Assistant Director & Senior Scientist
Madras Diabetes Research Foundation (MDRF)
Gopalapuarm, Chennai – 600 086, India.
Phone : 91 44 43968888, 47405900
Fax : 91 44 28350935, 47405921
Email: drbalu@mvdsc.org, balusignal@gmail.com
Mobile :+91 98408 35222
Qualifications:
MSc., M.Phil., PhD., MNASc.
Specialization:Cell Signaling in health and disease & Molecular Medicine with special reference to molecular mechanisms of pathogenesis of diabetes and its vascular complications; Insulin signaling & Proteomics – Epigenetics aspects of diabetes, Unraveling mechanisms of hyperglycemic memory, Redox signaling, Oxidative stress and biomarkers identification; Bioprospecting herbal molecules.
Positions held in chronological order:
2007 to till date: Assistant Director & Senior Scientist, Madras Diabetes Research Foundation, Chennai, India
1999 to August 2007: Senior Scientist, Madras Diabetes Research Foundation, Chennai
1996-1999: Faculty, Centre for Biotechnology, Anna University, Chennai
1991-1996: Post Doctoral Fellow, American Heart Association Affiliate, New Jersey Medical School, New Jersey, USA
1988-1991: Research Associate (CSIR), S.V.University, Tirupati
1986-1988: Senior Research Fellow (CSIR), S.V.University, Tirupati
1984-1986: Junior Research Fellow, S.V.University, Tirupati.
Additional Responsibilities:
1999-till date: Member, Institutional Ethics Committee, Madras Diabetes Research Foundation
1999-till date: Academic Coordinator, MDRF (Training programmes for BSc/BTech; MSc/MTech students; short-term exposure training and end-semester project training)
2008-till date: Member Secretary, Institutional Animal Ethics Committee, MDRF
Research Experience:
Possessing > 25 years of post-M.Sc. research experience since 1983. This includes an extensive Post Doctoral Fellow (PDF) training program (1991-95) at the University of Medicine and Dentistry of New Jersey (UMDNJ), New Jersey Medical School, New Jersey, USA, on the subject: “Biochemical machinery and Signal transduction in physiology and pathophysiology”.
Training at the University of San Diego, USA (2004) on human skeletal muscle/adipose biopsy and insulin signaling profiling.
Teaching experience:
25 years of total teaching experience which include teaching assignments at
a) Department of Zoology, S.V.University, Tirupati (1983-1991),
b) Centre of Biotechnology, Anna University, Chennai (1995-1999)
c) MDRF (1999 -till-to-date).
Research Grants:
1993-1995 American Heart Association Fellowship grant (PI)
1996-1997 Third World Academy of Sciences (TWAS), Italy - Research Grant (PI)
2002-2005 Department of Science & Technology (DST), New Delhi (PI)
2002-2007 FIST-DST Grant (Programme Coordinator)
2003-2006 Department of Biotechnology (DBT) (Co-Investigator)
2006-2010 Indian Council of Medical Research (ICMR) (Co-Investigator)
2003-2006 Department of Science & Technology (DST), New Delhi (Co-PI).
2007-2012 Department of Biotechnology (DBT), New Delhi (PI).
2009-2012 Department of Science & Technology, Indo-Korea Joint Research Project (PI)
PhD students under my supervision at the Cell and Molecular Biology, Department of MDRF (affiliated to the University of Madras) completed/working on the following topics:
i) Dr. Sampath Kumar - Altered signaling in diabetes and its complications with special reference to ion transport, redox imbalance and advanced glycation aspects (Thesis awarded).
ii) Dr. Adaikalakoteswari - Biochemical markers and molecular mechanisms of Oxidative Stress in Diabetes and its Complications (Thesis awarded).
