Andrew S. Goldstein, PhD
Epithelial cancers share many properties with adult tissue-specific stem cells, including the capacities to proliferate, self-renew and differentiate. Recent work has indicated that adult tissue-specific stem cells are likely target cells for acquiring the initial mutations that lead to epithelial cancers (cells of origin). Dr. Andrew Goldstein's lab is interested in 1) identifying stem and progenitor cells in the mouse and human genitourinary tract, 2) defining the unique mechanisms that progenitor cells utilize to survive, self-renew and generate cancer, and 3) interrogating the signaling pathways which can transform normal stem and progenitor cells.
Castration-resistant prostate cancer (CRPC) represents the advanced stage of the disease that recurs after androgen deprivation therapy. Few treatment options currently exist for men with CRPC. Goldstein's lab is developing new in vivo models of CRPC initiated in naive benign primary human prostate cells isolated from patient specimens. Commonly mutated pathways and newly identified alterations are being investigated to determine the requirements to transform naive benign cells to primary prostate cancer and CRPC. Defining the alterations that drive advanced disease may provide an opportunity to predict response to hormonal therapy, and defining new pathways regulating disease progression may lead to new targeted therapies for the treatment of CRPC.
Liu X, Grogan TR, Hieronymus H, Hashimoto T, Mottahedeh J, Cheng D, Zhang L, Huang K, Stoyanova T, Park JW, Shkhyan RO, Nowroozizadeh B, Rettig MB, Sawyers CL, Elashoff D, Horvath S, Huang J, Witte ON, Goldstein AS. Low CD38 Identifies Progenitor-like Inflammation-Associated Luminal Cells that Can Initiate Human Prostate Cancer and Predict Poor Outcome. Cell Rep. 2016 Dec 6;17(10):2596-2606. doi: 10.1016/j.celrep.2016.11.010.
Remacle F, Goldstein AS, Levine RD. Multivariate Surprisal Analysis of Gene Expression Levels. Entropy (2016), 18: 445; doi:10.3390/e18120445.
Stoyanova T, Cooper AR, Drake JM, Liu X, Armstrong AJ, Pienta KJ, Zhang H, Kohn DB, Huang J, Witte ON, Goldstein AS. Prostate cancer originating in basal cells progresses to adenocarcinoma propagated by luminal-like cells. Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20111-6. doi: 10.1073/pnas.1320565110. Epub 2013 Nov 26.
Goldstein AS, Drake JM, Burnes DL, Finley DS, Zhang H, Reiter RE, Huang J, Witte ON. Purification and direct transformation of epithelial progenitor cells from primary human prostate. Nat Protoc. 2011 May;6(5):656-67. Epub 2011 Apr 21.
Goldstein AS, Huang J, Guo C, Garraway IP, Witte ON. Identification of a cell of origin for human prostate cancer. Science. 2010 Jul 30;329(5991):568-71.