Current - McDonnell Genome Institute, Washington University School of Medicine
I am Assistant Professor (Department of Medicine, Division of Oncology and Department of Genetics) and Assistant Director at The McDonnell Genome Institute. My lab's research interests are best described as cancer informatics and clinical statistics. Specifically, I use computational methods for the analysis of large cancer datasets at the molecular and genomic level. I am engaged in a number of large-scale tumor sequencing projects on liver and breast cancer, investigating primary, relapse and drug resistant tumors. To this end I am working with others to develop end-to-end pipelines for clinical cancer sequencing that automate state-of-the-art methods for sequence alignment, somatic variation detection, RNA sequence analysis, and the integration of these data types into user-friendly reports of the most clinically relevant genome and transcriptome changes in a tumor or group of tumors. To aid in this effort I have developed a database and web tool for interrogating the druggable genome (www.dgidb.org). Projects under development include the Database of Curated Mutations (www.docm.info) and the CIViC resource for Clinical Interpretation of Variants in Cancer (www.civicdb.org). Visit the publications section for papers describing these projects in greater detail.
Past - Lawrence Berkeley National Laboratory
I was a post-doctoral fellow (Cancer and DNA Damage Responses, Life Sciences Division) at Lawrence Berkeley National Laboratory under the supervision of Dr. Joe Gray and Dr. Paul Spellman. There, I worked on developing methods for a systems biology approach to the analysis of next-generation sequencing data (e.g. Illumina) for metastatic breast cancer and its treatment. I helped to develop the Alexa-seq platform (www.alexaplatform.org) for analysis and visualization of RNA-seq data and applied it to a number of cell line and primary tumor datasets with the goal of identifying omic predictors of drug response in breast cancer (www.alexa-seq-lbl.org). I also developed a predictor for breast cancer recurrence that is currently under commercial development as a faster and cheaper alternative to existing products. Visit the publications section for papers describing these projects in greater detail.
Past - Genome Sciences Centre, BC Cancer Research Centre
I completed a PhD and post-doctoral fellowship (Dept. of Medical Genetics, University of British Columbia) at the British Columbia Cancer Research Centre and Genome Sciences Centre (GSC) under the supervision of Dr. Steven Jones (Associate Director, Head of Bioinformatics). My research focused on understanding how changes in the regulatory sequences of DNA contribute to cancer development and progression. I developed novel algorithms for investigating cancer expression data in the areas of differential coexpression and subspace clustering. Complementary to these approaches was the curation and collection of known regulatory sequences and mutations. To this end, I developed ORegAnno (www.oreganno.org), an open access database and curation system for regulatory sequences and polymorphisms. This system has captured the experimental results of hundred of studies of genetic and epigenetic regulation. I also worked on the identification of molecular markers at the DNA, RNA and protein level that are useful for diagnosis and prognosis of cancer. Using bioinformatics methods, I conducted extensive meta-analyses of expression profiling studies for thyroid cancer. This allowed the identification and ranking of high-confidence differentially expressed genes between cancer and non-cancer states. Such candidates were then validated by immunohistochemistry and tissue microarray analysis on a cohort of over two-hundred human thyroid tumour patient samples (in collaboration with Dr. Sam Wiseman, St. Paul's Hospital). This allowed the development of a panel of markers that can classify malignant versus benign thyroid neoplasms with high accuracy (>90%) and thus has potential utility as a diagnostic tool for thyroid cancer. The approach was also extended to colon and rectal cancer. Visit the publications section for papers describing these projects in greater detail.