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)
Roles of Mitochondrial Dysfunction and Lipid Mediators in
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.
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)
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
Mitochondrial protection after traumatic
brain injury by scavenging lipid peroxyl radicals.
Neurochem. 2010 Jul;114(1):271-80.
Vaishnav RA, Singh IN, Miller DM, Hall ED.
Lipid peroxidation-derived reactive
aldehydes directly and differentially impair spinal cord and brain
J Neurotrauma. 2010 Jul;27(7):1311-20.
Xiong Y, Singh IN,
Tempol protection of spinal cord
mitochondria from peroxynitrite-induced oxidative damage.
Free Radic Res.
Sauerbeck A, Pandya J, Singh IN, Bittman K, Readnower R, Bing G,
Sullivan P. Analysis of regional brain mitochondrial
bioenergetics and susceptibility to mitochondrial inhibition
utilizing a microplate based system. J Neurosci Methods.
2011 May 15;198(1):36-43.
link for SINGH
University of Kentucky
Chandler Medical Center
B467 Biomedical & Biological Sciences Research Building (BBSRB)
741 S. Limestone Street
Lexington, KY 40536-0509
Office: (859) 323-4866
Lab: (859) 323-6920
Fax: (859) 257-5737