Dr. Tolentino attended Deerfield Academy and received his honors bachelor’s degree in computer science and organizational behavior from Brown University and his Medical degree from the University of Massachusetts. After medical school, he did a post-doctoral angiogenesis research fellowship at the Harvard Medical School with Dr. Judah Folkman. During this fellowship he helped develop a xenograft model system to identify endogenous anti-angiogenic therapies. This model was the basis for isolating angiogenic inhibitors such as endostatin and angiostatin. Dr. Tolentino’s research focus in retinal diseases began by studying Verteporfrin (Photodynamic Therapy; PDT) and vascular endothelial growth factor (VEGF). He demonstrated that PDTs effect on vasculature was not a result of thermal damage. This work and the work of others lead to the FDA approval of Verteporfrin PDT, a drug marketed by QLT and Novartis. He also demonstrated that VEGF was sufficient and necessary to produce all the findings of diabetic retinopathy and macular degeneration. Dr. Tolentino has been very active in the clinical research of retinal diseases, acting as Principle Investigator in over 150 global clinical trials that led to multiple global approval for retina therapeutics.
Dr. Tolentino earned numerous awards and received several prestigious grants while at University of Pennsylvania including the Heed/Knapp, AOS, Ron Michels, AUPO fellowships as well as RPB and K08 NEI research grants. His research focused on gene, cellular and stem cell therapies. He collaborated with Drs. Jim Wilson (Inventor of Ex Vivo Gene Therapy) and Jean Bennett (Inventor of Gene therapy [Luxturna] for Leber Congenital Amaurosis scientific foundation for Spark Therapeutics) on the development of regulatable adeno-associated gene therapy vectors to deliver anti-angiogenic therapies. He invented a regulatable gene therapy adeno-associated virus (AAV) using a heat shock promoter that could be regulated by transpupillary thermotherapy.
His major accomplishment is the invention of a new class of gene silencing molecules called small interfering RNA (siRNA) against anti-angiogenic targets. He had 3 issued patents on the use of these molecules for treating neovascular diseases such as age-related macular degeneration and cancer. He was the first to demonstrate that the RNA interference mechanism worked in vertebrate organisms. The discovery of siRNA and its mechanisms in invertabrate worms resulted in the Nobel prize in Medicine for Craig Mello and Andrew Fire in 2006.
With these inventions, Dr. Tolentino co-founded and served as the interim CEO for Acuity Pharmaceuticals, where he raised approximately $27 million in private and venture funds. Acuity Pharmaceuticals merged with publicly traded Exegenic, owned completely by the Miami Based Frost Gamma private equity group, to form OPKO health (NYSE: OPK), a publicly traded biopharmaceutical company. OPKO’s current market cap is over $2 billion.
He has published over 80 peer-reviewed papers and over 100 publications in the field of anti-angiogenic, retinal, and macular degeneration therapies.
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