My research focus is to demonstrate the impact of inflammatory mediators on the pathogenesis of diabetic complications: neuropathy, nephropathy and gastroparesis. We have established that replication defective herpes simplex virus-mediated gene transfer of growth factors (NGF, NT-3, VEGF) can prevent diabetic and drug-induced peripheral sensory neuropathy in animals, and that gene transfer mediated release of inhibitory neurotransmitters (Enkephalin, GABA) in diabetic animals reduces pain concomitantly with a reduction in sodium channel NaV1.7 levels in dorsal root ganglion (DRG). Our recent studies show therapeutic benefits of HSV mediated release of anti-inflammatory mediators (IL-10, sTNFR) in the DRG with a reduction of pro-inflammatory cytokines, subsequently inhibiting painful neuropathy. We have also demonstrated exercise-mediated alleviation of painful neuropathy with a decrease in neuro-inflammation. Currently we are assessing if blocking the release of noxious cytokines improves renal dysfunction and gastric dysmotility in diabetic animals. We are trying to identify novel early biomarkers of inflammation and epigenetic modulators (histone modifications) involved in the progression of neuropathy, nephropathy and gastroparesis in diabetic animals, and are exploring whether inhibiting inflammation or epigenetic changes will alter the progression of these complications. Consequently, we are focusing on understanding the role of inflammation and nutritional deficits in the development of diabetic complications and co-morbidities.