Kerry L. Burnstein, Ph.D.
Professor of Molecular & Cellular Pharmacology
Description of Research
Dr. Burnstein is interested in the mechanisms of steroid hormone receptor action in endocrine cancers. Her lab is investigating androgen receptor signaling in prostate cancer and its role in the development of therapeutic resistance. While androgen deprivation therapy for advanced prostate cancer results in tumor regression, eventually prostate cancer growth resumes in virtually all patients. The androgen receptor continues to drive cancer progression in recurrent disease. Dr. Burnstein's lab demonstrated that Vav3, a Rho GTPase guanine nucleotide exchange factor, is sufficient for prostate cancer progression following androgen deprivation therapy. Vav3 enhances the activities of androgen receptor and androgen receptor variants and promotes prostate cancer growth in vivo. Vav3 is an activator of the small Rho GTPase, Rac1, and they showed further that Rac1 causes growth of prostate tumors under conditions of androgen deprivation. Similar to findings in prostate cancer, Vav3 is also up-regulated in breast cancer compared to normal breast tissue. Vav3 and Rac1 enhance estrogen receptor and androgen receptor activities, and inhibition of Rac1 effectively inhibits cancer growth. The Burnstein lab is currently examining the molecular basis for the tumorigenic activities of Vav3/Rac1 and evaluating novel therapeutic approaches in endocrine cancers.
In ongoing studies to identify novel therapies for prostate cancer, the Burnstein lab found that the clinically relevant androgen receptor variant (AR-V7) up-regulated the arginine vasopressin receptor 1a (AVPR1a) gene. Antagonism of AVPR1a (a G protein-coupled receptor) decreased growth of aggressive prostate cancer cells in mice. The Burnstein lab is currently collaborating with Drs. Conor Lynch (Moffitt Cancer Center) and Yehia Daaka (University of Florida College of Medicine) to evaluate AVPR1a antagonism in models of bone metastatic prostate cancer.
In studies of epigenetic processes that underlie prostate cancer growth and metastasis, Dr. Burnstein’s lab demonstrated that the microRNA cluster encoding miR-23b and miR-27b specifically inhibits prostate cancer invasion and in vivo metastasis. In studies of epigenetic processes that underlie aggressive prostate cancer, Dr. Burnstein’s lab demonstrated that the microRNA cluster encoding miR-23b and miR-27b specifically inhibits prostate cancer invasion and in vivo metastasis. Her lab is currently investigating the therapeutic use of these microRNAs in pre-clinical models of metastatic prostate cancer.
- Identified elevated Vav3/Rac1 signaling to the androgen receptor as a mechanism of prostate cancer progression. Vav3 and Rac1 are novel and potentially valuable therapeutic targets. (Wu et al. JBC 2013; Rao et al. Oncogene 2012; Peacock et al. Mol Endocrinol 2012)
- Demonstrated that the microRNA-23b/-27b cluster serves as a suppressor of prostate cancer invasion and metastasis. (Ishteiwy et al. PlosOne 2012; Rice et al. Oncogene 2016)
- Showed the anti-tumor activity of novel GHRH and IGF receptor antagonists in preclinical models of prostate cancer. (Fahrenholtz et al. PNAS 2014; Fahrenholtz et al. OncoTarget 2014; Fahrenholtz et al. Molec Cancer Therapeutics 2013)
- U.S. Patent Application No. 14/811,354; Inventor(s): Kerry L. Burnstein Title: Use of Arginine Vasopressin Receptor Antagonists for the Treatment of Prostate Cancer
Selected Cancer-Related Publications
- Rosenblatt AE, Burnstein KL. Inhibition of androgen receptor transcriptional activity as a novel mechanism of action of arsenic. Mol Endocrinol 23:412-21, 2009. Read more »
- Lee JG, Zheng R, McCafferty-Cepero JM, Burnstein KL, Nanus DM, Shen R. Endothelin-1 enhances the expression of the androgen receptor via activation of the c-myc pathway in prostate cancer cells. Mol Carcinog 48:141-9, 2009. Read more »
Collaborating in the Multidisciplinary Research Program(s):