Effect of nitroso-redox imbalance on male reproduction
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are byproducts of normal metabolic processes. They are necessary for normal cellular function and are kept in balance by antioxidant mechanisms. Alterations in levels of ROS and RNS can lead to nitroso-redox imbalance that in turn can negatively affect male reproduction. Strategies to decrease ROS/RNS involve evasion of exposures (smoking, meat intake, pollution, calorie-dense diet), managing lifestyle, and increasing the consumption of antioxidants (vitamin C, vitamin E, alpha-lipoic acid, taurine, quercetin). Targeted therapies focusing on nitroso-redox imbalance can be critical for treatment of male reproductive dysfunction. Our lab focuses on implications of endogenous and exogenous sources of ROS/RNS, their adverse effect on male reproduction, and strategies to control nitroso-redox imbalance.
Nitric oxide immunotherapy against castration-resistant prostate cancer
Immune targeted therapy of nitric oxide (NO) synthases are being considered as a potential frontline therapeutic to treat patients diagnosed with locally advanced and metastatic prostate cancer. However, the role of NO in castration-resistant prostate cancer (CRPC) is controversial because NO can increase in nitrosative stress while simultaneously possessing anti-inflammatory properties. Accordingly, we are testing the hypothesis- increased NO lead to tumor suppression of CRPC. Our results have shown that tumor burden is suppressed by NO by targeting tumor micro environment. Ongoing studies in our lab are focusing on evaluating the efficacy of NO treatment as a monotherapy or combinational therapy against CRPC.
Subcutaneous Leydig Stem Cell Autograft to Increase Serum Testosterone
Exogenous testosterone therapy can be used to treat testosterone deficiency; however, it has several adverse effects including infertility due to negative feedback on the hypothalamic-pituitary-gonadal (HPG) axis. Leydig stem cell (LSC) transplantation could provide a new strategy for treating testosterone deficiency, but clinical translatability of injecting stem cells inside the testis is not feasible. We are exploring the feasibility of subcutaneously autografting LSCs in combination with Sertoli and myoid cells to increase testosterone. We also focusing on the molecular mechanisms behind this regulation. Till now we have demonstrated that LSCs, when autografted subcutaneously in combination with Sertoli cells and myoid cells, can increase testosterone production. Therefore, LSC autograft may provide a new treatment for testosterone deficiency while simultaneously preserving the HPG axis. Further steps in this study includes evaluating paracrine factors released by the adjacent testicular environment which could potentiate the LSC differentiation and increase T levels.
If, after one year of unprotected sex, a pregnancy has not occurred, this means that the man, woman, or both, may have a fertility problem. In 40% of infertile couples, the male has a fertility problem. The condition in males where seminal fluid lacks any sperm is called as Azoospermia. As with many other diseases, genetic testing in human azoospermia was initially restricted to karyotype analyses (leading to diagnostic chromosome rearrangement tests for Klinefelter and other syndromes). With the advent of molecular biology in the 1980s, genetic screening was broadened to analyses of Y chromosome microdeletions and the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR). Decades later, the emergence of whole-genome techniques has led to the identification of other genetic defects associated with human azoospermia. We focus on using whole exome sequencing to identify genetic variants that could be potentially related to Azoospermia.
Research Training Opportunities
The laboratory vigorously welcomes students at the graduate and undergraduate levels to participate in research activities. Medical students are particularly encouraged to join the laboratory for an elective rotation, even for a short period of time. Post-doctoral fellows are also encouraged to consider the laboratory for further research development in the areas of Andrology and Urologic Oncology. Applicants are encouraged to contact Dr. Ramasamy directly via e-mail or by telephone contact to inquire about such opportunities.
The research personnel in the laboratory include Dr. Ranjith Ramasamy, M.D and Dr. Himanshu Arora, PhD. Besides these core personnel, the laboratory frequently is joined by post-doctoral fellows, graduate students and undergraduate students. Consistent with the collaborative activities of the laboratory, the laboratory interacts quite actively with scientists in the Departments of Urology, Andrology, Stem cell, Radiation Oncology, not to mention other collaborators within the Department of Urology.
In The News
American Cancer Society Awards Five Year Grant to Sylvester Urologic Surgeon
Ranjith Ramasamy, M.D., assistant professor in the Department of Urology, was awarded a Clinician Scientist Development Grant in the amount of $729,000 for his research study, Nitric Oxide Based Immunotherapy for Castration Resistant Prostate Cancer (CPRC), which was published last year in the journal, Proceedings of the National Academy of Sciences.
CTSI Names Four New KL2 Scholars and Awards Pilot Grants to 10 UM Faculty
The Miami Clinical & Translational Science Institute’s (CTSI) Pilot Awards support research that is translational, innovative, and interdisciplinary. These awards of $40,000 each allow investigators to generate preliminary data for a federal grant submission. Ranjith Ramasamy, M.D., assistant professor of urology, will look at the therapeutic role of nitric oxide in regulating the tumor microenvironment of castrate-resistant prostate cancer.
Sylvester Researchers Show Nitric Oxide Suppresses Drug-Resistant Prostate Cancer
Dr. Ranjith Ramasamy, M.D and Dr. Himanshu Arora, PhD, researchers at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine have shown in animal models that S-nitrosoglutathione (GSNO), a compound that increases nitric oxide (NO) levels, suppresses castration-resistant prostate cancer and has a major impact on tumor microenvironments. The discovery could lead to new therapies for prostate cancer patients with few options. The study was published in the journal Proceedings of the National Academy of Sciences.
Dr. Ranjith Ramasamy Reports on First Clinical Trials Using Shockwave Therapy to Treat ED
Ranjith Ramasamy, M.D., assistant professor of urology and director of reproductive urology at the University of Miami Miller School of Medicine, spoke recently before members of the American Urological Association at its annual convention in San Francisco. His presentation was a summary of randomized clinical trials he conducted on the effects of shockwave therapy for treating erectile dysfunction (ED), a chronic condition that affects 30 million men in the U.S.
Dr. Ranjith Ramasamy, Research Award Winner, Presents at Boston Conference
Ranjith Ramasamy, M.D., assistant professor of urology and director of male reproductive medicine and surgery at the University of Miami Miller School of Medicine, gave a presentation at the recent American Urological Association (AUA) annual meeting in Boston. Ramasamy, who specializes in the treatment of disorders of male infertility and sexual dysfunction, discussed the research he is conducting under a two-year grant as a recipient of an AUA Research Scholar Award. The award program funds mentored training for outstanding young investigators to encourage urologic research and foster their career success.