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Research interest:
Despite advances in therapeutic interventions, resistance to available therapies remains a major cause of poor long-term survival in cancer patients, including those with acute myeloid leukemia (AML). A major focus of our lab is to identify and functionally characterize genes/pathways contributing to drug resistance in AML patients. We employ a comprehensive functional genomics approach integrating in-house-developed CRISPR-Cas9 genome engineering epigenomics platforms with cellular, metabolic, and molecular pathways studies. We further translate the knowledge gained by applying functional genomics into cellular and preclinical disease models, aiming to discover and develop new prognostic and therapeutic strategies to overcome therapeutic resistance in AML patients with broader clinical implications.
Selected publications:
- 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.
Journal of Clinical Investigation. 2024 Feb 29;134(8). PMID: 38421735; https://www.jci.org/articles/view/161941 [IF = 15.9]
- Lin QXX, Rajagopalan D, Gamage AM, Tan LM, Venkatesh PN, Chan WOY, Kumar D, Agrawal R, Chen Y, Fong SW, Singh A, Sun LJ, Tan SY, Chai LYA, Somani J, Lee B, Renia L, Ng LFP, Ramanathan K, Wang LF, Young B, Lye D, Singhal A, Prabhakar S. Longitudinal single cell atlas identifies complex temporal relationship between type I interferon response and COVID-19 severity.
Nature Communications 2024 Jan 18;15(1):567. PMID: 38238298; https://www.nature.com/articles/s41467-023-44524-0 [IF = 16.6]
- Del Rosario RCH, Poschmann J, Lim C, Cheng CY, Kumar P, Riou C, Ong ST, Gerges S, Hajan HS, Kumar D, Marzuki M, Lu X, Lee A, Wijaya GC, Rayan NA, Zhuang Z, Du Bruyn E, Chee CBE, Lee B, Lum J, Zolezzi F, Poidinger M, Rotzschke O, Khor CC, Wilkinson RJ, Wang YT, Chandy GK, De Libero G, Singhal A, Prabhakar S. Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection. Nature Microbiology 2022 Feb;7(2):312-326. PMID: 35102304; https://www.nature.com/articles/s41564-021-01049-w [IF = 28.30]
- Kober-Hasslacher M, Oh-Strauß H, Kumar D, Soberon V, Diehl C, Lech M, Engleitner T, Katab E, Fernández-Sáiz V, Piontek G, Li H, Menze B, Ziegenhain C, Enard W, Rad R, Böttcher JP, Anders HJ, Rudelius M, Schmidt-Supprian M. c-Rel gain in B cells drives germinal center reactions and autoantibody production. ; Journal of Clinical Investigation 2020 Jun 1;130(6):3270-3286. PMID: 3219164; https://www.jci.org/articles/view/124382 [IF = 15.9]
- Kumar D*, Lee B, Puan KJ, Lee W, Luis BS, Yusof N, Andiappan AK, Del Rosario R, Poschmann J, Kumar P, DeLibero G, Singhal A, Prabhakar S, De Yun W, Poidinger M, Rötzschke O. Resistin expression in human monocytes is controlled by two linked promoter SNPs mediating NFKB p50/p50 binding and C-methylation. Scientific Reports. 2019 Oct 23;9(1):15245. PMID: 31645609. https://www.nature.com/articles/s41598-019-51592-0 [IF = 4.6]
- Kumar D, Puan KJ, Andiappan AK, Lee B, Westerlaken GH, Haase D, Melchiotti R, Li Z, Yusof N, Lum J, Koh G, Foo S, Yeong J, Alves AC, Pekkanen J, Sun LD, Irwanto A, Fairfax BP, Naranbhai V, Common JE, Tang M, Chuang CK, Jarvelin MR, Knight JC, Zhang X, Chew FT, Prabhakar S, Jianjun L, Wang Y, Zolezzi F, Poidinger M, Lane EB, Meyaard L, Rötzschke O. A functional SNP associated with atopic dermatitis controls cell type-specific methylation of the VSTM1 gene locus.
