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Neena Singh, M.D., Ph.D.Associate ProfessorMailing Address: fax: (216) 368-0494 email: Neena.Singh@Case.edu |
Biography
Academic Background
| 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 |
Academic/Professional Experience
| 1990-1993 | Residency in Clinical Pathology, Case Western Reserve University, 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, Case Western Reserve University, Cleveland, Ohio |
| 1994-2001 | Assistant Professor, Department of Pathology, Institute of Pathology, Case Western Reserve University, Cleveland, Ohio |
| 2001-present | Associate Professor, Department of Pathology, Institute of Pathology, Case Western Reserve University, Cleveland, Ohio |
Research
Prion disorders are fatal neurodegenerative conditions of humans and animals that are sporadic, inherited,
and infectious in nature. The transmission of “mad cow disease” to humans in Europe and spread of
“chronic wasting disease” in the deer and elk population in the U.S. has renewed public health concerns
and scientific interest in these disorders. In addition, these disorders invoke significant
scientific interest due to their novel mechanism of transmission and neurotoxicity. Unlike
other neurodegenerative conditions, the main pathogenic event in all prion disorders is a change
in conformation of an endogenous glycoprotein, the prion protein (PrPC), to a pathogenic
isoform termed PrP-scrapie (PrPSc) that is infectious and neurotoxic.
The main focus of my laboratory is to understand the mechanism of transmission and neurotoxicity in prion disorders. Current projects are centered on two broad aims: 1) to understand the physiological function of PrPC and whether loss or subversion of this function induces neurotoxicity, and 2) the mechanism of replication and neurotoxicity by PrPSc. Recent data from my laboratory indicate that PrPC is involved in iron transport, and PrPSc induces a state of iron dyshomeostasis in diseased brains. Ongoing projects are aimed at elucidating the mechanism of iron modulation by PrPC, and the role of redox-iron and other transition metals in the propagation and neurotoxicity of PrPSc.
A variety of experimental systems are used for these studies, including primary and transformed cells of neuronal, hematopoietic, hepatic, and intestinal origin transfected with normal and mutant PrP forms, C. elegans models expressing normal and mutant PrP, transgenic mice, and prion infected cell and animal models. Adequate training and safe facilities for performing these experimental procedures are accessible.
Positions are available for graduate and post-graduate training.
Publications
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.
This paper was featured in “This week in the Journal” in the Journal of Neuroscience (Vol. 24 p0),
Lancet Neurology (Vol. 4, p81), JAMA (Vol. 293: p285), News@nature.com, BBC news.com, MSNBC news.com,
and several other local, national, and international news organizations.
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.
Singh, A., Isaac, 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.
This report was selected as the ‘Featured Research’ in the February 2009 issue of Plos Pathogens,
and cited by several local, National, and International news agencies.
This article was also featured in the Nature Journal club (2009, 460: 669)
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.
This report was published in the autumn 2009 issue of Prion Science. Prionics AG 15.
Singh, N., Singh, A., Das, D., and Mohan, M.L. (2009) Redox control of prion and disease pathogenesis. Antioxidants and redox Signaling. Comprehensive invited review. In press.