Simon W. Hayward : Vanderbilt-Ingram Cancer Center

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Simon W. Hayward, Ph.D.

Associate Professor of Urologic Surgery and Cancer Biology
VICC Member
Researcher

Contact Information:

Vanderbilt University Medical Center
A-1302 Medical Center North
Nashville, TN 37232-2765
615-322-5823

Research Specialty

Prostate cancer, Stromal-epithelial interactions, in vivo models, tissue recombination, retroviral vectors.

Research Description

Research interests in my laboratory center around the relationships between the various cell types which comprise developing and adult prostate and the ways in which these change in development, benign disease and carcinogenesis. We can understand many aspects of biology only in a "whole organism" context and thus to examine these complex intercellular interaction problems in vivo models are essential. We use a number of different in vivo systems including xenografts of benign and malignant human tissues and applications of tissue recombination technology, an expertise for which we have been recognized by the National Cancer Institute as a national training resource.

Stromal-epithelial interactions are central determinants of organogenesis, development, and growth quiescence in adulthood. Such interactions also play a pivotal role in cancer progression. Stromal cells surrounding prostate tumors act to promote the growth of cancer foci. Much of the current work in the laboratory centers around the elucidating the mechanisms underlying this process. We are beginning to appreciate that signaling occurs between many different cell types. Previous studies have focussed upon paracrine signaling between stromal and epithelial cell populations, however we are now also starting to appreciate the role of juxtacrine signaling between different populations of stromal cells in informing the overall paracrine signaling environment. One of the long term aims of this laboratory is to understand the nature of these interactions and thus identify targets which direct therapy at the stromal compartment of the affected organ rather than at the tumor epithelium. This brings the prospect of perhaps restraining tumor growth and turning cancer into a chronic but treatable disease.

Tissue recombination and grafting, allows us to "mix and match" stromal and epithelial cells from different sources (different species, tissues and disease states) and to grow these in immunocompromised mice. We are able to genetically manipulate cells, either expressing or suppressing genes of interest in specific cell populations or sub-populations, to examine tissue specific gene functions. A number of examples of this technique are described in the references below.

Current projects in the laboratory include an examination of the role of TGFß signaling as a master regulator of the tumor microenvironment in prostatic carcinogenesis. This work is a part of the National Cancer Institute’s Tumor Microenvironment Network, a multi-center program which, at Vanderbilt, includes the Matrisian, Moses, Mundy, Bhowmick and Hayward laboratories. We are also interested in the role of TGFß signaling in benign prostatic hyperplasia. Additional projects include explorations of the potential of various oncogenes expressed in either stromal or epithelial cells to promote prostatic carcinogenesis and an examination of the potential of regulation of PPAR-gamma as a chemopreventive approach to prostate cancer.

