Irina Agoulnik, Ph.D.

Irina Agoulnik, Ph.D., is cancer researcher and cell biologist, and is widely published in top academic journals on the subjects of prostate cancer and steroid receptor signaling. Her current research examines hormone resistance in prostate cancer. Hormone refractory prostate cancer, which occurs when hormone therapy fails to stop the growth of prostate cancer, is incurable and the main cause of death among prostate cancer patients. The research in Agoulnik's laboratory is supported by the National Cancer Institute and focused on the role of androgen receptors and their co-regulators in prostate cancer progression.

Education

Postdoctoral fellowship, Baylor College of Medicine
Ph.D., Institute of Cytology and Genetics, Russia

Research

To date endocrine cancers are the most common noncutaneous malignancies in men and women. These cancers originate from epithelial compartments in breast, ovary, and prostate and require steroid receptor for maintenance and proliferation. As such, therapies targeting the steroid receptor signaling remain the cornerstone of therapeutic intervention in the management of advanced prostate and breast tumors. In our lab we study why breast and prostate tumors eventually fail antihormonal therapies and how metastatic dissemination of breast, ovarian, and prostate cancers is initiated.

Prostate tumors that spread beyond the prostate capsule, castration is the first line of therapy.  In spite of the initial regression in response to castration, tumors inevitably relapse and develop the incurable castration-resistant disease. My lab is focused on understanding the molecular and cellular changes that mediate the transition to castration-resistant disease and the role AR signaling plays in that transition. Previously we have shown that the AR coregulators SRC-1 and SRC-2 (TIF2) are necessary for the stimulatory effect of androgens on proliferation and correlate with poor prognosis. In addition, we and other groups have demonstrated that corepressors, such as NCoR, DAX-1, and SMRT are involved in both agonist and antagonist dependent regulation of AR action. We have shown that the AR corepressor NCoR plays a key role in the response to the anti-androgen casodex in AR-expressing prostate cancer cell lines. Most recently we identified the tumor suppressor gene INPP4B as a direct AR target gene in prostate cancer cells. INPP4B antagonizes oncogenic PIK3/Akt signaling, which is frequently hyperactive in prostate cancer, in addition to numerous other human malignancies. Loss of INPP4B accelerates prostate cancer cell proliferation and correlates with reduced time to biochemical recurrence and poor patient prognosis. Using inducible expression we found that INPP4B suppresses metastases and we are now investigating the mechanisms of this suppression.

In our preliminary investigations we established that these pathways modulate metastatic potential of both breast and ovarian cancers. Using our findings in prostate cancer we are investigating novel therapeutic signaling pathways in these malignancies.

In addition we have mouse models of breast and ovarian cancer that we use to validate our findings in cell-based models.
Along with my research, I am very involved in strengthening the environment at FIU for cancer research. I have organized and currently manage Cell Culture Core and Histopathology Core that are key to research of multiple investigators. I would like to create a core for rapid analysis of metastatic progression.

Publications:

1. Lopez SM, Hodgson MC, Packianathan C, Bingol-Ozakpinar O, Uras F, Rosen BP, Agoulnik IU. Determinants of the tumor suppressor INPP4B protein and lipid phosphatase activities. BBRC, in press, September 2013. DOI: 10.1016/j.bbrc.2013.09.077
   
   
2. Hodgson MC, Vanostran G, Alghamdi S, Poppiti RJ, Agoulnik AI, Agoulnik IU. Reduced androgen receptor expression accelerates the onset of ERBB2 induced breast tumors in female mice. PLoS One. 2013 Apr 8;8(4).PMID: 23593223 [PubMed - in process] PMCID PMC3620158
   
   
3. Agoulnik IU, Weigel NL. (2012) Roles of androgen receptor coregulators and cell signaling in the regulation of androgen-responsive genes. In Z. Wang, Androgen-Responsive Genes in Prostate Cancer. New York: Springer.
4. Agoulnik IU, Hodgson MC, Bowden WA, Ittmann MM. INPP4B: the new kid on the PI3K block. Oncotarget. 2011 Apr;2(4):321-8. (2011)
5. Hodgson MC, Shao LJ, Frolov A, Li R, Peterson LE, Ayala G, Ittmann MM, Weigel NL, Agoulnik IU. Decreased expression and androgen regulation of the tumor suppressor gene INPP4B in prostate cancer. Cancer Res, 71(2):572-82. (2011)
6. Feng S, Agoulnik IU, Truong A, Li Z, Creighton CJ, Kaftanovskaya EM, Pereira R, Han HD, Lopez-Berestein G, Klonisch T, Ittmann MM, Sood AK, Agoulnik AI. Suppression of relaxin receptor RXFP1 decreases prostate cancer growth and metastasis. Endocr Relat Cancer, 17(4):1021-33. (2010)
7. Agoulnik IU, Weigel, NL. Coactivator Selective Regulation of Androgen Receptor Activity. Steroids, , 74(8):669-74, (2009).
8. Agoulnik IU, Nakka M, Weigel NL. Target Gene Specific Regulation of Androgen Receptor Activity by p42/p44 MAPK. Mol Endo, 22(11):2420-32. (Nov. 2008).
9. Agoulnik IU, Weigel NL. Androgen receptor coactivators and prostate cancer. Adv Exp Med Biol, 617:245-55  (2008).
10. Agoulnik IU, Weigel NL. Androgen Receptor Coactivators and Prostate Cancer. Hormonal Carcinogenesis, Volume V. 5th International Symposium on Hormonal Carcinogenesis (2006).
11. Agoulnik IU, Vaid A, Nakka M, Alvarado M, Bingman WE III, Erdem H, Frolov A, Smith CL, Ayala G, Ittmann MM, Weigel NL. Androgen Receptor Coactivator TIF2 Expression, Biochemical Recurrence and Androgen Independence of Prostate Cancer. Cancer Research. 66:21; 10594-602  (Nov. 2006)
12. Agoulnik IU, Weigel NL. Androgen Receptor Action in Androgen Dependent and Recurrent Prostate Cancer. J Cell Biochem. 99:2;362-72  (Apr. 2006).
13. Dai H, Li R, Wheeler T, de Vivar AD, Chen X, Frolov A, Agoulnik IU, Thompson T, Rowley D, Ayala G. Pim-2 Upregulation: Biological Implications Associated with Perinueral Invasion and Disease Progression in Prostate Cancer. Prostate. 1:65;276-86 (Nov. 2005)
14. Agoulnik IU, Vaid A, Bingman WE III, Erdeme H, Frolov A, Smith CL, Ayala G, Ittmann MM, Weigel NL. A Role for SRC-1 in Promoting Prostate Cancer Cell Growth and Tumor Progression. Cancer Research. 1:65;7959-67  (Sep. 2005)