Genome Medicine. 2017 Feb 20;9(1):18. PMID: 28219444. https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-017-0404-6 [IF = 13.8]
- Kumar D, Hosse J, von Toerne C, Noessner E, Nelson PJ. JNK MAPK pathway regulates constitutive transcription of CCL5 by human NK cells through SP1. Journal of Immunology. 2009 Jan 15;182(2):1011-20. PMID: 19124744. https://journals.aai.org/jimmunol/article/182/2/1011/81512 [IF = 5.42]
* Corresponding Author
Publication Link:
https://www.ncbi.nlm.nih.gov/myncbi/dilip.kumar.8/bibliography/public/
Patents:
Kumar D, Singhal A. Method of treating acute myeloid leukemia. World Intellectual Property Organization (WIPO) - 2023 June 8; WO/2023/101608. (A*STAR Patent granted, Singapore, International) https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2023101608
Our lab aims to identify and functionally characterize genes and pathways contributing to drug resistance and relapse in AML patients, intending to develop prognostic and therapeutic strategies with broader clinical implications. Our scientific directions and goals are categorized into distinct themes with specific goals, which are described below:
(A) Identification
and functional characterization of genes and pathways contributing to
therapeutic resistance in AML: Drug resistance (Chemoresistance) is one of the major challenges in the
treatment of cancers in general, including acute myeloid leukemia (AML). AML is
an aggressive hematologic malignancy characterized by the
uncontrolled proliferation of poorly differentiated cells of myeloid immune
cell origin with poor long-term survival. The major contributing factors are
chemoresistance and relapse post-therapy, which are linked to minimal residual
disease (MRD). The MRD is represented by chemoresistant leukemic stem or
regenerating cells (LSCs/LRCs), which can initiate and sustain the disease. We aim to use AML as a chemoresistant cancer model to identify genes and
pathways driving the chemoresistance in LSCs/LRCs. The findings from our study
could lead to the discovery and development of innovative therapeutic
interventions not limited to enhancing treatment outcomes for patients with AML
relapse but with broader therapeutic and prognostic applications for cancer.
(B) The discovery and development of therapeutic approaches to overcome the TME-induced immune dysfunction of the host in cancer patients: Effective cancer therapies rely not only on their direct effects on cancer cells but also on the functional state of the host’s immune system. Therefore, immune reprogramming in the host by the tumor microenvironment (TME) remains one of the major concerns in cancer therapy. This project aims to delineate the molecular basis of AML-induced immune suppression through a xenograft-induced disease model in humanized mice, which enables a human-like interaction between xenografts and the host's immune system within the tumor microenvironment.
(C) Exploring the interactive role of AML-associated metabolic and epigenetic reprogramming in the development of chemoresistance: Metabolic changes are a distinctive feature of cancer cells and are often interconnected with epigenetic reprogramming. Our focus is on understanding the role of epigenetic reprogramming in promoting therapy resistance in cancer, specifically in AML. Our goal is to identify and characterize the cancer-associated metabolic alteration-induced epigenetically driven pathways that contribute to chemoresistance.
(D) Technology development for biomedical genomics
and discovery research: To establish agreement on the possible prognostic and therapeutic uses
of identified targets, concepts from human biomedical research driven by high
throughput data must be substantiated by proof of concept. Our laboratory's
initiatives center around data-driven biomedical research to pinpoint potential
targets that require in-depth molecular validation. This necessitates the
contentious efforts to update and develop new technological approaches for
discovery research and proof-of-concept studies. Our lab will continue to
develop further and apply in-house available CRISPR-Cas9 genome engineering and
epigenome platforms for discovery research and proof of concept studies in therapeutic
resistance in cancer.