Publications

Mullins, C, Lucia, MS, Hayward, SW, Lee, JY, Levitt, JM, Lin, VK, Liu, BC, Chinnaiyan, AM, Rubin, MA, Slawin, K, Star, RA, Getzenberg, RH, , A comprehensive approach toward novel serum biomarkers for benign prostatic hyperplasia: the MPSA Consortium. J Urol, 179(4), 1243-56, 2008.
Jin, RJ, Lho, Y, Wang, Y, Ao, M, Revelo, MP, Hayward, SW, Wills, ML, Logan, SK, Zhang, P, Matusik, RJ Down-regulation of p57Kip2 induces prostate cancer in the mouse. Cancer Res, 68(10), 3601-8, 2008.
Placencio, VR, Sharif-Afshar, AR, Li, X, Huang, H, Uwamariya, C, Neilson, EG, Shen, MM, Matusik, RJ, Hayward, SW, Bhowmick, NA Stromal transforming growth factor-beta signaling mediates prostatic response to androgen ablation by paracrine Wnt activity. Cancer Res, 68(12), 4709-18, 2008.
Cannon, GW, Mullins, C, Lucia, MS, Hayward, SW, Lin, V, Liu, BC, Slawin, K, Rubin, MA, Getzenberg, RH A preliminary study of JM-27: a serum marker that can specifically identify men with symptomatic benign prostatic hyperplasia. J Urol, 177(2), 610-4; discussion 614, 2007.
Ao, M, Franco, OE, Park, D, Raman, D, Williams, K, Hayward, SW Cross-talk between paracrine-acting cytokine and chemokine pathways promotes malignancy in benign human prostatic epithelium. Cancer Res, 67(9), 4244-53, 2007.
Oottamasathien, S, Wang, Y, Williams, K, Franco, OE, Wills, ML, Thomas, JC, Saba, K, Sharif-Afshar, AR, Makari, JH, Bhowmick, NA, Demarco, RT, Hipkens, S, Magnuson, M, Brock, JW, Hayward, SW, Pope, JC, Matusik, RJ Directed differentiation of embryonic stem cells into bladder tissue. Dev Biol, 2007.
He, Y, Franco, OE, Jiang, M, Williams, K, Love, HD, Coleman, IM, Nelson, PS, Hayward, SW Tissue-specific consequences of cyclin D1 overexpression in prostate cancer progression. Cancer Res, 67(17), 8188-97, 2007.
Vanpoucke, G, Orr, B, Grace, OC, Chan, R, Ashley, GR, Williams, K, Franco, OE, Hayward, SW, Thomson, AA Transcriptional profiling of inductive mesenchyme to identify molecules involved in prostate development and disease. Genome Biol, 8(10), R213, 2007.
Oottamasathien, S, Williams, K, Franco, OE, Wills, ML, Thomas, JC, Sharif-Afshar, AR, DeMarco, RT, Brock, JW, Bhowmick, NA, Hayward, SW, Pope, JC Urothelial inhibition of transforming growth factor-beta in a bladder tissue recombination model. J Urol, 178(4 Pt 2), 1643-9, 2007.
Sun, H, Chang, Y, Schweers, B, Dyer, MA, Zhang, X, Hayward, SW, Goodrich, DW An E2F Binding-Deficient Rb1 Protein Partially Rescues Developmental Defects Associated with Rb1 Nullizygosity. Mol Cell Biol, 26(4), 1527-37, 2006.
Wang, Y, Kasper, S, Yuan, J, Jin, RJ, Zhang, J, Ishii, K, Wills, ML, Hayward, SW, Matusik, RJ Androgen-dependent prostate epithelial cell selection by targeting ARR(2)PBneo to the LPB-Tag model of prostate cancer. Lab Invest, 86(10), 1074-88, 2006.
Oottamasathien, S, Williams, K, Franco, OE, Thomas, JC, Saba, K, Bhowmick, NA, Staack, A, Demarco, RT, Brock, JW, Hayward, SW, Pope, JC Bladder tissue formation from cultured bladder urothelium. Dev Dyn, 235(10), 2795-801, 2006.
Ao, M, Williams, K, Bhowmick, NA, Hayward, SW Transforming Growth Factor-{beta} Promotes Invasion in Tumorigenic but not in Nontumorigenic Human Prostatic Epithelial Cells. Cancer Res, 66(16), 8007-16, 2006.
Wang, Y, Xue, H, Cutz, JC, Bayani, J, Mawji, NR, Chen, WG, Goetz, LJ, Hayward, SW, Sadar, MD, Gilks, CB, Gout, PW, Squire, JA, Cunha, GR, Wang, YZ An orthotopic metastatic prostate cancer model in SCID mice via grafting of a transplantable human prostate tumor line. Lab Invest, 85(11), 1392-404, 2005.
