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Santosh R D'Mello
Professor-Biology Department
Office MailstopMail Box: FO31, RL 1.708, Room No.: RL 1.708 
Email Address    Primary Phone Number 972-883-2520    URL Personal Website    Media Contact
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Square, Eloise
 Professional Preparation
 PostdocNeurobiologyInstitute of Neurobiology-CNR, Rome, Italy1993
 PostdocNeurobiologyBoston University School of Medicine1991
 Ph.D.BiologyUniversity of Pittsburgh1989
 M.S.BiochemistryUniversity of Bombay1983
 B.S.ChemistryUniversity of Bombay1981
Collapse Section Expand Section Research and Expertise
Research Interests

Three major projects are underway in the laboratory

Signal transduction pathways regulating neuronal survival: Our studies have identified several molecules that play a pivotal role in determining whether a neuron lives or dies. Among the molecules of current interest are the histone deacetylases (HDACs), a family of proteins originally identified on the basis of their ability to deacetylate histones but now known to act on a number of other non-histone proteins and regulate a variety of cellular processes including cell transformation, proliferation, senescence, differentiation, survival, and death. We recently discovered that two members of the HDAC family, HDRP and HDAC4, have the ability to prevent the death of neurons.  Much effort is currently being spent in understanding the molecular mechanisms mediating neuroprotection by these HDACs.  Development of approaches to deliver these HDACs to the brain might represent a novel therapeutic strategy to treat neurodegenerative diseases.

Discovery of neuroprotective drugs: As part of this project, we recently identified a chemical compound called GW5074 that has impressive neuroprotective properties.  GW5074 prevents the loss of neurons and improves behavioral outcome in a mouse model of Huntington's disease.  Current efforts are aimed at understanding the molecular mechanism by which GW5074 protects against neurodegeneration. Using microchip gene-array and biochemical approaches we have discovered that B-Raf plays an important role in GW5074-mediated neuroprotection and that a downstream effect is the inhibition of ATF-3 expression. 

While neuroprotective at a rather narrow dose-range, GW5074 is neurotoxic when administered to cultured neurons or animals at high doses. We have begun to conduct a structure activity relationship analysis using GW5074 as the starting compound to identify chemical analogs that maintain neuroprotective efficacy but with minimal or no toxicity at higher doses.

The Flathead project:  In 1996 we identified a novel rat neurological mutant called Flathead.  Mutant mice have a small and flattened brain, display severe neurological abnormalities, and die within 4 weeks.  The reduced brain size and ensuing neurological deficits are due to a massive loss of brain cells during late gestation.  We discovered that the Flathead mutation is in the gene encoding Citron-K.  We are currently trying to find out why the effect of Citron-K mutation affects only the brain and why the mutant mice display no brain abnormality until the later stages of gestation.  Flathead is a useful model to study congenital brain defects seen in humans such as microcephaly, eplilepsy, and neurodegeneration.

Collapse Section Expand Section Publications
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  YearPublication  Type
Bardai FH, Verma P, Smith C, Rawat V, Wang L, D’Mello SR. Disassociation of HDAC3 from normal huntingtin underlies mutant huntingtin neurotoxicity. J. Neurosci. (in press).
Price V, Wang L, D’Mello SR (2013). Conditional deletion of HDAC4 in the CNS has no major effect on brain architecture or neuronal viability. J. Neurosci. Res. 91:407-15.
Ghosh Dastidar S, Bardai F, Ma C, Price V, Rawat V, Verma P, Narayanan V, D'Mello SR. (2012) Isoform-specific toxicity of Mecp2 in postmitotic neurons: Suppression of neurotoxicity by FoxG1. J. Neurosci. 32:2846-2855.
Ghosh Dastidar S, Narayanan S, Stifani S, D’Mello SR. (2012) Transducin-like enhancer of Split-1 (TLE1) combines with Forkhead box protein G1 (FoxG1) to promote neuronal survival. J Biol Chem. 287:14749-14759.
Bardai FH, Price V, Zaayman M, Wang L, D'Mello SR. (2012) Histone deacetylase (HDAC1) is a molecular switch between neuronal survival and death. J Biol Chem. 287:35444-35453. (Paper of the week - Oct 12, 2012); Best neuroscience paper in 2012)
Collapse Section Expand Section Appointments
DurationRankDepartment / SchoolCollege / OfficeUniversity / Company
2005-PresentProfessorDept of Molecular & Cell Biology University of Texas at Dallas
2001-2005Associate ProfessorDept of Molecular & Cell Biology University of Texas at Dallas
1998-2001Assistant ProfessorDept of Molecular & Cell Biology University of Texas at Dallas
1993-1998Visiting Assistant ProfessorDept Physiology & Neurobiology University of Connecticut
1991-1993Research Fellow,Institute of Neurobiology CNR, Rome, Italy
1989-1991Research AssociateBiomolecular Medicine Boston University School of Medicine
03/01/10-02/28/10SIRT1 and the control of neuronal survivalNIH / NINDS$410,071Current
07/01/00-01/31/12Signaling Pathways Regulating Neuronal ApoptosisNIH/ NINDS$1,665,000Current
04/01/08-03/31/10Understanding the role of HDAC4 in the brainNIH / NINDS$360,000Current
 News Articles
NIH Funds UT Dallas Study on Cause of Huntington’s Disease
UT Dallas News Center
Dr. Santosh D’Mello, professor of molecular and cell biology at The University of Texas at Dallas, has received a federal grant for research that may shed light on why and how specific brain cells are affected by Huntington’s disease, a devastating, degenerative brain disorder.
The grant from the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, provides $1.67 million over five years.
“Results from our studies could provide valuable insight into why specific brain cells degenerate in Huntington’s disease,” said D’Mello, who holds appointments in the School of Natural Sciences and Mathematics and the School of Behavioral and Brain Sciences. “I’m pleased with this new grant, particularly given the current funding environment. We’re eager to get started on this research.”

