The Accelerating Excellence In Translational Science (AXIS)Charles Drew University of Medicine and Science

Dr. Nestor Gonzalez-Cadavid

Diabetic limb ischemia, diabetic nephropathy, erectile dysfunction, Peyronie’s disease, muscular dystrophy, and environmental contaminants. At first glance, it would be difficult to see what unifies these topics. But one researcher, Dr. Nestor Gonzalez-Cadavid, Ph.D, has pursued these disparate topics with an eye to some of their underlying similarities. His work has been driven by intellectual curiosity and an interest in contributing to the diagnosis and therapy of significant medical conditions.

Dr. Gonzalez-Cadavid is a Professor of Medicine in the Division of Endocrinology at Charles R. Drew University, as well as a Professor of Urology at the David Geffen School of Medicine at UCLA. He also directs the urology research laboratory, at LA BioMed, at Harbor-UCLA Medical Center. He holds two PhD degrees in biochemistry from the University of Buenos Aires and the University of London. He is a Visiting Professor of the Sun Yat-sen University Medical School, Guangzhou, China, a regular member of an NIH Study Group, editor-in-chief of the International Journal of Impotence Research, and a member of the International Academy of Sexual Medicine.

Dr. Gonzalez-Cadavid’s current research focuses on the molecular pathophysiology of acute or chronic damage of skeletal muscle or penile smooth muscle and connective tissue. This damage leads to tissue atrophy and fibrosis, and in some cases necrosis (death) of the tissue. His research has further investigated adult stem cell therapy to facilitate tissue repair by combating these processes and replacing the lost functional cells.

Notes Dr. Gonzalez-Cadavid, “These processes cause conditions as diverse as erectile dysfunction or Peyronie’s disease in the penis, or critical limb ischemia in the lower extremities. In the case of erectile dysfunction or Peyronie’s disease, these disorders affect millions of men, severely impairing their quality of life and causing a burden on health care costs. Critical limb ischemia is a devastating disease that frequently leads to limb loss and mortality, mainly in diabetic patients.” Dr. Gonzalez-Cadavid observes that disadvantaged populations generally have a worse prognosis in this condition.

Dr. Gonzalez-Cadavid first started his work in adult stem cells a decade ago. Recently his lab has started studying the tissue repair ability of a single type of adult stem cell, named “muscle derived stem cells.” These have been planted into rat and mouse models of erectile dysfunction and critical limb ischemia, with good preliminary results boding well for their possible translation to the clinic. Adds Dr. Gonzalez-Cadavid, “Now we have started investigating the application for erectile dysfunction of another type of stem cell: inducible pluripotent stem cells, or iPS.” He further explains that these stems cells are derived by reprogramming differentiated cells, and they “may be even more promising than the native adult stem cells.”

Recently, Dr. Gonzalez-Cadavid’s work on erectile dysfunction led to a patent covering new mechanisms and uses for the phosphodiesterase 5 inhibitor (PDE 5) drugs like Viagra or Cialis. He is also participating in an important multi-investigator program organized by the NIH and FDA on the potential damaging effects of bisphenol A (BPA) leaked from plastics and acrylic resins on different organs and potential related medical disorders. Dr. Gonzalez-Cadavid is in charge of the erectile dysfunction study in a rat model. As he remarks, “BPA is an environmental contaminant. In an epidemiological study in factories, it was associated with higher erectile dysfunction rates in exposed workers in China.” He has recently started studies funded by the American Diabetes Association on the use of muscle derived stem cells in rodent models for the treatment of erectile dysfunction, and their reactivation by the iPS technology. He also recently began studies funded by an institutional bridge grant to study a similar application of iPS for erectile dysfunction after radical prostatectomy. He has two grants under consideration by the NIH, aiming to study the pharmacological modulation of adult stem cells in a mouse model for their use in the treatment of critical limb ischemia in diabetes. The grants will also study whether racial and ethnic disparities impact progression and outcomes after stem cell treatment in pilot clinical trials.

Dr. Gonzalez-Cadavid highly values the opportunities that have been available to him at Charles Drew University. He explains the appointment “gave me the opportunity to expand my basic research in urological topics to the field of an inhibitor of skeletal muscle mass, myostatin, and its role in the modulation of pluripotent stem cell differentiation.” The collaboration between UCLA and CDU “allowed an intellectual cross-fertilization that eventually led to ongoing projects and grants, and that hopefully will lead to new awards.”