Simon Hayward
Last active: 2/19/2015

Profile

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

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Tumor-secreted Hsp90 subverts polycomb function to drive prostate tumor growth and invasion. Nolan KD, Franco OE, Hance MW, Hayward SW, Isaacs JS (2015) J Biol Chem 290(13): 8271-82
    › Primary publication · 25670862 (PubMed) · PMC4375482 (PubMed Central)
  2. Stretching fibroblasts remodels fibronectin and alters cancer cell migration. Ao M, Brewer BM, Yang L, Franco Coronel OE, Hayward SW, Webb DJ, Li D (2015) Sci Rep : 8334
    › Primary publication · 25660754 (PubMed) · PMC4321168 (PubMed Central)
  3. Inhibition of NF-kappa B signaling restores responsiveness of castrate-resistant prostate cancer cells to anti-androgen treatment by decreasing androgen receptor-variant expression. Jin R, Yamashita H, Yu X, Wang J, Franco OE, Wang Y, Hayward SW, Matusik RJ (2015) Oncogene 34(28): 3700-10
    › Primary publication · 25220414 (PubMed) · PMC4362792 (PubMed Central)
  4. SOX2 expression in the developing, adult, as well as, diseased prostate. Yu X, Cates JM, Morrissey C, You C, Grabowska MM, Zhang J, DeGraff DJ, Strand DW, Franco OE, Lin-Tsai O, Hayward SW, Matusik RJ (2014) Prostate Cancer Prostatic Dis 17(4): 301-9
    › Primary publication · 25091041 (PubMed) · PMC4227931 (PubMed Central)
  5. Stromal androgen receptor in prostate development and cancer. Singh M, Jha R, Melamed J, Shapiro E, Hayward SW, Lee P (2014) Am J Pathol 184(10): 2598-607
    › Primary publication · 25088980 (PubMed) · PMC4188859 (PubMed Central)
  6. Hypertension is a major contributor to 20-hydroxyeicosatetraenoic acid-mediated kidney injury in diabetic nephropathy. Gangadhariah MH, Luther JM, Garcia V, Paueksakon P, Zhang MZ, Hayward SW, Love HD, Falck JR, Manthati VL, Imig JD, Schwartzman ML, Zent R, Capdevila JH, Pozzi A (2015) J Am Soc Nephrol 26(3): 597-610
    › Primary publication · 25071086 (PubMed) · PMC4341468 (PubMed Central)
  7. FOXA1 deletion in luminal epithelium causes prostatic hyperplasia and alteration of differentiated phenotype. DeGraff DJ, Grabowska MM, Case TC, Yu X, Herrick MK, Hayward WJ, Strand DW, Cates JM, Hayward SW, Gao N, Walter MA, Buttyan R, Yi Y, Kaestner KH, Matusik RJ (2014) Lab Invest 94(7): 726-39
    › Primary publication · 24840332 (PubMed) · PMC4451837 (PubMed Central)
  8. Recruitment of CD34(+) fibroblasts in tumor-associated reactive stroma: the reactive microvasculature hypothesis. San Martin R, Barron DA, Tuxhorn JA, Ressler SJ, Hayward SW, Shen X, Laucirica R, Wheeler TM, Gutierrez C, Ayala GE, Ittmann M, Rowley DR (2014) Am J Pathol 184(6): 1860-70
    › Primary publication · 24713391 (PubMed) · PMC4044710 (PubMed Central)
  9. F2-isoprostanes as a biomarker of oxidative stress in the mouse bladder. Clayton DB, Stephany HA, Ching CB, Rahman SA, Tanaka ST, Thomas JC, Pope JC, Adams MC, Brock JW, Clark PE, Hayward SW, Matusik RJ, Milne GL (2014) J Urol 191(5 Suppl): 1597-601
    › Primary publication · 24679873 (PubMed)
  10. Surgical intervention for symptomatic benign prostatic hyperplasia is correlated with expression of the AP-1 transcription factor network. Lin-Tsai O, Clark PE, Miller NL, Fowke JH, Hameed O, Hayward SW, Strand DW (2014) Prostate 74(6): 669-79
    › Primary publication · 24500928 (PubMed) · PMC4160824 (PubMed Central)