Prof Aids Quest for Possible Alzheimer’s Treatments
UT Dallas News Center
Researchers at UT Dallas and Southern Methodist University have partnered with a private company to develop potentially groundbreaking treatments for neurodegenerative diseases such as Alzheimer’s, Huntington’s and Parkinson’s.
Dr. Santosh D’Mello, professor of molecular and cell biology at UT Dallas, and Dr. Ed Biehl, professor of chemistry at SMU, published their findings in a recent issue of the Journal of Neuroscience Research showing that a family of novel small molecules proved effective in reducing neuronal loss in tissue culture and animal models of neurodegenerative disease.
Neurodegenerative diseases afflict millions of American costing the U.S. economy hundreds of millions of dollars annually.  There are no effective cures for these brain diseases.

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 Additional Information
Organizer and Chair
  • Organizer and chair of the conference on "Neuroprotective Strategies Against Neurodegenerative Conditions", Boston, MA (2005) and in College Park, MD (2006).
  • Chair and organizer of special symposium entitled “Histone deacetylases, epigenetics, and the regulation of neurodegeneration”.  To be held at the International Neurochemistry Meeting in Athens, Greece, September 2011.

  • Guest editor for special theme issue- "Neurodegeneration and Neuroprotective Strategies" in Current Drug Targets-CNS and Neurological Disorders (January 2006); Managing editor for special issue on neurodegenerative diseases in Frontiers in Bioscience (January 2008).

Editorial Board
  • Journal of Biological Chemistry;
  • Experimental Biology and Medicine;
  • Frontiers in Bioscience;
  • Journal of Cell Death

Ad hoc Reviewer
  • 1999, 2002 The Hospital for Sick Children Foundation, Toronto
  • 2001, 2008 Wellcome Trust Grant
  • 2000 U.S. Dept. of Veterans Affairs
  • 2002, 2003 NIH / NIAID; Biodefense. & Emerging Infectious Diseases Study Section
  • 2004 Health Research Council of New Zealand
  • 2005 NIH, ZRG1 Neuronal Degeneration and Glial Biology (NDBG) Special Emphasis Panel
  • 2005, 2006 High-Q Foundation
  • 2005 Biomedical Research Council - National funding agency of Singapore (2005)
  • 2005 NIH, Topics in Bacterial Pathogenesis (ZRG1 IDM-A) Study Section (2005)
  • 2005, 2006 NIH, Neuronal Degeneration and Glial Biology (NDBG) Study Section
  • 2007 NIH, Cellular and Molecular Biology of Glia (CMBG) Study Section
  • 2007 -2009 NIH, Cellular and Molecular Biology of Neurodegeneration (CMND) Study Section
  • 2009 NSF 

Charter member
  • 2008 - 2011 Department of Veterans Affairs; Neurobiology - E
  • 2009 - 2012 NIH, Cellular and Molecular Biology of Neurodegeneration (CMND) Study Section

Personal Statement
Dr. D'Mello is a professor of molecular and cell biology with a joint appointment in the School of Behavioral and Brain Sciences. Research in his lab is centered on understanding the molecular mechanisms regulating neurodegeneration. Specifically, primary cultures of neurons, transgenic and knockout mice, and animal models of neurological disease are used to study genes, proteins, and signal transduction pathways regulating neuronal cell death. He is also also interested in identifying chemical compounds that protect the brain from neurodegeneration. The long-term objective of the laboratory's research is to develop strategies to prevent, treat, or cure degenerative diseases of the brain. Recently, the lab has expanded interests to investigate neurodevelopmental disorders also.

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