Position title: University of Wisconsin-Madison KURe Program
Website: Institutional Profile
Dr. Grimes is an Assistant Professor (CHS) in the Department of Urology at the School of Medicine and Public Health. His mentors are Drs. Wade Bushman and Chad Vezina.
The title of Dr. Grimes’ work is loss of CD44 expression drives altered collagen structure in lichen sclerosus. Lichen sclerosus (LS) is a poorly understood chronic inflammatory condition of the genital skin with an estimated prevalence of 1:300. Approximately 20% of men with LS develop urethral stricture disease (USD). These patients commonly develop profound fibrosis of the entire anterior urethra requiring complex and morbid surgical reconstruction with low success rates. The mechanisms by which LS leads to USD are unknown and represent a critical knowledge gap in benign urology.
Dr. Grimes’ long-term career goal is to develop minimally invasive and nonsurgical treatments of LS and USD through improved understanding of its molecular pathogenesis. This proposal focuses on the principal hyaluronic acid receptor CD44. Human LS skin lesions are characterized by a loss of CD44 and an overabundance of extracellular hyaluronic acid. Lichen sclerosus skin lesions and associated stricture are characterized by prominent collagen fibrosis in the extracellular matrix. A mouse model of genetic epithelial CD44 depletion recapitulates this pattern of increased hyaluronic acid abundance and collagen fibrosis. The proposed research plan will directly test the overarching hypothesis that loss of CD44 expression in patients with lichen sclerosus triggers extracellular hyaluronic acid accumulation, TGF-β pathway activation, and collagen accumulation.
While conducting this work, Dr. Grimes will complete a Certificate Program in the Foundations of Clinical Research and be mentored by a diverse team with expertise in advanced microscopy, image analysis, and utilization of transgenic animal and in vivo functional testing to link molecular mechanisms to physiological outcomes. The proposed research will provide preliminary data for a subsequent K23 application, and the proposed training plan will prepare Dr. Grimes to achieve his long-term goals as an independent researcher. By defining the mechanisms driving fibrosis in LS he will identify putative therapeutic targets and alter the current “surgery first” treatment of LS and related USD.