Lisa A. Ridnour Ph.D

Dr. Ridnour received her PhD from the late Dr. Larry Oberley where her work demonstrated an imbalance in peroxide generating versus peroxide metabolizing enzymes in the tumor suppressive effects of MnSOD. She completed her post-doctoral training at Washington University in the laboratory of Dr. Douglas Spitz, where she identified thiol-dependent mechanisms associated with NO-induced resistance to peroxide stress. Dr. Ridnour joined the research group of Dr. David Wink (NCI) in 2003 where her research interests include NO regulation of extracellular matrix during cancer progression. In collaboration with Dr. David Roberts (NCI), she discovered a novel biphasic crosstalk relationship between NO and the angiogenesis inhibitor thrombospondin-1 (TSP-1). Her collaborations with Dr. Stefan Ambs (NCI), showed correlations between NOS2 and both TIMP-1 and MMP-9 in breast cancer survival where tyrosine nitration at two key residues critical for TIMP-1 inhibition of MMP-9 activity was identified. This nitration event occurred at NO concentrations that increase MMP-9 secretion and activity as well as TIMP-1 binding to its receptor CD63, which promotes tumor cell survival through CD63/PIK3/AKT/BAD signaling. Her collaboration with Dr. Carol Colton at Duke University demonstrated a protective role for NO regulation of MMP-9/TIMP-1 balance and increased plaque clearance in Alzheimer's disease. These studies have demonstrated a regulatory role of NO in matrix reorganization as it occurs in inflammatory diseases. Her current studies involve examination of NOS2/COX2 regulation of the tumor immune microenvironment where she demonstrated that NOS inhibition improved radiation therapeutic efficacy by limiting IL-10-mediated immunosuppression. This work has in part led to the development of spatial imaging platforms for more detailed spatial analyses of how tumor NOS2/COX2 expression direct the tumor immune microenvironment in aggressive cancers. These studies have revealed that COX inhibition using clinically available NSAIDs improves radiation therapeutic efficacy, which involves in part augmented M1/Th1 antitumor immune response.