iii) Dr. Srinivasan - Molecular convergence of hexosamine biosynthetic pathway and endoplasmic reticulum (ER) stress in insulin resistance (Thesis awarded)
iv) Dr. Gokulakrishanan - Biochemical and intracellular studies on cardiovascular risk factors in relation to glucose intolerance (Thesis awarded)
v) Mr. Sameer Mahmood - Glucolipotoxicity induced molecular alterations in insulin secretion and insulin resistance: Role of Gallic acid (Thesis awarded)
vi) Ms. Sandhya - Clinical significance of non-alcoholic fatty liver disease (NAFLD) in diabetic patients and fatty-acid induced molecular perturbations in hepatocytes and adipocytes (Thesis submitted)
vii) Mr. Finny Monickaraj - Does oxidation/inflammation impose accelerated cellular senescence in adipocytes and modify their secretory profile and function? (Persuing)
viii) Mr. S. Aravind - Exploring novel mechanisms of insulin resistance and Type 2 diabetes using miRNA and RNAi technologies (Persuing)
ix) Ms. S. Raji - Molecular intricacies of endoplasmic reticulum (ER) stress in diabetes with special reference to pancreatic beta cells (Persuing)
x) Mr. Balakumar – Novel animal models to study the molecular mechanisms of “hyperglycemic memory” and epigenetic alternations (Persuing)
xi) Mr. Sathishkumar.C – Gene expression alternations in type2 diabetes (Persuing)
xii) Mr. Prabu.P – Role of circulating microRNA in type 2 diabetes(Persuing)
xiii) Mr. Sai Raj – Autocrine and endocrine effects of asymmetric dimethyl arginine (ADMA) in its relevance to insulin resistance and vascular dysfunction (Persuing)
Summer training & End-semester project training to students:
So far, >200 summer students trained and above 35 project students were directly supervised and guided for their end-semester project work.
Nominated & Served as PhD examiner for students outside the MDRF:
Conducted PhD viva-voce examination and served as examiner for students from:
University of Madras
Tuberculosis Research Centre
Department of Biotechnology - CLRI
Central University Hyderabad
National Institute of Pharmaceutical Education and Research (NIPER)
Post-Graduate Institute of Medical Education & Research (PGIMER)
Centre for Biotechnology, Anna University
Professional Recognition(s):
(i) Served as Guest-Editor for a special issue on Diabetes Mellitus in “Current Science” (2002, Vol: 83(12).
(ii) Co-organizer of the meetings organized by MDRF including
a) Brain Storming session on “Cell transplantation” sponsored by Department of Science & Technology (DST), Govt of India, 2002 at MDRF, Chennai
Scientific Organising Secretary: for
b) MDRF-ADA Post-graduate Course in Diabetology 2002
c) MDRF –ADA Post-graduate Course in Diabetology 2004
d) MDRF –ADA Post-graduate Course in Diabetology 2006
(iii) Organising Secretary – Indo-Swedish Symposium on Genomics and Proteomics of Diabetes (April 1-2, 2006)
(iv) Served as Guest-Editor for a special issue on Diabetes Research in “Indian Journal of Medical Research” (Vol 125) 2007.
(v) Assisted in organization of:
a) International Conference on “Current trends in multidisciplinary approaches to diabetes research” (9 -10th July 2009) at the Sri Sathya Sai University, Puttaparthi
b) International Conference on “New Frontiers in Diabetes Research” (13 -14th August 2010) at the Sri Sathya Sai Institute of Higher Learning, Puttaparthi
(vi) Organizing Secretary: DST-sponsored INSPIRE Science Camp for the students during 27th Dec to 31st Dec 2010, in Chennai.
Referee for various journals including:
Molecular and Cellular Biochemistry
Indian Journal of Experimental Biology
Current Science
Indian Journal of Medical Research
European Journal of Biology
Diabetes Technology & Therapeutics
BMC Endorcine disorders
DRCP, JCMM, IJEB, Diabetes Care, Metabolism
Scientific Services:
Member - Task Force committee on Cardio-vascular diseases (CVD) in Department of Biotechnology (DBT), Govt of India
Member – Expert Committee on Clinical Proteomics, Department of Biotechnology, Govt. of India
Member – Life Sciences Research Board (LSRB) under DRDO, New Delhi
Member – Board of Studies, Biotechnology, Loyola College, Chennai
Editorial Board Member: Diabetes Technology & Therapeutics (DTT)
Editorial Board Member: Journal of Clinical Endocrinology & Metabolism (JCEM)
Editorial Board Member: Indian Journal of Clinical Biochemistry (IJCB)
Memberships & Research Awards:
1) 2011: Institute of Advanced Studies (IAS) Visiting Fellow Award, University of Warwick, UK
2) 2011: Secretary, Madras Science Foundation, Chennai
3) 2009: Member of the National Academy of Sciences, India (MNASc)
4) 2009: Executive Member of the Madras Science Foundation, Chennai
5) 2008 Elected Member – Madras Science Foundation (MSF), Chennai
6) Elected Member - Asia Pacific International Molecular Biology Network (A-IMBN), 2001
7) International Diabetes Society grant to attend 5th IDS Congress, Chennai, 1999
8) MABMS award - Membership of the Indian Association of Biomedical Scientists 1999
9) Fellow - Indian Association of Biomedical Scientists, 1998
