Ranjith Ramasamy, MD is the Director of Reproductive Urology and Assistant Professor at the University of Miami. He is actively engaged in both clinical and translational research, and is working at the Interdisciplinary Stem Cell Institute under the mentorship of Joshua Hare, MD, with additional mentorship from Dipen Parekh, MD. His two-year Research Scholar Award, made possible by the Sexual Medicine Society of North America (SMSNA), investigating the role of Leydig stem cell autograft to increase testosterone in mouse models with Klinefelter syndrome.
Klinefelter syndrome (KS) is a genetic condition that results when a boy is born with an extra copy of the X chromosome and affects 1 in 500 males. Men with KS have low serum testosterone, which can result in fatigue, depression, low libido, worsening cognition, lack of pubic and axillary hair, delayed puberty, osteoporosis and breast enlargement. The current standard of care for men with KS is lifelong exogenous testosterone therapy. However, exogenous testosterone therapy results in negative feedback on the hypothalamic-pituitary-gonadal (HPG) axis, inhibiting follicle stimulating hormone (FSH) and luteinizing hormone (LH) production, which results in infertility. However, based on a number of alarming recent studies, the FDA issued a report warning that men who take exogenous testosterone may face increased risk of stroke and heart attack.
Moreover, it is well established that exogenous testosterone can have suppressive effects on LH, resulting in lower Leydig cell testosterone production and therefore in reduced intratesticular testosterone and sperm. Consequently, there is a need to develop a different long-term approach to increase serum testosterone while simultaneously preserving the HPG axis and fertility. Isolating Leydig stem cells from the testes and performing a subcutaneous autograft can not only increase testosterone but also simultaneously preserve the production of the pituitary hormones FSH and LH.
Dr. Ramasamy is evaluating the effect of Leydig stem cell autograft in mouse models and studying the mechanisms of Leydig stem cell maturation within the autograft. In addition, he is evaluating Leydig stem cells obtained from men undergoing testis biopsies for infertility. By optimizing a protocol to autograft adult Leydig stem cells from testis biopsies to an ectopic site, a safe and effective treatment for hypogonadal men can be developed. If proven successful and safe, the potential impact of Leydig stem cell autograft as a therapy to increase testosterone could be paradigm shifting for the clinical treatment of hypogonadism in men who desire children.
Mentoring is a critical component to developing the next generation of urologic researchers, and is an important criterion of the Research Scholar Award program.
Mentors not only provide direction but also serve as a constant source of encouragement and support for young faculty. In addition to Drs. Hare and Parekh who are working with Dr. Ramasamy on this project, Dr. Ramasamy has also been mentored by Larry Lipshultz, MD; Dolores Lamb, PhD and Peter Schlegel, MD. Mentorship also often forms the basis for future collaborations. As a Research Scholar, Dr. Ramasamy will continue to forge a relationship with the SMSNA, a key stakeholder in the sexual function and dysfunction research space. He will be presenting his work at the SMSNA session at the 2017 AUA Annual Meeting in Boston, MA.
Dr. Ramasamy hopes that the Research Scholar Award will lay the groundwork for a successful career as a surgeon-scientist. His long term goal is to pursue a career in academic medicine with a focus on translational research in male reproduction.