Faculty Members

Research

Role of host genomics in determining susceptibility to tuberculosis

Traditionally, infectious diseases were textbook examples of “non-genetic diseases.” But now beyond doubt it has been proven that genetic factors determine susceptibility to various infectious diseases and their clinical courses upon infection. About one third of world’s population is infected with M.tb causing tuberculosis with India accounting about 1.8 million new cases annually. 5-10% of the infected individuals develop active disease at some point of his life, whereas 90% of infected individuals remain asymptomatic. Individuals with latent disease serves as a reservoir for the disease and is a major obstacle for controlling the disease. Studies with twins and genome wide analysis suggest that host genetics has strong role in determining susceptibility towards TB.

To address the issue of inter individual differences to disease susceptibility we are performing genomic studies to identify host factors that independently or along with pathogen factors modulate course of infection, disease progression and response to treatment. High throughput genotyping and sequencing platforms are used to identify variations in innate immune genes and other cytokines. We have identified that CXCL10 a chemokine is the most significantly altered cytokines in tuberculosis and correlates with severity of disease. Stimulation of CXCL10 expression by ESAT6 compared to Rv2031c reinforced the importance of CXCL10 in the active stage of infection. CXCL10 may, therefore, be considered as a potential biomarker of active phase of infection. In an exome-wide study we have identified a novel locus HLA-DRA associated with protection from tuberculosis. We have replicated and validated these findings on a independent set of TB cases and controls from West Bengal. Through this, we identified a SIGLEC15 missense SNP to be associated with TB risk in our cohort. We have further expanded upon this study using a genome-wide approach to identify disease associated SNPs and also performed an RNA-sequencing study to understand TB associated host transcriptomic changes (Fig 1).

Molecular action of CXCL10 through transcriptome analysis

We are currently investigating the role of the pleiotropic chemokine CXCL10/IP-10 in host immune response to M.tb infection, as its role in downstream cell signaling during TB infection remains largely unexplored. Our research aims to elucidate whether CXCL10 acts as a positive or negative regulator of TB immunity and to uncover its implications in cellular processes during M.tb infection. By integrating transcriptomics studies and immunological assays, we strive to bridge the gap in understanding the function of CXCL10 in TB pathogenesis and immunity.

Mechanisms of cell death induced during tuberculosis infection

We are also investigating the molecular mechanisms underlying cell death pathways (apoptosis, necroptosis, and pyroptosis) triggered by M.tb antigens and inflammatory cytokines in the context of host-pathogen interactions. Using THP-1-derived macrophages as a model, the research focuses on identifying key genes and signaling pathways involved in these processes. We will be using techniques such as gene knockouts using CRISPR-Cas9, transcriptomics, and cytokine profiling to dissect the crosstalk between immune responses and cell death pathways in TB pathology. The findings will provide insights into how M.tb exploits host cell death mechanisms to evade immunity and could uncover novel targets for therapeutic intervention. The study leverages molecular biology, immunology, and genomics expertise to contribute to the broader understanding of TB pathogenesis and immune regulation. We will also perform unbiased genome wide CRISPR screen to get the novel host factors which are involved in TB pathogenesis and infection.

Exploring gut lung axis to decipher interplay between host and microbiome dynamics:

Additionally, Our lab focuses on understanding the complex interplay between the host immune system, microbiome dynamics, and Mycobacterium tuberculosis (M.tb) infection. We investigate how dysbiosis in the sputum and gut microbiomes influences TB pathogenesis, immune regulation, and treatment outcomes. Central to our research is the gut-lung axis, a bidirectional communication system through which changes in microbial communities impact immune responses in both the gut and lungs. By integrating microbiome profiling with immune characterization, we aim to identify microbial biomarkers that can serve as diagnostic tools, monitor disease progression, and predict treatment responses. Additionally, we explore the impact of anti-TB therapies on microbial communities and immune homeostasis, seeking to develop microbiome-targeted therapeutic interventions. Our work bridges microbiology, immunology, and systems biology to advance precision medicine approaches for TB and other infectious diseases.

We intend to understand the disease from different angles which includes genomics, transcriptomics studies and findings are functionally validated. We have recently expanded our study to other regions of India and developed strong collaboration with institutes pan India.