Wang, Y, Revelo, MP, Sudilovsky, D, Cao, M, Chen, WG, Goetz, L, Xue, H, Sadar, M, Shappell, SB, Cunha, GR, Hayward, SW Development and characterization of efficient xenograft models for benign and malignant human prostate tissue. Prostate, 64(2), 149-59, 2005.
Davis, JN, McCabe, MT, Hayward, SW, Park, JM, Day, ML Disruption of Rb/E2F pathway results in increased cyclooxygenase-2 expression and activity in prostate epithelial cells. Cancer Res, 65(9), 3633-42, 2005.
Gao, N, Ishii, K, Mirosevich, J, Kuwajima, S, Oppenheimer, SR, Roberts, RL, Jiang, M, Yu, X, Shappell, SB, Caprioli, RM, Stoffel, M, Hayward, SW, Matusik, RJ Forkhead box A1 regulates prostate ductal morphogenesis and promotes epithelial cell maturation. Development, 132(15), 3431-43, 2005.
Ricke, WA, Wang, Y, Kurita, T, Hayward, SW, Cunha, GR Hormonal and stromal regulation of normal and neoplastic prostatic growth. Prog Mol Subcell Biol, 40183-216, 2005.
Joesting, MS, Perrin, S, Elenbaas, B, Fawell, SE, Rubin, JS, Franco, OE, Hayward, SW, Cunha, GR, Marker, PC Identification of SFRP1 as a candidate mediator of stromal-to-epithelial signaling in prostate cancer. Cancer Res, 65(22), 10423-30, 2005.
Cheng, N, Bhowmick, NA, Chytil, A, Gorksa, AE, Brown, KA, Muraoka, R, Arteaga, CL, Neilson, EG, Hayward, SW, Moses, HL Loss of TGF-beta type II receptor in fibroblasts promotes mammary carcinoma growth and invasion through upregulation of TGF-alpha-, MSP- and HGF-mediated signaling networks. Oncogene, 245053-5068, 2005.
Staack, A, Hayward, SW, Baskin, LS, Cunha, GR Molecular, cellular and developmental biology of urothelium as a basis of bladder regeneration. Differentiation, 73(4), 121-33, 2005.
Ricke, WA, Ishii, K, Ricke, EA, Simko, J, Wang, Y, Hayward, SW, Cunha, GR Steroid hormones stimulate human prostate cancer progression and metastasis. Int J Cancer, 2005.
Williams, K, Fernandez, S, Stien, X, Ishii, K, Love, HD, Lau, YF, Roberts, RL, Hayward, SW Unopposed c-MYC expression in benign prostatic epithelium causes a cancer phenotype. Prostate, 63(4), 369-84, 2005.
Ishii, K, Shappell, SB, Matusik, RJ, Hayward, SW Use of tissue recombination to predict phenotypes of transgenic mouse models of prostate carcinoma. Lab Invest, 851086-1103, 2005.
Jiang, Ming, Shappell, Scott B, Hayward, Simon W Approaches to understanding the importance and clinical implications of peroxisome proliferator-activated receptor gamma (PPARgamma) signaling in prostate cancer. J Cell Biochem, 91(3), 513-27, 2004.
Ishii, Kenichiro, Otsuka, Takashi, Iguchi, Kazuhiro, Usui, Shigeyuki, Yamamoto, Hajime, Sugimura, Yoshiki, Yoshikawa, Kazuhiro, Hayward, Simon W, Hirano, Kazuyuki Evidence that the prostate-specific antigen (PSA)/Zn2+ axis may play a role in human prostate cancer cell invasion. Cancer Lett, 207(1), 79-87, 2004.
Cunha, GR, Ricke, W, Thomson, A, Marker, PC, Risbridger, G, Hayward, SW, Wang, YZ, Donjacour, AA, Kurita, T Hormonal, cellular, and molecular regulation of normal and neoplastic prostatic development. J Steroid Biochem Mol Biol, 92(4), 221-36, 2004.
Jin, RJ, Wang, Y, Masumori, N, Ishii, K, Tsukamoto, T, Shappell, SB, Hayward, SW, Kasper, S, Matusik, RJ NE-10 neuroendocrine cancer promotes the LNCaP xenograft growth in castrated mice. Cancer Res, 64(15), 5489-95, 2004.
Staack, Andrea, Kassis, Adrienne P, Olshen, Adam, Wang, Yuzhuo, Wu, David, Carroll, Peter R, Grossfeld, Gary D, Cunha, Gerald R, Hayward, Simon W Quantitation of apoptotic activity following castration in human prostatic tissue in vivo. Prostate, 54(3), 212-9, 2003.
Hayward, Simon W, Wang, Yuzhuo, Day, Mark L Rescue and isolation of Rb-deficient prostate epithelium by tissue recombination. Methods Mol Biol, 21817-33, 2003.
