Anand JEYASEKHARAN

Principal Investigator and Facility Head (Microscopy), Cancer Science Institute of Singapore, NUS
Consultant, Department of Haematology-Oncology, National University Cancer Institute, Singapore
Assistant Professor; Department of Medicine, Yong Loo Lin School of Medicine, NUS
Assistant Director of Research (Medical Oncology), Department of Haematology-Oncology, National University Hospital, Singapore
Co-lead; Research based molecular diagnostics platform, Singapore Translational Cancer Consortium

csiadj[at]nus.edu.sg


Work in the ADJ laboratory focuses on how the immune system recognizes cancer cells upon treatment with DNA damaging chemotherapy.  Our eventual aim is to use this information to guide the rational design of immunotherapy-chemotherapy combinations for cancer treatment. Our research involves both fundamental research (molecular and cellular biology of chemotherapy responses) and translational research (using clinical samples) in a variety of cancer types. We have a specific interest in lymphomas; and work closely with colleagues in the NUH Lymphoma team to develop novel therapeutic strategies for clinical use.

Research

We are interested in the effects of genotoxic chemotherapy on the immune mileu in cancer. This interest stems from 2 key observations:

  1. Defects in DNA repair in cancer contribute to the generation of immunogenic nucleic acids and peptide neo-antigens
  2. Genotoxic chemotherapy activates innate and adaptive immune responses through immunogenic cell death and cytosolic nucleic acid sensors

 

We hypothesize that intracellular changes in cancer differentially affect the ability of distinct chemotherapeutics to result in immune clearance of tumours. A comprehensive understanding of these intracellular components that regulate immune activation after DNA damage will facilitate the development of predictive biomarkers for chemotherapy-immunotherapy combination trials.

Accordingly, current work in my laboratory spans two broad themes:

1. Intracellular changes in cancer that influence the activation of the immune response after DNA damage

2. Combination strategies to potentiate the action of genotoxic chemotherapy, through cell-intrinsic and cell-extrinsic mechanisms.

 

 

 

 

 

 

 

To facilitate the above studies, we have:

  1. Acquired a range of cell line models for epithelial and lymphoid cancers
  2. Setup systems and assays for DNA repair and immune activation studies in-vitro
  3. Setup platforms for quantitative microscopy in histological material, to interrogate immune modulation pathways in samples of human cancer
  4. Established international and local collaborations for the acquisition of well-annotated clinical samples
  5. Established connections with pharmaceutical companies and medical technology companies, to translate our research findings to clinical trials and biomarker development.

 

Graduate students and post-doctoral researchers in the lab lead specific projects, and we collaborate with local and overseas colleagues to test our findings in relevant clinical tissue collections. The ADJ lab also hosts overseas elective students, NUH residents and medical students who are interested in translational cancer research. We are committed to promoting diversity in science #heforshe, and a culture of mutual respect #scienceisnotapyramid. ADJ is a DORA signatory; https://sfdora.org/

Lab Members

Selected Publications

1. Ngoi N, Lim J, Ow S, Jen WY, Lee M, Teo W, Ho J, Sundar R, Tung ML, Lee YM, Ngo E, Lim SW, Ong J, Lim F, Bonney G, Vellayappan B, Ho F, Tey J, Chan N, de Mel S, Poon M, Lee SY, Koh LP, Liu TC, Tan LK, Wong A, Wong A, Lim SE, Yeoh A, Wong JE, Tan D, Goh BC, Chng WJ, Soo R, Chee CE, Chee YL, Lee SC, Jeyasekharan AD, National University Cancer Institute, Singapore (NCIS). A Segregated-Team Model to Maintain Cancer Care During the COVID-19 Outbreak at an Academic Center in Singapore. Ann Oncol. 2020 Mar 31: S0923-7534(20)36410-3. doi: 10.1016/j.annonc.2020.03.306. PMID: 32243893

