Nancy Allbritton, MD, PhD (Bioengineering)
Research in my laboratory focuses on the development of novel methods and technologies to answer fundamental questions in biology & medicine. Much of biology & medicine is technology limited in that leaps in knowledge follow closely on the heels of new discoveries and inventions in the physical and engineering sciences; consequently, interdisciplinary groups which bridge these different disciplines are playing increasingly important roles in biomedical research. Our lab has developed partnerships with other investigators in the areas of biology, medicine, chemistry, physics, and engineering to design, fabricate, test, and utilize new tools for biomedical and clinical research. Collaborative projects include novel strategies to measure enzyme activity in single cells using microelectrophoresis innovations, to build organ-on-a-chips particularly intestine-on-chip, array-based methods for cell screening and sorting. An additional focus area is the development of software and instrumentation to support these applications areas. The ultimate goal is to design and build novel technologies and then translate these technologies into the marketplace to insure their availability to the biomedical research and clinical communities to enable humans to lead healthier and more productive lives.
German Gornalusse, PhD, MSc (Obstetrics & Gynecology)
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.
Jason G. Smith, PhD (Microbiology)
Our laboratory cultures enteroid “mini guts” from adult intestinal epithelial stem cells to study the genetics of inflammatory bowel disease (IBD), Paneth cell development and function, and host pathogen interactions in the gut.
Elia Tait Wojno, PhD (Immunology)
Dr. Elia Tait Wojno and her team work on dissecting how immune and epithelial responses at mucosal barriers are regulated during helminth parasite infection and allergy, with a special emphasis on how cytokines and prostaglandins influence stem cell function to promote inflammation. Currently, we do not fully understand how immune and epithelial stem cells in the lung and intestine control altered tissue function and inflammation. We use in vitro and in vivo studies of immune, epithelial, and stem cell biology in mice and humans to identify basic mechanisms that underlie mucosal barrier inflammation and host protection against infection. These studies will reveal the importance of stem cell-mediated effects on promoting inflammation in tissues and have the potential to inform the development and use of new, stem cell-directed therapies to manage inflammatory conditions in the lung and gut.