Lalitha Madhavan

Associate Professor, Neurology

Associate Professor, Medicine

Associate Professor, Neuroscience - GIDP

Associate Professor, Molecular and Cellular Biology

Associate Professor, Evelyn F Mcknight Brain Institute

Associate Professor, Clinical Translational Sciences

Associate Professor, Physiological Sciences - GIDP

Associate Professor, BIO5 Institute

Primary Department

Neurology

Department Affiliations

Neurology

Contact

(520) 626-2330

lmadhavan@arizona.edu

Research Interest

Dr. Madhavan M.D., PhD, is an Assistant Professor of Neurology at the University of Arizona. She is also a member of the Arizona Cancer Center and the Evelyn F. McKnight Brain Institute, and is affiliated with the Neuroscience, Physiology and Molecular, Cellular Biology graduate programs at UA. Dr. Madhavan’s research centers on stem cells and neurological diseases. The ultimate goal of the work is to devise brain repair strategies for neural disorder using stem cells, and other alternate approaches. Currently, her lab is focused on Parkinson’s Disease, and is engaged in three main endeavors: (1) Understanding the therapeutic potential of stem cells in the context of aging, (2) Creating patient-specific induced pluripotent stem cells to study the etiology of Parkinson’s Disease, and (3) Testing the therapeutic feasibility of various types of adult stem cells in preclinical Parkinson’s Disease models. These projects are united by a common goal, which is to investigate core problems hindering the development of effective stem cell-based therapies for Parkinson’s Disease. In addition, the work represents a novel path of research for not only Parkinson’s Disease therapy, but has broad implications for developing treatments for several other age-related neurodegenerative disorders. Visit the Madhavan Lab website to learn more.

Publications

Striatal pleiotrophin overexpression provides functional and morphological neuroprotection in the 6-hydroxydopamine model

Gombash, S. E., Lipton, J. W., Collier, T. J., Madhavan, L., Steece-Collier, K., Cole-Strauss, A., Terpstra, B. T., Spieles-Engemann, A. L., Daley, B. F., Wohlgenant, S. L., Thompson, V. B., Manfredsson, F. P., Mandel, R. J., & Sortwell, C. E. (2012). Striatal pleiotrophin overexpression provides functional and morphological neuroprotection in the 6-hydroxydopamine model. Molecular therapy : the journal of the American Society of Gene Therapy, 20(3), 544-54.

Neurotrophic factors are integrally involved in the development of the nigrostriatal system and in combination with gene therapy, possess great therapeutic potential for Parkinson's disease (PD). Pleiotrophin (PTN) is involved in the development, maintenance, and repair of the nigrostriatal dopamine (DA) system. The present study examined the ability of striatal PTN overexpression, delivered via psueudotyped recombinant adeno-associated virus type 2/1 (rAAV2/1), to provide neuroprotection and functional restoration from 6-hydroxydopamine (6-OHDA). Striatal PTN overexpression led to significant neuroprotection of tyrosine hydroxylase immunoreactive (THir) neurons in the substantia nigra pars compacta (SNpc) and THir neurite density in the striatum, with long-term PTN overexpression producing recovery from 6-OHDA-induced deficits in contralateral forelimb use. Transduced striatal PTN levels were increased threefold compared to adult striatal PTN expression and approximated peak endogenous developmental levels (P1). rAAV2/1 vector exclusively transduced neurons within the striatum and SNpc with approximately half the total striatal volume routinely transduced using our injection parameters. Our results indicate that striatal PTN overexpression can provide neuroprotection for the 6-OHDA lesioned nigrostriatal system based upon morphological and functional measures and that striatal PTN levels similar in magnitude to those expressed in the striatum during development are sufficient to provide neuroprotection from Parkinsonian insult.

Lalitha Madhavan