Agoulnik, Irina

Agoulnik, Irina Graduate Faculty

Positions

Professor, Human and Molecular Genetics , Herbert Wertheim College of Medicine

iagoulni@fiu.edu

biography

Dr. Agoulnik comes to FIU from the Baylor College of Medicine where she was an assistant professor in the Department of Molecular and Cellular Biology. She earned her Ph.D. at the Institute of Cytology and Genetics in Russia and did a postdoctoral fellowship at Baylor College of Medicine.

A cancer researcher and cell biologist, she 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 receptor and its co-regulators in prostate cancer progression.

research interests

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 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.