  11. ALCAM/CD166 is a TGF-β-responsive marker and functional regulator of prostate cancer metastasis to bone. Hansen AG, Arnold SA, Jiang M, Palmer TD, Ketova T, Merkel A, Pickup M, Samaras S, Shyr Y, Moses HL, Hayward SW, Sterling JA, Zijlstra A (2014) Cancer Res 74(5): 1404-15
    › Primary publication · 24385212 (PubMed) · PMC4149913 (PubMed Central)
  12. Reduction of pro-tumorigenic activity of human prostate cancer-associated fibroblasts using Dlk1 or SCUBE1. Orr B, Grace OC, Brown P, Riddick AC, Stewart GD, Franco OE, Hayward SW, Thomson AA (2013) Dis Model Mech 6(2): 530-6
    › Primary publication · 23136397 (PubMed) · PMC3597035 (PubMed Central)
  13. The stress response mediator ATF3 represses androgen signaling by binding the androgen receptor. Wang H, Jiang M, Cui H, Chen M, Buttyan R, Hayward SW, Hai T, Wang Z, Yan C (2012) Mol Cell Biol 32(16): 3190-202
    › Primary publication · 22665497 (PubMed) · PMC3434546 (PubMed Central)
  14. Androgen hormone action in prostatic carcinogenesis: stromal androgen receptors mediate prostate cancer progression, malignant transformation and metastasis. Ricke EA, Williams K, Lee YF, Couto S, Wang Y, Hayward SW, Cunha GR, Ricke WA (2012) Carcinogenesis 33(7): 1391-8
    › Primary publication · 22535887 (PubMed) · PMC3499049 (PubMed Central)
  15. Investigating prostate cancer tumour-stroma interactions: clinical and biological insights from an evolutionary game. Basanta D, Scott JG, Fishman MN, Ayala G, Hayward SW, Anderson AR (2012) Br J Cancer 106(1): 174-81
    › Primary publication · 22134510 (PubMed) · PMC3251863 (PubMed Central)
  16. Identification of stromally expressed molecules in the prostate by tag-profiling of cancer-associated fibroblasts, normal fibroblasts and fetal prostate. Orr B, Riddick AC, Stewart GD, Anderson RA, Franco OE, Hayward SW, Thomson AA (2012) Oncogene 31(9): 1130-42
    › Primary publication · 21804603 (PubMed) · PMC3307063 (PubMed Central)
  17. E2f binding-deficient Rb1 protein suppresses prostate tumor progression in vivo. Sun H, Wang Y, Chinnam M, Zhang X, Hayward SW, Foster BA, Nikitin AY, Wills M, Goodrich DW (2011) Proc Natl Acad Sci U S A 108(2): 704-9
    › Primary publication · 21187395 (PubMed) · PMC3021049 (PubMed Central)
  18. TGF-β1 induces an age-dependent inflammation of nerve ganglia and fibroplasia in the prostate gland stroma of a novel transgenic mouse. Barron DA, Strand DW, Ressler SJ, Dang TD, Hayward SW, Yang F, Ayala GE, Ittmann M, Rowley DR (2010) PLoS One 5(10): e13751
    › Primary publication · 21060787 (PubMed) · PMC2966419 (PubMed Central)
  19. Expression of pleiotrophin in the prostate is androgen regulated and it functions as an autocrine regulator of mesenchyme and cancer associated fibroblasts and as a paracrine regulator of epithelia. Orr B, Vanpoucke G, Grace OC, Smith L, Anderson RA, Riddick AC, Franco OE, Hayward SW, Thomson AA (2011) Prostate 71(3): 305-17
    › Primary publication · 20812209 (PubMed) · PMC3045659 (PubMed Central)
  20. Kinase expression and chromosomal rearrangements in papillary thyroid cancer tissues: investigations at the molecular and microscopic levels. Weier HU, Kwan J, Lu CM, Ito Y, Wang M, Baumgartner A, Hayward SW, Weier JF, Zitzelsberger HF (2009) J Physiol Pharmacol : 47-55
    › Primary publication · 20083851 (PubMed) · PMC3033354 (PubMed Central)
  21. The role of transforming growth factor-beta-mediated tumor-stroma interactions in prostate cancer progression: an integrative approach. Basanta D, Strand DW, Lukner RB, Franco OE, Cliffel DE, Ayala GE, Hayward SW, Anderson AR (2009) Cancer Res 69(17): 7111-20
