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

Professor and Chair Department of Pediatrics
Professor  Department of Neurology
Pediatrician-in-Chief  Golisano Children's Hospital
Tel: (585) 275-4673
Email: nina_schor@urmc.rochester.edu

The laboratory of Dr. Nina F. Schor began with a focus on designing and testing in preclinical models targeted therapy for neuroblastoma, the most common solid tumor of childhood and a derivative of the neural crest. Therapeutic approaches that have been pioneered in Dr. Schor’s laboratory include

(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.

Selected References

Mi Z, Mirnics ZK, Schor NF. Bcl-2 overexpression disrupts the morphology of PC12 cells through reduced ERK activation. Brain Res 1112:46-55, 2006.

Fritz MD, Mirnics ZK, Nylander KD, Schor NF. p75NTR enhances PC12 cell tumor growth by a non-receptor mechanism involving downregulation of cyclin D2. Exp Cell Res 312:3287-3297,2006.

Korade Z, Mi Z, Portugal C, Schor NF. Expression and p75 neurotrophin receptor dependence of cholesterol synthetic enzymes in adult mouse brain. Neurobiol Aging (E-pub ahead of print, PMID: 16887237.