SCoBIRC FACULTY

Indrapal N. Singh, Ph.D.

Research Assistant Professor
Spinal Cord & Brain Injury Research Center (SCoBIRC) and Department of Anatomy & Neurobiology

Ph. D in Neurochemistry from Central University of Hyderabad, India
Post-doctotal Training at Eunice Kennedy Shriver Center for Mental Retardation, Inc, Waltham and Department of Neurology, Harvard Medical School, Boston, USA; University of Manitoba, Winnipeg, Manitoba, Canada.

Curriculum Vitae (pdf)

Research Interests

Roles of Mitochondrial Dysfunction and Lipid Mediators in Post-traumatic Neurodegeneration
My current research interests are towards sphingolipid signaling, in particular Sphingosine-1-Phosphate (Sph-1-P), in the acute pathophysiology of CNS injury and repair mechanisms. There is a strong rationale for the idea that pharmacological agents that either promote or mimic and in some instances antagonize the activities of Sph-1-P may be therapeutic in the context of acute CNS injury and perhaps neurodegenerative diseases. However, drug discovery efforts aimed at modulation of sphingolipid signaling such as specific Sph-1-P receptor agonists or antagonists have been limited. Thus, far only one Sph-1-P -related compound, FYT720, has been examined in a handful of model systems and taken into clinical development. The FTY720 acts as a prodrug and is converted to an active aminophosphate (FTY720-P) metabolite through SphK₂-mediated phosphorylation in vivo. It is being explored as an immunomodulator and has been reported to have efficacy in a phase III clinical trial in relapsing multiple sclerosis. This active metabolite generated upon phosphorylation in vivo, acts as a potent agonist on four of the five known Sph-1-P receptors, namely S1P₁, S1P₃, S1P₄, and S1P₅. The FTY720 at micromolar concentration induced alterations in mitochondrial membrane potential ( _m) and Bax cleavage, followed by translocation of cytochrome c and Smac/Diablo from mitochondria to the cytosol. It would be interesting to determine whether FTY720 might act as sphingolipid-based therapeutic drug by antagonizing the pathophysiological features of acute CNS injury including mitochondrial dysfunction, lipid hydrolysis, oxidative damage and apoptotic cell death.

Representative Publications

Vidya N. Nukala; Indrapal N. Singh; Laurie M. Davis; Patrick G. Sullivan. Cryopreservation of Brain Mitochondria Using Dimethyl Sulfoxide: A Practical Methodology for Functional Studies. J Neurosci Methods. 152(1-2):48-54 (2006).

Indrapal N. Singh; Patrick G. Sullivan; Ying Deng; Lamin H. Mbye; Edward D. Hall. Time Course of Post-traumatic Mitochondrial Oxidative Damage and Dysfunction in A Mouse Model of Focal Brain Injury: Implications for Neuroprotective Therapy. J Cereb Blood Flow Metab. 26: 1407-1418 (2006).

Tatiana Yakovleva; Igor Bazov; Guido Cebers; Zoya Marinova; Yuko Hera; Aisha Ahmed; Mila Vlaskovska; Bjorn Johansson; Ute Hochgeschwender; Indrapal N. Singh; Annador J. Bruce-Keller; Yasmin L. Hurd; Takeshi Kaneko; Lars terenius; Tomas J. Ekstrom; Kurt F. Hauser; Virginia M. Pickel; Georgy Bakalkin. Prodynorphin Storage and processing in Axon Terminals and Dendrites. FASEB J. 20: E1430-E1440/ 2124-2126 (2006).

Indrapal N. Singh; Patrick G. Sullivan; Edward D. Hall. Peroxynitrite-mediated oxidative damage to brain mitochondria: Protective effects of peroxynitrite scavengers. J Neurosci Res. 85: 2216-2223 (2007).