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Cell & Molecular Biology
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The Department of Cell & Molecular Biology under the supervision of Dr. M. Balasubramanyam was started in 1999 with the objective studying and adding new information to the existing knowledge on the pathogenesis of diabetes and its complications at the cell and molecular level. The department 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.
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Vision |
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The vision of the department is 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 higher learning, contract research and consultancy work in the areas of specialization |
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Mission |
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1. To perform cutting-edge research, identify novel drug targets related to insulin secretion, insulin sensitization and vascular function and to reveal prognostic and diagnostic biomarkers that will pave way for the development of newer therapeutics.
2. To enhance research capacity building with special reference to higher education and human resource development in the area of specialization. |
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Portfolio of Current Activities of the Department |
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1. DBT Project: Exploring novel mechanisms of insulin resistance and Type 2 diabetes using miRNA and RNAi technologies
(PI: Dr.M.Balasubramanyam; Co-Investigator: Dr. V. Mohan)
Project Objectives:
- Identification of differentially expressed miRNAs by miRNA microarray profiling in skeletal muscle from prediabetes and Type 2 diabetes subjects and validation of certain selective genes by quantitative PCR.
- To study how miR-29 (and other miRNAs) regulate insulin signaling pathways and how miRNA alterations (overexpression or silencing) affect regulatory molecules of insulin signaling pathway in skeletal muscle.
2. DBT Project: Does oxidation/inflammation impose accelerated cellular senescence in adipocytes and modify their secretory profiles and function?
(PI: Dr.M.Balasubramanyam; Co-Investigator: Dr. V. Mohan)
Project Objectives:
- To impose oxidative/inflammatory stress in 3T3L1 adipocytes/human adipocytes maintained in tissue culture and to see whether induction of senescence/ telomere shortening occurs in relation to changes in the secretory profiles of adipocytes and insulin resistance.
- To test whether priming of the cells with bioactive molecules could offer protection against induction of senescent markers, telomere shortening and insulin resistance.
3. DBT Programme Grant: Search for susceptibility genes for Type 2 diabetes in Indians (Co-Investigator: Dr.M.Balasubramanyam)
Project Objectives:
To perform gene expression profiling in human skeletal muscle to identify genetic factors contributing to the predisposition of Type 2 diabetes.
4. DST: Indo-Korea Joint research programme: “Role of NF-E2-related factor-2/ Hemoxygenase-1 (Nrf2/HO-1) signaling in the retinal vasculature”
(PI: Dr.M.Balasubramanyam; Co-Investigator: Dr.Rema Mohan).
Objectives:
- To test the effects of high-glucose/VEGF/methylglyoxol on the retinal endothelial cells/pericytes with special reference to alterations in Nrf2/HO1 signaling, antioxidant response elements (ARE) and cell proliferation/apoptosis.
- To demonstrate the differential regulation and expression of Nrf2/HO-1 signals in retinal endothelial cells and pericytes (isolated from human cadaver eyes) from non-diabetic subjects and patients with diabetic retinopathy.
- To test whether the dietary components (curcumin, epigallocatechin-3-gallate) resist high-glucose/VEGF/methylglyoxol induced alterations via influencing Nrf2/HO-1 signaling in the retinal endothelial cells/pericytes
5. Animal Studies (on-going)
- Exploring a role of ‘hyperglycemic memory’ by subjecting the animals to good glycemic and poor glycemic control.
- Activation of Nrf2 and/or HO-1 induction in animal models to identify novel drug targets for insulin resistance and Type 2 diabetes
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Portfolio of Past Activities of the Department |
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Through its work the department of Cell and Molecular Biology has delineated the molecular mechanisms of “hyperglycemic memory” and oxidative stress often persistent in Type 2 diabetes patients without and with microangiopathy. In the sub-set of subjects from CURES, we have shown elevated oxidative reactions and increased advanced glycation end products (AGEs) 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 arising either from a cumulative burden of oxidative stress and/or other phosphorylation or epigenetic post-translational mechanisms. Another study 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. 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. 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. 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-induced 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. |
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Future trends |
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To emerge as a ‘Centre of Excellence’ for conducting preclinical studies and translational research utilizing state-of-the-art technologies in all aspects of diabetes and its complications. To serve as a ‘nodal’ centre with capabilities for high-quality diabetes research and to develop team-expertise to undertake contractual and consultancy work in the areas of specialization. |
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Dr. M. Balasubramanyam
Aravind. S
Samantha. K.S
Anand Chakraborty
Balakumar. M
Saravanan. T
Ganesan. S
Prabhu. P
Sathish Kumar
Prabhu. D |
Head of Department
Ph.D Student
Ph.D Student
Ph.D Student
Ph.D Student
& Animal Pharmacologist
Senior Research Assistant
Senior Research Assistant
Project Assistant
Project Assistant
Animal House Keeper |
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Saravanan. T, Samantha. K.S , Anand Chakraborty, Sathish Kumar, Finny Monickaraj, Ganesan. S, Balakumar. M, Raji S , Dr. V. Gopalakrishnan, Dr. M. Balasubramanyam, Prabhu. P, Prabhu. D, Aravind. S |
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