRAPHIC DISPARITIES IN TREATMENT AND SURVIVAL OF OVARIAN SEROMUCINOUS CARCINOMA: A NATIONAL CANCER DATABASE STUDY (Hematology and Oncology / Bone Marrow Transplant)
Nikhil Furtado, BS, Creighton University School of Medicine
Ovarian seromucinous carcinoma (OSMC) is a rare and controversial epithelial ovarian malignancy, initially designated as a distinct histologic entity in the 2014 World Health Organization classification but redefined in 2020 as a variant of endometrioid carcinoma with mucinous differentiation due to overlapping morphological and molecular characteristics. OSMC is characterized by a complex papillary architecture, biphasic serous and mucinous epithelial differentiation, and a strong association with endometriosis. Despite reclassification, OSMC demonstrates a unique oncologic trajectory, with survival outcomes more closely resembling mucinous carcinoma than endometrioid carcinoma.

ENHANCING IMMUNOTHERAPY EFFICACY IN MYELOMA WITH A DUAL-ACTION MITOCHONDRIAL-TOXIC PEPTIDE THAT ACTIVATES T CELLS AND INDUCES TUMOR CELL DEATH (Hematology and Oncology / Bone Marrow Transplant)
Smriti Gurung, PhD, Indiana University
Immunotherapy that redirects T cells to tumor-specific antigens shows promise in myeloma, but resistance is universal, caused by both tumor and T cell factors. Tumors upregulate Programmed Death Ligand -1 (PD-L1), which promotes tumor growth and binds to Programmed Death Receptor-1 (PD-1) on T cells, suppressing their function and enabling immune escape. The bone marrow microenvironment exacerbates this resistance by promoting tumor survival and further impairing T cell function. We previously developed PP-k, a novel PD-L1-blocking peptide conjugated with a mitochondrial-targeted peptide (KLAKLAK)2. PP-k binds PD-L1 on tumor cells, blocking PD-L1/PD-1 signaling between tumors and T cells while disrupting mitochondria, leading to direct tumor cell killing.