Srinivasa Subramaniam

Srinivasa Subramaniam, Ph.D.

Associate Professor

Department: SR-NEURO-SUBRAMANIAM LAB
Business Phone: (561) 228-2104
Business Email: subramaniams@ufl.edu

About Srinivasa Subramaniam

Dr. Srini Subramaniam is an Associate Professor (Tenure Track.) He obtained his PhD in 2004 from the University of Heidelberg, Germany, where he worked on the molecular signaling that triggers neuronal death. At Johns Hopkins University for his postdoctoral research, he addressed the mechanisms for tissue-specific dysfunctions, focusing Huntington’s and Parkinson’s disease. Both experiences continue to inform his work at The Scripps Research Institute. His hobbies involve running, boxing and sketching.

Related Links:
Additional Positions:
Assistant Professor, Neuroscience
2012 – 2016 · Scripps Research
Research Associate, Department of Neuroscience
2011 – 2012 · School of Medicine, Johns Hopkins University
Postdoctoral Fellow, Department of Neuroscience
2006 – 2011 · School of Medicine, Johns Hopkins University

Accomplishments

Daniel Nathan’s Research Award
2010 · Johns Hopkins Medical School
Travel Grant Award
2009 · Gordon Triplet Disorder Research Conference
Travel Grant Award
2009 · Gordon Triplet Disorder Research Seminars
Winner of “Kaveri Idol 2009”
2009 · Washington/Maryland Kaveri Indian Association
Invited Young Scientist
2005 · 55th Meeting of Nobel Laureates, an Interdisciplinary Event for Nobel Laureates in Chemistry, Physics and Physiology/Medicine, Lindau, Germany
Wolfgang-Bargmann Prize for the best PhD dissertation
2005 · Anatomical Societies, Germany
Young Investigator Award
2005 · University of Heidelberg, Heidelberg, Germany
2004 Summa Cum laude, Die Naturwissenshaftlich-Mathematische Gesamtfakultat,
2004 · University of Heidelberg, Heidelberg, Germany
Secretary
2003 · Heidelberg Indian Student Association, Heidelberg, Germany
Pre-Doctoral fellowship
2002 · German Research Foundation
Gold Medal
1996 · State Open Taekwondo Championship, Bangalore, India
Second Prize, Best Lecture for the Talk “Embryonic Body-Plan in Drosophila”
1996 · University of Bangalore, Bangalore, India
Gold Medal
1995 · State Taekwondo Championship, Bangalore, India
Gold Medal
1994 · South Indian Taekwondo Championship, Kadappa, India
Participant
1994 · National Games, Pune, India
State Referee
1994 · World Taekwondo Federation, Bangalore, India
Silver Medal
1992 · State Taekwondo Championship, Bangalore, India
Bronze Medal
1991 · State Taekwondo Championship, Bangalore, India

Research Profile

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

Open Researcher and Contributor ID (ORCID)

