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

 Indrapal N. Singh; Edward D. Hall. Multi-faceted roles of sphingosine-1-phosphate: How does this bioactive sphingolipid fit in acute neurological injury? J Neurosci Res. 86: 1419-1433 (Review) (2008).

Ying Deng-Bryant, Indrapal N. Singh, Kimberly M. Carrico, and Edward D. Hall. Neuroprotective effects of tempol, a catalytic scavenger of peroxynitrite-derived free radicals, in a mouse traumatic brain injury model. J Cereb Blood Flow Metab. 28(6): 1114-26 (2008).

L. N. Mbye, I. N. Singh, K. M. Carrico, K. E. Saatman, and Edward D. Hall. Comparative neuroprotective effects of Cyclosporin A and NIM811, a nonimmunosuppressive cyclosporine A analog, following traumatic brain injury. J Cereb Blood Flow Metab. 29(1): 87-97 (2009).

Mustafa AG, Singh IN, Wang J, Carrico KM, Hall ED. Mitochondrial protection after traumatic brain injury by scavenging lipid peroxyl radicals. J Neurochem. 2010 Jul;114(1):271-80.

 pubmed link for SINGH