    › Primary publication · 19706777 (PubMed) · PMC2748342 (PubMed Central)
  22. Methodologies in assaying prostate cancer stem cells. Li H, Jiang M, Honorio S, Patrawala L, Jeter CR, Calhoun-Davis T, Hayward SW, Tang DG (2009) Methods Mol Biol : 85-138
    › Primary publication · 19582423 (PubMed)
  23. Hypoxia and the metabolic phenotype of prostate cancer cells. Higgins LH, Withers HG, Garbens A, Love HD, Magnoni L, Hayward SW, Moyes CD (2009) Biochim Biophys Acta 1787(12): 1433-43
    › Primary publication · 19524545 (PubMed)
  24. Prostate tumor progression is mediated by a paracrine TGF-beta/Wnt3a signaling axis. Li X, Placencio V, Iturregui JM, Uwamariya C, Sharif-Afshar AR, Koyama T, Hayward SW, Bhowmick NA (2008) Oncogene 27(56): 7118-30
    › Primary publication · 18724388 (PubMed) · PMC3222150 (PubMed Central)
  25. Temporal-spatial protein expression in bladder tissue derived from embryonic stem cells. Thomas JC, Oottamasathien S, Makari JH, Honea L, Sharif-Afshar AR, Wang Y, Adams C, Wills ML, Bhowmick NA, Adams MC, Brock JW, Hayward SW, Matusik RJ, Pope JC (2008) J Urol 180(4 Suppl): 1784-9
    › Primary publication · 18721943 (PubMed)
  26. Directed differentiation of bone marrow derived mesenchymal stem cells into bladder urothelium. Anumanthan G, Makari JH, Honea L, Thomas JC, Wills ML, Bhowmick NA, Adams MC, Hayward SW, Matusik RJ, Brock JW, Pope JC (2008) J Urol 180(4 Suppl): 1778-83
    › Primary publication · 18721942 (PubMed) · PMC4802964 (PubMed Central)
  27. Critical and distinct roles of p16 and telomerase in regulating the proliferative life span of normal human prostate epithelial progenitor cells. Bhatia B, Jiang M, Suraneni M, Patrawala L, Badeaux M, Schneider-Broussard R, Multani AS, Jeter CR, Calhoun-Davis T, Hu L, Hu J, Tsavachidis S, Zhang W, Chang S, Hayward SW, Tang DG (2008) J Biol Chem 283(41): 27957-72
    › Primary publication · 18662989 (PubMed) · PMC2562067 (PubMed Central)
  28. NTP-CERHR expert panel report on the reproductive and developmental toxicity of bisphenol A. Chapin RE, Adams J, Boekelheide K, Gray LE, Hayward SW, Lees PS, McIntyre BS, Portier KM, Schnorr TM, Selevan SG, Vandenbergh JG, Woskie SR (2008) Birth Defects Res B Dev Reprod Toxicol 83(3): 157-395
    › Primary publication · 18613034 (PubMed)
  29. A role for polyploidy in the tumorigenicity of Pim-1-expressing human prostate and mammary epithelial cells. Roh M, Franco OE, Hayward SW, van der Meer R, Abdulkadir SA (2008) PLoS One 3(7): e2572
    › Primary publication · 18596907 (PubMed) · PMC2440349 (PubMed Central)
  30. Cell differentiation lineage in the prostate. Wang Y, Hayward S, Cao M, Thayer K, Cunha G (2001) Differentiation 68(4-5): 270-9
    › Primary publication · 11776479 (PubMed)
  31. Monitoring signal transduction in cancer: cDNA microarray for semiquantitative analysis. Hsieh HB, Lersch RA, Callahan DE, Hayward S, Wong M, Clark OH, Weier HU (2001) J Histochem Cytochem 49(8): 1057-8
    › Primary publication · 11457934 (PubMed)
  32. Mesenchymal-epithelial interactions in bladder smooth muscle development: effects of the local tissue environment. Baskin L, DiSandro M, Li Y, Li W, Hayward S, Cunha G (2001) J Urol 165(4): 1283-8
    › Primary publication · 11257702 (PubMed)
  33. Understanding bladder regeneration: smooth muscle ontogeny. Wu HY, Baskin LS, Liu W, Li YW, Hayward S, Cunha GR (1999) J Urol 162(3 Pt 2): 1101-5
