Neena Singh, M.D., Ph.D.Professor
2103 Cornell Rd.
Cleveland, OH 44106-7288
phone: (216) 368-2617
fax: (216) 368-0494
|1982||Specialization in Anatomic and Clinical Pathology (M.D), Maulana Azad Medical College, New Delhi, India|
|1990||Ph.D. in Cell Biology, Case Western Reserve University, Cleveland, Ohio|
|1990-1993||Residency in Clinical Pathology, University Hospitals, Cleveland, Ohio|
|1992-1995||Post-doctoral Research Fellowship, Case Western Reserve University, Cleveland, Ohio. (Funded by the National Institutes of Health)|
|1993||Visiting scholar, Department of Pediatrics and Biochemistry, Amsterdam Medical Center, The Netherlands|
|1994||Fellowship in Immunopathology, University Hospitals, Cleveland, Ohio.|
|1994-2001||Assistant Professor, Department of Pathology, Case Western Reserve University, Cleveland, Ohio|
|2001-2011||Associate Professor, Department of Pathology, Case Western Reserve University, Cleveland, Ohio|
|2011-present||Professor, Departments of Pathology and Neurology, Case Western Reserve University, Cleveland, Ohio|
Research in my laboratory is directed at understanding the role of iron, copper, and zinc in the pathogenesis of neurodegenerative conditions of protein misfolding such as sporadic Creutzfeldt-Jakob disease (sCJD), Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Ongoing investigations are focused on the function of prion protein in systemic and brain iron metabolism, the cross-talk between prion protein and Alzheimer precursor protein and A-beta, and the underlying cause of iron imbalance in sCJD and AD brains. Considerable effort is being directed at developing a disease-specific pre-mortem diagnostic test for sCJD and AD based on the change in brain iron status with disease progression. The ultimate goal is to identify common pathogenic processes leading to metal dyshomeostasis in sCJD, AD, PD, and HD, and to develop therapeutic strategies based on restoring metal homeostasis in diseased brains.
A variety of experimental systems are used for these studies, including primary and transformed cells of neuronal, hematopoietic, hepatic, and intestinal origin transfected to express relevant proteins, C. elegans models expressing normal and mutant prion protein, and mouse models representing these disorders. Adequate training and safe facilities for performing the studies are accessible.
Singh N, Haldar S, Tripathi AK, Horback K, Wong J, Sharma D, Beserra A, Suda S, Anbalagan C, Dev S, Mukhopadhyay CK, Singh A. (2014) Brain iron homeostasis: from molecular mechanisms to clinical significance and therapeutic opportunities. Antioxidants & redox signaling, 20(8):1324-1363. PMID: 23815406 PMCID: PMC3935772.
Singh N, Haldar S, Tripathi AK, McElwee MK, Horback K, Beserra A. (2014) Iron in Neurodegenerative Disorders of Protein Misfolding: A Case of Prion Disorders and Parkinson's Disease. Antioxidants & redox signaling, Epub 2014/02/12. doi: 10.1089/ars.2014.5874. PMID: 24512387.
Singh N. The role of Iron in prion disease and other neurodegenerative diseases. (2014) Invited review, Plos Pathog. 10(9):e 1004335. PMID: 25232824
Haldar S, Tripathi AK, Qian J, Bessera A, Suda S, McElwee M, Turner J, Hopfer U, Singh N. (2014) The ferrireductase activity of prion protein promotes iron uptake by the kidney. 2014. Under review.
Tripathi AK, Haldar S, Qian J, Beserra A, Suda S, Singh A, Kaplan J, Ward D, Chen SG, Garrick M, Turner J, Knutson M, Singh N. (2014) Prion protein promotes uptake of NTBI by hepatocytes through Zip14 and DMT1. Under review.
Mishra, R.S., Basu, S., Gu, Y., Luo, X., Zou, W., Mishra, R., Li, R., Chen, S.G., Gambetti, P., Fujioka, H., and Singh, N. (2004) Protease resistant human prion protein and ferritin are co-transported across Caco-2 epithelial cells: Implications for species barrier in prion uptake from the intestine. J. Neurosci. 24:11280-11290.
Featured in "This week in the Journal" in J. Neurosci. (Vol. 24 p0), News@nature.com, and other news agencies. Featured in Lancet Neurology (Vol. 4, p81), JAMA (Vol. 293: p285)
Basu, S., Mohan, M.L., Luo, X., Kundu, B., Kong, Q., and Singh, N.. (2007) Modulation of PK-resistant PrPSc in cells and infectious brain homogenate by redox-iron: Implications for prion replication and disease pathogenesis. Mol Biol Cell. 18: 3302-3312.
Singh, A, Mohan, M.L., Isaac, Alfred O., Luo, X., and Singh, N.. (2009) Prion protein modulates cellular iron metabolism: Implications for prion disease pathogenesis. PLoS ONE 4: e4468. PMCID: PMC2637434
Singh, A., Isaac, A.O., Luo, X., Mohan, M.L., Bartz, J., Kong, K., Cohen, M., and Singh, N.. (2009) Abnormal brain iron homeostasis in human and animal prion disorders. PLoS Pathogens 5:e1000336. PMCID: PMC2652663.
Selected as 'Featured Research' in February 2009 issue of Plos Pathogens, and cited by several local, National, and International news agencies. Featured in 'Nature Journal club' 460: 669, 2009.
Singh, A., Kong, Q., Luo, X., Petersen, R.B., Meyerson, H., and Singh, N.. (2009) Prion protein knock-out mice show altered iron metabolism: A functional role for PrP in iron metabolism. Plos ONE 4:e6115. PMID: 19568430. PMCID:PMC2699477.
Published in the autumn 2009 issue of Prion Science. Prionics AG 15.
Singh, N.., Singh, A., Das, D., and Mohan, M.L. (2010) Redox control of prion and disease pathogenesis. Antioxid Redox Signal. 12:1271-94.
Singh, A., Beveridge, AJ., and Singh, N.. (2011) CSF transferrin is down-regulated in sCJD: a potential pre-mortem diagnostic test for prion disorders. PloS ONE, 6(3): e16804. doi:10.1371/journal.pone.0016804. Selected for press release by the journal.
Singh, A., Qing, L., Kong, Q., and Singh, N.. (2012) Change in the characteristics of ferritin induces iron imbalance in prion disease affected brains. Neurobiol Dis 45: 930-938. PMID:22182691.
Singh A, Haldar S, Horback K, Tom C, Zhou L, Meyerson H, and Singh N. (2013) Prion protein regulates iron transport by functioning as a ferrireductase. Journal of Alzheimers Dis 35: 541-552. Selected for press release by the journal. PMID:23478311.
Haldar S, Beveridge A, Wong J, Singh A, Galimberti D, Borroni B, Zhu X, Blevins J, Greenlee J, Perry G, Mukhopadhyay C, Schmotzer C., Singh N. (2013) A low molecular-weight ferroxidase is increased in the CSF of sCJD cases: CSF ferroxidase and transferrin as diagnostic biomarkers for sCJD. Antioxid Redox Signal. 2013 April 16. PMID:23379482.
Singh N, Haldar S, Tripathi AK, Horback K, Wong J, Sharma D, Bessera A, Suda S, Anbalagan C, Dev S, Mukhopadhyay CK, Singh A. (2013) Brain iron homeostasis: From molecular mechanisms to clinical significance and therapeutic opportunities. Invited review, Antioxid Redox Signal. In press.