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Olga I. Astapova, M.D., Ph.D.

Contact Information

Phone Numbers

Office: (585) 275-2901

URMFGA member of the University of Rochester Medical Faculty Group

groupAn Accountable Health Partner

assignmentAccepting New Patients

Research Labs

Faculty Appointments

Patient Care Setting

Endocrinology

Biography

Research

I am a new faculty member at the Division of Endocrinology, but a familiar face to the people here. After completing my fellowship in endocrinology, which included working in the Hammes lab, I recently became assistant professor and now run my own lab. My research focus is on the mechanisms of androgen actions in the ovary, and ultimately I want to improve the management of female fertility and ovarian hormone balance. While androgens are traditionally considered essential for male fertility, they are also critical regulators of ovarian function and fertility. In women, disorders of follicle development, specifically polycystic ovary syndrome (PCOS) and diminished ovarian reserve (DOR), contribute to the majority of cases of infertility. Disregulated androgen signaling has been implicated in both of these conditions: hyperandrogenemia is associated with excessive numbers of persistent antral follicles and anovulation in PCOS, while androgen deficiency is linked to accelerated follicle loss in DOR. Therefore, it is paramount to understand the mechanisms of androgen actions in the ovary in order to reduce the healthcare burden of androgen-related disorders in women.

Recently I undertook a study to assess the androgen-regulated transcriptome in granulosa cells using RNA sequencing. Surprisingly, I found that in both mouse and human granulosa cells, gene transcription activity of the androgen receptor is negligible to nill. This was unexpected, given that it is well known from studies done in Dr. Hammes’ lab and others that androgens promote follicle growth via androgen receptor in granulosa cells. I showed that ligand binding induces marked nuclear localization of the androgen receptor in these cells and enhances the receptor protein expression by several-fold by protecting it from proteasome degradation in the cytoplasm, but does not result in any significant mRNA-transcription activity. This suggests that non-gene coding androgen actions may be at play in GCs. I therefore became interested in non-classical androgen signaling in the ovary.

Current research activity in my lab aims to investigate the non-coding transcriptional activity of androgen receptor in granulosa cells and the role of cytoplasmic adaptor protein paxillin in the ovary. Our working hypothesis is that androgens shift the microRNA expression profile of granulosa cells in the anti-apoptotic direction, resulting in increased survival of granulosa cells and follicle growth. In cases of androgen excess, such as in PCOS, this shift may interfere with the establishment of a dominant follicle and ovulation. We also believe that paxillin may be involved in this pathway upstream of the androgen receptor. Work by the Hammes lab has shown that paxillin mediates non-genomic androgen signaling in prostate cancer, and we are evaluating similar mechanisms in granulosa cells. In fact, we have found that in granulosa cells, paxillin is necessary for androgen receptor protein expression. We have created a granulosa cell-specific paxillin knockout mouse model to better understand this pathway.

While research occupies the majority of my time, 20% of my appointment is clinical. My clinical interest is in managing the symptoms and reducing the metabolic risks associated with PCOS, as well as managing other conditions of disordered sex steroids: gender dysphoria, early menopause, male and female hypogonadism.

Credentials

Specialties

  • Endocrinology, Diabetes and Metabolism - American Board of Internal Medicine
  • Internal Medicine - American Board of Internal Medicine

Education

2014
MD, PhD | Wayne State University School of Medicine

Post-doctoral Training & Residency

07/01/2019 - 06/30/2020
Fellowship in Endocrinology, Diabetes and Metabolism at University of Rochester Medical Center

07/01/2016 - 06/30/2019
Fellowship in Endocrinology, Diabetes and Metabolism at University of Rochester Medical Center

07/01/2015 - 06/30/2016
Residency in Internal Medicine at University of Rochester Medical Center

06/11/2014 - 06/24/2015
Internship in Internal Medicine at University of Rochester Medical Center

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Publications

Journal Articles

5/1/2019
Astapova O, Minor BMN, Hammes SR. "Physiological and Pathological Androgen Actions in the Ovary." Endocrinology.. 2019 May 1; 160(5):1166-1174.

2018
Astapova O, Biswas A, DiMauro A, Moalem J, Hammes SR. "Bilateral Pheochromocytomas in a Patient with Y175C Von Hippel-Lindau Mutation." Case reports in endocrinology.. 2018 2018:8967159. Epub 2018 Jul 10.

8/2014
Beckett EM, Astapova O, Steckler TL, Veiga-Lopez A, Padmanabhan V. "Developmental programing: impact of testosterone on placental differentiation." Reproduction : the official journal of the Society for the Study of Fertility.. 2014 Aug 0; 148(2):199-209. Epub 2014 May 19.

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