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Research interests


Personal statement

I am an Assistant Professor of Genetics and Assistant Director of the McDonnell Genome Institute at Washington University School of Medicine. I have more than 13 years of experience in the fields of genomics, bioinformatics, data mining, and cancer research. My research is focused on improving our understanding of cancer biology and the development of personalized medicine strategies for cancer using genomics and informatics technologies. I develop bioinformatics and statistical methods for the analysis of high throughput sequence data and identification of biomarkers for diagnostic, prognostic and drug response prediction. In collaboration with our Genomics Tumor Board, I am currently leading analyses of sequence data from the genomes and transcriptomes of living cancer patients that have exhausted standard-of-care treatment options. I am also leading the analysis of several large-scale genomics projects to help discover genomic signatures relevant to cancer initiation, progression and treatment response. I am an instructor for the Canadian Bioinformatics Workshops and Cold Spring Harbor Laboratory high-throughput sequencing workshop series. I have received numerous competitive research awards from the Natural Sciences and Engineering Research Council, University of Winnipeg, University of British Columbia, National Cancer Institute of Canada and British Columbia Cancer Agency. I was also a Junior and Senior Trainee of the Michael Smith Foundation for Health Research. I was profiled as an "up and coming" investigator in Genome Technology Magazine and listed in Wired Magazine second annual smart list as an emerging talent. Most recently, I was awarded an NHGRI K99 Pathway to Independence Award to developed integrated analysis and interpretation methods for whole genome, exome and transcriptome sequence data in cancer. In particular, I am focused on applying these methods to better understand the regulatory consequence of somatic mutations that are otherwise of unknown functional significance. I have also made substantial contributions to open source and open access resources for the scientific community including creation of platforms for alternative expression analysis (www.alexaplatform.org), regulatory region annotation (www.oreganno.org), mining drug-gene interactions (www.dgidb.org), genome analysis development (https://github.com/genome/gms), curation of functional cancer mutations (www.docm.info), the clinical interpretation of variants in cancer (www.civicdb.org). I have published 39 papers with major areas of focus in precision medicine, AML, colon cancer, lung cancer, cancer genomics, cancer biomarkers, sequence analysis, and alternative splicing. The following paragraphs describe some general contributions to science and provide an overview of my current research interests. For more specific details refer to the publications section.


Genomics technology

For the past 12 years I have worked continuously at two large-scale genome sequencing and analysis centers. Early access to new technologies has allowed me to develop cutting edge approaches for genome, transcriptome, and epigenome analysis. For example, I helped to develop some of the first massively parallel sequencing assays for microRNAs, alternative expression analysis of RNA-seq data, copy number variant analysis by tumor whole genome sequencing, RNA-seq and cDNA capture of challenging archival (FFPE) clinical samples, and epigenetic profiling by ChIP-seq.


Alternative splicing and gene regulation

An area of particular focus in my research has been the development of new massively parallel assays to study alternative expression (alternative transcript initiation, splicing, and polyadenylation). Following on from early work in the Mammalian Gene Collection project to produce a catalogue of all human transcripts, I developed a custom microarray design platform for alternative expression analysis (ALEXA, www.alexaplatform.org/alexa_arrays/). With the advent of massively parallel sequencing, I adapted the principles and analysis methods learned from my work with splicing microarrays to create an alternative splicing analysis platform ALEXA-seq to mine RNA-seq data (www.alexaplatform.org/alexa_seq/). I have since applied these approaches to address several specific biological questions relating to the mechanisms of RNA transcript processing and aberrant RNA splicing observed in tumors, particularly blood cancers where mutations in certain splicing factors such as U2AF1 are common.


Bioinformatics

In addition to tools and algorithms developed for analysis of RNA-seq data in the context of alternative splicing I have helped to release many other bioinformatic tools, databases, and web resources including tools with very focused applications such as SciClone, ALEXA-Seq and DGIdb but also resources with much broader application including the Genome Modeling System and an RNA-seq analysis resource for cloud computing (www.rnaseq.wiki). I am currently co-leading the development of the first completely open-source and open-access resource to define a community consensus on the clinical interpretation of variants in cancer (www.civicdb.org). A theme of all of these efforts is transparent development including version tracked source code and unrestrictive licensing of both the code and the content produced so that the community can benefit most efficiently from this work.


Cancer biology

Developing new methods, assays, algorithms and bioinformatics tools is a means to an end in my research program. My goal is to apply these to improve our understanding of cancer biology and to translate discoveries into improved outcomes for patients suffering from cancer. I have applied these new methods to address specific biological questions in several cancer types and treatment scenarios. These studies range from creating the first genomic landscapes of some cancer types such as lung cancer, to pursuing specific candidate biomarkers of therapeutic resistance in colon cancer, to defining the clonal architecture of AML.


Precision medicine

My greatest research interest is personalized or precision medicine. I am broadly interested in the translation of genomics data from whole genome, exome and transcriptome sequencing into clinically actionable observations and personalized cancer therapies. In 2010, I was involved in one of the first attempts to sequence the genome of a patient in real time and personalize therapy based on the analysis of this data. In 2011, I helped to lead the analysis of a second case that lead to a widely reported discovery of aberrant FLT3 over-expression and unique therapeutic intervention in a case of adult ALL. Since those two cases I have continued to focus on the work needed to make clinical genome sequencing of individual patients a reality. To date, I have contributed to the analysis of hundreds of tumors representing more than ten tumor types in collaboration with over a dozen clinicians.



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