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

Transplantation of subventricular zone neural precursors induces an endogenous precursor cell response in a rat model of Parkinson's disease

Madhavan, L., Daley, B. F., Paumier, K. L., & Collier, T. J. (2009). Transplantation of subventricular zone neural precursors induces an endogenous precursor cell response in a rat model of Parkinson's disease. The Journal of comparative neurology, 515(1), 102-15.

Realistically, future stem cell therapies for neurological conditions including Parkinson's disease (PD) will most probably entail combination treatment strategies, involving both the stimulation of endogenous cells and transplantation. Therefore, this study investigates these two modes of neural precursor cell (NPC) therapy in concert in order to determine their interrelationships in a rat PD model. Human placental alkaline phosphatase (hPAP)-labeled NPCs were transplanted unilaterally into host rats which were subsequently infused ipsilaterally with 6-hydroxydopamine (6-OHDA). The reaction of host NPCs to the transplantation and 6-OHDA was tracked by bromodeoxyuridine (BrdU) labeling. Two weeks after transplantation, in animals transplanted with NPCs we found evidence of elevated host subventricular zone NPC proliferation, neurogenesis, and migration to the graft site. In these animals, we also observed a significant preservation of striatal tyrosine hydroxylase (TH) expression and substantia nigra TH cell number. We have seen no evidence that neuroprotection is a product of dopamine neuron replacement by NPC-derived cells. Rather, the NPCs expressed glial cell line-derived neurotrophic factor (GDNF), sonic hedgehog (Shh), and stromal cell-derived factor 1 alpha (SDF1alpha), providing a molecular basis for the observed neuroprotection and endogenous NPC response to transplantation. In summary, our data suggests plausible synergy between exogenous and endogenous NPC actions, and that NPC implantation before the 6-OHDA insult can create a host microenvironment conducive to stimulation of endogenous NPCs and protection of mature nigral neurons.

Lalitha Madhavan