Chronic Diseases represent long-term non communicable medical conditions that are generally progressive. The contribution of most of the major non-communicable disease groups to the total disease burden has increased all over India since 1990, including Cardiovascular Diseases, Hypertension, Asthma, Diabetes, Chronic Respiratory Diseases, Mental Health and Neurological Disorders, Cancers, Musculoskeletal Disorders, and Chronic Kidney Disease. As per the recent reports three of the five leading individual causes of disease burden in India were non-communicable, with Ischemic Heart Disease and Chronic Obstructive Pulmonary disease as the top two causes. Overall, 61.8 % of all deaths in India are due to non- communicable diseases.A brief overview of the programs supported and significant achievements/outcomes of the Chronic Disease Biology division during the last 5 years is summarized below:

Research and Development

• Projects Supported- 364
• Publications- 326
• Technologies/Products developed– 7 (Celiac test kit, Folding Foropter, OIO, KALPANA, GAURI, Fluoro Doc, STIM)

CANCER

• Two Virtual National Cancer Institutes (VNCIs), one on Hormone Resistant Breast Cancer & the other on Oral Cancer have been initiated. VNOCI has identified the protein Nucleophosmin (NPM1) as an important contributor to oral cancer pathogenesis. VNCI Breast Cancer has generated Whole exome sequencing (WES) and Whole Transcriptome Sequencing (RNA-Seq) and Whole genome sequencing (WGS) data from resistant and sensitive patient tumours. It has also established PDX models of Hr. Resistant Breast Cancer for the first time in India.
• 5 CoE sand 7 UoE have been supported. Achievements include successful development of PDX model in NSG mice from Indian TNBC patients; establishment of low cost effective care using arsenic trioxide (ATO) in acute promyelocyticleukemia (APL); establishment of a panel based NGS test for Multiple Myeloma that is useful in clinical practice and demonstrating the role of BLM helicase as a global tumor suppressor.
• Multi-dimensional Research to Enable Systems Medicine: Accelerating Using a Cluster Approach (SyMeC) has been established at Kalyani, West Bengal to generate basic andtranslational research evidence for oral and cervical cancer.

METABOLIC DISORDERS

The Program Division has supported 91 projects in areas such as Translational Research Studies in some Disorders of the Eye, Gene Environment Interactions, Host-microbe interactions, Inflammation, Innate Immunity & Adaptive Immune Response, Toxicity of Energy Fuels, Micro and Macro Vascular Complications of Diabetes, Proteomics and Metabolomics studies.

• Cardiovascular Disease: Results have shown that Star-PAP controlled alternative polyadenylation coupled poly (A) tail length regulates expression in hypertrophic heart.  Small molecule library screen has led to identification of Dopamine β-hydroxylase (DBH), and human Cytochrome b reductase 3 (hCyb5R3) inhibitors which caused significant lowering in the blood pressure in spontaneously hypertensive rats (SHRs).

• Diabetes: Research supported by the PD has revealed that young adults with overweight, but not yet obese, are at risk for Type 2 Diabetes Mellitus, and the risk is more in men compared to women. Insights into the role of butyrate induced cTregs in the suppression of Type 1 Diabetes have also been obtained.

• Indian Chronic Kidney Disease (ICKD) Study: This has established one of the first prospective cohort of patients with CKD in a developing country. The ICKD study is a part of International Network of Chronic Kidney Disease cohort studies (iNET-CKD). A total of 3927 patients have been enrolled in this study till date. A central biobank with archived blood and urine samples of all the enrolled patients has been created at PGIMER, Chandigarh. Diabetes mellitus, glomerular diseases, chronic interstitial nephritis, hypertensive nephrosclerosis and ADPKD constitute majority of CKD cases in the study participants. The ICKD study data will become a national resource to define and identify risk factors for progression CKD in our country.

• Systemic Lupus Erythematosus (SLE) Study: Given the fact that there is no known data on SLE from India, DBT has implemented a Multi-centric Network Program on SLE.The study aims to establish an inception cohort from different parts of India for the assessment of clinical features, socio-demographic features, auto-antibodies, disease progression and outcome and evaluation of regional differences. 767 patients with SLE have been enrolled till date and sample collection is underway for storage in the central Bio-repository at SGPGIMS, Lucknow.