0000-0002-7428-4953

Publications

2022
Abnormal RasGRP1 Expression in the Post-Mortem Brain and Blood Serum of Schizophrenia Patients.
Biomolecules. 12(2) [DOI] 10.3390/biom12020328. [PMID] 35204828.
2022
Deletion of SUMO1 attenuates behavioral and anatomical deficits by regulating autophagic activities in Huntington disease
Proceedings of the National Academy of Sciences. 119(5) [DOI] 10.1073/pnas.2107187119. [PMID] 35086928.
2022
Rhes protein transits from neuron to neuron and facilitates mutant huntingtin spreading in the brain
Science Advances. 8(12) [DOI] 10.1126/sciadv.abm3877. [PMID] 35319973.
2022
Striatal Induction and Spread of the Huntington’s Disease Protein: A Novel Rhes Route.
Journal of Huntington's disease. 11(3):281-290 [DOI] 10.3233/JHD-220548. [PMID] 35871361.
2021
Global Rhes knockout in the Q175 Huntington’s disease mouse model.
PloS one. 16(10) [DOI] 10.1371/journal.pone.0258486. [PMID] 34648564.
2021
Mutant Huntingtin stalls ribosomes and represses protein synthesis in a cellular model of Huntington disease.
Nature communications. 12(1) [DOI] 10.1038/s41467-021-21637-y. [PMID] 33674575.
2021
Ribosome traffic jam in neurodegeneration: decoding hurdles in Huntington disease.
Cell stress. 5(6):86-88 [DOI] 10.15698/cst2021.06.251. [PMID] 34124583.
2020
Cyclic GMP-AMP synthase promotes the inflammatory and autophagy responses in Huntington disease.
Proceedings of the National Academy of Sciences of the United States of America. 117(27):15989-15999 [DOI] 10.1073/pnas.2002144117. [PMID] 32581130.
2020
Exaggerated mitophagy: a weapon of striatal destruction in the brain?
Biochemical Society Transactions. 48(2):709-717 [DOI] 10.1042/bst20191283.
2020
RasGRP1 is a causal factor in the development of l -DOPA–induced dyskinesia in Parkinson’s disease
Science Advances. 6(18) [DOI] 10.1126/sciadv.aaz7001. [PMID] 32426479.
2020
Rhes Tunnels: A Radical New Way of Communication in the Brain’s Striatum?
BioEssays : news and reviews in molecular, cellular and developmental biology. 42(6) [DOI] 10.1002/bies.201900231. [PMID] 32236969.
2020
The mammalian target of rapamycin (mTOR) kinase mediates haloperidol-induced cataleptic behavior.
Translational psychiatry. 10(1) [DOI] 10.1038/s41398-020-01014-x. [PMID] 33009372.
2019
Rhes travels from cell to cell and transports Huntington disease protein via TNT-like protrusion.
The Journal of cell biology. 218(6):1972-1993 [DOI] 10.1083/jcb.201807068. [PMID] 31076452.
2019
Rhes, a striatal-enriched protein, promotes mitophagy via Nix.
Proceedings of the National Academy of Sciences of the United States of America. 116(47):23760-23771 [DOI] 10.1073/pnas.1912868116. [PMID] 31676548.
2019
Selective Neuronal Death in Neurodegenerative Diseases: The Ongoing Mystery.
The Yale journal of biology and medicine. 92(4):695-705 [PMID] 31866784.
2017
Forebrain depletion of Rheb GTPase elicits spatial memory deficits in mice.
Neurobiology of aging. 50:134-143 [DOI] 10.1016/j.neurobiolaging.2016.11.006. [PMID] 27960107.
2016
RasGRP1 promotes amphetamine-induced motor behavior through a Rhes interaction network (“Rhesactome”) in the striatum.
Science signaling. 9(454) [PMID] 27902448.
2015
Ectopic expression of the striatal-enriched GTPase Rhes elicits cerebellar degeneration and an ataxia phenotype in Huntington’s disease.
Neurobiology of disease. 82:66-77 [DOI] 10.1016/j.nbd.2015.05.011. [PMID] 26048156.
2015
Rheb Inhibits Protein Synthesis by Activating the PERK-eIF2α Signaling Cascade.
Cell reports. 10(5):684-693 [DOI] 10.1016/j.celrep.2015.01.014. [PMID] 25660019.
2014
Huntingtin promotes mTORC1 signaling in the pathogenesis of Huntington’s disease.
Science signaling. 7(349) [DOI] 10.1126/scisignal.2005633. [PMID] 25351248.
2014
Rheb GTPase regulates β-secretase levels and amyloid β generation.
The Journal of biological chemistry. 289(9):5799-808 [DOI] 10.1074/jbc.M113.532713. [PMID] 24368770.
2014
Rhes, a striatal-selective protein implicated in Huntington disease, binds beclin-1 and activates autophagy.
The Journal of biological chemistry. 289(6):3547-54 [DOI] 10.1074/jbc.M113.536912. [PMID] 24324270.
