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National Brain Research Centre
NH-8, Manesar, Gurgaon,
Haryana-122 052, India
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Contact Info
Phone: +91 124-2845-200
National Brain Research Centre
NH-8, Manesar, Gurgaon,
Haryana-122 052, India
Follow Us

Dr. Sagar Sengupta

Director

Contact Information

director@nbrc.ac.in

Research

Research Interest: Understanding the mechanisms of genome integrity in nucleus and mitochondria

Summary of Research:

A. Development of therapeutics against colon cancer detection:

Colon cancer is one of the most common type of cancer in India. A major issue for colon cancer treatment is the recurrence. Recurrence occur due to the development of chemoresistance to the drugs used to treat the primary colon cancer. Using a unbiased screening procedure and multiple mice models we have identified three small molecules (which are FDA) we have identified three molecules which can act to prevent chemoresistance and allow the chemotherapeutic drugs like cisplatin, camptothecin and oxaliplatin to optimally function (Kaur et al., Journal of Clinical Investigation, 2024). A clinical trial is ongoing with ACTREC, Navi Mumbai with one of the molecules described in this publications where 292 patients are being recruited.

B. Determine how tumour suppressors recognize the damaged DNA:

Over the years our work has tried to understand how DNA damage was recognized by the cells so that it could be repaired by either of the two main repair pathways – homologous recombination and non-homologous end joining. Ubiquitylation of tumour suppressor BLM by chromatin associated E3 ligases (RNF8/RNF168), interactions with process specific proteins and a biphasic mode of recruitment to the site of damage which was dependent on cell cycle – were some of the key determinants of this process (Tikoo et al., The EMBO Journal, 2013; Tripathi et al., Nature Communications, 2018). Very recently we have shown that ubiquitylation of another key factor, RMI1 by RNF8 helps in its recruitment to the sites of stalled replication forks (Arun et al., Cell Mol Life Sci, 2026). This in turn helps in the resolution of the stalled forks and helps to maintain genome integrity.

C. Understanding p53 functions:

Apart from the role of p53 as a transcriptional activator and repressor, p53 also has transactivation-independent functions. Till now it was thought that DREAM causes transcriptional repression through the “canonical” p53-p21-Rb axis. Recently we provided evidence that apart from the “canonical” axis, repression by the DREAM complex is also mediated by p53 via a “non-canonical” pathway which involves direct interaction and recruitment of the DREAM complex by p53. Infact p53 is recruited along with the DREAM complex over the entire genome and regulates multiple pathways that lead to neoplastic transformation, thus providing an understanding of understanding of p53's role in transcriptional repression through its transactivation-independent function (Agrawal and Sengupta, The EMBO Journal, 2025).

E. Development of a DNA damage response agonist:

ATM plays a key role in DNA Damage Response (DDR) and is essential for maintaining genomic integrity. No biological reagent or tool has yet been identified that can enhance the DDR on demand despite knowing for a long time that DDR is the primary bulwark against cancer initiation. We identified a 20 amino acid stretch of residues in BLM which could activate ATM and act as a DDR agonist and thereby sustain DDR response (Agrawal et al.,
Nucleic Acids Research, 2025). Thus the work opened up the possibility of the usage of this peptide in boosting the ATM-mediated DDR and thereby delaying and/or prevention of both cancer and aging.

F. Understanding B cell development to find a potential cure for haematological cancers:

Using B cell specific BLM knockout mice we found that BLM maintains MALT1 expression and thereby sustains NF-κB signaling. Hence loss of BLM leads to impaired B-cell proliferation and development. Interestingly, we found that this same mechanism can be exploited in the treatment of B-cell cancers. Reducing or inhibiting BLM suppressed the progression of lymphoma and leukaemia and made the cancer cells more sensitive to chemotherapy (Agrawal et al., Cell Death & Disease, 2026).

G. Reverting Progressive external ophthalmoplegia (PEO) due to POLG mutations by FDA approved small molecules:

Mutations in POLGA, a key regulator of mtDNA replication, can cause PEO and mitochondrial dysfunction. Currently, there are no therapies for PEO, and treatment largely focuses on managing symptoms. We have identified PEO-associated POLG mutant aggregates as a druggable mechanism contributing to PEO pathology. Disrupting aggregates by two FDA approved small molecules can restore PEO mutant mitochondrial import and improve mitochondrial homeostasis in mice models of PEO (Mohammed et al, EMBO Molecular Medicine, 2026, In Press).