Molecular mechanisms underlying Congenital heart disease

Congenital Heart Disease (CHD) is a group of diseases with various anomalies in heart that occur during embryonic development. Molecular mechanisms of such defects include mutations in transcription factors regulating cardiac gene network, regulatory signaling proteins or sarcomeric proteins. MicroRNA dysfunction, epigenetics also contribute to CHD. The molecular etiology of congenital heart disease has been explored in great details, but lot more remains unanswered. We are interested in understanding the genetic alteration and its cellular effects that leads to different abnormal phenotypes of CHD like septal defect, valve stenosis, hypertrophic cardiomyopathy and many more both in syndromic and nonsyndromic disease involving heart defect. Our research focus is to investigate role of genetic variations, dysregulation of microRNA leading to altered gene expression in case of ASD. Different genomic tools are used for exploring such mechanisms.

Molecular mechanisms underlying Noonan Syndrome

Noonan Syndrome (NS) is a common multisystem genetic disorder characterized by a wide range of phenotypes, including distinctive facial features, congenital heart defects, developmental delays, and skeletal abnormalities. We aim to study is to implement advanced molecular genetic approaches, specifically exome sequencing, in our lab to identify causal mutations and modulatory variants in Noonan Syndrome (NS) patients evaluated at the endocrinology clinic of IPGMER, Kolkata. By addressing the current lack of molecular diagnostics, our lab seeks to explore the genetic basis of NS, which is caused by mutations in over 20 genes, predominantly inherited in an autosomal dominant manner. Exome sequencing will allow us to efficiently detect both known and novel mutations, as well as uncover modulatory variants contributing to phenotypic variability and synergistic effects. Through this approach, we aim to establish genotype-phenotype correlations, understand inheritance patterns, and enhance molecular diagnostics for personalized care of NS patients.

Projects:

• Whole Genome Sequencing of MTB Clinical Strains for Determining Drug Resistance and Strain lineage in India: A structured Nationwide approach (Ongoing)
• Genomics-driven Dissection of Susceptibility and Drug Resistance to Pulmonary Tuberculosis, with a Geographical Focus on NER (DBT funded, completed)
• Understanding the regulatory dynamics of tubercular granulomas through genomic and proteomic analyses: implications for latency and re-activation (DBT funded, completed)
• Replication and Functional validation of genomic correlates of tuberculosis susceptibility (WB-DBT funded ongoing)
• Exploring underlying Molecular mechanisms of defects in congenital heart disease (WB DSTBT funded, completed)

CV

Name: BHASWATI PANDIT

Email: bp1nibmg.ac.in

Present Position:   Associate Professor

Highest educational Qualification:  Ph.D.

 

Year	University	Degree
2001	University of Calcutta	Ph.D
1995	University of Calcutta	M.Sc
1993	University of Calcutta	B.Sc

 

Professional Appointments

• Assistant Professor, 2010-2019, National Institute of Biomedical Genomics
• Assistant Professor, 2008-2010, SN. Pradhan Center for Neurosciences, University of Calcutta
• Post Doctoral fellow, 2005-2008 Center for Molecular Cardiology Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, NY, USA
• Post Doctoral Fellow, 2001-2005 Division of Endocrinology, Diabetes and Medical Genetics, Medical University of South Carolina, USA

Professional Memberships

• Indian Society for Human Genetics
• Calcutta Consortium of Human Genetics
• DNA Society of India

Awards/Honors

2007      Best publication of the year 2007, Mount Sinai School of Medicine

 

Invited/Special lectures

2025 International Conference on Advances on Medical   Biotechnology ‘Exploration of Myeloid cell driven Gene Signature in tuberculosis’, Heritage Institute of Technology,

2024 International conference on Biological innovations, Technology, Engineering & Sciences ’Genome wide association study (GWAS) on Tuberculosis from India: The pros and cons of using existing genotyping arrays,’ NIT Rourkela

2024, Science Setu lecture series, ‘Tuberculosis: A journey from ancient to modern times’, Science, Durgapur College 

2023 Microbes and social Equity’ ‘Genetic underpinning of tuberculosis infection’ Department of Microbiology, Bankura Sammilani College.

2022 World TB day March 24, ‘Need for integration of clinicians and basic scientists for tuberculosis research’, AIIMS Kalyani

2022 Faculty Development Programme entitled “Molecular Biology For Biomedical Research”, ‘A journey through Genomics’ Mahatma Gandhi Medical Advanced Research Institute (MGM ARI), Puduchery. 

2022 Advancement in Microbiology in the context of Louis Pasteur, ‘Vaccines : an overview’ Department of Microbiology, Bankura Sammilani College.

