UW-Madison School of Pharmacy

Navigation Options

head shot image

Paul C Marker, Ph.D

Professor
Associate Dean for Research, Vice Chair of Pharmaceutical Sciences

 

 

 


Research in the Marker laboratory is focused on understanding the biology of the prostate gland at the molecular level. Interest in understanding the biology of the prostate is driven both by the fascinating nature of the developmental processes that function during organogenesis of the prostate and by the high incidence in humans of prostatic diseases including prostatic adenocarcinoma and benign prostatic hyperplasia. The Marker lab is particularly interested in the role of intercellular communication between epithelial and mesenchymal/stromal cells during prostatic branching morphogenesis and during the progression of human prostate diseases.

One current project in the lab seeks to investigate the molecular basis of benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS). BPH is a highly prevalent condition in aging men that is frequently associated with LUTS. While the etiology of BPH and LUTS remain largely unclear, available data are consistent with the hypothesis that changing hormone levels in aging men and/or the reactivation of developmental growth-regulatory pathways are underlying causes of BPH and associated LUTS. In support of the potential role of steroid hormones in BPH and LUTS, our studies have shown that male mice treated with testosterone + estradiol (T+E2) at doses that mimic the hormonal milieu in aging human males developed benign enlargement of the prostate that was associated with the appearance of proliferating foci along the urethra that resembled developmental prostatic buds, changes in the morphology of the prostatic peri-urethral region, and a high incidence of urinary retention. The hormone-induced mouse model also exhibited gene expression changes in the prostate that have been reported to occur in human BPH including the up-regulation of Secreted frizzled related protein 1 (Sfrp1). Ongoing studies are investigating the roles of this and other developmental signaling pathways in BPH and LUTS.

A second project in the lab utilizes a forward genetic screen in mice to identify new genes involved in prostate cancer progression using transposon-mediated insertional mutagenesis. A secondary screen is used to validate the importance of candidate genes identified using the mouse model by examining the human orthologues of the candidates for altered expression in human prostate cancers. This project has already identified new candidate oncogenes, including PDE4D, that are over-expressed in human prostate cancers. Ongoing studies include continued screens for novel prostate cancer genes, functional evaluation of candidate genes to determine their roles in prostate cancer initiation and/or progression, and the investigation of new candidate cancer genes as potential targets for drug therapies.

Background: Dr. Marker received his BA degree from Grinnell College in 1991 and his PhD in developmental biology from Stanford University in 1998. He conducted postdoctoral research on the molecular basis of prostate development and prostate cancer progression with Gerald Cunha at the University of California San Francisco from 1998-2002. From 2002-2007, he was an Assistant Professor at the University of Minnesota. He moved to the School of Pharmacy in the Fall of 2007.

Education:

  • BA 1991 - Grinnell College
  • PhD 1998 Developmental Bio - Stanford University
Highlighted Publications:
  • Powers GP and Marker PC, Recent advances in prostate development and links to prostatic diseases, WIREs Systems Biology and Medicine, Published Online: Jan 17 2013 ahead of print.
  • Buresh-Stiemke RA, Malinowskia RL, Keil KP, Vezina CM, Oosterhofc A, van Kuppevelt TH, and Marker PC, Distinct expression patterns of Sulf1 and Hs6st1 spatially regulate heparan sulfate sulfation during prostate development, Developmental Dynamics, 2012, 241: 2005-2013
  • Keil KP, Mehta V, Branham AM, Abler LL, Buresh RA, Joshi PS, Schmitz CT, Marker PC, Vezina CM, Wnt inhibitory factor 1 (Wif1) is regulated by androgens and enhances androgen-dependent prostate development, Endocrinology, 2012, available online ahead of print October 18.
  • Nicholson TM, Ricke EA, Marker PC, Miano JM, Mayer RD, Timms BG, vom Saal FS, Wood RW, Ricke WA, Testosterone and 17ß estradiol induce glandular prostatic growth, bladder outlet obstruction, and voiding dysfunction in male mice, Endocrinology, 2012, 153(11):5556-5565
  • Buresh RA, Kuslak SL, Rusch MA, Vezina CM, Selleck SB, and Marker PC, Sulfatase 1 is an inhibitor of ductal morphogenesis with sexually dimorphic expression in the urogenital sinus, Endocrinology, 2010, 151(7):3420-31
  • Buresh RA, Kuslak SL, Rusch MA, Vezina CM, Selleck SB, and Marker PC, Sulfatase 1 is an inhibitor of ductal morphogenesis with sexually dimorphic expression in the urogenital sinus, Endocrinology, 2010, 151(7):3420-31
  • Rahrmann EP, Collier LS, Knutson TP, Doyal ME, Kuslak SL, Green LE, Malinowski RL, Roethe L, Akagi K, Waknitz M, Huang W, Largaespada DA, Marker PC. Identification of PDE4D as a proliferation promoting factor in prostate cancer using a Sleeping Beauty transposon based somatic mutagenesis screen. Cancer Research, 2009; 69:4388-4397. PMCID: PMC2710962
  • Ho AM, Marker PC, Peng H, Kingsley DM, Huard J. Dominant negative Bmp5 mutation reveals a key role of BMPs in skeletal response to mechanical stimulation. BMC Developmental Biology 2008; 8:35. PMCID: PMC2335095
  • Joesting MS, Cheever TR, Volzing KG, Yamaguchi T, Wolf V, Naf D, Rubin JS, and Marker PC, Secreted frizzled related protein 1 is a paracrine modulator of epithelial branching morphogenesis, proliferation, and secretory gene expression in the prostate, 2008, Developmental Biology; 317: 161-173
  • Kuslak SL, Thielen JL, and Marker PC, The mouse seminal vesicle shape mutation is allelic with Fgfr2, Development, 2007, 134: 557-565Kuslak SL and Marker PC, Fibroblast growth factor receptor signaling through MEK-ERK is required for prostate bud induction, Differentiation, 2007, 75: 638-651
  • Thielen JL, Volzing KG, Collier LS, Green LE, Largaespada DA, and Marker PC, Markers of prostate region-specific epithelial identity define anatomical locations in the mouse prostate that are molecularly similar to human prostate cancers, Differentiation, 2007, 75: 49-61
  • Joesting MS, Perrin S, Elenbaas B, Fawell SE, Rubin JS, Franco OE, Hayward SW, Cunha GR, and Marker PC, Identification of SFRP1 as a candidate mediator of stromal-to-epithelial signaling in prostate cancer, Cancer Research, 2005, 65:10423-10430