Mithal (Divakar) Laboratory
Our lab focuses on questions at the intersection of neuroscience and mitochondrial metabolism. The primary focus is on mechanisms linking mitochondrial metabolism and changes to specific neuronal subpopulations. We examine these questions through the lens of mitochondrial diseases, but also with an eye to the broader implications of mitochondria metabolism.
Current projects in the lab are in collaboration with Dr. Navdeep Chandel at Northwestern University, a world expert on mitochondrial metabolism. We are studying the effects of manipulating complex I in the electron transport chain specifically in GABAergic interneurons. We are able to target key metabolic pathways using advanced genetic techniques to evaluate the role of mitochondria in interneurons. In a current project we are targeting the conversion of NADH to NAD+. Techniques include immunohistochemistry, metabolomics, and behavioral analysis. We use a combination of In vitro human-derived stem cell techniques and in vivo mouse modeling. We are also interested in using different gene delivery techniques to alter neurometabolism in highly targeted ways, with a long term goal of delivering treatments for mitochondrial diseases.
Research Topics
Neuroscience
Mitochondrial Disease
Metabolism
Genetic
Neurocritical Care
Contact
Divakar S. Mithal, MD, PhD
dmithal@luriechildrens.org
Principal Investigator
Divakar S. Mithal, MD, PhD
From early in his training, Dr. Divakar Mithal, MD, PhD, was fascinated by every aspect of the brain. After an undergraduate degree in Brain and Cognitive Sciences from MIT, he pursued an MD-PhD degree at Northwestern University Feinberg School of Medicine. During his PhD he studies the role of chemokines, typically thought of as mediators of inflammation, in brain development. The possibility of studying neuro inflammatory conditions in the developing brain led him to pursue a residency in Child Neurology, but during his clinical training he became interested in two additional aspects of neurology. Firstly, he saw that genetic causes of disease were an increasingly important aspect of neurology, and he became fascinated by a specific subset of these diseases that impair cellular metabolism in the brain. Secondly, and linked to the first observation, he became interested in the most acute and severe forms of neurologic illness, those that required management in a critical care setting. In particular, he began to see an emerging pattern where children severely affected by genetic disorders often require critical care while also lacking any targeted therapies for their specific genetic disorder. The clinical observations led him to pursue post-doctoral research in mitochondrial metabolism, supervised by Dr. Navdeep Chandel at Northwestern University. He also completed an advanced clinical fellowship in Pediatric NeuroCritical Care at Ann & Robert H. Lurie Children’s Hospital of Chicago. He is now a junior faculty member at Northwestern and Lurie Children's, where he is expanding his niche as a physician-scientist at the intersection mitochondrial diseases and NeuroCritical care by studying basic aspects of mitochondrial metabolism in the neuronal subpopulations.