University of Wisconsin–Madison

Nithya Harihan

MD

Research Specialist

harihan@neurosurgery.wisc.edu

Nicky is the Researcher and Laboratory Manager in Dr. Iskandar’s Central Nervous System Regeneration Laboratory. She received a medical degree at Dharbangha Medical College, Dharbangha, India followed by a diploma in Pediatrics at Ranchi Medical College, Ranchi, India, and an Associate Degree in Biotechnology at MATC in Madison, WI.

The role of folic acid supplementation has proven to be extremely effective in preventing the occurrence of neural tube defects and other congenital abnormalities in humans. Because this suggests that folic acid can modulate or enhance key mechanisms for growth and differentiation in the CNS, our laboratory has been instrumental in hypothesizing and proving a significant role for folic acid in regeneration and repair of the adult CNS after injury, with inherent implications on healing from stroke and cancer, degenerative diseases, congenital illness, as well as brain and spinal cord trauma. As part of an effort to study the mechanism of such a pro-regenerative response, we have shown that folate-mediated CNS regeneration depends on injury-related induction of folate receptor FOLR1 expression, intact intracellular folate activation, and a functional methylation cycle. The effect of folate on the regeneration of afferent spinal neurons is biphasic and dose-dependent, and correlates closely over its dose range with global and gene-specific DNA methylation, and with expression of both the folate receptor FOLR1 as well as the de novo DNA methyltransferases. Most recently, we’ve demonstrated that such methylation-mediated phenotypic changes are transmitted through multiple generations. Accordingly, we hypothesize an epigenetic mechanism in CNS repair, and through our laboratory efforts, we seek to understand the underpinnings of this mechanism and its implications. This work, funded by the NIH, the March of Dimes, and the UW Institute for Clinical and Translational Research, provides a more profound understanding of tissue healing and repair, with possible avenues for new dietary and pharmacologic approaches to treating brain and spinal cord injuries, and is likely to enhance our understanding of how behavior, habits, diet, and therapy interact to affect our children and their progeny.