Srini Subramaniam, Ph.D.
Assistant Professor
Ph.D., University of Heidelberg, Germany, 2004
Department of Neuroscience
The Scripps Research Institute
130 Scripps Way 3C2
Jupiter, Florida 33458
Telephone: 561-228-2104
Fax: 561-228-2107
Email: SSubrama@scripps.edu
Research Interests
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 causes profound deficits in hippocampal neurons; Parkinson disease (PD) patients lose neurons in the substantia nigra; Spinal muscular atrophy (SMA) patients lose motor neurons; 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 Huntington disease
• Signaling mechanisms in motor neuron death in spinal muscular atrophy
• Novel modulators of Alzheimer disease pathogenesis
Selected Publications
Subramaniam S*, Strelau J* and 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
Subramaniam S*, Zirrgiebel U, von Bohlen Und Halbach O, Strelau J, Laliberte C, Kaplan DR and 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
Subramaniam S*, Shahani N, Strelau J, Laliberte C, Brandt R, Kaplan D and 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
Subramaniam S* and Unsicker K (2006) Extracellular signal-regulated kinase as an inducer of non-apoptotic neuronal death. Neuroscience 138, 1055-1065. Review. *Corresponding author
Subramaniam S*, Strelau J and 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
Subramaniam S, Sixt KM, Barrow R and Snyder SH (2009) Rhes, a Striatal Specific Protein, Mediates Mutant-Huntingtin Cytotoxicity. Science 324, 1327-1330.
Subramaniam S* and Unsicker K (2010) ERK in neuronal death. FEBS J 277, 22-9. Review. *Corresponding author
Subramaniam S and Snyder SH (2011). Huntington's disease is a disorder of the corpus striatum: focus on Rhes (Ras homologue enriched in the striatum). Neuropharmacology. 60, 1187-92. Review
Subramaniam S*, Mealer R*, Sixt KM, Barrow R, Usiello A and Snyder SH (2010) RHES, a physiological regulator of sumoylation, mediates cross-sumoylation among basic sumo enzymes E1 and Ubc9. J Biol Chem 285, 20428-32. *Contributed equally
Subramaniam S*, Napolitano F*, Mealer RG, Kim S, Errico F, Barrow R, Shahani R, Tyagi R, Snyder SH, and Usiello A (2011) Rhes, a striatal-enriched small G-protein, mediates mTOR signaling and L-DOPA-induced dyskinesia. Nat Neurosci. Dec 18. doi: 10.1038/nn.2994). *Contributed equally
Awards, Recognition, Appointments, and Honors
Academic:
1996 2nd Prize, Best Lecture “Embryonic Body Plan in Drosophila,” Bangalore, India
1996 Project Trainee, Indian Institute of Science, Bangalore, India
1996-98 Lecturer in Chemistry and Biochemistry, MLA and NMKRV College, India
1998 Project Assistant, Indian Institute of Science, Bangalore, India
1999 Research Assistant, University of Muenster, Germany
2002 Pre-Doctoral Fellowship, German Research Foundation, Germany
2004 Summa Cum laude, University of Heidelberg, Heidelberg, Germany
2005 Invited Young Scientist, 55th Meeting for Nobel Laureates, Germany
2005 Wolfgang-Bargmann Prize, Anatomical Society, Germany
2005 Young Investigator Award, University of Heidelberg, Heidelberg, Germany
2009 Travel Grant Award, Gordon Triplet Disorder Research Seminars, USA
2009 Travel Grant Award, Gordon Triplet Disorder Research Conference, USA
2010 Daniel Nathan’s Research Award by Johns Hopkins School of Medicine, USA
Non-Academic:
1991 Bronze Medal, State Taekwondo Championship, Bangalore, India
1992 Silver Medal, State Taekwondo Championship, Bangalore, India
1992-96 Instructor, YPR Taekwondo School, Bangalore, India
1994 State Referee, World Taekwondo Federation, Bangalore, India
1994 Participant, National Games, Pune, India
1994 Gold Medal, South India Taekwondo Championship, Kadappa, India
1995 Gold Medal, State Taekwondo Championship, Bangalore, India
1996 Gold Medal, State Open Taekwondo Championship, Bangalore, India
2003 Secretary, Heidelberg Indian Student Association, Heidelberg, Germany
2004 President, Samatva Trust for Promoting Rural-Children Education, India
2009 Winner of “Kaveri Idol” by Kaveri Washington/Maryland association, USA
2011 Runner up “Kaveri Idol” by Kaveri Washington/Maryland association, USA