German Gornalusse PhD, MSc

Obstetrics & Gynecology, Global Health
Research Assistant Professor

Email: germag@uw.edu | Phone: 206.616.1158

Our research focuses on the mechanisms of HIV latency and reactivation in the human gut. We are currently using in vitro models to test the hypothesis that microfold cells, highly specialized enterocytes, drive T cell proliferation and HIV reactivation via their increase activity of type I/III interferon pathways. The differentiation programs that lead to the generation of M cells are largely unknown. Their isolation and ex vivo culture is challenging, and there are no available immortalized M-cell lines. There are, however, protocols to generate M cell-like cells in vitro. Our co-Investigator Dr. Jason Smith has established in his lab a culture system using duodenal and ileal enteroids to generate M cells; these enteroids arise from stem cells found in intestinal crypts. Therefore, we are currently employing these stem-cell derived enteroid models to investigate whether secreted products from M cells (e.g. soluble ISG15 and other cytokines) reactivate HIV and/or induce proliferation in latently infected CD4+ T cells from people living with HIV and other cellular models. If we find that certain factors derived from M cell cultures drive CD4+ T cell proliferation in vitro, we will go back to ex vivo duodenal and ileal tissues and further define which molecular networks are involved. In summary, we are employing stem-cell derived cellular systems to model in vitro the dynamics of the HIV reservoir. This project, along with an ongoing clinical study, will provide key information about the intestinal microarchitecture of the HIV reservoir that is necessary for the development of novel latency reversal agents or strategies to target latently infected cells via M cells.