2023 National Seminar on New Horizons in Biotechnology, ‘Host genomic variations and it influence on susceptibility to tuberculosis’, Haldia Institute of Technology

 

Past Major Projects

• Gene discovery of Noonan Syndrome
• Genetic and biochemical study of sterol metabolic disorder: Sitosterolemia and Smith Lemli Opitz syndrome
• Genetic instability in Chinese hamster V79 cells

Publications

• A novel genetic association of IL32 with tuberculosis, Gautam A, Bhattacharyya C, Dasgupta A, Bhattacharjee S, Pandit B, Cytokine, 2024;184:156783.
• Genetic association of missense (rs2919643), intergenic (rs2057178) and a 3'UTR (rs1009170) variant with tuberculosis: A replication study from India, Gautam A, Dasgupta A, Rout S, Bhattacharjee S, Pandit B, Infection Genetics & Evolution, 2024;126:105690.
• Kaveri Srivastava, Bhaswati Pandit, Genome-wide CRISPR screens and their applications in infectious disease, Frontiers in Genome Editing, (2023) Sep19;5:1243731
• Anuradha Gautam, Bhaswati Pandit, IL32: The multifaceted and unconventional cytokine, Human Immunology, (2021), Sep;82(9):659-667.
• Bhaswati Pandit, Samsiddhi Bhattacharjee, Bornali Bhattacharjee, Association of clade-G SARS-CoV-2 viruses and age with increased mortality rates across 57 countries and India, Infection, Genetics and Evolution, (2021) 90. 104734
• Analysis of variants in mitochondrial genome and their putative pathogenicity in tuberculosis patients from Mizoram, North east India, Tonsing MV, Sailo CV, Zothansang, Chhakchhuak L, Chhakchhuak Z, Pandit B, Kumar D, Majumder PP, Senthil NK. Mitochondrion, (2020) 54:21-25.
• An exom-wide association study of pulmonary tuberculosis patients and their asymptomatic household contacts, Bhattacharyya C, Majumder PP, Pandit B. Infection Genetics Evolution. (2019) 71:76-81.
• Sputum Proteomics Reveals a Shift in Vitamin D-binding Protein and Antimicrobial Protein Axis in Tuberculosis Patients, Bishwal SC, Das MK, Badireddy VK, Dabral D, Das A et.al. Scientific Report, (2019) 31;9(1):1036.
• CXCL10 is overexpressed in active Tuberculosis patients compared to M. tuberculosis-exposed household contacts, Bhattacharyya C, Majumder PP, Pandit B. Tuberculosis (2018) 109:8-16.
• Genes and Genetics of tuberculosis, Pandit B. International Journal of Pulmonary& Respiratory Sciences (2017) 1(4):55567.
• Dissecting host factors that regulate the early stages of tuberculosis infection, Agrawal N, Bhattacharyya C, Mukherjee A, Ullah U, Pandit B, Rao KVS, Majumder PP. Tuberculosis, (2016)100 :102-113.
• Roles for transcription factors Sp1, NF-kB, IRF3 and IRF7 in expression of the human IFNL4 gene, Chinnaswamy S, Bhusan A, Behera AK, Ghosh S, Rampurkar V, Chandra V, Pandit B, Kundu TK. Viral Immunology (2016)Jan-Feb 29(1)49-63.
• Deregulated tyrosine-phenylalanine metabolism in pulmonary tuberculosis patients- Das MK,Bishwal SC, Das A, DabralD, Badireddy VK, Pandit B, Varghese GM, Nanda RK. J Proteome Research (2015) 14(4): 1947-56.
• Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy- Pandit B, Sarkozy A, Pennacchio LA, Carta C, Oishi K,Martinelli S, Pogna EA, Schackwitz W, Ustaszewska A, Landstrom A, Bos JM, Ommen SR, Esposito G, Lepri F, Faul C, Mundel P, López Siguero JP, Tenconi R, Selicorni A, Rossi C, Mazzan L, Torrente I, Marino B, Digilio MC, Zampino G, Ackerman MJ, Dallapiccola B, Tartaglia M, Gelb BD, Nature Genetics (2007) 39(8):1007-1012.
• Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome, Tartaglia M, Pennacchio LA, Zhao C, Yadav KK., Fodale V, Sarkozy A, Pandit B, Oishi K, Martinelli S, Schackwitz W, Ustaszewska A, Martin J, Bristow J, Carta C, Lepri F, Neri C, Vasta I, Gibson K, Curry CJ, López Siguero JP, Digilio MC, Zampino G, Dallapiccola B, Bar-Sagi D, Gelb BD. Nature Genetics (2007) 39(1):75-79.
• Increased expression of genes in a radioresistant cell strain: modulation of hnRNP E2, Hsp90 and SSBP2 genes in γ-irradiated Chinese hamster V79 cells Roychoudhury P, Pathak R, Pandit B, Chaudhuri K, Bhattacharyya NP. Int J of Low Radiation (2007) 4(4), 313-331.
• Loss of Apolipoprotein E exacerbates the neonatal lethality of the Smith-Lemli-Opitz Syndrome mouse-Solca C*, Pandit B*, Yu H, Tint GS, Patel SB. Molecular Genetics and Metabolism (2007) 91(1):7-14.* equal contribution.
• A detailed Hapmap of the STSL locus spanning 69kb; Differences between Caucasians and African-Americans, Pandit B, Ahn GS, Hazard SE, Gordon D, Patel SB. BMC Medical Genetics (2006)7(1): 13.
• Sitosterolemia in Switzerland: Molecular genetics links to the US Amish Mennonites to their European roots, Solca C, Stanga Z, Pandit B, Diem P, Greeve J, Patel SB. Clinical Genetics (2005) 68:174-178.
• Induction of apoptosis by Benzamide and its inhibition by Aurin triboxylic Acid (ATA) in Chinese hamster V79 cells, Ghosh U, Pandit B, Dutta J, Bhattacharyya NP. Mutation Research (2004) 554:121-129.
• Identification of two differentially expressed mitochondrial genes in a methotrexate – resistant chinese hamster cell derived from V79 cells using RNA fingerprinting by arbitrary primed polymerase chain reaction, Chaudhuri K, Banerjee R, Pandit B, Mukherjee A, Das S, Sengupta S, Roychoudhury S, Bhattacharyya NP. Radiation Research (2003) Jul; 160(1):77-85.
• The rat STSL locus: characterization, chromosomal assignment, genetic variations in sitosterolemic hypertensive rats, Yu H, Pandit B, Klett EL, Lee MH, Lu K, Helou K, Ikeda I, Egashira N, Sato M, Klein RL, Batta A, Salen G, Patel SB. BMC Cardiovascular Disorders (2003) 3:4, 1-19.
• Co-amplification of dhfr and a homologue of hmsh3 in a Chinese hamster methotrexate-resistant cell line correlates with resistance to a range of chemotherapeutic drugs, Pandit B, Roy M, Dutta J, Padhi BK, Bhowmik G, Bhattacharyya NP. Cancer Chemotherapy & Pharmacology (2001) 48:312-318.
• In vitro and in vivo inhibition of telomerase activity from Chinese hamster V79 cells, Pandit B & Bhattacharyya NP. Indian Journal of Biochemistry & Biophysics (2001) 38,42-47.
• Detection of telomerase activity in Chinese hamster V79 cells and its inhibition by 7 deaza deoxy guanosine triphosphate and (TTAGGG)4 in vitro Pandit B & Bhattacharyya NP. Biochemical and Biophysical Research Communications (1998), 251:620-624.

