Paul C Marker, PhD
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 endocrine hormones and paracrine hormones in regulating the biology of prostatic epithelial 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. Ongoing studies in this area are collaborative effort within the U54 GEORGE M. O’BRIEN CENTER FOR BENIGN UROLOGY RESEARCH that brings together investigators from the University of Wisconsin-Madison Schools of Pharmacy, Medicine and Public Health, and Veterinary Medicine as well as investigators from the University of Massachusetts-Boston and the University of Texas-Southwestern.
A second project in the lab focuses on the role of the Growth Hormone (GH)/IGF-1 axis in prostate and breast cancers. We are using mouse genetics, human patient samples, and other preclinical models to investigate the role of the GH/IGF-1 axis in these cancers as well as the molecular mechanisms regulated by this pathway that contribute to cancer progression and chemotherapy resistance. Genetic and epidemiological studies in humans support the concept that the GH/IGF-1 axis contributes in some way to breast and prostate cancer initiation and/or progression. Studies using animal models have shown that mice and rats that lack functional GH or GHR have dramatically impaired progression of experimentally induced breast and prostate carcinogenesis indicating that an intact GH/IGF-1 axis is required for cancer progression. In addition, data from The Cancer Genome Atlas (TCGA) project also show increased GHR expression in prostate cancers with ERG-fusion genes or ETV1-fusion genes that represent about half of prostate cancer cases. Together with our recently published data that show dramatically increased tumor growth when mGhr is modestly overexpressed in prostate cancer xenografts, these data further support the concept that alterations in the GH/IGF-1 axis including increased GHR expression may directly contribute to prostate cancer progression. Our ongoing research in these areas are significant because they will clarify the best ways to employ pegvisomant, a GHR antagonist approved by the FDA for the treatment of acromegaly, or other agents targeting the GH/IGF-1 axis for the treatment of breast and/or prostate cancers. In addition, our ongoing studies will create a new clinically relevant mouse prostate cancer model that recapitulates genetic and gene expression changes commonly observed in human prostate cancer.
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.
- BA 1991 - Grinnell College
- PhD 1998 Developmental Bio - Stanford University
- Unterberger CJ, McIlwain SJ, Tsourkas PK, Maklakova VI, Prince JL, Onesti A, Hu R, Kopchick JJ, Swanson SM, Marker PC. Conditional gene regulation models demonstrate a pro-proliferative role for growth hormone receptor in prostate cancer. Prostate. 2022 Dec 22;. doi: 10.1002/pros.24474. [Epub ahead of print] PubMed PMID: 36562110; NIHMSID:NIHMS1858851.
- Unterberger CJ, McGregor SM, Kopchick JJ, Swanson SM, Marker PC. Mammary Tumor Growth and Proliferation Are Dependent on Growth Hormone in Female SV40 C3(1) T-Antigen Mice. Endocrinology. 2022 Dec 19;164(2). doi: 10.1210/endocr/bqac174. PubMed PMID: 36269749; PubMed Central PMCID: PMC9923789.
- Unterberger CJ, Maklakova VI, Lazar M, Arneson PD, Mcilwain SJ, Tsourkas PK, Hu R, Kopchick JJ, Swanson SM, Marker PC. GH Action in Prostate Cancer Cells Promotes Proliferation, Limits Apoptosis, and Regulates Cancer-related Gene Expression. Endocrinology. 2022 May 1;163(5). doi: 10.1210/endocr/bqac031. PubMed PMID: 35383352; PubMed Central PMCID: PMC8995093.
- Repp L, Unterberger CJ, Ye Z, Feltenberger JB, Swanson SM, Marker PC, Kwon GS. Oligo(Lactic Acid)8-Docetaxel Prodrug-Loaded PEG-b-PLA Micelles for Prostate Cancer. Nanomaterials (Basel). 2021 Oct 17;11(10). doi: 10.3390/nano11102745. PubMed PMID: 34685195; PubMed Central PMCID: PMC8540550.
- Lantvit DD, Unterberger CJ, Lazar M, Arneson PD, Longhurst CA, Swanson SM, Marker PC. Mammary Tumors Growing in the Absence of Growth Hormone Are More Sensitive to Doxorubicin Than Wild-Type Tumors. Endocrinology. 2021 Apr 1;162(4). doi: 10.1210/endocr/bqab013. PubMed PMID: 33475144; PubMed Central PMCID: PMC7881836.
- Wegner KA, Ruetten H, Girardi NM, O'Driscoll CA, Sandhu JK, Turco AE, Abler LL, Wang P, Wang Z, Bjorling DE, Malinowski R, Peterson RE, Strand DW, Marker PC, Vezina CM. Genetic background but not prostatic epithelial beta-catenin influences susceptibility of male mice to testosterone and estradiol-induced urinary dysfunction. Am J Clin Exp Urol. 2021;9(1):121-131. eCollection 2021. PubMed PMID: 33816700; PubMed Central PMCID: PMC8012832.
- Wei P, Hao L, Thomas S, Buchberger AR, Steinke L, Marker PC, Ricke WA, Li L. Urinary Amine Metabolomics Characterization with Custom 12-Plex Isobaric DiLeu Labeling. J Am Soc Mass Spectrom. 2020 Sep 2;31(9):1854-1860. doi: 10.1021/jasms.0c00110. Epub 2020 Aug 4. PubMed PMID: 32678615; PubMed Central PMCID: PMC7484200.
- Thomas S, Hao L, DeLaney K, McLean D, Steinke L, Marker PC, Vezina CM, Li L, Ricke WA. Spatiotemporal Proteomics Reveals the Molecular Consequences of Hormone Treatment in a Mouse Model of Lower Urinary Tract Dysfunction. J Proteome Res. 2020 Apr 3;19(4):1375-1382. doi: 10.1021/acs.jproteome.9b00451. Epub 2020 Mar 16. PubMed PMID: 32108482; PubMed Central PMCID: PMC7339119.
- Ruetten H, Wegner KA, Kennedy CL, Turco A, Zhang HL, Wang P, Sandhu J, Sandhu S, Morkrid J, Wang Z, Macoska J, Peterson RE, Bjorling DE, Ricke WA, Marker PC, Vezina CM. Impact of sex, androgens, and prostate size on C57BL/6J mouse urinary physiology: urethral histology. Am J Physiol Renal Physiol.2020 Mar 1;318(3):F617-F627. doi: 10.1152/ajprenal.00540.2019. Epub 2020 Jan 6. PubMed PMID: 31904290; PubMed Central PMCID: PMC7099510.
- Wegner KA, Mueller BR, Unterberger CJ, Avila EJ, Ruetten H, Turco AE, Oakes SR, Girardi NM, Halberg RB, Swanson SM, Marker PC, Vezina CM. Prostate epithelial-specific expression of activated PI3K drives stromal collagen production and accumulation. J Pathol. 2020 Fe 250(2):231-242. doi: 10.1002/path.5363. Epub 2019 Nov 28. PubMed PMID: 31674011; PubMed Central PMCID: PMC7071816.
- Complete List of Published Work in MyBibliography:https://www.ncbi.nlm.nih.gov/myncbi/1zWdjnynYDrAg/bibliography/public/