The VICC.ORG Investigator Directory

Simon W. Hayward, Ph.D.

Professor of Urologic Surgery, 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:

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