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.
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:
- Genetic instability pathways: From cellular regulation to Biomarkers
Mammalian cells have multiple distinct DNA repair pathways to deal with different forms of damage to the genome. While DNA repair defects underlie the sensitivity of most cancers to genotoxic therapy, we lack clinically validated tools to identify the pathways responsible for genetic instability within a given tumour. We aim to develop such tools, building on knowledge gained from the cellular understanding of DNA repair proteins, with a vision to refining patient selection in clinical trials of agents targeting DNA repair. Our approach harnesses recent advances in fluorescent and quantitative microscopy for detection of these markers.
- Cell-surface DNA damage responses: clinical applications
Protein alterations on the cell surface are increasingly recognized as an important facet of the DNA damage response. They are also relevant clinically, in the context of early diagnosis. The DNA damage response is activated early in cancer, and the cell-surface compartment is accessible to antibodies and aptamers. We aim to develop reagents to selected surface DDRs’ as fluorescent markers to aid with early endoscopic diagnosis of tumours. This work is performed in collaboration with A/Prof. Yeoh Khay Guan, Singapore Gastric Cancer Consortium.
- Jeyasekharan AD, Liu Y, Hattori H, Pisupati V, Jonsdottir AB, Rajendra E, Lee M, Sundaramoorthy E, Schlachter S, Kaminski CF, Ofir-Rosenfeld Y, Sato K, Savill J, Ayoub N, Venkitaraman AR. A cancer-associated BRCA2 mutation reveals masked nuclear export signals controlling localization. Nat Struct Mol Biol. 2013 Oct; 20(10):1191-1198.
- Mahen R, Hattori H, Lee M, Sharma P, Jeyasekharan AD, Venkitaraman AR. A-type lamins maintain the positional stability of DNA damage repair foci in Mammalian nuclei. PLoS One. 2013 May 2;8(5):e61893.
- Kurosawa M, Jeyasekharan AD, Surmann EM, Hashimoto N, Kurosawa G, Furukawa K, Venkitaraman AR, Kurosawa Y. Expression of LY6D is induced at the surface of MCF10A cells by X-ray irradiation. FEBS J. 2012 Dec;279(24):4479-91.
- Sato K, Sundaramoorthy E, Rajendra E, Hattori H, Jeyasekharan AD, Ayoub N, Schiess R, Aebersold R, Nishikawa H, Sedhukina A, Wada H, Ohta T and Venkitaraman AR. The BRCA1 E3 ligase triggers Claspin ubiquitylation, CHK1 activation and homology-directed repair during a subset of DNA-damage responses. Current Biology. 2012 Sep 25;22(18):1659-66.
- 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
- 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
- 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.
- Ayoub N, Rajendra E, Su X, Jeyasekharan AD, Mahen R, Venkitaraman AR. The carboxy terminus of Brca2 links the disassembly of Rad51 complexes to mitotic entry. Curr Biol. 2009 Jul 14;19(13):1075-85.
- Ayoub N, Jeyasekharan AD, Bernal JA, Venkitaraman AR. Paving the way for H2AX phosphorylation. Chromatin changes in the DNA damage response. Cell Cycle. 2009 May 15;8(10):1494-500
- 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
|Name||Anand Devaprasath JEYASEKHARAN|
|Affiliations||Principal Investigator, Cancer Science Institute of Singapore, NUS
Associate Consultant, Dept of Haematology Oncology, NUHS
Investigator, Molecular Imaging and Marker Development, Singapore Gastric Cancer Consortium
|Institute||Degree (if applicable)||Year(s)|
|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|
|•||Resident Physician, Department of Medicine, NUHS||2010 – 2013|
|•||MRC Career Development Fellow, Cancer Cell Unit/ Hutchison-MRC Research Centre, Cambridge, UK||2008 – 2010|
|•||Junior Research Fellow, Wolfson College, University of Cambridge||2009 – 2010|
|•||Gates Cambridge Scholar, Department of Oncology, University of Cambridge||2005 – 2008|
|•||Medical Officer, International Cancer Centre, KK Medical Mission, Neyyoor, India||2003 – 2005|
|•||Intern, Christian Medical College Hospital, Vellore, India||2002 – 2003|
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.