Department of Neuroscience
Faculty, Graduate Program
Neurodegenerative diseases are quickly becoming one of the most significant problems facing both the scientific community and the world at large. While our ability to provide symptomatic relief has increased over the past few decades, there are currently no therapies capable of modifying or halting disease progression. Our lab focuses on identification and characterization of signaling networks in neurodegenerative diseases with a goal of developing clinical therapeutics. While many of the inciting insults that cause disease are known, the complex, downstream molecular networks that fail to bring neurons back into homeostasis are poorly understood. This complexity is perhaps best characterized by our paucity of understanding in how different neurogenerative diseases have divergent neuropathologies. For example, Alzheimer’s disease (AD) causes profound deficits in hippocampal neurons; Parkinson disease (PD) patients lose neurons in the substantia nigra; and Huntington disease (HD) patients exhibit nearly complete loss of striatal neurons. Our focus is on understanding the signaling networks that mediate this phenomenon of selective vulnerability. We employ a variety of techniques to study protein-protein interactions, posttranslational modifications and signaling pathways. By elucidating the molecular mechanisms of downstream, etiology-relevant signaling pathways, we hope to discover drug-able target genes and eventually develop novel therapeutics.
Our areas of research include:
• Signaling mechanisms mediating striatal damage in HD
• Signaling mechanisms mediating abnormal movements in PD
• Novel modulators of AD pathogenesis
Ph.D., Neuroscience, University of Heidelberg, Heidelberg, Germany, 2004
M.Sc., Biochemistry, Central College, University of Bangalore, Bangalore, India, 1996
B.Sc., Chemistry, Botany, Zoology, National College, University of Bangalore, Bangalore, India, 1992
2010- 2012 Research Associate Johns Hopkins University, Baltimore, MD Department of Neuroscience Mentor: Prof. Solomon Snyder
2006- 2010 Postdoctoral Fellow Johns Hopkins University, Baltimore, MD Department of Neuroscience Mentor: Prof. Solomon Snyder
2005-2006 Research Assistant University of Heidelberg, Heidelberg, Germany Interdisciplinary Center for Neuroscience Mentor: Prof. Klaus Unsicker
2001-2004 Ph.D. University of Heidelberg, Heidelberg, Germany Interdisciplinary Center for Neuroscience Mentor: Prof. Klaus Unsicker
1999-2000 Research Assistant Institute for Experimental Pathology and Molecular Neurobiology, Muenster, Germany. PI: Dr. Juergen Brosius.
1998-1999 Project Assistant Department of Biochemistry, Indian Institute of Science, Bangalore, India, PI: Dr. HS Savithri.
Apr-July 1996 Project Trainee Developmental Biology and Genetics Laboratory, Indian Institute of Science, Bangalore, India, PI: Dr. Vani Brahmachari.
2010 Daniel Nathan’s Research Award by Johns Hopkins Medical School
2009 Travel Grant Award, Gordon Triplet Disorder Research Conference
2009 Travel Grant Award, Gordon Triplet Disorder Research Seminars
2009 Winner of “Kaveri Idol 2009” organized by Washington/Maryland Kaveri Indian Association
2005 Young Investigator Award, from the University of Heidelberg, Heidelberg, Germany
2005 Wolfgang-Bargmann Prize for the best PhD dissertation, from the Anatomical Societies, Germany
2005 Invited Young Scientist at the 55th Meeting of Nobel Laureates, an Interdisciplinary Event for Nobel Laureates in Chemistry, Physics and Physiology/Medicine, Lindau, Germany
2004 Summa Cum laude, Die Naturwissenshaftlich-Mathematische Gesamtfakultat, University of Heidelberg, Heidelberg, Germany
2003 Secretary, Heidelberg Indian Student Association, Heidelberg, Germany
2002 Pre-Doctoral fellowship, German Research Foundation
1996 Second Prize, Best Lecture for the Talk “Embryonic Body-Plan in Drosophila”, University of Bangalore, Bangalore, India
1996 Gold Medal, State Open Taekwondo Championship, Bangalore, India
1995 Gold Medal, State Taekwondo Championship, Bangalore, India
1994 Gold Medal, South Indian Taekwondo Championship, Kadappa, India
1994 Participant, National Games, Pune, India
1994 State Referee, World Taekwondo Federation, Bangalore, India
1992 Silver Medal, State Taekwondo Championship, Bangalore, India
1991 Bronze Medal, State Taekwondo Championship, Bangalore, India
1. Srinivasa Subramaniam, Francesco Napolitano, Robert G. Mealer, Seyun Kim, Francesco Errico, Roxanne Barrow, Neelam Shahani, Richa Tyagi, Solomon H. Snyder and Alessandro Usiello (2011, submitted) Rhes, a striatal-enriched small G-protein, mediates mTOR signaling and L-DOPA-induced dyskinesia.
