Nina F. Schor, M.D., Ph.D.

(1) adjunctive use of 6-hydroxydopamine (tumor cell ablative agent) with TEMPOL (selective normal cell chemoprotectant);

(2) adjunctive use of neocarzinostatin (non-selective chemotherapeutic prodrug) with 6-mercaptodopamine (neural crest-selective activator of neocarzinostatin);

(3) caspase 3-dependent potentiation of apoptosis induced by enediyne chemotherapeutic agents in Bcl-2-overexpressing tumors; and

(4) potentiation of apoptosis induced by chemotherapeutic agents with agonists and antagonists at specific neurotrophin receptors.

In the process of this work, Dr. Schor's laboratory has evolved several distinct lines of inquiry and drug and mechanism discovery. For example, the peripheral administration of 6-hydroxydopamine alone resulted in an autonomic neuropathy that mimicked that seen in patients with Parkinson's disease. Dr. Schor's group has used this model to examine the development of auto-recycling antioxidants for use in Parkinson's disease. Since moving from the University of Pittsburgh to the University of Rochester, Dr. Schor and her colleagues have been piloting mitochondrially-targeted auto-recycling antioxidants and gene therapy with constructs that code for endogenous neuroprotective species (e.g., the intracellular domain of the p75 neurotrophin receptor), respectively, in this model system.

Another example of work that developed from the targeted chemotherapeutic strategies relates to the discovery by Dr. Schor and her group that, not only is the p75 neurotrophin receptor an excellent substrate for presenilin, liberating its intracellular domain; this intracellular domain is protective against oxidative stress and facilitatory of antimitotic activity by a mechanism that involves translocation of NF-kappaB to the nucleus and up-regulation of all of the enzymes responsible for cholesterol biosynthesis. This is of particular interest in Alzheimer's disease because, while p75 is ubiquitously expressed in the embryonic brain, it is selectively highly expressed in the nucleus basalis of Meynert in the adult brain. Furthermore, genetically engineered cells that express only the familial Alzheimer's disease mutant presenilin do not exhibit p75-mediated protection from oxidative stress.

Read full Research bio »