Profile
The immune system is responsible for safeguarding living organisms against both internal and external dangers, such as infectious agents and abnormal cells that can lead to cancer. However, when the immune system is deregulated, it can result in various human pathologies. Our laboratory aims to explore genes, pathways, and biological processes that contribute to immune-related pathologies in humans. We hope to develop new prognostic and therapeutic strategies by using CRISPR-Cas9-based functional genomics, along with molecular, cellular, and preclinical studies. Our main objective is to identify potential prognostic and therapeutic targets that can help overcome the challenge of therapy resistance in cancers.
Current Focus Areas
(A) Drug resistance or Chemoresistance: Identification and functional characterization of genes and pathways contributing to cancer relapse.
(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.
(C) The Role of epigenetic reprogramming in immune pathologies. We have initiated the establishment of an epigenetic map contributing to the context of therapy resistance using our in-house CRISPR-Cas9 platform based functional screening.
Selected Publications
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]
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*, 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] (co-corresponding author)
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
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]