2. de Mel S, Rashid MBM, Zhang XY, Goh J, Lee CT, Poon LM, Chan EHL, Liu X, Chng WJ, Chee YL, Lee J, Yuen YC, Lim JQ, Chia BKH, Laurensia Y, Huang D, Pang WL, Cheah DMZ, Wong EKY, Ong CK, Tang T, Lim ST, Ng SB, Tan SY, Loi HY, Tan LK, Chow EK, Jeyasekharan AD. Application of an ex-vivo drug sensitivity platform towards achieving complete remission in a refractory T-cell lymphoma. Blood Cancer J. 2020 Jan 27;10(1):9. doi: 10.1038/s41408-020-0276-7. PMID: 31988286

3. Krishnan V, Lim DXE, Hoang PM, Srivastava S, Matsuo J, Huang KK, Zhu F, Ho KY, So JBY, Khor C, Tsao S, Teh M, Fock KM, Ang TL, Jeyasekharan AD, Tan P, Yeoh KG, Ito Y. DNA damage signalling as an anti-cancer barrier in gastric intestinal metaplasia. Gut. 2020 Jan 14. pii: gutjnl-2019-319002. doi: 10.1136/gutjnl-2019-319002. [Epub ahead of print]. PMID: 31937549

4. Oon ML, Hoppe MM, Fan S, Phyu T, Phuong HM, Tan SY, Hue SS, Wang S, Poon LM, Chan HLE, Lee J, Chee YL, Chng WJ, de Mel S, Liu X, Jeyasekharan AD*, Ng SB*. The contribution of MYC and PLK1 expression to proliferative capacity in diffuse large B-cell lymphoma. Leuk Lymphoma. 2019 Jul 1:1-11. doi: 10.1080/10428194.2019.1633629. PMID: 31259656

5. Hong G, Fan S, Phyu T, Maheshwari P, Hoppe MM, Phuong HM, de Mel S, Poon M, Ng SB, Jeyasekharan AD. Multiplexed Fluorescent Immunohistochemical Staining, Imaging, and Analysis in Histological Samples of Lymphoma.  J. Vis. Exp.2019 (143), e58711, doi:10.3791/58711.

6. Srinivas US, Tan BWQ, Vellayappan BA, JeyasekharanAD. ROS and the DNA damage response in cancer. Redox Biol. 2018 Dec 21:101084. doi: 10.1016/j.redox.2018.101084. PMID: 30612957

7. Hoppe MM, Sundar R, Tan DSP, Jeyasekharan AD. Biomarkers for Homologous Recombination Deficiency in Cancer. J Natl Cancer Inst. 2018 July, 110(7):704-713; PMID:29788099.

8. Tay SH, Wong AS, Jeyasekharan AD. A patient with pembrolizumab-induced fatal polymyositis Eur J Cancer.  2018 Jan, 91:180-182; PMID:29329695.

9. Ng SB, Fan S, Hoppe M, De Mel S, Jeyasekharan AD. Quantitative Analysis of a Multiplexed Immunofluorescence Panel in T-Cell Lymphoma. SLAS Technol 2017 Dec, PMID:29241019

10. Jeyasekharan AD, Liu Y, Hattori H, Pisupati VN, Jonsdottir, Eeson Rajendra et al, and Venkitaraman AR. A cancer-associated BRCA2 mutation reveals masked nuclear export signals controlling localization. Nat Struct Mol Biol. 2013 Oct;20(10):1191-8, PMID: 24013206.

Honors & Awards

2016 Clinician-Scientist Transition Award, National Medical Research Council, Singapore
2015 NUHS Clinician-Scientist Program Award, National University Hospital, Singapore
2014 NRF Singapore nomination to attend the 64th Lindau Nobel meeting (Medicine and Physiology)
2011 Academic Development Award, National University Hospital, Singapore
2009-2010 Junior Research Fellowship, Wolfson College, Cambridge
2005-2008 Gates Cambridge Scholarship, Gates Cambridge Trust, University of Cambridge, UK