Education

AA, Cabrillo College, Aptos CA. 1984

BA, University of California, Santa Cruz 1986

PhD, University of California, Santa Cruz 1992

Post-doctoral Fellowship, Stanford University School of Medicine 1992-1996

Research Interests     

The current focus of my research is on the molecular dissection of signaling pathways in prostatic cells, the identification of prostate progenitor or stem cells, and understanding epithelial-stromal interactions in normal and abnormal ductal morphogenesis.

The three systems are highly integrated both conceptually and programmatically.  The figure is a schematic to help illustrate this point as you read below.

Signaling

Our previously published studies have used genetic models for investigating the signaling pathways involved in vitamin D growth inhibition, and also have demonstrated strong synergistic growth inhibition between vitamin D and genistein on prostatic cells.  In addition, our data demonstrate that vitamin D and genistein cooperatively induce p21 protein.  Our data also demonstrate that genistein upregulates vitamin D receptor (VDR) content by modulating protein stability.  The effect of genistein on VDR content leads to the hypothesis that one mechanism of synergism between vitamin D and genistein is by enhanced VDR signaling.  We are currently testing this hypothesis.

Stem Cells

We are developing techniques to isolate cells from the prostate with stem-cell like properties.  We have developed an in vitro 3-dimensional culture system and are currently evaluating the effects of different culture conditions on ductal morphogenesis and differentiation.  Our goal is to make fully functional prostatic structures in vitro using defined medium.  These structures should exhibit the correct histology (basal and lumenal layers) and make prostatic secretory proteins.

Epithelial Stromal Interactions

The development of normal and abnormal glandular structures in the prostate is controlled at the endocrine and paracrine levels by reciprocal interactions between epithelium and stroma.  To study these processes we have developed an efficient method of fresh human prostate tissue acquisition for reproducible isolation of cells from defined histologies.  Using this system we have demonstrated fundamental differences in the inductive capabilities of stromal cells derived from normal or diseased prostatic tissue.  Normal stromal cells have no apparent ability to induce epithelial cell growth in a prostate recombination model.  Stromal cells derived from benign prostatic hyperplasia induce sharply circumscribed structures.  Histological examination of these grafts reveals densely packed, well-organized tubular epithelium with minimal stroma, sharply demarcated from surrounding renal tissue. Stunningly, recombinants with cancer associated stromal cells produce much more robust growth than the other recombinants tested.  Histological assessment of the grafts reveals moderately differentiated, highly vascularized tumors with invasion into surrounding renal tissue.  The results support a growing body of work from a number of different epithelial tumor systems demonstrating that the tumor microenvironment, and specifically, epithelial-mesenchymal interactions are critically important for tumorigenesis.  These studies argue that more focused attention should be directed towards the nature of cancer associated stroma.  To this end we plan to compare expression profiles of the normal, BPH and cancer stromal cells to identify candidates for further study using our genetically defined systems.

Selected Publications

Barclay WW, Cramer SD 2005 Culture of mouse prostatic epithelial cells from genetically engineered mice. Prostate: 2004 Dec 14; [Epub ahead of print]

Barclay WW, Woodruff RD, Hall MC, Cramer SD.  2005 A System for Studying Epithelial-Stromal Interactions Reveals Distinct Inductive Abilities of Stromal Cells from Benign Prostatic Hyperplasia and Prostate Cancer. Endocrinology: 146: 13-18

Rao A, Coan A, Welsh J-E, Barclay WW, Koumenis C, Cramer SD.  2004 Vitamin D Receptor and p21/WAF1 are Targets of Genistein and 1,25-dihydroxyvitamin D₃ in Human Prostate Cancer Cells.   Cancer Research: 64:2143-2147

Cramer SD, Chang B-L, Rao A, Hawkins GA, Zheng SL, Wade WN, Cooke R, Thomas LN, Bleeker ER, Catalona WJ, Sterling DA, Meyers DA, Ohar J, Xu J. 2003 Association Between Genetic Polymorphism in the Prostate-Specific Antigen Gene Promoter and Serum Prostate-Specific Antigen Levels.  The Journal of the National Cancer Institute: 95(14):1044-53.

Rao A, Chang B-L, Hawkins G, Hu JJ, Rosser CJ, Hall, MC, Meyers DA, Xu JF,  Cramer SD.   2003 Analysis of the G/A Polymorphism in the Androgen Response Element I of the PSA Gene and Its Interactions with Androgen Receptor Polymorphisms.  Urology:61:864-869

Wade WN, Kute T. Koumenis C, Willingham MC, Cramer SD. 2002  p27Kip1 is Essential for the Antiproliferative Action of 1,25-dihydroxyvitamin D3 in Primary but not Immortalized Mouse Fibroblasts.  Journal of Biological Chemistry: 277:37301-37306.

Rao A, Woodruff RD, Wade WN, Kute TE, Cramer SD, 2002 Synergistic Inhibition of Prostatic Epithelial Cell Growth by Genistein and Vitamin D.  Journal of Nutrition: 132:3191-3194.

Webster KE, Ferree PM, Holmes RP, Cramer SD 2000 Identification of Missense, Nonsense, and Deletion Mutations in the GRHPR Gene in Patients with Primary Hyperoxaluria Type II (PH2). Human Genetics: 107:176-185

Barreto AM, Woodruff R, Schwartz GG, Cramer SD.  2000 25-Hydroxyvitamin D3, the Prohormone of 1,25-Dihydroxyvitamin D3, Inhibits the Proliferation of Primary Prostatic Epithelial Cells.  Cancer Epidemiology, Biomarkers, & Prevention:9:265-270

Cramer SD, Ferree P, Lin K, Milliner D, Holmes RP. 1999 The Gene encoding Hydroxypyruvate Reductase (GRHPR) is Mutated in Patients with Primary Hyperoxaluria Type II.  Human Molecular Genetics: 8:2063-2069
 
 
   

Phone: 336-713-7651
e-mail address: scramer@wfubmc.edu

Updated 1/2005