Research Group

PhD students:

BRIC NII

Savita
Tavleen Kaur

BRIC NIBMG

Sadananda Kumbhakar
Hanif Ahmed

Project Personnel

BRIC NIBMG

Priyanka Panwar
Samanwita Ghosh

  1. Mohammed A, Kaur T, Panwar P, Ghosh S, Ahmad H, Kumbhakar S, Muftuoglu M, Viscomi C, Sengupta S “Small molecules rescue pathogenic POLG aggregation and restore its functions in a mouse model of PEO.” EMBO Mol Med. (In Press). (2026)

  2. Mudgal PP, Veliz SPZ, Lourda M, Kadni TS, Varma M, Mazumder A, Budhiraja S, Jaggi N, Mukhopadhyay C, Sengupta S, Maitra A, Hug K, Sinha I, Ambikan AT, Filipovic I, Neogi U “A multicenter prospective observational multi-omics study protocol to identify biomarkers for severe dengue: COMBAT study clinical protocol.” BMC Infect Dis. (2026)

  3. Young C, Tiwary D, Ekstrand M, Gupta H, Gupta S, Kapadia A, Kumar S, Mahantshetty U, Mishra SK, Sharma P, Parikh A, Rajkumar T, Sengupta S, Singh S, Srivastava N, Thakar A, Yegnasubramanian S, Varma S, White C, Are C “ASO Special Article: Proceedings of the Inaugural Joint US-India Cancer Dialogue: Accelerating Collaboration to Advance Cancer Prevention, Early Detection, Treatment, and Care.” Ann Surg Oncol. (2026)

  4. Agrawal R, Ghosh S, Kumar N, Mukherjee C, Sharma V, Arun R, Deb R, Sarkar S, Savita, Kumar D, Rath S, Maitra A, Sengupta S “BLM regulates MALT1-driven NF-κB signalling and is targetable in B-cell malignancies.” Cell Death Dis (2026)

  5. Arun R, Kumbhakar S, Kaur T, Kaur S, Sengupta S “K63-linked ubiquitylation of RMI1 by RNF8 is essential to its recruitment to stalled forks.” Cell Mol Life Sci. (2026)

  6. Jha SK, Kumar S, Jain D, Pandey N, Chakraborty R, Rana K, Mehta D, Nath D, Ralhan J, Saini M, Chourasiya NK, Rani P, Pal S, Sengupta S, Pal A, Bajaj A “A biologically inert tamoxifen-derived long-lasting hydrogel-mediated immunochemotherapy can mitigate tumour progression and activate T cell immunity.” Chem Mater. (2025)

  7. Sharma S, Dhar S, Sengupta S “Balancing genome integrity and carcinogenesis: Insights into DNA damage response, repair pathways, and cancer therapies.” Curr Opin Pharmacol. (2025)

  8. Agrawal R, Sengupta S “p53 regulates DREAM complex-mediated repression in a p21-independent manner.” EMBO J. (2025)

  9. Agrawal R, Agarwal H, Mukherjee C, Chakraborty B, Sharma V, Tripathi V, Kumar N, Priya S, Gupta N, Jhingan GD, Bajaj A, Sengupta S “Phosphorylated BLM peptide acts as an agonist for DNA damage response.” Nucleic Acids Res. (2025)

  10. Kumari N, Kaur E, Raghavan SC, Sengupta S “Regulation of pathway choice in DNA repair after double-strand breaks.” Curr Opin Pharmacol. (2025)

  11. Yadav P, Rana K, Nardini V, Khan A, Pani T, Kar A, Jain D, Chakraborty R, Singh R, Jha SK, Mehta D, Sharma H, Sharma RD, Deo SVS, Sengupta S, Patil VS, Faccioli LH, Dasgupta U, Bajaj A “Engineered Nanomicelles inhibit the tumour progression via abrogating the prostaglandin-mediated immunosuppression.” J Control Release. (2024)