2. Subramaniam S. and Snyder S.H. (2010), Huntington disease is a disorder of corpus striatum: Focus on Rhes (Ras homologue enriched in the striatum). Neuropharmacology, Oct 31. [Epub ahead of print].
3. Subramaniam S.*, Mealer R.,*, Sixt K.M., Barrow R., Usiello A. & Snyder S.H. (2010) RHES, a physiological regulator of sumoylation, mediates cross-sumoylation among basic sumo enzymes E1 and Ubc9. The Journal of Biological Chemistry 285, 20428-32. *Contributed equally.
4. Subramaniam S.# & Unsicker K (2010) ERK in cell death: ERK1/2 in neuronal death (review). FEBS J, 277, 22-9. #Corresponding author.
5. Subramaniam S., Sixt K.M., Barrow R. and Snyder S.H. (2009) Rhes, a Striatal Specific Protein, Mediates Mutant-Huntingtin Cytotoxicity. Science 324, 1327-1330.
6. Alavian K.N., Sgado P., Alberi L., Subramaniam S. & Simon H.H. (2009) Elevated P75NTR expression causes death of engrailed-deficient midbrain dopaminergic neurons by Erk1/2 suppression. Neural Dev 4, 11.
7. Subramaniam S.#, Strelau J. & Unsicker K. (2008) GDNF prevents TGF-beta-induced damage of the plasma membrane in cerebellar granule neurons by suppressing activation of p38-MAPK via the phosphatidylinositol 3-kinase pathway. Cell Tissue Res 331, 373-383. #Corresponding author.
8. Narayanan K.L., Irmady K., Subramaniam S., Unsicker K. & von Bohlen und Halbach O (2008) Evidence that TRPC1 is involved in hippocampal glutamate-induced cell death. Neurosci Lett 446, 117-122.
9. Subramaniam S.#, & Unsicker K. (2006) Extracellular signal-regulated kinase as an inducer of non-apoptotic neuronal death. Neuroscience 138, 1055-1065 (review). #Corresponding author
10. Shahani N., Subramaniam S., Wolf T., Tackenberg C. & Brandt R. (2006) Tau aggregation and progressive neuronal degeneration in the absence of changes in spine density and morphology after targeted expression of Alzheimer's disease-relevant tau constructs in organotypic hippocampal slices. J Neurosci 26, 6103- 6114.
11. Shahani N., Subramaniam S. & Brandt R. (2006) Purification of MINUS: A negative regulator of microtubule nucleation in a variety of organisms. Int J Biol Macromol 39, 15-22.
12. Subramaniam S.#, Shahani N., Strelau J., Laliberte C., Brandt R., Kaplan D. & Unsicker K. (2005) Insulin-like growth factor 1 inhibits extracellular signal-regulated kinase to promote neuronal survival via the phosphatidylinositol 3-kinase/protein kinase A/c-Raf pathway. J Neurosci 25, 2838-2852. #Corresponding author
13. Subramaniam S.#, Zirrgiebel U., von Bohlen Und Halbach O., Strelau J., Laliberte C., Kaplan D.R. & Unsicker K. (2004) ERK activation promotes neuronal degeneration predominantly through plasma membrane damage and independently of caspase-3. J Cell Biol 165, 357-369. #Corresponding author
14. Subramaniam S.*, Strelau J.* & Unsicker K. (2003) Growth differentiation factor-15 prevents low potassium-induced cell death of cerebellar granule neurons by differential regulation of Akt and ERK pathways. J Biol Chem 278, 8904-8912. *Contributed equally.
15. Scholzke M.N., Potrovita I., Subramaniam S., Prinz S. & Schwaninger M. (2003) Glutamate activates NFkappaB through calpain in neurons. Eur J Neurosci 18, 3305-3310.
16. Schuster N., Bender H., Philippi A., Subramaniam S., Strelau J., Wang Z. & Krieglstein K. (2002) TGF-beta induces cell death in the oligodendroglial cell line OLI-neu. Glia 40, 95-108.