Cunha, Gerald R, Hayward, Simon W, Wang, Y Z, Ricke, William A Role of the stromal microenvironment in carcinogenesis of the prostate. Int J Cancer, 107(1), 1-10, 2003.
Hayward, Simon W Approaches to modeling stromal-epithelial interactions. J Urol, 168(3), 1165-72, 2002.
Shou, Jianyong, Soriano, Robert, Hayward, Simon W, Cunha, Gerald R, Williams, P Mickey, Gao, Wei-Qiang Expression profiling of a human cell line model of prostatic cancer reveals a direct involvement of interferon signaling in prostate tumor progression. Proc Natl Acad Sci U S A, 99(5), 2830-5, 2002.
Kim, Minjung J, Bhatia-Gaur, Rajula, Banach-Petrosky, Whitney A, Desai, Nishita, Wang, Yuzhuo, Hayward, Simon W, Cunha, Gerald R, Cardiff, Robert D, Shen, Michael M, Abate-Shen, Cory Nkx3.1 mutant mice recapitulate early stages of prostate carcinogenesis. Cancer Res, 62(11), 2999-3004, 2002.
Day, Kathleen C, McCabe, Michael T, Zhao, Xin, Wang, Yuzhuo, Davis, Joanne N, Phillips, John, Von Geldern, Marion, Ried, Thomas, KuKuruga, Mark A, Cunha, Gerald R, Hayward, Simon W, Day, Mark L Rescue of embryonic epithelium reveals that the homozygous deletion of the retinoblastoma gene confers growth factor independence and immortality but does not influence epithelial differentiation or tissue morphogenesis. J Biol Chem, 277(46), 44475-84, 2002.
Cunha, Gerald R, Hayward, Simon W, Wang, Y Z Role of stroma in carcinogenesis of the prostate. Differentiation, 70(9-10), 473-85, 2002.
Wang, Y, Sudilovsky, D, Zhang, B, Haughney, P C, Rosen, M A, Wu, D S, Cunha, T J, Dahiya, R, Cunha, G R, Hayward, S W A human prostatic epithelial model of hormonal carcinogenesis. Cancer Res, 61(16), 6064-72, 2001.
Cunha, G R, Wang, Y Z, Hayward, S W, Risbridger, G P Estrogenic effects on prostatic differentiation and carcinogenesis. Reprod Fertil Dev, 13(4), 285-96, 2001.
Hayward, S W, Wang, Y, Cao, M, Hom, Y K, Zhang, B, Grossfeld, G D, Sudilovsky, D, Cunha, G R Malignant transformation in a nontumorigenic human prostatic epithelial cell line. Cancer Res, 61(22), 8135-42, 2001.
Phillips, J L, Hayward, S W, Wang, Y, Vasselli, J, Pavlovich, C, Padilla-Nash, H, Pezullo, J R, Ghadimi, B M, Grossfeld, G D, Rivera, A, Linehan, W M, Cunha, G R, Ried, T The consequences of chromosomal aneuploidy on gene expression profiles in a cell line model for prostate carcinogenesis. Cancer Res, 61(22), 8143-9, 2001.
Li, Y, Liu, W, Hayward, S W, Cunha, G R, Baskin, L S Plasticity of the urothelial phenotype: effects of gastro-intestinal mesenchyme/stroma and implications for urinary tract reconstruction. Differentiation, 66(2-3), 126-35, 2000.
Wang, Y, Hayward, S W, Donjacour, A A, Young, P, Jacks, T, Sage, J, Dahiya, R, Cardiff, R D, Day, M L, Cunha, G R Sex hormone-induced carcinogenesis in Rb-deficient prostate tissue. Cancer Res, 60(21), 6008-17, 2000.
Hayward, S W, Cunha, G R The prostate: development and physiology. Radiol Clin North Am, 38(1), 1-14, 2000.
Olumi, A F, Grossfeld, G D, Hayward, S W, Carroll, P R, Tlsty, T D, Cunha, G R Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res, 59(19), 5002-11, 1999.
Baskin, L S, Hayward, S W, DiSandro, M S, Li, Y W, Cunha, G R Epithelial-mesenchymal interactions in the bladder. Implications for bladder augmentation. Adv Exp Med Biol, 46249-61, 1999.
Hayward, S W Overview of cancer of the bladder. Adv Exp Med Biol, 462395-7, 1999.
Hayward, S W, Haughney, P C, Lopes, E S, Danielpour, D, Cunha, G R The rat prostatic epithelial cell line NRP-152 can differentiate in vivo in response to its stromal environment. Prostate, 39(3), 205-12, 1999.
