As a clinical oncologist Dr. Denmeade has been the lead investigator on clinical trials testing new hormone therapies for prostate cancer. Dr. Denmeade also is a laboratory scientist focused on the development of novel ways to treat prostate cancer. His main research focus has been on the design and characterization of prodrugs and protoxins targeted for activation by cancer specific proteases. This research is based on the strategy that lethal drugs/toxins could be disguised as a prodrug and only released when exposed to the enzymatic activity of proteases such as PSA which are only present in its enzymatically active form in the tumor and not elsewhere in the body. One of these prodrugs termed G202 consists of an analog of the highly toxic natural product thapsigargin coupled to a peptide recognized as a substrate by the protease Prostate-Specific Membrane Antigen. The G202 prodrug is currently being evaluated for its toxicity and therapeutic effectiveness in clinical trials sponsored by GenSpera, Inc. Dr. Denmeade is a co-founder of GenSpera and serves as its Chief Medical Advisor. Dr. Denmeade is also one of the co-inventors of PRX302 which is a modified form of the potent bacterial toxin proaerolysin that has been reengineered for activation by the protease Prostate-Specific Antigen (PSA). PRX302 is currently under clinical development by Protox (now Sophiris), Inc. as therapy for benign prostatic hyperplasia. Dr. Denmeade was the former Chief Scientific Officer for Protox and now serves as a consultant for Sophiris. Dr. Denmeade's work has been supported by research grants from the National Cancer Institute, the Department of Defense, the Prostate Cancer Foundation and the One-in-Six Foundation. Dr. Denmeade has published over 100 papers in the area of prostate cancer research. He holds 12 US patents related to his work on cancer therapeutics.