Education & Training:
Panjab University, India, 1965, B.S. in Biochemistry
Panjab University, India, 1967, M.S. in Biochemistry
Iowa State University, Ames, 1974, Ph.D. in Biochemistry
EKS Research Center/ Massachusetts General Hospital, Boston, 1976,
Postdoctoral Fellow in Neurochemistry
Panjab University, India, 2017, D.Sc. in Science
Research Interests:
Research interests of our laboratory are to understand the cellular signaling mechanisms and the pathobiology of disease conditions and identification of potential new and effective drug therapies for diseases such as Adrenoleukodystrophy, Kraabbe’s disease, multiple sclerosis (MS), hypoxia /Stroke, Optic neuritis, Spinal cord injury (SCI), Traumatic Brain Injury (TBI) and Vascular / Alzheimer’s dementia using respective disease cell culture and animal models and subsequently to evaluate the potential drug candidates in human studies.
We have a long standing in interest in X-ALD and MS disease mechanisms. Our laboratory was the first to report the inflammatory/immune regulatory properties of statins using cell culture and animal model of EAE leading to a 30 MS patient study showing efficacy of use of atorvastatin (Lancet 2004) and the efficacy of lovastatin in patients with AMN (New Eng.J. Med. 1998). Subsequently, we also reported that statin mediated modulation of RhoA (small GTPase) and AICAR mediated modulation of AMPK provides neuroprotection and neurorepair by induction of OPC differentiation into myelin producing mature oligodendrocytes and thus remyelination.
Recent studies from our laboratory have described a novel role of the NO metabiolome /GSNO in immune/vascular disease mechanisms using animal models of hypoxia/stroke, MS, traumatic brain, spinal cord injury and vascular dementia. The underlying GSNO mediated mechanisms include regulation of extracellular matrix protein (CAMS) expression and thus extravasation of vascular immune cells as well as S-nitosylation mediated regulations of NOS/ NFkB/ STATs/ AMPK/Calpain mediated cellular signaling mechanisms.
The novelty of these studies is the clinical relevance of Statin/NO based therapeutics in human disease.
Highlight Publications:
1.Singh I., Moser, A. E., Goldfisher,S., Moser, H.W. (1984) Lignoceric Acid in peroxisomes: Implications for Zellweger Cerebro-Hepato-Renal syndrome and X-Adrenoleukodystrophy. Proc. Natl. Acad. Sci., 81:4203-4207, PMID: 6588384
2. Lazo, O., Contreras, M., Hashmi, M., Stanley, W., and Singh, I. (1988) Peroxisomal Lignoceroyl-CoA ligase deficiency in Adrenoleukodystrophy and Adrenomyeloneuropathy. Proc. Natl. Acad. Sci., 85:7647-7651, PMID: 3174658
3. Singh I., Khan, M., Key, L., and Pai. Lovastatin for Adrenoleukodystrophy (1998) New Eng. J. Med., 339: 702-703, PMID: 9729143
4. Pahan, K., Seikh, K., Namboodiri, S.M. and Singh, I. (1997) Lovastatin and Phenylacetate inhibit the induction of Nitric Oxide Synthetase and Cytokines in primary astrocytes, microglia and macrophages. J. Clin. Invest., 100: 2671-2679, PMID: 9389730
5. Nath, N., Giri, S., Prasad, R., Singh, A.K. and Singh, I. (2004) Potential Targets of 3-hydroxy methylglutaryl CoA reductase inhibitors for Multiple Sclerosis Therapy. J. Immunol.,172: 1273-1286, PMID: 14707106
6. Vollmer T., Key, L.L., Durkasky, V., Tyor, W., Corrboy, J., Markovic,-Plese, S., Preningenova, J., Rizzo, M., and Singh, I. (2004) Oral Simvastatin treatment in relapsing-remitting multiple Sclerosis. Lancet, 363: 1607-1608, PMID: 15145635
7. Paintalia, AS., Paintalia, Mk., Khan, M., Vollmer,T., Singh, A. K. and Singh, I. (2005) HMG-CoA reductase inhibitot augments survival and differentiation of oligodendrocyte proginitors in animal model Multiple Sclerosis. FASEB, J., 19: 1407-1421, PMID: 16126908
8. Baarine, M. Khan, M., Singh A. and Singh, I. (2015) Functional Characterization of IPSC-derived Brain Cells as a model for X-Adrenoleukodystrophy. PLoS One, 18:1-19, PMID: 26581106
9. Singh, I., Samuvel, DJ. Choi, S., Sexena, N., Singh, AK, and Won, JS (2018) Combination therapy of lovastatin and AMP activated protein kinase activator improves mitochondria and peroxisomal functions in experimental autoimmune encephalomyelitis model. Immunology, 154, 434-451, PMID: 29331024
10. Sexena N., Won, JS, Choi, S., Singh, AK. and Singh, I. (2018) S-nitrosoglutathione reductase inhibitor is an immune modulator in experimental autoimmune encephalomyelitis. Free Rad. Biol. Med., 121: 57-68, PMID: 29694854
11. Sakakima H, Khan M, Dhammu TS, Shunmugavel A, Yoshida Y, Singh I. and Singh AK (2012), Stimulation of functional recovery via the mechanisms of neurorepair by S-nitrosoglutathione and motor exercise in a rat model of transient cerebral ischemia and reperfusion. Restorative Neurology and Neuroscience, 30: 527-528, PMID: 22717646
12. Khan M, Dhammu TS, Sakakima H, Shunmugavel A, Gilg AG, Singh AK, Singh I (2012) The inhibitory effect of S-nitrosoglutathione on blood-brain barrier disruption and peroxynitrite formation in a rat model of experimental stroke. J Neurochem., 123, 86-97, PMID: 23050646
13. Khan M, Dhammu TS, Matsuda F, Baarine M, Dhindsa TS, Singh I, Singh AK (2015), Promoting endothelial function by S-nitrosoglutathione through the HIF-1α/VEGF pathway stimulates neurorepair and functional recovery following experimental stroke in rats. Drug Design, Development and Therapy, 9:2233-2247, PMID: 25945035
14. Khan, M., Dammu,TD.,Qiao,F.,Kumar, P., Singh, AK. and Singh, I. (2109) S-Nitrosogluatathione mimics the beneficial activity of endothelial nitric oxide synthase-derived nitric oxide in mouse model oh stroke, J. Stroke Cerebrovasc. Dis.,Dec 28(12)104470. PMID31680031