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Principal Investigator |
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Raghu Vemuganti,
PhD Assistant Professor Department of Neurological Surgery H4/334 Clinical Phone: 608-263-4055 Fax: 608-263-1728 Email: vemugant@neurosurg.wisc.edu |
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Lab Members |
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Yiping Yan, MD, PhD Kellie
Bowen
Ramya Kapadia, MS
(Scientist)
(Research Tech.)
(PhD in progress)
Brad Lang, BS
Ashutosh Dharap, MS (PhD in progress) |
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Research Projects |
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JAK-STAT-SOCS signaling in
post-ischemic cerebral inflammation
When induced, SOCS family of proteins controls cytokine production by negative
feedback regulation of JAK-STAT pathways. We observed increased expression of
SOCS3 and activation of STAT3 in the post-ischemic brain. As cytokines
promote inflammation and neuronal damage, we are evaluating the mechanism of
action of ischemia-induced SOCS3 by using antisense, RNAi and adenoviral
vectors. To identify the complete complement of genes down-stream to SOCS3
signaling, we are conducting GeneChip analysis following knockdown and
overexpression of specific proteins of SOCS/STAT pathway.
Role
of transcription factors Egr1 and C/EBPβ in cerebral inflammation The molecular mechanisms of
inflammatory progression in brain are not well understood. We observed
increased expression of the transcription factors Egr1 and C-EBPβ after
focal ischemia and hypothesize that these two start the pro-inflammatory
cascades in brain. We are currently analyzing the functional significance,
down-stream effectors and the
interactive mechanism of action of Egr1 and C-EBPβ in controlling
the post-ischemic cerebral inflammation using knockout mice, adenoviruses and
antisense. Therapeutic
potential of PPAR-g agonists in
controlling cerebral inflammation PPAR are ligand-activated
transcription factors known to control lipid metabolism, glucose metabolism
and inflammation. Thiozolinediones rosiglitazone and pioglitazone acts as
potent exogenous agonists of PPAR-g and we are
currently trying to understand if these compounds minimize cerebral
inflammation following stroke and if yes, what is their molecular mechanism
of action. Gene
expression profiling following CNS Injury Acute CNS insults alter the
expression of several genes with significant functional consequences. To
develop a viable therapy, it is essential to identify and understand the role
of the novel molecular pathways affected by an insult. My laboratory recently
conducted a massive gene expression profiling following focal cerebral
ischemia, traumatic brain injury and spinal cord injury. These studies
identified inflammatory gene expression driven by pro-inflammatory
transcription factors as a common molecular mechanism underlying excitotoxic
pathologies. We use microarrays and proteomics to identify novel therapeutic
targets to develop neuroprotective drugs. Stem
cell proliferation after Stroke Our lab showed that stroke stimulates
neural progenitor cell proliferation in adult rats. As increasing
neurogenesis in the post-ischemic brain has tremendous potential to replace
lost neurons, we are studying if growth factors promote post-ischemic
survival and differentiation of the neural progenitor cells. |
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Research Funding |
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Transcription Factors & Inflammatory
Mediators in Stroke NIH RO1 01/2003
to 01/2008 Principal
Investigator ·
Neurogenesis after stroke: effect of growth
factors NIH RO1 01/2003
to 01/2006 Co-Investigator
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Role of Egr-1 in Post-ischemic Inflammation and
Brain Damage NIH RO1 01/2006
to 01/2010 Principal
Investigator ·
Therapeutic Potential of PPAR-γ agonists in
Stroke Neuroprotection American Heart Assoc. 07/2005
to 06/2007 Principal
Investigator ·
Folic Acid Enhances
Repair Mechanism in the Adult CNS NIH RO1 01/2006
to 01/2010 Co-Investigator
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Role of Inflammatory Mediators in Ischemic
Neuronal Damage American Heart Assoc. 01/2003
to 01/2004 Principal
Investigator ·
Inflammatory Control in Preventing Stroke-induced
Neuronal Death American Heart Assoc. 01/2003
to 01/2005 Principal
Investigator ·
Role of Polyamines in Neuroplasticity after
Cerebral Ischemia American Heart Assoc. 01/2001
to 01/2003 Co-Investigator ·
