Scripps Florida - The Scripps Research Institute Department of Neuroscience

Department of Neuroscience

FACULTY DIRECTORY

Srini Subramaniam, Ph.D.

Srini Subrmaniam

Associate Professor

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

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
Website: http://www.scripps.edu/subramaniam/index.html

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; 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.

Currently, we are pursuing a number of lines of investigation. We have demonstrated a novel role for Rhes – a small G-protein highly enriched in the striatum – in mediating cellular toxicity through its interactions with mutant huntingtin, the protein which causes HD. Mechanistically, Rhes modifies proteins by the addition of a small ubiquitin-like protein, SUMO, via its interactions with the enzymes of SUMO pathway. Further, we found novel roles for Rhes as a mediator of L-DOPA-induced dyskinesia in PD. Thus, we believe that drugs targeting Rhes may have therapeutic benefits for one or more diseases. We are currently pursuing these and other lines of inquiry in both cell culture and animal models.

Our areas of research include:

•     Signaling mechanisms mediating striatal dysfunction in Huntington disease
and Parkinson disease
•     Novel modulators of Aging and Alzheimer disease

Selected Publications

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

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).

Shahani N, Pryor W, Swarnkar S, Kholodilov N, Thinakaran G, Burke RE, Subramaniam S*. (2013) Rheb GTPase Regulates β-Secretase Levels and Amyloid β Generation. J Biol Chem. Dec 24. [Epub ahead of print] *Corresponding author

Mealer RG, Murray AJ, Shahani N, Subramaniam S*, Snyder SH. (2013) Rhes, a Striatal-Selective Protein Implicated in Huntington Disease, Binds Beclin-1 and Activates Autophagy. J Biol Chem. Dec 9. [Epub ahead of print] *Co-corresponding author

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):4206-10.

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. (F1000 Selection)

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, Sixt KM, Barrow R and Snyder SH (2009) Rhes, a Striatal Specific Protein, Mediates Mutant-Huntingtin Cytotoxicity. Science 324, 1327-1330. (F1000 Selection)

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*, 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

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
2013 Featured in "Palm Beach Post" in a the Accent section, West Palm Beach, FL Feb 2013
2013 Featured in "Boomer Times Radio Show", Boca Raton, FL March 2013