I (Valerio Rasi) am ecstatic to receive this F30 predoctoral fellowship opportunity through the NIH. The Ruth Kirschstein National Research Service Award supports M.D./Ph.D. students by enhancing the integration of research and clinical training. I joined Dr. Hoft’s lab at the end of my second year of medical school. I am fortunate to have joined his lab as I have exposure to both cutting edge basic science projects, as well as clinical research studies that he supervises as director of the SLU Center for Vaccine Development. My research project involves understanding how Gamma Delta (gd) T cells inhibit the intracellular replication of Mycobacterium tuberculosis within infected macrophages through the action of Granzyme A. I will continue to add to our understanding of the role of extracellular Granzyme A, and I look forward to returning to medical school to continue my physician scientist training.

Emily Cybulla is a 5th year M.D./Ph.D. candidate in Alessandro Vindigni's lab, which recently relocated from the Department of Biochemistry and Molecular Biology at SLU to the Division of Molecular Oncology at Washington University in St. Louis. Emily submitted her Ruth L. Kirschstein National Research Service Award (NRSA) application in December of 2019. This F30 application, titled "Targeting Rad18-dependent replication stress pathways to modulate chemoresponse in BRCA1-deficient cancers" was officially funded through the NIH's National Cancer Institute in July of 2020. Emily's F30 proposal combines research aimed at defining molecular mechanisms underlying chemoresponse in breast and ovarian cancers, collaboration and mentorship opportunities with physician scientists and cancer clinicians, and continued integration of her scientific interests in the DNA replication and repair fields with her clinical interests in medical oncology. The F30 fellowship will support Emily's remaining time in her graduate program and also her remaining clinical years in medical school.

Daniel Pike was lucky enough to receive an F30 for my work in Dr. Ford's lab, which was focused on investigating the role of neutrophil-derived chlorinated lipids in endothelial dysfunction in sepsis. When neutrophils are activated in order to fight off bacteria, one of the important enzymes in their response is myeloperoxidase, which produces hypochlorous acid (HOCl). HOCl has potent microbicidal activity, but it can react with host molecular species as well. When HOCl reacts with a specific membrane phospholipid, a plasmalogen, a chlorinated fatty aldehyde is released. This product can be oxidized into the more stable chlorinated fatty acid (2-CLFA). Since neutrophils are systemically activated during sepsis, our lab was interested in investigating the role of these lipids in this disease. Our lab demonstrated 2-CLFA induces endothelial dysfunction and propagates neutrophil activity, and we have also shown that plasma 2-CLFA is increased in those patients with sepsis that will go on to die within a 30 day window. My project was focused on developing a sepsis model in rats that we can use to study 2-CLFA production, localization, metabolism, and in vivo activity during sepsis. I demonstrated that 2-CLFA is elevated systemically in a cecal slurry (CS) model of sepsis in rats. Additionally, I replicated our human results by demonstrating that at an early time point 8 hr post-CS, plasma 2-CLFA is higher in those rats that will go on to die than in those that ultimately survived. Finally, I demonstrated that in the absence of infection, 2-CLFA administration to rats resulted in increased endothelial permeability in the kidneys up to 4 hours post-injection. After a productive and very enjoyable few years in the Ford Lab, the remaining two years of the F30 will cover my return to third and fourth year of medical school.