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. Ho, J. S. Y., B. W.-Y. Mok, L. Campisi, T. Jordan, S. Yildiz, S. Parameswaran, J. A. Wayman, N. N. Gaudreault, D. A. Meekins, S. V. Indran, I. Morozov, J. D. Trujillo, Y. S. Fstkchyan, R. Rathnasinghe, Z. Zhu, S. Zheng, N. Zhao, K. White, H. Ray-Jones, V. Malysheva, M. J. Thiecke, S.-Y. Lau, H. Liu, A. J. Zhang, A. C.-Y. Lee, W.-C. Liu, S. Jangra, A. Escalera, T. Aydillo, B. S. Melo, E. Guccione, R. Sebra, E. Shum, J. Bakker, D. A. Kaufman, A. L. Moreira, M. Carossino, U. B. R. Balasuriya, M. Byun, R. A. Albrecht, M. Schotsaert, A. Garcia-Sastre, S. K. Chanda, E. R. Miraldi, A. D. Jeyasekharan, B. R. TenOever, M. Spivakov, M. T. Weirauch, S. Heinz, H. Chen, C. Benner, J. A. Richt and I. Marazzi (2021). TOP1 inhibition therapy protects against SARS-CoV-2-induced lethal inflammation. Cell 184(10): 2618-2632.e2617.
  2. Hoppe, M. M., P. Jaynes, J. D. Wardyn, S. S. Upadhyayula, T. Z. Tan, S. Lie, D. G. Z. Lim, B. N. K. Pang, S. Lim, J. P. S. Yeong, A. Karnezis, D. S. Chiu, S. Leung, D. G. Huntsman, A. S. Sedukhina, K. Sato, M. D. Topp, C. L. Scott, H. Choi, N. R. Patel, R. Brown, S. B. Kaye, J. J. Pitt, D. S. P. Tan and A. D. Jeyasekharan (2021). Quantitative imaging of RAD51 expression as a marker of platinum resistance in ovarian cancer. EMBO Mol. Med.13(5): e13366.
  3. Ngoi, N., J. Lim, S. Ow, W. Y. Jen, M. Lee, W. Teo, J. Ho, R. Sundar, M. L. Tung, Y. M. Lee, E. Ngo, S. W. Lim, J. Ong, F. Lim, G. Bonney, B. Vellayappan, F. Ho, J. Tey, N. Chan, S. de Mel, M. Poon, S. Y. Lee, L. P. Koh, T. C. Liu, L. K. Tan, A. S. C. Wong, A. L. A. Wong, S. E. Lim, A. Yeoh, J. E. Wong, D. Tan, B. C. Goh, W. J. Chng, R. Soo, C. E. Chee, Y. L. Chee, S. C. Lee, A. D. Jeyasekharan for National University Cancer Institute (NCIS) (2020). A segregated-team model to maintain cancer care during the COVID-19 outbreak at an academic center in Singapore.  Ann. Oncol 31(7): 840-843.
  4. de Mel, S., M. B. M. Rashid, X. Y. Zhang, J. Goh, C. T. Lee, L. M. Poon, E. H. L. Chan, X. Liu, W. J. Chng, Y. L. Chee, J. Lee, Y. C. Yuen, J. Q. Lim, B. K. H. Chia, Y. Laurensia, D. Huang, W. L. Pang, D. M. Z. Cheah, E. K. Y. Wong, C. K. Ong, T. Tang, S. T. Lim, S. B. Ng, S. Y. Tan, H.-Y. Loi, L. K. Tan, E. K. Chow and A. D. Jeyasekharan (2020). Application of an ex-vivo drug sensitivity platform towards achieving complete remission in a refractory T-cell lymphoma. Blood Cancer J. 10(1): 9.
  5. Srinivas, U. S., B. W. Q. Tan, B. A. Vellayappan and A. D. Jeyasekharan (2019). ROS and the DNA damage response in cancer. Redox Biol.25: 101084.
  6. Oon, M. L., M. M. Hoppe, S. Fan, T. Phyu, H. M. Phuong, S.-Y. Tan, S. S.-S. Hue, S. Wang, L. M. Poon, H. L. E. Chan, J. Lee, Y. L. Chee, W.-J. Chng, S. de Mel, X. Liu, A. D. Jeyasekharan* and S.-B. Ng* (Joint senior authorship) (2019). The contribution of MYC and PLK1 expression to proliferative capacity in diffuse large B-cell lymphoma. Leuk. Lymphoma 60(13): 3214-3224.
  7. Hoppe, M. M., R. Sundar, D. S. P. Tan and A. D. Jeyasekharan (2018). Biomarkers for Homologous Recombination Deficiency in Cancer. J. Natl. Cancer Inst. 110(7): 704-713.
  8. Jeyasekharan, A. D., Y. Liu, H. Hattori, V. Pisupati, A. B. Jonsdottir, E. Rajendra, M. Lee, E. Sundaramoorthy, S. Schlachter, C. F. Kaminski, Y. Ofir-Rosenfeld, K. Sato, J. Savill, N. Ayoub and A. R. Venkitaraman (2013). A cancer-associated BRCA2 mutation reveals masked nuclear export signals controlling localization. Nat. Struct. Mol. Biol 20(10): 1191-1201.
  9. Jeyasekharan, A. D., N. Ayoub, R. Mahen, J. Ries, A. Esposito, E. Rajendra, H. Hattori, R. P. Kulkarni and A. R. Venkitaraman (2010). DNA damage regulates the mobility of Brca2 within the nucleoplasm of living cells. Proc. Natl. Acad. Sci. U. S. A. 107(50): 21937-21942.
  10.   Ayoub, N., A. D. Jeyasekharan, J. A. Bernal and A. R. Venkitaraman (2008). HP1-? mobilization promotes chromatin changes that initiate the DNA damage response. Nature 453(7195): 682-686.

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