NEUROSCIENCES

• Dementia Science Program A multi-institutional program has been supported for setting-up of three long-term population based cohorts; setting-up of 4 hospital based registries, setting-up of Bio-bank and Bio-repository at NBRC.

• Centres of Excellence in areas of Epilepsy, Cerebral Stroke Biology, and Neuro-engineering Platform for Excellence in Innovation and Translational Research.

• Hypoxia Ischemic Brain Injury (HIBI): The role of normaobaric oxygen therapy, Fluoxetine and Transcranial Direct current stimulation; study of hypoxia on different neural cell type; creation of invitro model to design therapeutic strategies against cerebral palsy in preterm infants, hypoxia induced changes in Blood Brain Barrier and adjunct therapeutic interventions are being studied.

• Glial Cell Biology: Projects shave been implemented to explore issues pertaining to neuro-inflammation, glial activation in hypertension, neurodegeneration, neuronal cell death during JE and HIV mediated neuro-pathogenesis.

Infrastructure and Human Resource Capacity Building

• Manpower (JRF/SRF/RA etc.) Supported- 390
• Scientists Supported – 284
• Workshop/Training Programs Organized- 18

• New Facilities Established – 2 (Magneto-Encephalogram (MEG) facility, NBRC, Manesar; High throughput Genome sequencing Centre at NIBMG, Kalyani).

• Bio-banks Created – 4 (SGPGIMS, Lucknow for SLE; ACTREC, Mumbai for Gingivobuccal cancer; PGIMER, Chandigarh for Indian Chronic Kidney disease; NBRC forDementia Science Program)

• Pilot Projects for Young Investigators in Cancer Disease Biology- 113 (This program has witnessed 166 publications published by the PIs with an average impact factor of 5.41; 73 conference presentations with 12 PhDs produced by the PIs and 94JRFs and project staff trained).

Collaborations- National and International

• DBT DAE Partnership for Cancer Research: DBT and DAE have signed a MoU for supporting joint collaborative research and clinical trials under the already implemented Cancer Network Program. The MoU shall help in strengthening various initiatives specifically development of new and affordable technologies, conducting of clinical trials, and training of manpower and infrastructure development.



• DBT- CRUK Affordable Approaches to Cancer: Government of India’s Department of Biotechnology (DBT) and Cancer Research UK (CRUK) have signed a MoU for a Cancer Research Initiative, “Affordable Approaches to Cancer” which is a £ 10 million and 5-year research initiative. This will be implemented in three phases; Phase I: Identifying Core Challenges; Phase II: Establishing New Research Partnerships, and Phase III: Program Awards. The Bilateral Initiative has successfully completed phase I and II with identification of seven thematic areas/core challenges - (1) Prevention, (2) Early Detection, (3) Early Diagnosis, (4) Computational Approaches, (5) Small Molecule Treatment, (6) Affordable Treatment, and (7) Children’s and Young People’s Cancer. In Phase II, 7 seed grant applications have been funded.



• International Cancer Genome Consortium (ICGC) DBT-India Project: India is one of the 7 founding members of ICGC. ICGC-India Project has established a dedicated bio-repository with best international practices at ACTREC, Mumbai and State-of-the-art high throughput Genome sequencing centre at NIBMG. The research has lead to the identification of certain signatures in oral cancer as biomarkers for early detection.

Focus Areas during the Next 5 Years

• Non Invasive Cancer Diagnostics
• Cancer Immunology and Cancer Immunotherapy & Clinical Trials
• Diabetes and its complications
• Respiratory Diseases
• Cardiovascular Diseases
• Bone Biology & Osteoporosis
• Life Style & Chronic Diseases
• National Alliance for Translational Research in Autoimmune Diseases
• Autism and behavioural disorders in children
• Acute Encephalopathy / encephalitis syndrome

Contacts Concerned Officer for more information