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.
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:
- Setup systems and assays for DNA repair studies in-vitro
- Setup platforms for quantitative microscopy in histological material, to interrogate DNA repair and immune modulation pathways in samples of human cancer
- Established international and local collaborations for the acquisition of well-annotated clinical samples
- 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.
- 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.
- 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
- 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.
- Tay SH, Wong AS, Jeyasekharan AD. A patient with pembrolizumab-induced fatal polymyositis. Eur J Cancer. 2018 Jan, 91:180-182; PMID:29329695.
- 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:
- 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:
- 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.
- 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.
- 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.
- 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.
- 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.
- Mahen R, Jeyasekharan AD, Barry N, Venkitaraman AR. Continuous polo-like kinase 1 activity regulates diffusion to maintain centrosome self-organization during mitosis. Proc Natl Acad Sci USA. 2011 May 31;108(22):9310-5, PMID:21576470.
- Jeyasekharan AD, Ayoub N, Ries J, Mahen R, Rajendra E, Kulkarni R, Venkitaraman AR. Regulation of Brca2 intranuclear mobility promotes its assembly on damaged DNA. Proc Natl Acad Sci USA. 2010 Dec 14;107(50):21937-42, PMID:21098284.
- Ayoub N*, Jeyasekharan AD*, Venkitaraman AR (*Equally contributed). Mobilization and recruitment of HP1; A bimodal response to DNA breakage. Cell Cycle. 2009 Sep 15;8(18):2945-50, PMID:19657222.
- Ayoub N, Jeyasekharan AD, Bernal JA, Venkitaraman AR. HP1 mobilization promotes chromatin changes that initiate the DNA damage response. Nature. 2008 May 29;453(7195):682-6, PMID:18438399.
|Name||Anand Devaprasath JEYASEKHARAN|
|Affiliations||Principal Investigator, Cancer Science Institute of Singapore, NUS
Assistant Professor, Department of Medicine, Yong Loo Lin School of Medicine, NUS
Consultant, Department of Haematology-Oncology, National University Hospital, Singapore
|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|
I am a Pathologist with interest in oncoresearch in developing novel biomarkers to guide the choice of chemotherapy and immunotherapy in cancer.
Upadhyayula SAI SRINIVAS
Understanding the role of mitotic kinases in DNA damage response and DNA repair.
Joanna (Asia) WARDYN
Investigation of genomic instability in progression of Diffuse Large B-Cell Lymphomas.
HOANG MAI Phuong
Studying DNA Damage Response in malignant lymphoma.
Senior Laboratory Executive
In charge of the Microscope Facility and lab supervisor role for level 13 labs.
Michal Marek HOPPE
Validation of Biomarkers for Homologous Recombination and DNA Repair.
|•||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|