Robert A. Sikes, Ph.D.

Teaching

  • BISC 401 - Molecular Biology of the Cell
  • BISC 625 - Cancer Biology

Research Interests

The "Lethal Phenotype" of cancer is a direct consequence of cancer spreading to secondary sites, a process called metastasis. Lethal prostate cancer is no exception. The number of men affected by prostate cancer is staggering. In North America, there are approximately 240,000 new cases of prostate cancer in 2011 and around 33,000 deaths. This translates into a 1 in 6 lifetime chance of acquiring prostate cancer if you are an American male. This translates into >27 new cases of prostate cancer diagnosed every hour of every day. These numbers are going to increase as our population ages.

Initially, prostate cancer is sensitive to the levels of male steroid hormones or androgens. Removal of the androgens (Male Sex Hormones), by surgical or chemical castration, is still a gold standard for therapy in cases of advanced prostate cancer. For a time, the cancer responds by regressing under the conditions of androgen deprivation, however, the cancer invariably adapts and continues growing in the absence of androgens or in the presence of reduced levels of androgens. The cancer has now shifted from being androgen dependent or sensitive to an androgen insensitive or castration resistant state. The development of metastases, cancer deposits away from the initial prostate cancer, along with the shift from androgen sensitive to castrate resistance is termed progression.

Research in my laboratory is concerned with the mechanism(s) that contribute to the development of advanced and castrate resistant prostate cancer as defined above. The following areas of research are actively being pursued:

  1. The role of growth factor presentation and signaling in the development of aggressive, lethal phenotype of prostate cancer and metastasis to bone. Specifically, we are interested in the signaling interplay of TGF beta family members between bone marrow stromal cells and prostate cancer cells.
  2. We are examining several novel transmembrane proteins for their role in cancer migration and invasion. These include G-protein coupled receptors involved in purinergic/pyrimidinergic signaling as well as the accessory proteins of the voltage sensitive ion channel family, principally beta-2.
  3. Steps in gland development mimic cancer invasion. We are examining the expression of prostate precursor tissues or Urogenital Sinus (UGS)-for genes involved in shaping tissues and controlling cancer behavior.

Current Projects

  • IGF and TGFβ in prostate cancer progression and the colonization of bone - By mediating the mesenchymal transition of prostate cancer cells, TGFβ influences cell adhesion to and extravasation through endothelial cells. The signaling mediating this process is poorly understood. We now believe that these events are mediated in part by Smad independent signaling involving Rho GTPases. IGF1 is a survival factor for prostate cancer and appears o play a critical role in the survival of prostate cancer in the bone. We are examining receptor blockade to interfere with this process.
  • Role of novel extracellular adhesion molecules in prostate cancer progression and perineural migration - 85% of prostate cancer has histological evidence of direct association with peripheral nerve bundles. We are examining the molecules hat mediate this association and mediate prostate cancer metastasis.
  • Prostate cancer interactions with the bone microenvironment - This project examines factors that mediate prostate cancer cell death and neuroendocrine differentiation of prostate cancer cells through interactions with bone marrow stromal cells.
  • Ligand-independent effects of insulin-like growth factor binding protein 2 and androgen in prostate cancer progression - Structural analysis of IGFBP-2 with respect to cell aggressiveness and signaling.

Research Group

  • Madhura Joglekar, Ph.D.-Post-doctoral fellow-Preclinical deveopment of novel anti-androgens
  • Anshul Arora, Ph.D.-Post-doctoral fellow- Preclinical development of anti-androgens; bone marrow stromal interactions with prostate cancer
  • Jomnarang Lertsuwan, B.S. Graduate Student (B.S., Thailand)-purinergic signaling and breast cancer metastasis, racial disparity
  • Kornkamon Nopmonkol, B.S.-Graduate Student (B.S., Thailand)-isolation and purification of toxic bone stromal cell factors
  • Senem Kurtoglu, B.S.- Graduate Student (B.S. Turkey)-Mechanisms of TGF beta driven suppression of stromal cell toxicity
  • Meghan Kirk- Undergraduate, role of beta 2 in perineural invasion and PCa metastasis.
  • Irene Marwa- Undergraduate, solation and purification of toxic bone stromal cell factors
  • Stefan Feliciano-Undergraduate, RNA seq analysis of TGF beta effects on one marrow stromal cells
  • Erin Moffet-Undergraduate, RNA seq analysis of TGF beta effects on one marrow stromal cells
  • John Favate-Undergraduate, role of endoglin in bone marrow stromal cell killing of prostate cancer cells

Selected Publications

Associate Professor
Director, Center for Translational Cancer Research
Senior Research Scientist, Helen F. Graham Cancer Center, Christiana Care Health System

Phone: (302) 831-6050

Fax: (302) 831-2281

Email: rasikes@udel.edu

Office: 326 Wolf Hall

Lab: 333 Wolf Hall

Address:
Department of Biological Sciences
326 Wolf Hall
University of Delaware
Newark, DE 19716

Education

  • B.A. - University of Colorado
  • Ph.D. - University of Texas
  • Postdoctoral - University of Texas, Health Science Center
  • Postdoctoral - University of Texas, M.D. Anderson Cancer Center