Morley D. Hollenberg
M.D. (Doctor of Medicine)
Preferred method of communication
Research and teaching
- Spinal Cord / Nerve Injury & Pain
My research interests over time have focused on the biosynthesis and actions of neuropeptides hormones (oxytocin, vasopressin), insulin, and epidermal growth factor and on the molecular pharmacology and pathophysiology of receptor-mediated signalling by growth factors and G-protein coupled receptors (GPCR). This focus seeks to understand rapid events occurring in tissues such as smooth muscle, responsible for regulation of blood vessel and intestinal motility and neurons, responsible for neurogenic inflammation. Recent work is studying the hormone-like signalling properties of proteinases that act in part via the 'proteinase-activated receptor (PAR)' family of GPCRs. The PARs regulate diverse pathophysiological processes ranging from vascular angiogenesis and contractility to arthritic and intestinal inflammation and pain. These receptors also play roles in neurodegeneration, multiple sclerosis and stroke.
As one major focus, we are studying the activation of these receptors (PARs 1, 2 and 4) by thrombin, trypsin and other serine proteinases, like the tumor-derived tissue kallikrein family. We are particularly interested in the signalling pathways for the PARs that are in common with those for growth factor receptors, resulting in activation of cellular tyrosine kinase pathways in the vasculature, neurons and other target tissues. A major direction related to signalling by proteinases seeks to identify, with the use of activity-based covalent proteinase labeling probes and proteomic analysis, those serine proteinases responsible for regulating cell and tissue function via the PARs in the setting of health and disease.