10) ICSU/INSA award to attend XIII International Biophysics Congress, New Delhi -2000
11) Third World Academy of Sciences (TWAS, Italy) Associateship award, 1998
12) Young Physiologist Foreign Guest at the Physiological Society meetings, Dublin (Ireland) March 23-26, 1997
13) The Welcome Trust (UK) award for subsistence at the EC School/Conference on Calcium and Signal Transduction (Liverpool, UK, 14-20, March 1997)
14) Research Grant award from Third World Academy of Sciences (TWAS), Italy (Principal Investigator), 1996
15) International Union of Biochemistry and Molecular Biology (IUBMB, Germany), Young Scientist Travel Fellowship Award for participation in IUBMB Congress 1994, New Delhi, India
16) Junior Scientist Award from the Association of Scientists of India Origin in America Inc., (ASIOA), Mississippi, USA, 1993
17) American Heart Association (AHA, USA), New Jersey affiliate, Post-doctoral Fellowship Grant (Principal Investigator) (Diabetes Work), 1993-1995
18) Government of India sponsored Study abroad PDF scholarship award for Specialized Post doctoral training - New Jersey Medical School, Newark, New Jersey, USA, 1991-1992
19) Young Scientist Travel award for participation in the Fifth International Theriological Congress, Rome, Italy - Financed by DST, New Delhi, INDIA & V-ITC, Rome, ITALY, 1989
Membership of Academies/Research Societies:
Asia-Pacific International Molecular Biology Network (A-IMBN)
Member- Madras Science Foundation (MSF)
Member Indian Biophysics Society (IBS)
Life member Indian Association of Biomedical Scientists (IABMS)
Life member Indian Society of Cell Biology (ISCB)
Life member-European Calcium Society (ECS, Germany)
Member Alliance for Cell Signaling (AFCS, USA)
Member Society of Biological Chemists (India) (SBC)
Member Indian Science Congress Association (ISCA)
Member Inter Academy of Biomedical Forum – (IABF)
Brief Profile:
Dr.M.Balasubramanyam is Assistant Director & Senior Scientist at the Cell and Molecular Biology department of the Madras Diabetes Research Foundation (MDRF). He is a member of the Asia-Pacific International Molecular Biology Network (A-IMBN) and had an extensive post-doctoral training (1991-95) at the Hypertension Research Centre, New Jersey Medical School, USA, in the areas of signal transduction in health and metabolic diseases with special reference to molecular pathogenesis of Type 2 diabetes and vascular biology. Having worked as a faculty at the Center for Biotechnology, Anna University, Chennai for 3 years (1996-99) he has joined MDRF in 1999. He is instrumental in setting up the basic infrastructural facilities at MDRF and coordinates various research programmes and educational activities from time-to-time.
Mission & Vision:
Dr.Balu’s laboratory is involved in studying cell and molecular signatures with special reference to insulin secretion, insulin action and vascular function. Our research integrates physiological and pharmacological approaches with biochemical, molecular biological and proteomics techniques to study mechanisms underlying development and progression of diabetes, its complications and cardiovascular diseases. This challenging multi-disciplinary research specialization dwells around the following themes:
a) Insights into biochemistry and molecular biology of diabetes and its vascular complications by studying nutrient-sensing pathways, redox signaling, advanced glycation end products, calcium signaling and epigenetic mechanisms.
b) Investigating the role of organellar dysfunction (Endoplasmic reticulum (ER) stress and mitochondrial mess) in insulin resistance and Type 2 diabetes utilizing the target tissue specific (skeletal muscle, adipose, β-cell) microarray, proteomics, siRNA and epigenetics studies.
c) Bio-prospecting biomarker(s) potential in body fluids and tissue biopsies (human skeletal muscle and adipocytes) adapting to proteomic tools and identification of prediabetes/diabetes/diabetic complications-specific molecular fingerprints and protein post-translational modifications.
d) Studying telomere biology and test whether shortening of telomeres are related to inter-individual differences in biological ageing that predisposes one to ‘lifestyle diseases’ and serve as a long-term biomarker.
e) Demonstration of oxidative stress as a therapeutic target, testing natural products (herbals, marine resources) from the Indian biodiversity for their molecular actions beyond antioxidant property and validation of their utility as novel insulin secretatgogues/insulin sensitizers/vascular protectants.
The department now serves as an excellent 'interface' for biomedical/biotechnology/biopharmaceutical work with translational applications. The goal of the department is set to evolve as a ‘Centre for Cellular and Molecular Medicine’ (CCMM) with state-of-the-art facilities for preclinical research, biomarker(s) identification, high-throughput cell-based assay systems, and to offer world-class contract research and consultancy work in the areas of specialization.
