Associate Professor, Department of Microbiology & Molecular Genetics
Associate Professor, BioMolecular Science Gateway
Location: 775 Woodlot Dr Room 1318
As a trained molecular virologist and cancer biologist my goal has been to advance our understanding of the molecular pathogenesis of HIV/AIDS infection, cancer, and transplantation. I studied medicine in Frankfurt/Main and Mainz, Germany, and spent my final year at the Hammersmith Hospital in London, U.K. In my graduate studies in the laboratory of Dr. James I. Mullins in the Dept. of Cancer Biology at the Harvard School of Public Health I focused on the molecular epidemiology of human and feline immunodeficiency viruses. Working first as a postdoctoral fellow and then as a research scientist in the laboratory of Dr. Christopher Contag at Stanford University, I advanced bioluminescence imaging (BLI) methodology and applied it to a number of animal models of human disease, including cancer and infection. Over the last decade, I have been combining BLI with molecular genetic screens to study how the immune system interacts with cancer cells and immunologically mismatched transplants and how it could possibly be modulated for the benefit of patients. ###Education M.D., 1985, Johannes Gutenberg University, Mainz, Germany Sc.D., 1996, Harvard University, Boston, MA Postdoctoral Fellow, 1995-96, Dept. of Psychiatry & Psychosocial Medicine, Stanford University, Stanford, CA Postdoctoral Fellow, 1996-2002, Dept. of Pediatrics, Stanford University, Stanford, CA Research Scientist, 2002-2017, Dept. of Pediatrics, Stanford University, Stanford, CA ###Research Our lab addresses three major medical and public health challenges: understanding the immunology of cancer and transplantation, and developing effective antimicrobials. We are therefore pursuing the following questions: 1. Cancer Immune Escape: How do cancer cells escape from surveillance by the immune system that normally removes such altered cells? So far, a number of genes, signaling molecules and pathways have been implicated, yet, it remains unclear what constitutes a sufficient minimal set to achieve this capability in cancer cells. Once we know this and fully understand the cancer immune escape mechanisms more effective immunotherapies – which are currently revolutionizing cancer treatment – can be designed so that these are no longer fraught with dangers, such as severe autoimmunity, and in some cases unfortunately, faster disease progression. 2. Transplantation: How can we minimize the effects of the immunosuppressive therapy currently needed to prevent the natural transplant rejection response by the immune system? For this, we are taking our cues from exceptional patients who develop so-called “operational” tolerance towards their immunologically mismatched organ transplants, even though they have stopped taking immunosuppressive drugs. Thus, our goal is to find the genes that can induce this special immunological state of tolerance towards mismatched cells and organs and translate our findings into localized immunomodulation therapy. For both of these questions, we are investigating candidate genes in mouse models of disease for their causal role. Genes are either transferred in vitro into cells of interest for overexpression, or knocked out using mobile genetic elements called ‘transposons’. The gene-modified cells are subsequently introduced into mice where we then monitor the cells’ survival in real time using bioluminescence imaging (BLI). Cells with prolonged survival can then be recovered and analyzed for overexpressed or knocked out genes. Finally, in the case of cancer, we are also analyzing RNA sequence data of mouse tumors and publically available human cancer genomics databases to confirm the significance of the identified genes as contributors to disease progression. 3. Antimicrobial Resistance: What can we do to help overcome the growing bacterial resistance to antimicrobial agents, which has become a major medical concern and public health emergency? To widen our focus we are seeking to learn from evolutionary biology about antimicrobial resistance (AMR). Together with Dr. Jonathan Hardy, also in the Dept. of Microbiology and Molecular Genetics, we are testing plant and fungal extracts on bacteria that are either naturally bioluminescent or genetically labeled with luciferase and thus can be easily assayed by BLI. Subsequent testing in mouse models of infection using these bioluminescent bacteria will allow us to test the compounds’ treatment efficacy before moving them into the clinic.