1. Introduction

Debdutta Ganguli
Ph.D Human Physiology

2. Research experience

1. Administrative-Lead in Genomics at TTCRC.
2. Instrumental in establishing a High-Throughput genomics facility in TTCRC equipped with Next-Seq 550 sequencing platform.
3. Involved in development and standardisation of a Targeted Exome Sequencing Panel for exploring the mutational landscape of Acute Lymphoblastic Leukaemia (ALL) in Indian patients.
4. Involved in standardisation of a RNA-Sequencing pipeline to identify gene-expression profiles and new gene fusions in ALL patients using TruSeq Stranded Total RNA Library prep and in-house Next-Seq 550 platform.
5. Supervising a team of skilled technicians involved in developing a real-time PCR based approach for monitoring Minimal Residual Disease (MRD) detection to track the progression of disease as well as treatment outcome in leukemic patients.
6. Mentoring and guiding a core team in genomics including master students, trained technicians, post-doctoral fellows in standardising new pipelines and approaches for screening ALL patients treated in TMC.

3. Research interest

The current clinical trial protocol (ICiCle) of ALL patients is mostly dependent on the karyotypic results as well as on the three probe-based FISH strategy which helps the clinicians to risk stratify patients into standard (SR), intermediate (IR) and high risk (HR) groups prior to treatment. The current ICiCLe strategy works very well for the SR patients (including low risk cytogenetic subtype) but HR as well as IR patients need further optimisation in order to improve outcome and treatment-related adverse effects. The current strategy to monitor treatment outcome (as Minimal Residual Disease) in patients is driven by either a flow-based assay or a real-time based (Ig/TCR) technique. It is possible that the existing flow-based assay is suboptimal to predict the treatment-related adverse effects and therefore there is a possibility of presence of low level subclones with deleterious mutations and cryptic fusions not being detected by the conventional strategy.

In TTCRC, my goal is to establish a genomic pipeline to refine the molecular subtypes of ALL in Indian patients. We combine genomic findings with clinical information from patients to better understand how genetics contribute to the variation between patients in their disease severity and response to treatment. We have standardised a pipeline to screen the common genetic variants in ALL patients by developing a Targeted NGS panel with Agilent. We are also using transcriptomic (total / mRNA) profiling of ALL patients to identify novel fusion transcripts and to investigate the gene-dosage effect of chromosomal gains in specific ALL subtypes. We are further developing our understanding for NGS-based MRD approach to refine the disease monitoring in ALL patients which will help to predict the early as well as late relapse events in patients.

4. Current project

Development and Evaluation of Novel Diagnostic and Prognostic Next Generation Assays for Patient Centric Therapy in Children with Acute Lymphoblastic Leukaemia in India

(Extramurally funded by DST Early Career Research Award Scheme)

The study hypothesized that the identification of subclonal mutations or gene fusions in HH and B-Other patients through Targeted Next Generation Sequencing and RNA Sequencing approach will offer further optimisation to the ICiCLe risk stratification and will identify patients who may benefit from targeted therapy. Moreover the study will also explore new genomic MRD markers for tracking disease in follow-up samples.

5. Previous working experience

September, 2011 – March, 2014
1. Post-doctoral research as a Senior Technical Specialist in Genomics, International Cancer Genome Consortium (ICGC), India Project on Oral Cancer in National Institute of Biomedical Genomics (NIBMG), Kalyani under the supervision of Prof Partha Pratim Majumder.
2. A key member of wet-lab team to standardise and execute the Whole Genome Sequencing (WGS) and Whole Exome Sequencing (WES) experiments using Next-Generation Sequencing (NGS) platforms like Roche 454 GS-FLX, Illumina HiSeq-2000, 2500 and Ion-Torrent PGM for exploring mutational landscape of oral cancer in India.
3. Involved in developing Standard Operational Protocols (SOPs) library preparation using an in-solution sequence capture method by True-Seq Exome Enrichment kit of Illumina and NimbleGen SeqCap EZ Exome Library preparation kit from Roche in more than 150 blood and tumor paired- samples.
4. Involved in developing SOPs for Ion Ampliseq Library Preparation for Targeted sequencing using Ion-Torrent PGM Sequencer from ABI.

6. Publications

1. India Project Team of International Cancer Genome Consortium*(2018) Profiling of genomic alterations of mitochondrial DNA in gingivobuccal oral squamous cell carcinoma: Implications for disease progress. Mitochondrion, 46: 361-9. (*As a member of the International Cancer Genome
Consortium-India Project)
2. Ganguli D, Parihar M, Islam R, Saha D, Basu A, Roy P, Dhar S, Arora N, Mishra D, Das S, Malhotra S, Varma B, Srinivasan R, Saxena A, Krishnan S, Saha V. (2017) Development of a targeted sequencing panel for Indian patients with acute Lymphoblastic Leukaemia. Pediatric Hematology Oncology Journal, 2 (2):S3-S4.
3. Parihar M, Singh MK, Islam R, Saha D, Ganguli D, Basu A, Roy P, Mishra D, Saha V, Krishnan S. (2017) Distinct heterogeneity in Indian patients with high hyperdiploid precursor B cell all identified by high density array analysis. Pediatric Hematology Oncology Journal, 2(2): S2.
4. Islam R, Saha D, Ganguli D, Basu A, Arora N, Mishra D, Saha V, Krishnan S. (2017) PCR-based MRD testing for acute lymphoblastic leukaemia in India. Pediatric Hematology Oncology Journal, 2 (2): S14-S15.
5. Mukherjee S, Ganguli D and Majumder PP. (2014) Global Footprints of Purifying Selection on Toll-Like Receptor Genes Primarily Associated with Response to Bacterial Infections in Humans. Genome Biology and Evolution, 6 (3): 551-8.
6. India Project Team of International Cancer Genome Consortium*(2013) Mutational Landscape of Gingivo-Buccal Oral Squamous Cell Carcinoma Reveals New Recurrently-Mutated Genes and Molecular Subgroups. Nature Communications, 4, Article number: 2873: doi: 10.1038/ncomms3873 (*As a member of the International Cancer Genome Consortium-India Project)
7. Mukherjee S, Ganguli D and Majumder PP. (2013) Discovery of High Frequencies of the Gly-Ile Haplotype of TLR4 in Indian Populations Requires Reformulation of the Evolutionary Model of its Maintenance. Infection, Genetics and Evolution, 19: 223-5.
8. Ganguli D, Das N, Saha I, Chaudhuri D, Ghosh S and Dey S. (2013) Risk factors for hypertension in a population-based sample of postmenopausal women in Kolkata, West Bengal, India. Asia Pacific Journal of Public Health, 25 (5): 388-97.
9. Ganguli D, Das N, Saha I, Chaudhuri D, Biswas P, Mukherjee B, Ghosh S and Dey S. (2011) Major dietary patterns and their associations with cardiovascular risk factors among women in West Bengal, India. British Journal of Nutrition, 105 (10): 1520-9.
10. Ganguli D, Das N, Saha I, Sanapala KR, Chaudhuri D, Ghosh S and Dey S. (2011) Association between inflammatory and cardiovascular risk factors in women of Kolkata, W.B, India. Arquivos Brasileiros de Cardiologia, 96 (1): 38-46.