Research Highlights:
One of the thrust areas of research at the Madras Diabetes Research Foundation (MDRF) is to use the biochemical and proteomic technologies for identifying novel biomarkers and drug targets in the development and progression of diabetes and its associated complications. In the sub-set of subjects from CURES, we have shown elevated oxidative reactions (Sampathkumar et al 2005) and increased advanced glycation end products (AGEs) (Sampathkumar et al 2004) in patients with Type 2 diabetes and its vascular complications. Related to oxidative damage, our pilot observations indicated that there was increased lipid and protein oxidation as early in the stage of impaired glucose tolerance (prediabetes). In addition, we have seen telomere shortening in prediabetes subjects and patients with Type 2 diabetes (Adaikalakoteswari et al 2005; Adaikalakoteswari et al 2007), arising either from a cumulative burden of oxidative stress and/or other phosphorylation or epigenetic post-translational mechanisms. Another study (Adaikalakoteswari et al 2007) has demonstrated an association of oxidative DNA damage with PARP and NFkB activation, indicating a role for poly (ADP)-ribosylation in the pathogenesis of Type 2 diabetes. Moreover, a role for oxidative stress in diabetes patients was also substantiated with differential expression of NADPH oxidase and hemoxygenase gene (Adaikalakoteswari et al 2006). While these effects have been studied by classic biochemical and molecular biology methods, the recent onset of proteomics methods are expected to allow studying oxidative stress responses on a much wider scale with more emphasis and focus on identification of biomarkers. In this direction, in collaboration with Indian Institute of Science, Bangalore, we have recently identified increased positivity for glutathionylated hemoglobin (HbSSG) as a specific biomarker in diabetic patients with microangiopathy (Sampathkumar et al 2005b). As a prerequisite to study the proteomics & genomics of Type 2 diabetes, we have standardized in-house, the culturing of human skeletal muscle cells (HSMCs). Since insulin resistance of skeletal muscle primarily results from impaired glucose uptake and glycogen synthesis, these two metabolic read-out assays were first standardized in HSMCs (Balasubramanyam, 2006). The fact that defects in these metabolic read-outs are persisted in culture conditions of HSMCs obtained from patients with Type 2 diabetes, indicates that these cells are an excellent model system to study the proteomics & genomics of Type 2 diabetes. From the clinical proteomics view, our pilot studies also indicated protein spots with region-specific differences in plasma samples of subjects exhibiting varying degrees glucose tolerance. Other interesting studies which yielded preliminary data include: convergence of ER stress and insulin resistance in L6 skeletal muscle cells, palmitate-inudced impairment of multimerization of adiponectin in 3T3 adipocytes, characterization of a novel PTP inhibiting activity in prodigiosin, etc. As a part of the NMITLI diabetes project on herbal medicine, both curcumin and gallic acid have been extensively studied and scientifically documented for their specific molecular actions. Gallic acid has been shown to possess novel (hitherto unknown) actions at the interface of transcription factors, membrane transport, down regulation of oxidants and upregulation of antioxidant enzymes etc.
Specialized training:
Dr.M.Balasubramanyam is a member of the Asia-Pacific International Molecular Biology Network (A-IMBN) and had an extensive post-doctoral training (1991-95) at the Hypertension Research Centre, New Jersey Medical School, USA, in the areas of signal transduction in health and metabolic diseases with special reference to molecular pathogenesis of Type 2 diabetes and vascular biology. Under the Scientific Investigator training programme at AIIMS, New delhi, he has learned both basic and advanced applications of Electron Microscopy techniques. He is well-versed with transport assays, fluorescence imaging techniques and flowcytometry applications. In the year 2003, he has visited the University of San Diego and learned techniques related to human skeletal muscle and adipose tissue culturing, differentiation protocols, and he is well-versed with the insulin signaling assays such as, glucose uptake, lipolysis, tyrosine phosphorylation, PTP inhibition, glycogen synthase activity, lipid accumulation, palmitate oxidation etc. He has participated in several training programmes of frontier technologies including microarray, siRNA, 2-Dgel electrophoresis and mass spectrometry and his team is actively collaborating with Indian Institute of Science (Prof.P.Balaram & Dr.Utpal Tatu) on body fluid and tissue proteomics profiling and JNCASR (Dr.Tapas Kundu) on epigenetic analysis. He is instrumental in setting up the basic science infrastructure in MDRF and with his efforts the tissue culture facility at MDRF is now fully tuned to conduct research on target-specific cells such as human skeletal muscle cells, human retinal endothelial cells, 3T3-L1 adipocytes, L6 muscle cells, THP-1 monocytes and beta cells. He is also instrumental in establishing the animal laboratory at MDRF. The training offered at this department is considered unique in that it is tailor-made for the students of biotechnology and pharmaceutical research.
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