Education:
A.B. Indiana University, Zoology and Chemistry, Highest Distinction
M.D. Indiana University, Highest Distinction
Resident in Internal Medicine, Yale University
Chief Resident in Internal Medicine, Yale University
Fellow in Nephrology, Yale University
Fellow, Alexander von Humboldt Stiftung, Medizinische Hochschule Hannover Germany

Clinical and Academic Activities:
Professor of Medicine in Residence, Step 9, emeritus 2020
Chief, Nephrology Section SFVAMC, 1995-2019

University/Public Service:
Principal Investigator UCSF T32 Academic Training Program in Nephrology 2006-2016
Member, UCSF Committee on Academic Personnel 2016-2017
Vice Chair, UCSF Committee on Academic Personnel 2017-2018
Chair, UCSF Committee on Academic Personnel 2018-2019

Scholarly Activity: Our laboratory has primarily focused in recent years on an examination of the role of matrix metalloproteinase 2 in progressive cardiac and renal failure. These studies have included determinations of transcriptional regulatory networks, impact of promoter haplotypes on gene expression and generation of a series of transgenic mice to directly test the significance of MMP-2 expression on renal and cardiac disease. We have demonstrated that MMP-2 alone is sufficient to trigger the entire process of progressive renal disease seen in humans, including glomerulosclerosis, tubular atrophy and interstitial fibrosis without the requirement for superimposed injury. In the heart we have published a series of studies demonstrating that MMP-2 directly mediates cardiomyocyte apoptosis and contractile failure. More recently we have characterized (Lovett, et al., PLoS One 2012) a novel intracelllular isoform of MMP-2 that activates innate immunity. The isoform is generated by oxidative stress mediated activation of an alternative promoter in the first intron of the MMP-2 gene, thereby generating an intracellular, active N-terminal truncated enzyme. Transgenic mice expressing this isoform in the heart develop severe cardiomyocyte hypertrophy, inflammation and sytolic failure. Transgenic mice expressing this isoform in the kidney develop progressive tubular atrophy due mitochondrial damage mediated regulated necrosis. We are currently determining the extent of expression of this MMP-2 isoform in clinical specimens of cardiac and renal tissue using a combination of histochemical and epigenetic approaches. In addition, we are studying the epigenetic regulation of the MMP-2 intronic promoter using a novel series of transgenic reporter mice and epigenetic techniques. We believe that both isoforms of MMP-2 represent appealing therapeutic targets and we are currently developing antibody and siRNA-based strategies to selectively inhibit the MMP-2 isoforms in models of cardiac and renal disease.