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Sean Wen

Sean Wen

Postdoctoral Fellow

Education / Training

Kuala Lumpur, Kuala Lumpur

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About Sean Wen:

I am currently a Postdoctoral Fellow at AstraZeneca, United Kingdom. I have more than 10 years of experience in biomedical research with focus on cancer biology and genetic epidemiology. I am passionate about nurturing the next generation of students and scientist and therefore looking for opportunities in academia in Kuala Lumpur and Selangor.

Experience

                  My research career began in Cancer Research Malaysia (2014-2017) as a research assistant. My main task was establishing the institute’s first NGS library preparation platform and accompanying analytical pipeline. To this end, I have established a cost-efficient targeted (panel)-sequencing platform (High-Plex) to interrogate inherited breast and ovarian cancer susceptibility genes with the ultimate aim of identifying mutation carriers. This enabled the genetic screening of 218 high-risk Malaysian ovarian cancer patients, 108 high-risk Malaysian breast cancer patients, 2,575 unselected Malaysian breast cancer patients and 2,809 healthy controls, and in a fruitful collaboration with the Genome Institute of Singapore (GIS) we led the analysis of 5,122 unselected European breast cancer patients. This led to the discovery of population differences in BRCA1/2 germline mutations whereby significantly higher prevalence of these gene carriers were identified among women of Asian descent compared to that of European descent. This genetic screening platform has been patented and is currently used for routine mutation profiling of breast and ovarian cancer patients.

                  Realising the limitations of research infrastructure in my home country, I ventured overseas to expand my research horizon. During my time as a PhD student at the University of Oxford (2018-2022), I assisted in the development and optimisation of single-cell joint mutation profiling (DNA-sequencing) and gene expression profiling (RNA-sequencing), and subsequently led the establishment of analytical framework for these datasets. This enabled the genetic mutation and gene expression analysis of the cancer stem cell compartment of TP53-mutant blood cancer patients. Notably, we discovered a p53-mutant expression signature that is predictive of overall survival in blood cancer patients, among other findings. In parallel, as part of my main PhD project, I have developed novel analytical frameworks for detecting, quantifying, analysing, and validating alternative splicing at single-cell resolution. These are available as R packages, namely MARVEL and VALERIE. This enabled the team to unravel candidate mis-spliced genes as potential therapeutic biomarkers. Specifically, we discovered aberrant isoforms of GNAS and STAT1 (both genes are bona fide oncogenes) as potential disease-driving candidates in U2AF1- and SF3B1-mutant blood cancer patients (both are splicing factors frequently mutated in cancer patients).

                  Having my interest piqued at the intersection of the scientific rigor of academia and the translational focus of the industry, I proceeded to join AstraZeneca and the University of Cambridge as a Postdoctoral Fellow (2023-present). In my current role, I leverage whole-exome sequencing (WES), whole-genome sequencing (WGS), proteomics, and SNP genotyping arrays to assess clonal haematopoiesis (a pre-leukemic disease) as a potential therapeutic biomarker in oncology and cardiovascular clinical trials. To this end, we identified the risk factors, genetic causes, and disease consequences of this disease in 552,519 individuals. We further applied machine learning approaches to identify a novel sub-group of individuals with clonal haematopoiesis without any identifiable driver gene mutations. Lastly, in effort to assess the potential utility of clonal haematopoiesis as a druggable biomarker, we revealed metformin causally decreases the risk of this pre-leukemic disease (and presumably the risk of future blood cancers).

                  Collectively, my experience over the past ten years will enable me to lead, execute, and guide analytic frameworks of the various “-omics” spanning across the central dogma of molecular biology (DNA, RNA, proteome). Beyond the technical expertise, I have learned to work with and manage the expectations of various stakeholders including clinicians, wet-lab scientists, and dry-lab scientists from both academia and industrial settings. Finally, it is the diversity of talent and science that drives me. To this end, this year (2025), I am looking for opportunities in academia in Malaysia. Specifically, I hope to nurture the next generation of students and scientist, and in parallel, lead research projects to further our understanding of cancer with the ultimate aim for finding a cure for devastating disease.

Education

  • PhD in Medical Science at University of Oxford (2018-2022)
  • MSc in Medical Science at University Malaya (2015-2017)
  • BSc in Biomedical Science at International Medical University (2010-2013)

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