Year | Degree | University |
2010 | Ph.D | Ludwig-Maximilians-Universität München, Germany |
2001 | M.Sc | Veer Kunwar Singh University, Ara, Bihar, India |
1998 | B.Sc | Veer Kunwar Singh University, Ara, Bihar, India |
Professional appointments:
2024 – till date | Assistant Professor, National Institute of Biomedical Genomics, Kalyani, West Bengal, India |
2018-2024 | Senior Scientist Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore |
2019 | Assistant Professor T.M. Bhagalpur University, Bhagalpur, Bihar, India (Not Availed) |
2011-2017 | Scientist Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore |
2009-2011 | Postdoctoral fellow Max Planck Institute of Biochemistry, Munich, Germany |
Awards and Honors:
Year | Award | Source |
2022 | Best presentation award (Runner) in translational research at the NCIS Annual Research Meeting 2022 | National University Cancer Institute of Singapore (NCIS) and Science Institute of Singapore, (CSI) |
2020 | Career Development Award - 2021 | Agency for Science, Technology and Research (A*STAR), Singapore |
2018 | D. P. Burma Award for the best poster at the 86th annual meeting of SBC | Society Of Biological Chemists (SBC) |
2005-2009 | DFG doctoral fellowship | German Research Foundation (DFG) |
2002-2004 | Junior Research Fellowship | Indian Council of Medical Research |
2002 | National Eligibility Test-JRF | The Council of Scientific and Industrial Research - University Grants Commission |
2002 | Graduate Aptitude Test in Engineering (GATE-2002) | Indian Institutes of Technology |
Professional membership:
2022-2025: Singaporean Society for Immunology (SgSI)
2023-2025 Singapore Society for Microbiology and Biotechnology
2022: The Society for Integrative Biosciences (SiBio)
Invited talks:
2022 | Translational research: NFkB-p65 – ‘‘ATP13A2 axis mediated metabolic adaptation supports acute myeloid leukemia pathologies” NCIS Annual Research Meeting 2022, Singapore |
2022 | The SIBio Immunology and Microbiology Lecture Series 2022: ‘‘Deciphering the viral-induced aberrant immune responses and immune-associated malignancies using functional genomic approach”, JNU, New Delhi, India |
2022 | Young Immunologists Symposium 2022: ‘‘ATP13A2 axis mediated metabolic adaptation supports acute myeloid leukemia pathologies” organized by the Singaporean Society for Immunology (SgSI), Singapore |
2019 | International Symposium on Cancer Prevention and Treatment 2019: “Mapping of NF-kB Mediated Pathways Associated Functional Networks Using an Oligo-based Paired gRNA CRISPR Genome Editing System” organized by Cancer Research and Cancer Academy, JNU, New Delhi, India |
2018 | International Conference on “Trends in Biochemical and Biomedical Research: Advances and Challenges” 2018: “Translating resistin promoter associated genetic variants to casualty and potential mechanisms of disease predisposition” organized by Department of Biochemistry, Institute of Science, BHU, Varanasi, India |
2017 | Asia Pacific Bacteriology and Parasitology Conference 2017, Singapore |
Selected poster presentation:
2018 | Bridging Biomedical Worlds 2018, Genome Editing: The Next Frontier, Singapore |
2017 | 86th annual meeting of the Society of Biological Chemists (SBC) 2017, New Delhi, India |
2015 | 6th Congress of the Federation of Immunological Societies of Asia-Oceania (FIMSA 2015), Singapore |
2010 | 3rd International GK Symposium, Erlangen, Germany |
2008 | 8th EMBL Transcription meeting 2008, Heidelberg, Germany |
1. Amali AA, Paramasivam K, Huang CH, Joshi A, Hirpara JL, Ravikumar S, Sam QH, Tan RYM, Tan Z, Kumar D, Neckers LM, Pervaiz S, Foo R, Chan CYY, Zhu J, Lee C, Chai LYA. Mitochondrial chaperon TNF-receptor- associated protein 1 as a novel apoptotic regulator conferring susceptibility to Pneumocystis jirovecii pneumonia. Front Immunol. 2024 Aug 19;15:1423086. doi: 10.3389/fimmu.2024.1423086. [IF = 5.7]
