Anand JEYASEKHARAN

Work in the ADJ laboratory aims to identify molecules and pathways that are activated by aberrant replication and damage to DNA in cancer. We are particularly interested in DNA damage responses that contribute to immune modulation, during tumour evolution and upon treatment with genotoxic chemotherapy. We hypothesise that such knowledge could guide the clinical evaluation and use of novel immunotherapy compounds, as well as agents targeting the DNA damage response. In addition to fundamental research into DNA repair regulation in cancer, the ADJ lab has a translational component that interfaces with clinical teams (Lymphoma, GI and Gynae-Oncology) within and outside Singapore.

csiadj@nus.edu.sg

Biosketch

Tumours are traditionally classified based on morphological appearance and cellular compartment of origin, offering limited information to predict responses to therapy. The advent of personalized medicine necessitates markers to stratify tumours (and patients) on the basis of their deregulated pathways, to subtype them for targeted therapy. While some success has been achieved with proliferative oncogenes and Receptor Tyrosine Kinases, there is little clinical information regarding subtyping tumours on the basis of genetic instability, a universal feature in solid malignancies.

Anand trained in molecular biology at the MRC Cancer Cell Unit, Cambridge UK, with an interest in understanding how cells repair DNA damage. He is currently pursuing his clinical specialty training in medical oncology, and runs a lab investigating novel markers of DNA repair pathways and their application to the practice of cancer medicine.

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

Institute Degree (if applicable) Year(s)
Specialist Accreditation Board (Singapore) Board Certification in Medical Oncology 2016
Royal College of Physicians (UK) MRCP UK 2012
Gonville and Caius College; University of Cambridge, UK Ph.D 2008
Christian Medical College, Vellore, India MBBS 2003
Associate Consultant (Medical Oncology), Department of Haematology-Oncology, NUHS 2016 – 2018
Senior Resident (Medical Oncology), Department of Haematology-Oncology, NUHS 2013 – 2016
Resident Physician, Department of Medicine, NUHS 2010 – 2013
Junior Research Fellow, Wolfson College, University of Cambridge 2009 – 2010
MRC Career Development Fellow, Cancer Cell Unit/ Hutchison-MRC Research Centre, Cambridge, UK 2008 – 2010
Gates Cambridge Scholar, Department of Oncology, University of Cambridge 2005 – 2008
Medical Officer, International Cancer Centre, KK Medical Mission, Neyyoor, India 2003 – 2005
House Officer, Christian Medical College Hospital, Vellore, India 2002 – 2003
Clinician-Scientist Transition Award, National Medical Research Council, Singapore 2016
NUHS Clinician-Scientist Program Award, National University Hospital, Singapore 2015
Academic Development Award, National University Hospital, Singapore 2011
NRF Singapore nomination to attend the 64th Lindau Nobel meeting (Medicine and Physiology) 2014
Junior Research Fellowship, Wolfson College, Cambridge 2009-2010
Gates Cambridge Scholarship, Gates Cambridge Trust, University of Cambridge, UK 2005-2008

Research

I am interested in translating the mechanistic understanding of cellular processes into biomarkers to guide clinical trials and practice in Oncology.

Work in my laboratory spans two themes:

1. Genetic instability pathways: From cellular regulation to Biomarkers
2. Cell-surface DNA damage responses: clinical applications

We are interested in understanding the clinical relevance of the DNA Damage Response (DDR) defects in cancer. Characterizing DDR defects in cancer is relevant to the prediction of clinical responses to chemotherapy, radiotherapy, immunotherapy and small-molecule inhibitors of DNA repair pathways. We aim to ultimately use such information to guide the rational design of clinical trials combining traditional chemotherapy with immunotherapy and targeted agents. The figure below outlines our laboratory research program tackling these areas of study:

The DNA damage response is relevant to both epithelial and non-epithelial cancers, and we use a variety of cancer models in our research. We however have a specific interest in lymphomas, on account of my clinical practice as a medical oncologist on the NUH Lymphoma team. To facilitate the above studies, we have:

  1. Setup systems and assays for DNA repair studies in-vitro
  2. Setup platforms for quantitative microscopy in histological material, to interrogate DNA repair and immune modulation pathways in samples of human cancer
  3. Established international and local collaborations for the acquisition of well-annotated clinical samples
  4. Established connections with pharmaceutical companies and medical technology companies, to identify prospects for our research findings in clinical trials and biomarker development.

I also run the microscopy core at the CSI, the CSI-NCIS Translational Exchange club, and the NUHS clinician-scientist program for residents.

Lab Members

Selected Publications

1. 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.

2. 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

3. 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.

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

5. 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

6. Ng SB, Chung TH, Kato S, Nakamura S, Takahashi E, Ko YH, Khoury JD, Yin CC, Soong R, Jeyasekharan AD, Hoppe MM, Selvarajan V, Tan SY, Lim ST, Ong CK, Nairismägi ML, Maheshwari P, Choo SN, Fan S, Lee CK, Chuang SS, Chng WJ. EBV-associated primary nodal T/NK-cell lymphoma shows distinct molecular signature and copy number changes. Haematologica 2017 Nov 2, 180430; PMID:29097495 

7. Sundar R, Jeyasekharan AD, Pang B, Soong R et al; Low levels of NDRG1 in nerve tissue are predictive of severe paclitaxel-induced neuropathy. PLoS One 2016 Oct 7;11(10):e0164319, PMID:27716814.

8. Roy RK, Hoppe MM, Srivastava S, Samanta A, Sharma N, Tan KT, Yang H, Voon DC, Pang B, Teh M, Murata-Kamiya N, Hatakeyama M, Chang YT, Yong WP, Ito Y, Ho KY, Tan P, Soong R, Koeffler PH, Yeoh KG, Jeyasekharan AD. CEACAM6 is upregulated by Helicobacter pylori CagA and is a biomarker for early gastric cancer. Oncotarget. 2016 Aug 23:7(34):55290-55301, PMID:27421133.

9. Nagasawa S, Sedukhina AS, Nakagawa Y, Maeda I, Kubota M, Ohnuma S, Tsugawa K, Ohta T, Roche-Molina M, Bernal JA, Narváez AJ, Jeyasekharan AD, Sato K. LSD1 overexpression is associated with poor prognosis in basal-like breast cancer, and sensitivity to PARP inhibition. PLoS One. 2015 Feb 13;10(2), PMID:25679396.

10. Khoury-Haddad H, Guttmann-Raviv N, Ipenberg I, Huggins D, Jeyasekharan AD, Ayoub N. PARP1-dependent recruitment of KDM4D histone demethylase to DNA damage sites promotes double-strand break repair.Proc Natl Acad Sci U S A. 2014 Feb 18;111(7):E728-37, PMID: 24550317.