|Associate Professor of Medicine and Medical Microbiology & Immunology|
|3301 Microbial Sciences Building|
1550 Linden Drive
|Office: (608) 263-2994|
1988, Purdue University, W. Lafayette, IN
1995, M.D., Washington U., St Louis, MO
1995, Ph.D., Dr Hultgren (Assembly and Specificity of P pili), Wash U., St Louis, MO
1996-1998, Internal Medicine Residency, CPMC, San Francisco, CA
1998-2001, Infectious Diseases Post-Doctoral Fellow: Stanford University.
1999-2001, Howard Hughes Postdoctoral Fellow, Dr Kirkegaard (In vitro and In vivo studies of the HCV RNA polymerase).
Our group strives to improve therapy for human infectious diseases. This includes both making new antimicrobials as well as better stewardship and application of antimicrobials we have. Since microbes have short generation times and rapid evolution, the optimal may also need to change and be tailored to individual patients as new science becomes available. Our overall goal is to develop antimicrobials and biomarkers useful to practicing clinicians individualizing the care of patients with infections.
Currently our work is focused on two areas:
Laboratory based development of inhibitors of pathogen specific phosphorylation events. Both host and pathogens use kinases for critical signal transduction during their interactions. There are now dozens of useful kinase inhibitors for human disease, selectively targeting a portion of the 518 human kinases making this drug category one of the fastest growing. Yet there are no kinase inhibitors that are specific for pathogen kinases, and no recommended use of human kinase inhibitors to treat infectious diseases despite feasibility demonstrated in animal models and human case reports. We use molecular biology, biochemistry and mass spectrometry to identify critical phosphorylation events in infectious diseases that could be targeted to improve outcomes. A major focus currently is selective bacterial kinase inhibition of so called PASTA kinases in Methicillin Resistant Staphylococcus (MRSA) and other organisms.
Individualizing therapy for human viral infections:
RNA viral infections are highly variable. This variability applies to both the degree of disease they induce as well as the viral genome that rapidly evolves. We have been studying how variation into both Hepatitis C (HCV) genetics and response to therapy can guide therapeutic decisions. Since HCV infects ~ 3 million people, therapy is expensive and many of the people with HCV have limited financial resources and medical access, it can be critical to optimize the treatment and care delivery. We are studying how viral genetics and care delivery can be tailored to specific patients. Ultimately we aim to individualize care for HIV patients as well with quantitative measurements of the reservoir and adjusting antiviral potency to make sure the reservoir shrinks without over treating patients. A key resource in these ambitious goals is the Veteran’s Affairs Million Veteran Program (VA) which may eventually be the largest study in the world to link clinical data with human genetics. Our Madison VA is a Million Veteran Research Site. In order to measure the HIV reservoir in a clinically useful, reproducible way we are collaborating with the Beebe lab on campus (http://mmbwisc.squarespace.com) and a local biotechnology company (Salus Discovery, http://www.salusd.com) who have long-standing interests in diagnostics for resource limiting settings. Finally, we benefit from and work to support the AIDS Resource Center of Wisconsin (ARCW, www.arcw.org) and are working towards the World’s Health Organization goals that only Sweden so far has achieved of 90-90-90 control of HIV in our region/ country.