    › Primary publication · 10458440 (PubMed)
  34. Mesenchymal-epithelial interactions in bladder smooth muscle development: epithelial specificity. DiSandro MJ, Li Y, Baskin LS, Hayward S, Cunha G (1998) J Urol 160(3 Pt 2): 1040-6; discussion 1079
    › Primary publication · 9719273 (PubMed)
  35. Androgens and masculinization of genitalia in the spotted hyaena (Crocuta crocuta). 1. Urogenital morphology and placental androgen production during fetal life. Licht P, Hayes T, Tsai P, Cunha G, Kim H, Golbus M, Hayward S, Martin MC, Jaffe RB, Glickman SE (1998) J Reprod Fertil 113(1): 105-16
    › Primary publication · 9713383 (PubMed)
  36. Phenotypic and cytogenetic characterization of a human corpus cavernosum cell line (DS-1). Dahiya R, Sikka S, Hellstrom WJ, Hayward SW, Narayan P, Tanagho EA, Lue TF (1993) Biochem Mol Biol Int 30(3): 559-69
    › Primary publication · 8401313 (PubMed)
  37. Regression of LNCaP human prostate tumor xenografts in athymic nude mice by 13-cis-retinoic acid and androgen ablation. Dahiya R, Zhang DY, Ho RJ, Haughney PC, Hayward SW, Cunha GR, Narayan P (1995) Biochem Mol Biol Int 35(3): 487-98
    › Primary publication · 7773185 (PubMed)
  38. Establishment and characterization of an immortalized but non-transformed human prostate epithelial cell line: BPH-1. Hayward SW, Dahiya R, Cunha GR, Bartek J, Deshpande N, Narayan P (1995) In Vitro Cell Dev Biol Anim 31(1): 14-24
    › Primary publication · 7535634 (PubMed)
  39. Enzyme studies in human transitional cell carcinoma of the urinary bladder. Mitchell I, Hayward S, Deshpande N, Towler JM (1989) J Urol 141(5): 1234-7
    › Primary publication · 2523490 (PubMed)
  40. Divergent effects of interferons on the growth of human benign prostatic hyperplasia cells in primary culture. Deshpande N, Hallowes RC, Cox S, Mitchell I, Hayward S, Towler JM (1989) J Urol 141(1): 157-60
    › Primary publication · 2462066 (PubMed)
  41. The effects of interferons on the activity of alpha-glycerolphosphate dehydrogenase in benign prostatic hyperplasia cells in primary culture. Hayward S, Cox S, Mitchell I, Hallowes R, Deshpande N, Towler J (1987) J Urol 138(3): 648-53
    › Primary publication · 2442423 (PubMed)
  42. A randomized clinical trial to investigate the usefulness of the addition of prednisolone to tamoxifen as adjuvants to mastectomy in primary breast cancer patients with a high risk of recurrence: a preliminary report. DiMartino L, Demontis B, Mitchell IP, Hayward SW, Deshpande N (1991) Anticancer Res 11(2): 869-72
    › Primary publication · 2064345 (PubMed)
  43. Tumor enzymes and prognosis in transitional cell carcinoma of the bladder: prediction of risk of progression in patients with superficial disease. Deshpande N, Mitchell IP, Hayward SW, Love S, Towler JM (1991) J Urol 146(5): 1247-51
    › Primary publication · 1942272 (PubMed)
  44. Effects of flutamide and hydroxy-flutamide on the growth of human benign prostatic hyperplasia cells in primary culture: a preliminary report. Hallowes R, Cox S, Hayward S, Deshpande N, Towler J (1991) Anticancer Res 11(5): 1799-805
    › Primary publication · 1722658 (PubMed)
  45. A functional model of adult human prostate epithelium. The role of androgens and stroma in architectural organisation and the maintenance of differentiated secretory function. Hayward SW, Del Buono R, Deshpande N, Hall PA (1992) J Cell Sci : 361-72
    › Primary publication · 1400638 (PubMed)