2. 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. Journal of Clinical Investigation. 2024 Feb 29;134(8). PMID: 38421735; https://www.jci.org/articles/view/161941 [IF = 15.9]
3. Lin QXX, Rajagopalan D, Gamage AM, Tan LM, Venkatesh PN, Chan WOY, Kumar D, Agrawal R, Chen Y, Fong SW, Singh A, Sun LJ, Tan SY, Chai LYA, Somani J, Lee B, Renia L, Ng LFP, Ramanathan K, Wang LF, Young B, Lye D, Singhal A, Prabhakar S. Longitudinal single cell atlas identifies complex temporal relationship between type I interferon response and COVID-19 severity. Nature Communications 2024 Jan 18;15(1):567. PMID: 38238298; https://www.nature.com/articles/s41467-023-44524-0 [IF = 16.6]
4. Del Rosario RCH, Poschmann J, Lim C, Cheng CY, Kumar P, Riou C, Ong ST, Gerges S, Hajan HS, Kumar D, Marzuki M, Lu X, Lee A, Wijaya GC, Rayan NA, Zhuang Z, Du Bruyn E, Chee CBE, Lee B, Lum J, Zolezzi F, Poidinger M, Rotzschke O, Khor CC, Wilkinson RJ, Wang YT, Chandy GK, De Libero G, Singhal A, Prabhakar S. Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection. Nature Microbiology 2022 Feb;7(2):312-326. PMID: 35102304; https://www.nature.com/articles/s41564-021-01049-w [IF = 28.30]
5. Puan KJ, San Luis B, Yusof N, Kumar D, Andiappan AK, Lee W, Cajic S, Vuckovic D, Chan J, Döllner T, Hou HW, Jiang Y, Tian C, Rapp E, Poidinger M, Wang Y, Soranzo N, Lee B, Rötzschke O. FUT6 deficiency compromises basophil function by selectively abrogating their sialyl-Lewis x expression. Communications Biology 2021 Jul 2;4(1):832. PMID: 34215830; https://www.nature.com/articles/s42003-021-02295-8 [IF = 5.9]
6. Penny HL, Sieow JL, Gun SY, Lau MC, Lee B, Tan J, Phua C, Toh F, Nga Y, Yeap WH, Janela B, Kumar D, Chen H, Yeong J, Kenkel JA, Pang A, Lim D, Toh HC, Hon TLK, Johnson CI, Khameneh HJ, Mortellaro A, Engleman EG, Rotzschke O, Ginhoux F, Abastado JP, Chen J, Wong SC. Targeting Glycolysis in Macrophages Confers Protection Against Pancreatic Ductal Adenocarcinoma. International Journal of Molecular Sciences 2021 Jun 14;22(12). PMID: 34198548; https://www.mdpi.com/1422-0067/22/12/6350 [IF = 5.6]
7. Andiappan AK, Andiappan AK, Puan KJ, Lee B, Yeow PT, Yusof N, Merid SK, Kumar D, Lum J, Foo S, Koh G, Poidinger M, Zolezzi F, Wang Y, Melén E, Rotzschke O. Inverse association of FCER1A allergy variant in monocytes and plasmacytoid dendritic cells. The Journal of Allergy and Clinical Immunology 2021 Apr;147(4):1510-1513.e8. PMID: 33160967. https://www.jacionline.org/article/S0091-6749(20)31562-1 [IF = 14.29]
8. Kober-Hasslacher M, Oh-Strauß H, Kumar D, Soberon V, Diehl C, Lech M, Engleitner T, Katab E, Fernández-Sáiz V, Piontek G, Li H, Menze B, Ziegenhain C, Enard W, Rad R, Böttcher JP, Anders HJ, Rudelius M, Schmidt-Supprian M. c-Rel gain in B cells drives germinal center reactions and autoantibody production. J Clin Invest. 2020 Jun 1;130(6):3270-3286. PMID: 32191641; Journal of Clinical Investigation https://www.jci.org/articles/view/124382 [IF = 15.9]
9. Lee SWL, Seager RJ, Litvak F, Spill F, Sieow JL, Leong PH, Kumar D, Tan ASM, Wong SC, Adriani G, Zaman MH, Kamm ARD. Integrated in silico and 3D in vitro model of macrophage migration in response to physical and chemical factors in the tumor microenvironment. Integrative Biology (Camb). 2020 Apr 20;12(4):90-108. PMID: 32248236; https://academic.oup.com/ib/article-abstract/12/4/90/5816011 [IF = 3.17]
