Faculty Members

Research

Our functional genomics of diseases lab aims to investigate genes, pathways, and biological processes that contribute to the development and progression of immune-related pathologies in humans. We employ a comprehensive functional genomics approach that integrates 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 for immune-related human pathologies.

Kindly find below a graphical representation outlining the scientific direction of our laboratory.

Our research endeavors are systematically structured and categorized into distinct scientific themes with specific goals, which are described below:

(A) Drug resistance or Chemoresistance: Identification and functional characterization of genes and pathways contributing to cancer relapse.

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 very poor long-term survival. The major contributing factor is relapse of the patients post-therapy and complete remission. The relapse of AML patients has been linked to the Minimal residual disease (MRD) 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 in order 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) Cancer therapy and tumor microenvironment (TME): 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, the major challenge for cancer therapies remains the reprogramming of the host’s immune system induced by the tumor microenvironment (TME). 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) Host-Directed-Therapy (HDT) for Viral induced pathologies: 

Despite the considerable research conducted worldwide on the pathologies induced by RNA viruses, including SARS-CoV2, there is still an elusive understanding of the molecular mechanisms that drive pathologies in severe and recovered patients. Our goal is to investigate the molecular changes in the host’s immune system during the acute disease progression post-infection until the convalescent disease state is reached using the epigenomic approach.

(D) Technology development for biomedical genomics and discovery research. 

In order to establish agreement on the possible prognostic and therapeutic uses of identified targets, concepts arising 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, with the goal of pinpointing potential targets that necessitate additional 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 further develop and apply in-house available CRISPR-Cas9 genome engineering and epigenome platforms for discovery research and proof of concept studies.

Research funding:

CV

Professional appointments:

Awards and Honors:

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:

Selected poster presentation:

Publications

1. 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]

2. 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]

3. 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]

4. 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]

5. 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]

6. 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]

7. 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]

8. 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]

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]

10. 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]

11. 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]

12. 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]

13. 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]

14. 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]

15. 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]

16. 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  

               Kumar D, Rotzschke O, Singhal A. Paired guide RNAs library preparation using oligonucleotides for                 lentiviral CRISPR-CAS9-based applications in mammalian cells (Patent filed, Singapore)

Lab members

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.

Come, join us. Let's ENJOY together!!!