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Department of Neuroscience


Srinivasa Subramaniam, PhD

Scripps Research Affiliate
Department of Neuroscience
Florida Campus
Laboratory Website
ssubrama@scripps.edu
(561) 228-2104

Scripps Research Joint Appointments

Faculty, Graduate Program

Other Joint Appointments

Affiliate Research Professor, Center for Molecular Biology and Biotechnology (CMBB), Charles E Scmidt College of Science, Florida Atlantic University

Research Focus

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

Education

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

Professional Experience

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.

Awards & Professional Activities

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

Selected References

  1. Eshraghi, Mehdi & Karunadharma, Pabalu & Blin, Juliana & Shahani, Neelam & Ricci, Emiliano & Michel, Audrey & Urban, Nicolai & Galli, Nicole & Sharma, Manish & Ramirez-Jarquin, Uri & Florescu, Katie & Hernandez, Jennifer & Subramaniam, Srinivasa*. (2021). Mutant Huntingtin stalls ribosomes and represses protein synthesis in a cellular model of Huntington disease. Nature Communications. 12. 10.1038/s41467-021-21637-y.
  2. Ramirez-Jarquin, Uri & Shahani, Neelam & Pryor, William & Usiello, Alessandro & Subramaniam, Srinivasa*. (2020). The mammalian target of rapamycin (mTOR) kinase mediates haloperidol-induced cataleptic behavior. Translational Psychiatry. 10. 10.1038/s41398-020-01014-x.
  3. Park, Sophia & Ramirez-Jarquin, Uri & Shahani, Neelam & Rivera, Oscar & Sharma, Manish & McManus, Francis & Thibault, Pierre & Subramaniam, Srinivasa*. (2020). SUMO Modifies GβL and Mediates mTOR Signaling. 10.1101/2020.09.03.281881.
  4. Sharma, Manish & Rajendrarao, Sumitha & Shahani, Neelam & Ramirez-Jarquin, Uri & Subramaniam, Srinivasa*. (2020). Cyclic GMP-AMP synthase promotes the inflammatory and autophagy responses in Huntington disease. Proceedings of the National Academy of Sciences. 117. 10.1073/pnas.2002144117.
  5. Eshraghi, Mehdi & Ramirez-Jarquin, Uri & Shahani, Neelam & Nuzzo, Tommaso & Rosa, Arianna & Swarnkar, Supriya & Galli, Nicole & Rivera, Oscar & Tsaprailis, George & Scharager-Tapia, Catherina & Crynen, Gogce & Li, Qin & Thiolat, Marie-Laure & Bezard, Erwan & Usiello, Alessandro & Subramaniam, Srinivasa*. (2020). RasGRP1 is a causal factor in the development of l-DOPA–induced dyskinesia in Parkinson’s disease. Science Advances. 6. eaaz7001. 10.1126/sciadv.aaz7001.
  6. Subramaniam, Srinivasa*. (2020). Rhes Tunnels: A Radical New Way of Communication in the Brain's Striatum?. BioEssays. 42. 1900231. 10.1002/bies.201900231.
  7. Sharma, Manish & Rajendrarao, Sumitha & Shahani, Neelam & Ramirez-Jarquin, Uri & Subramaniam, Srinivasa*. (2020). cGAS, a DNA Sensor, Promotes Inflammatory Responses in Huntington Disease. 10.1101/2020.01.08.898718.
  8. Sharma, Manish & Nimrod, Uri & Ramirez-Jarquin, Uri & Rivera, Oscar & Kazantzis, Melissa & Eshraghi, Mehdi & Shahani, Neelam & Sharma, Vishakha & Tapia, Ricardo & Subramaniam, Srinivasa*. (2019). Rhes, a striatal-enriched protein, promotes mitophagy via Nix. Proceedings of the National Academy of Sciences. 116. 10.1073/pnas.1912868116.
  9. Eshraghi, Mehdi & Ramirez-Jarquin, Uri & Shahani, Neelam & Swarnkar, Supriya & Galli, Nicole & Rivera, Oscar & Tsaprailis, George & Scharager-Tapia, Catherina & Crynen, Gogce & Usiello, Alessandro & Subramaniam, Srinivasa*. (2019). RasGRP1 (CalDAG-GEF-II) Mediates L-DOPA-induced Dyskinesia in a Mouse Model of Parkinson Disease. 10.1101/739631.
  10. Sharma, Manish & Ramirez-Jarquin, Uri & Rivera, Oscar & Karantzis, Melissa & Eshraghi, Mehdi & Shahani, Neelam & Sharma, Vishakha & Tapia, Ricardo & Subramaniam, Srinivasa*. (2019). Rhes, a Striatal-Enriched Protein, Promotes Mitophagy Via Nix. 10.1101/703934.
  11. Shahani, Neelam & Swarnkar, Supriya & Giovinazzo, Vincenzo & Morgenweck, Jenny & Bohn, Laura & Scharager-Tapia, Catherina & Pascal, Bruce & Martinez-Acedo, Pablo & Khare, Kshitij & Subramaniam, Srinivasa*. (2016). RasGRP1 promotes amphetamine-induced motor behavior through a Rhes interaction network ("Rhesactome") in the striatum. Science Signaling. 9. ra111-ra111. 10.1126/scisignal.aaf6670.
  12. Shahani, Neelam & Huang, Wen-Chin & Varnum, Megan & Page, Damon & Subramaniam, Srinivasa*. (2016). Forebrain Depletion of Rheb Elicits Spatial Memory Deficits in Mice. Neurobiology of Aging. 50. 10.1016/j.neurobiolaging.2016.11.006.