2014
Role of transient receptor potential channel 1 (TRPC1) in glutamate-induced cell death in the hippocampal cell line HT22.
Journal of molecular neuroscience : MN. 52(3):425-33 [DOI] 10.1007/s12031-013-0171-9. [PMID] 24242951.
2013
Rhes deletion is neuroprotective in the 3-nitropropionic acid model of Huntington’s disease.
The Journal of neuroscience : the official journal of the Society for Neuroscience. 33(9):4206-10 [DOI] 10.1523/JNEUROSCI.3730-12.2013. [PMID] 23447628.
2011
Huntington’s disease is a disorder of the corpus striatum: focus on Rhes (Ras homologue enriched in the striatum).
Neuropharmacology. 60(7-8):1187-92 [DOI] 10.1016/j.neuropharm.2010.10.025. [PMID] 21044641.
2011
Rhes, a striatal-enriched small G protein, mediates mTOR signaling and L-DOPA-induced dyskinesia.
Nature neuroscience. 15(2):191-3 [DOI] 10.1038/nn.2994. [PMID] 22179112.
2010
ERK and cell death: ERK1/2 in neuronal death.
The FEBS journal. 277(1):22-9 [DOI] 10.1111/j.1742-4658.2009.07367.x. [PMID] 19843173.
2010
Rhes, a physiologic regulator of sumoylation, enhances cross-sumoylation between the basic sumoylation enzymes E1 and Ubc9.
The Journal of biological chemistry. 285(27):20428-32 [DOI] 10.1074/jbc.C110.127191. [PMID] 20424159.
2009
Elevated P75NTR expression causes death of engrailed-deficient midbrain dopaminergic neurons by Erk1/2 suppression.
Neural development. 4 [DOI] 10.1186/1749-8104-4-11. [PMID] 19291307.
2009
Rhes, a striatal specific protein, mediates mutant-huntingtin cytotoxicity.
Science (New York, N.Y.). 324(5932):1327-30 [DOI] 10.1126/science.1172871. [PMID] 19498170.
2008
Evidence that TRPC1 is involved in hippocampal glutamate-induced cell death.
Neuroscience letters. 446(2-3):117-22 [DOI] 10.1016/j.neulet.2008.09.034. [PMID] 18822346.
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 and tissue research. 331(2):373-83 [PMID] 18071753.
2006
Purification of MINUS: A negative regulator of microtubule nucleation in a variety of organisms.
International journal of biological macromolecules. 39(1-3):15-22 [PMID] 16420961.
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.
The Journal of neuroscience : the official journal of the Society for Neuroscience. 26(22):6103-14 [PMID] 16738255.
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.
The Journal of neuroscience : the official journal of the Society for Neuroscience. 25(11):2838-52 [PMID] 15772344.
2004
ERK activation promotes neuronal degeneration predominantly through plasma membrane damage and independently of caspase-3.
The Journal of cell biology. 165(3):357-69 [PMID] 15123736.
2003
Glutamate activates NF-kappaB through calpain in neurons.
The European journal of neuroscience. 18(12):3305-10 [PMID] 14686903.
2003
Growth differentiation factor-15 prevents low potassium-induced cell death of cerebellar granule neurons by differential regulation of Akt and ERK pathways.
The Journal of biological chemistry. 278(11):8904-12 [PMID] 12514175.
2002
TGF-beta induces cell death in the oligodendroglial cell line OLI-neu.
Glia. 40(1):95-108 [PMID] 12237847.
Rhes Deletion Prevents Age-Dependent Selective Motor Deficits and Reduces Phosphorylation of S6K in Huntington Disease Hdh150Q(CAG) Knock-In Mice
. [DOI] 10.1101/2021.06.16.448681.
Rhes protein transits from neuron to neuron and facilitates mutant huntingtin spreading in the brain
. [DOI] 10.1101/2021.08.27.457956.

Grants

Sep 2022 ACTIVE
Rhes-SUMO Pathway in Huntington disease
Role: Principal Investigator
Funding: NATL INST OF HLTH NINDS
Sep 2022 ACTIVE
Validating cGAS-STING pathway as drug target in Huntington disease mouse model
Role: Principal Investigator
Funding: NATL INST OF HLTH NINDS

Education

Ph.D.
2004 · Heidelberg University, Interdisciplinary Center for Neuroscience
Master's of Science in Biochemistry
1996 · Bangalore University, Central College
Bachelor's of Science in Chemistry, Botany, and Zoology
1992 · Bangalore University, National College

Contact Details

Phones:
Business:
(561) 228-2104
Emails:
Addresses:
Business Mailing:
Location C323
130 SCRIPPS WAY BLDG 3B3
JUPITER FL 33458