Hayward, S W A simple method for freezing and storing viable tissue fragments. In Vitro Cell Dev Biol Anim, 34(1), 28-9, 1998.
Kopachik, W, Hayward, S W, Cunha, G R Expression of hepatocyte nuclear factor-3alpha in rat prostate, seminal vesicle, and bladder. Dev Dyn, 211(2), 131-40, 1998.
Hayward, S W, Grossfeld, G D, Tlsty, T D, Cunha, G R Genetic and epigenetic influences in prostatic carcinogenesis (review). Int J Oncol, 13(1), 35-47, 1998.
Hayward, S W, Haughney, P C, Rosen, M A, Greulich, K M, Weier, H U, Dahiya, R, Cunha, G R Interactions between adult human prostatic epithelium and rat urogenital sinus mesenchyme in a tissue recombination model. Differentiation, 63(3), 131-40, 1998.
Haughney, P C, Hayward, S W, Dahiya, R, Cunha, G R Species-specific detection of growth factor gene expression in developing murine prostatic tissue. Biol Reprod, 59(1), 93-9, 1998.
Baskin, L S, Hayward, S W, Sutherland, R A, DiSandro, M S, Thomson, A A Cellular signaling in the bladdeR. Front Biosci, 2d592-5, 1997.
Baskin, L S, Sutherland, R S, Thomson, A A, Nguyen, H T, Morgan, D M, Hayward, S W, Hom, Y K, DiSandro, M, Cunha, G R Growth factors in bladder wound healing. J Urol, 157(6), 2388-95, 1997.
Hayward, S W, Rosen, M A, Cunha, G R Stromal-epithelial interactions in the normal and neoplastic prostate. Br J Urol, 79 Suppl 218-26, 1997.
Baskin, L S, Sutherland, R S, DiSandro, M J, Hayward, S W, Lipschutz, J, Cunha, G R The effect of testosterone on androgen receptors and human penile growth. J Urol, 158(3 Pt 2), 1113-8, 1997.
Sutherland, R S, Baskin, L S, Elfman, F, Hayward, S W, Cunha, G R The role of type IV collagenases in rat bladder development and obstruction. Pediatr Res, 41(3), 430-4, 1997.
Hayward, SW, Brody, JR, Cunha, GR An edgewise look at basal epithelial cells: three-dimensional views of the rat prostate, mammary gland and salivary gland. Differentiation, 60(4), 219-27, 1996.
Hayward, SW, Baskin, LS, Haughney, PC, Cunha, AR, Foster, BA, Dahiya, R, Prins, GS, Cunha, GR Epithelial development in the rat ventral prostate, anterior prostate and seminal vesicle. Acta Anat (Basel), 155(2), 81-93, 1996.
Baskin, L S, Sutherland, R S, Thomson, A A, Hayward, S W, Cunha, G R Growth factors and receptors in bladder development and obstruction. Lab Invest, 75(2), 157-66, 1996.
Baskin, L S, Hayward, S W, Sutherland, R A, DiSandro, M J, Thomson, A A, Goodman, J, Cunha, G R Mesenchymal-epithelial interactions in the bladder. World J Urol, 14(5), 301-9, 1996.
Hayward, S W, Cunha, G R, Dahiya, R Normal development and carcinogenesis of the prostate. A unifying hypothesis. Ann N Y Acad Sci, 78450-62, 1996.
Baskin, L S, Hayward, S W, Young, P F, Cunha, G R Ontogeny of the rat bladder: smooth muscle and epithelial differentiation. Acta Anat (Basel), 155(3), 163-71, 1996.
Sutherland, RS, Baskin, LS, Hayward, SW, Cunha, GR Regeneration of bladder urothelium, smooth muscle, blood vessels and nerves into an acellular tissue matrix. J Urol, 156(2 Pt 2), 571-7, 1996.
Baskin, L S, Hayward, S W, Young, P, Cunha, G R Role of mesenchymal-epithelial interactions in normal bladder development. J Urol, 156(5), 1820-7, 1996.
Cunha, G R, Hayward, S W, Dahiya, R, Foster, B A Smooth muscle-epithelial interactions in normal and neoplastic prostatic development. Acta Anat (Basel), 155(1), 63-72, 1996.
Hayward, SW, Baskin, LS, Haughney, PC, Foster, BA, Cunha, AR, Dahiya, R, Prins, GS, Cunha, GR Stromal development in the ventral prostate, anterior prostate and seminal vesicle of the rat. Acta Anat (Basel), 155(2), 94-103, 1996.

Vanderbilt-Ingram Cancer Center