Monographs

• Radiation resistance in a cell strain derived from Chinese Hamster V79 cells, B Pandit & N.P Bhattacharyya. Trends in Radiation and Cancer Biology (1998), edited by R. N. Sharan, 104-110.
• Mutator phenotype in Chinese hamster cell strain? B Pandit, G. Bhaumik and N.P. Bhattacharyya. Recent Aspects of Cellular and Applied Radiobiology (1999), edited by R. N. Sharan, 165-169.

Review

• Sitosterolemia: of mice and man, Patel SB, Klett EL, Ahn GS, Yu H, Chen J, Pandit B, Lee MH, Salen G. International Congress Series (2004)1262:300-304.

Book Chapters:

• GC×GC-TOFMS Measurement of Actively Sampled Indoor Air VOCs Mrinal Kumar Das, Aleena Das, Subasa Chandra Bishwal, Ankur Varshney, Satish Pendurthi, I. Ibungo Singh, W. Asoka Singh, George M. Varghese, Bhaswati Pandit and Ranjan Kumar Nanda. (2016): 78-88

Lab members

Names of lab members listed according to the positions eg. Post Doctoral fellows, PhD Students, Projects fellows etc. A group photo of the lab will be included in this page. Institute will contact photographer and arrange for the photographs in specified dates).

PhD Students

Anuradha Gautam

Samadrita Ojha

Kaveri Srivastav

Project personnel

Rohan Sharma

iPhD student

Gautam Kumar