Chronic spinal cord injury and neuropathic pain UW Med School 05/2004
to 04/2005 Co-investigator ·
Glutamate transporter function following focal
ischemia American Heart Assoc. 07/1999
to 06/2002 Principal
Investigator ·
Ornithine Decarboxylase and Ischemic Brain Edema NIH RO1 04/1998
to 03/2000 Co-Investigator
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Polyamines and neuroplasticity after cerebral
ischemia American Heart Assoc. 07/2001
to 06/2003 Co-Investigator
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Glutamate transporter and transient focal
ischemia American Heart Assoc. 07/1998
to 06/2000 Principal
Investigator ·
Role of glutamate transporters in transient
global ischemia UW Med School 04/1998
to 03/1999 Principal
Investigator |
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Representative
Publications (click on the journal name for the PDF) |
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Tureyen K, Kapadia R, Bowen KK,
Satriotomo I, Liang J, Feinstein DL, Vemuganti R (2007)
Peroxisome proliferator-activated receptor-γ agonists induce
neuroprotection following transient focal ischemia in normotensive,
normoglycemic as well as hypertensive and type-2 diabetic rodents. J Neurochem (online
early) ·
Kapadia R, Tureyen K, Bowen KK, Kalluri H,
Johnson PF, Vemuganti R (2006) Decreased brain damage and curtailed inflammation in
transcription factor C/EBP-β knockout mice following transient focal
cerebral ischemia. J
Neurochem 98:1718-1731 ·
Satriotomo I, Bowen KK, Vemuganti R (2006) JAK2
and ·
Vemuganti R, Dempsey RJ (2006) Increased expression of genes that control
ionic homeostasis, 2nd messenger signaling & metabolism in
carotid plaques from symptomatic stroke patients. J Neurochem 97:2-96 ·
Vemuganti R, Kalluri H, Ye S, Hazell AS (2006)
Microarray analysis reveals gene expression changes associated with
inflammation, cellular stress, and structural damage in the thalamus and
inferior colliculus following oxidative impairment in experimental Wernicke's
encephalopathy. Eur J
Neurosci 23:1172-1188 ·
Yan Y, Sailor KS, Vemuganti R, Dempsey RJ
(2006) Insulin like growth factor-1 is an endogenous mediator of focal
ischemia-induced neural progenitor proliferation. Eur J Neurosci 24:45-54 ·
Bowen KK, Naylor M, Vemuganti R (2006)
Prevention of inflammation is a mechanism of preconditioning-induced
neuroprotection against focal cerebral ischemia. Neurochem Int 49:127-35 ·
Vemuganti R, Carson MJ (2006)
Cerebral inflammation: How homeland defense is handled in the ·
Naylor M, Bowen KK, Sailor KA, Dempsey
RJ, Vemuganti R (2005)
Preconditioning-induced ischemic tolerance stimulates growth factor
expression and neurogenesis in adult rat hippocampus. Neurochem Int
47:565-572 ·
Vemuganti R, Dempsey RJ (2005) Carotid
atherosclerotic plaques from symptomatic patients share molecular
fingerprints to develop in a neoplastic fashion: A microarray study. Neuroscience 131:359-374 Additional
data ·
Vemuganti R, Dempsey RJ, Bowen KK (2004)
Inhibition of ICAM-1 expression by antisense oligonucleotides is
neuroprotective after middle cerebral artery occlusion. Stroke 35:179-184 ·
Dhodda VK, Sailor KA, Vemuganti R (2004)
Putative Endogenous Mediators of Preconditioning-Induced Ischemic Tolerance in
Rat Brain Identified by Genomic and Proteomic Analysis. J Neurochem 89:73-89 ·
Dempsey RJ, Sailor K, Bowen K, Tureyen K, Vemuganti R (2003)
Stroke-induced progenitor cell proliferation in adult spontaneously
hypertensive rat brain: Effect of exogenous IGF-1 and GDNF. J Neurochem 87:586-597 ·
Vemuganti R, Dhodda V, Song G, Bowen KK, Dempsey
RJ (2003) Traumatic Brain Injury-Induced Acute Gene Expression Changes in Rat
Cerebral Cortex Identified by GeneChip Analysis. J Neurosci Res 71:208-219 ·
Vemuganti R, Bowen KK, Dhodda V, Song G, Franklin
J, Dempsey RJ (2002) Microarray analysis of the gene expression changes in
rat brain after focal ischemia. J Neurochem 83:1072-1086
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Vemuganti R, Dogan A, Todd KG, Bowen KK, Kim B-T,
Rothstein JD, Dempsey RJ (2001) Antisense knockdown of the glial glutamate
transporter ·
Vemuganti R, Dogan A, Rao AM, Bowen KK, Hatcher
J, Dempsey RJ (2001) Knockdown of ·
Vemuganti R, Dogan A, Bowen KK, Todd KG, Dempsey
RJ (2001) Antisense knockdown of the glial glutamate transporter ·
Song G, Cechvala C, Resnick DK, Dempsey RJ, Vemuganti R (2001)
GeneChip analysis after acute spinal cord injury in rat. J Neurochem 79: 804-815 |
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Last update: December 11, 2006 |