10. Kumar D*, Lee B, Puan KJ, Lee W, Luis BS, Yusof N, Andiappan AK, Del Rosario R, Poschmann J, Kumar P, DeLibero G, Singhal A, Prabhakar S, De Yun W, Poidinger M, Rötzschke O. Resistin expression in human monocytes is controlled by two linked promoter SNPs mediating NFKB p50/p50 binding and C-methylation. Scientific Reports. 2019 Oct 23;9(1):15245. PMID: 31645609. https://www.nature.com/articles/s41598-019-51592-0 [IF = 4.6]
11. Puan KJ, Andiappan AK, Lee B, Kumar D, Lai TS, Yeo G, Bercin D, Starke M, Haase D, Lum J, Chew FT, Connolly J, Wong SC, Zolezzi F, Poidinger M, Wang Y, Rötzschke O. Systematic characterization of basophil anergy. Allergy. 2017 Mar;72(3):373-384. PMID: 27271846. https://onlinelibrary.wiley.com/doi/10.1111/all.12952 [IF = 14.71]
12. Kumar D, Puan KJ, Andiappan AK, Lee B, Westerlaken GH, Haase D, Melchiotti R, Li Z, Yusof N, Lum J, Koh G, Foo S, Yeong J, Alves AC, Pekkanen J, Sun LD, Irwanto A, Fairfax BP, Naranbhai V, Common JE, Tang M, Chuang CK, Jarvelin MR, Knight JC, Zhang X, Chew FT, Prabhakar S, Jianjun L, Wang Y, Zolezzi F, Poidinger M, Lane EB, Meyaard L, Rötzschke O. A functional SNP associated with atopic dermatitis controls cell type-specific methylation of the VSTM1 gene locus. Genome Medicine. 2017 Feb 20;9(1):18. PMID: 28219444. https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-017-0404-6 [IF = 13.8]
13. Shelar SB, Kaminska KK, Reddy SA, Kumar D, Tan CT, Yu VC, Lu J, Holmgren A, Hagen T, Chew EH. Thioredoxin-dependent regulation of AIF-mediated DNA damage. Free Radical Biology and Medicine. 2015 Oct;87:125-36. PMID: 26119781. https://www.sciencedirect.com/science/article/pii/S089158491500297X [IF = 8.1]
14. Andiappan AK, Melchiotti R, Poh TY, Nah M, Puan KJ, Vigano E, Haase D, Yusof N, San Luis B, Lum J, Kumar D, Foo S, Zhuang L, Vasudev A, Irwanto A, Lee B, Nardin A, Liu H, Zhang F, Connolly J, Liu J, Mortellaro A, Wang Y, Poidinger M, Larbi A, Zolezzi F, Rotzschke O. Genome-wide analysis of the genetic regulation of gene expression in human neutrophils. Nature Communications 2015 Aug 10;6:7971. PMID: 26259071. https://www.nature.com/articles/ncomms8971 [IF = 16.6]
15. Chu Y, Vahl JC, Kumar D, Heger K, Bertossi A, Wójtowicz E, Soberon V, Schenten D, Mack B, Reutelshöfer M, Beyaert R, Amann K, van Loo G, Schmidt-Supprian M. B cells lacking the tumor suppressor TNFAIP3/A20 display impaired differentiation and hyperactivation and cause inflammation and autoimmunity in aged mice. Blood. 2011 Feb 17;117(7):2227-36. PMID: 21088135. https://ashpublications.org/blood/article/117/7/2227/28236 [IF = 22.11]
16. Kumar D, Hosse J, von Toerne C, Noessner E, Nelson PJ. JNK MAPK pathway regulates constitutive transcription of CCL5 by human NK cells through SP1. Journal of Immunology. 2009 Jan 15;182(2):1011-20. PMID: 19124744. https://journals.aai.org/jimmunol/article/182/2/1011/81512 [IF = 5.42]
17. Kumar D, Singhal A. Method of treating acute myeloid leukemia. World Intellectual Property Organization (WIPO)- 2023 June 8; WO/2023/101608. (Patent granted, Singapore, International) https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2023101608
18. Kumar D, Rotzschke O, Singhal A. Paired guide RNAs library preparation using oligonucleotides for lentiviral CRISPR-CAS9-based applications in mammalian cells. SG) patent; A*STAR ref: IP2023-318-01 SIGN
PhD students:
1. RIYA DEB
2. ALOKE MANDI (jointly with Dr. Soumitra Mohanty)
Integrated MS-PhD students:
1. ARJUN SINGH
We are constantly looking for highly motivated PhD and postdoctoral fellows. Prior experience in CRISPR-Cas9 genome engineering, molecular biology, genomics, bioinformatics, or preclinical animal models is preferred but not mandatory. Interested candidates are encouraged to contact at dk1@nibmg.ac.in. Undergraduate and postgraduate students interested in research training are also encouraged to apply.