  13. Tyagi, R#, Shahani N#,Gorgen L, Ferretti M, Pryor W, Chen, PY, Swarnkar, S, Worley PF, Karbstein K, Snyder SH* and Subramaniam S* (2015). Rheb Inhibits Protein Synthesis by Activating the PERK-eIF2a Signaling Cascade. Cell Reports (in press). *Correspondence
  14. Pryor WM, Biagioli M, Shahani N, Swarnkar S, Huang WC, Page DT, MacDonald ME, Subramaniam S*. (2014) Huntingtin promotes mTORC1 signaling in the pathogenesis of Huntington's disease.  Science  Signaling. 7(349):ra103. *Corresponding author. (F1000 selection)
  15. Shahani N, Seshadri S, Jaaro-Peled H, Ishizuka K, Hirota-Tsuyada, Y, Wang Q, Koga M, Sedlak TM, Korth C,Brandon NJ, Kamiya A, Subramaniam S, Tomoda T and Sawa A. (2014) DISC1 regulates trafficking and processing of APP and Aβ generation. Mol. Psychiatry: (10.1038). 100
  16.  Shahani N, Pryor W, Swarnkar S, Kholodilov N, Thinakaran G, Burke RE, Subramaniam S* (2014) Rheb GTPase Regulates β-Secretase Levels and Amyloid β Generation J Biol Chem. 289(9):5799.  *Corresponding author
  17.  Mealer RG, Murray AJ, Shahani N, Subramaniam S*, Snyder SH. (2014) Rhes, a Striatal-Selective Protein Implicated in Huntington Disease, Binds Beclin-1 and Activates Autophagy. J Biol Chem. 289(6):3547. *Co- correspondence
  18.  Narayanan KL, Subramaniam S, Bengston CP, Irmady K, Unsicker K, von Bohlen Und Halbach O. (2014) Role of Transient Receptor Potential Channel 1 (TRPC1) in Glutamate-Induced  Cell  Death  in  the  Hippocampal  Cell  Line HT22 . J Mol Neurosci. 52(3):425
  19.  Mealer RG, Subramaniam S and Snyder SH. (2013). Rhes deletion is neuroprotective in 3-nitropropionic acid (3NP) toxin mouse model of Huntington’s disease. J Neurosci. 33(9):4206
  20.  Srinivasa  Subramaniam*,  Francesco  Napolitano*,  Robert  G.  Mealer,  Seyun  Kim,  Francesco  Errico,  Roxanne Barrow, Neelam Shahani, Richa Tyagi, Solomon H. Snyder and Alessandro Usiello. (2012). Rhes, a striatal-enriched small G-protein, mediates mTOR signaling and L-DOPA-induced dyskinesia. Nature Neuroscience. 15(2):191. *First authors (F1000 selection)
  21.  Subramaniam S and Snyder SH. (2010). Huntington’s disease is a disorder of corpus striatum: Focus on Rhes (Ras homologue enriched in the striatum). Neuropharmacology, 60(7-8):1187
  22.  Subramaniam S*, Mealer R*, Sixt KM, Barrow R, Usiello A & Snyder SH. (2010). RHES, a physiological regulator of sumoylation, mediates cross-sumoylation among basic sumo enzymes E1 and  Ubc9. J Bio. Chem. 285, 20428.*Contributed  equally
  23.  Subramaniam S* & Unsicker K. (2010). ERK in cell death: ERK1/2 in neuronal death (review). FEBS J, 277, 22. *Corresponding  author
  24.  Subramaniam S, Sixt KM, Barrow R and Snyder SH. (2009). Rhes, a Striatal Specific Protein, Mediates Mutant- Huntingtin Cytotoxicity. Science 324, 1327. (F1000 selection)
  25.  Alavian KN, Sgado P, Alberi L, Subramaniam S & Simon HH. (2009). Elevated P75NTR expression causes death of engrailed-deficient midbrain dopaminergic neurons by Erk1/2 suppression. Neural Dev 4, 11
  26.  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. *Corresponding author
  27.  Narayanan KL, 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
  28.  Subramaniam  S*  &  Unsicker  K.  (2006).  Extracellular  signal-regulated  kinase  as  an  inducer  of  non-apoptotic neuronal death. Neuroscience 138, 1055-1065 (review). *Corresponding author
  29.  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
  30.  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
  31.  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. *Corresponding author
  32.  Subramaniam  S*,  Zirrgiebel  U,  von  Bohlen  Und  Halbach  O,  Strelau  J,  Laliberte  C,  Kaplan  DR  &  Unsicker  K. (2004).  ERK  activation  promotes  neuronal  degeneration  predominantly  through  plasma  membrane  damage  and independently of caspase-3. J Cell Biol 165, 357. *Corresponding author
  33.  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 78, 8904. *Contributed equally
  34.  Scholzke  MN,  Potrovita  I,  Subramaniam  S,  Prinz  S  &  Schwaninger  M.  (2003). Glutamate  activates  NF-kappaB through calpain in neurons. Eur J Neurosci 18, 3305
  35.  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

 

 

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