  12. Kaur E, Agrawal R, Arun R, Madhavan V, Srivastava V, Kumar D, Rath PP, Kumar N, Vedagopuram S, Pandey N, Priya S, Legembre P, Gourinath S, Bajaj A, Sengupta S “Small molecules that disrupt RAD54-BLM interaction hamper tumor proliferation in colon cancer chemoresistance models.” J. Clin. Invest. (2024)

  13. Hussain M, Mohammed A, Saifi S, Priya S, Sengupta S “Hyper-ubiquitylation of DNA helicase RECQL4 by E3 ligase MITOL prevents mitochondrial entry and potentiates mitophagy.” J. Biol Chem. (2023)

  14. Kar A, Jain D, Kumar S, Rajput K, Pal S, Rana K, Kar R, Jha SK, Medatwal N, Yavvari PS, Pandey N, Mehta D, Sharma H, Bhattacharya D, Pradhan MK, Sharma RD, Srivastava A, Agrawal U, Mukhopadhyay A, Sengupta S, Patil VS, Bajaj A, Dasgupta U “A localized hydrogel-mediated chemotherapy causes immunogenic cell death via activation of ceramide-mediated unfolded protein response.” Sci Adv. (2023)

  15. Mondal I, Fatima SW, Priya S, Sengupta S, Khare SK, Kulshreshtha R “Transglutaminase-Polyethyleneimine Nanoflowers Mediated Cellular Delivery of Anti-miR- 210 for Effective Glioblastoma Therapy.” ACS Biomater Sci Eng. (2023)

  16. Hussain M, Saifi S, Mohammed A, Sengupta S “Protocol to detect in vitro and in cell ubiquitylation of mitochondrial DNA polymerase gamma by mitochondrial E3 ligase MITOL.” STAR Protoc. (2022)

  17. Priya S, Kaur E, Kulshrestha S, Pandit A, Gross I, Kumar N, Agarwal H, Khan A, Shyam R, Bhagat P, Prabhu JS, Nagarajan P, Deo SVS, Bajaj A, Freund JN, Mukhopadhyay A, Sengupta S “CDX2 inducible microRNAs sustain colon cancer by targeting multiple DNA damage response pathway factors.” J Cell Sci. (2021)

  18. Sreekanth V, Pal S, Kumar S, Komalla V, Yadav P, Shyam R, Sengupta S, Bajaj A “Self-assembled supramolecular nanomicelles from bile acid-docetaxel conjugate are highly tolerable with improved therapeutic efficacy.” Biomater Sci. (2021)

  19. Kaur E, Agrawal R, Sengupta S “Functions of BLM helicase in cells: is it acting like a double-edged sword?” Front Genet. (2021)

  20. Hussain M, Mohammed A, Saifi S, Khan A, Kaur E, Priya S, Agarwal H, Sengupta S “MITOL-dependent ubiquitylation negatively regulates the entry of PolgA into mitochondria.” PLoS Biol. (2021)

  21. Sreekanth V, Kar A, Kumar S, Pal S, Yadav P, Sharma Y, Komalla V, Sharma H, Shyam R, Sharma RD, Mukhopadhyay A, Sengupta S, Dasgupta U, Bajaj A. “Bile acid tethered Docetaxel-based nanomicelles mitigate tumor progression through epigenetic changes.” Angew Chem Int Ed Engl. (2021)

No lab students found.

S. No. Year Honors/ Awards/Fellowship
1. 1991 Silver medallist in M.Sc., University of Calcutta, India.
2. 1997 Best thesis award, Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.
3. 2011 National Bioscience award for Career Development by Department of Biotechnology, India
4. 2011 Elected as a member of Guha Research Conference
5. 2015 Elected Fellow of the National Academy of Science (NASI)
6. 2017 Elected Fellow of the Indian Academy of Sciences (IASc)
7. 2017 Elected Fellow of the Indian National Science Academy (INSA)
8. 2018 J C Bose Fellowship
9. 2021 Professor Vishwa Nath Memorial Award Lecture by INSA
10. 2022 Elected Vice President of Indian Association of Cancer Research
11. 2023 GK Manna Memorial Award Lecture by All India Congress of Genetics and Genomics
12. 2023 Lalji Singh Memorial Award Lecture by the Society for Mitochondrial Research & Medicine
13. 2024 J C Bose Fellowship (2nd term)
14. 2026 Indian Association of Cancer Research (IACR) Oration Award 2026

No Alumni found.

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