Research

Current Research

My ongoing research interest is the development of computational tools to aid collaborative visualization, interpretation, and discovery of clinically relevant genomic events in patient cancers.

I'm currently working as an NCI postdoctoral research fellow with the Griffith lab at the McDonnell Genome Institute of Washington University in St. Louis, where we are investigating the genomic architecture of cancers.

In a set of related projects, I co-developed multiple open-source, API accessible webtools enabling precision medicine. Among these tools are:

  • The Drug-Gene Interaction Database (DGIdb) - consolidates disparate data sources describing drug-gene interactions and gene druggability.
  • The Clinical Interpretations of Variants in Cancer Database (CIViC) - community-sourced curation tool for clinical interpretations of cancer variants.
  • The Database of Curated Mutations in cancer (DoCM) - an expert-curated list of biologically-relevant mutations in cancer.
I also co-developed software for the visualization of genomic features using R (GenVisR).

In another project, I am investigating the genomics of relapsed and chemo-resistant small cell lung cancers (SCLCs), using a combination of exome and transcriptome sequencing to profile the primary and relapsed tumors of 30 patients with SCLC. This work has led to identification of key genetic alterations that appear to be specific or strongly enriched in chemo-resistant SCLCs (manuscript in progress).


Doctoral Research

My Ph.D. work was under the mentorship of Terry Braun at the University of Iowa’s Coordinated Laboratory for Computational Genomics. While there, I studied computational methods for identification of disease-associated variations in exome sequencing. I also developed a method for predicting genetic variants associated with heritable retinal dystrophies, using a novel machine learning strategy (PULP).

Another focus of my work was on improving the accuracy of the CLCG variant detection pipeline. Working with Dr. Edwin Stone at the Wynn Institute for Vision Research, we developed a technique for identifying synonymous and intronic variants that were associated with Stargardt’s Disease through integrating patient exome data with control (reference) transcriptome sequence. We also developed a model for improving the specificity of detected variants from our exome sequencing experiments.

Finally, I developed web resources to help characterize healthy and diseased retinal tissue. The ocular tissue database (OTDB) provides a look at expression of 10 tissues of the human eye, while the TRIPOD web tool (manuscript in preparation) provides an interface for the study and evaluation of phenotypic and genotypic associations in rare, heritable retinal dystrophies.

Selected Publications

This is a list of publications most relevant to my doctoral and postdoctoral research objectives. Click here for a complete bibliography on Google Scholar.

M Griffith, NC Spies, K Krysiak, JF McMichael, AC Coffman, AM Danos, BJ Ainscough, CA Ramirez, DT Rieke, L Kujan, EK Barnell, AH Wagner, et al. (2017) "CIViC is a community knowledgebase for expert crowdsourcing the clinical interpretation of variants in cancer". Nature Genetics. doi: 10.1038/ng.3774

BJ Ainscough, M Griffith, AC Coffman, AH Wagner, J Kunisaki, MNK Choudhary, JF McMichael, RS Fulton, RK Wilson, OL Griffith, ER Mardis (2016) "DoCM: a database of curated mutations in cancer". Nature Methods. doi: 10.1038/nmeth.4000

ZL Skidmore, AH Wagner, R Lesurf, KM Campbell, JKunisaki, OL Griffith, M Griffith (2016) "GenVisR: Genomic Visualizations in R". Bioinformatics. doi: 10.1093/bioinformatics/btw325

M Griffith, OL Griffith, K Krysiak, ZL Skidmore, MJ Christopher, JM Klco, A Ramu, TL Lamprecht, AH Wagner, KM Campbell, R Lesurf, J Hundal, J Zhang, NC Spies, BJ Ainscough, DE Larson, SE Heath, C Fronick, S O'Laughlin, RS Fulton, V Magrini, S McGrath, SM Smith, CA Miller, CA Maher (2016) "Comprehensive genomic analysis reveals FLT3 activation and a therapeutic strategy for a patient with relapsed adult B-lymphoblastic leukemia". Experimental Hematology. doi: 10.1016/j.exphem.2016.04.011

AH Wagner, AC Coffman, BJ Ainscough, NC Spies, ZL Skidmore, KM Campbell, K Krysiak, D Pan, JF McMichael, JM Eldred, JR Walker, RK Wilson, ER Mardis, M Griffith*, OL Griffith* (2015) "DGIdb 2.0: mining clinically relevant drug–gene interactions". Nucleic acids research. doi: 10.1093/nar/gkv1165.

SS Whitmore, AH Wagner, AP DeLuca, AV Drack, EM Stone, BA Tucker, S Zeng, TA Braun, RF Mullins, TE Scheetz (2014) “Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq”. Experimental Eye Research. doi:10.1016/j.exer.2014.11.001

TA Braun, RF Mullins, AH Wagner, J Andorf, R Johnston, B Bakall, AP DeLuca, G Fisherman, R Weleber, A Cideciyan, S Jacobson, V Sheffield, B Tucker, EM Stone (2013) “Non-exomic and synonymous variants in ABCA4 are an important cause of Stargardt disease”. Human Molecular Genetics. doi: 10.1093/hmg/ddt367

AH Wagner, KR Taylor, AP DeLuca, TL Casavant, RF Mullins, EM Stone, TE Scheetz, TA Braun (2013), “Prioritization of Retinal Disease Genes: An Integrative Approach.” Human Mutation. doi: 10.1002/humu.22317

AH Wagner, VN Anand, W Wang, JE Chatterton, D Sun, AR Shepard, N Jacobson, L Pang, AP DeLuca, TL Casavant, TE Scheetz, RF Mullins, TA Braun, AF Clark (2013) “Exon-level expression profiling of ocular tissues”. Experimental Eye Research. doi: 10.1016/j.exer.2013.03.004

*Authors contributed equally to the work.

CV

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Bio

Born in Long Beach, California, I spent the latter years of my childhood growing up in Rockford, Illinois. During this time, I learned how to code in BASIC and acquired an interest in computer science.

In 2003 I pursued a bachelor's degree in computer engineering at Iowa State University in Ames, Iowa. I spent summers working in a variety of different roles--including extension education support, college of education IT support, and mapping of the Soy genome--before going on to finish my bachelor's degree in biology with a minor in mathematics.

Afterwards I went to work at the Mayo Clinic in Rochester, MN. There I had the opportunity to learn about clinical diagnostics using inductively coupled plasma mass spectrometry (ICP-MS) and develop computational tools to improve detection of clinically significant events from the ICP-MS instrument data.

Next, I attended the University of Iowa to work with Dr. Terry Braun, which is outlined in more detail above.

Currently I'm working as a postdoctoral research associate at the Washington University Medical School, where I'm focusing on cancer genomics.

In my spare time, I enjoy a variety of sports and activities, including bicycling, hiking, coding, political activism, and board games with friends. My second child is expected in March.

Contact

                       

Email

Phone

480-ALEX-PHD   (480-253-9743)

Mailing Address

The McDonnell Genome Institute
Washington University School of Medicine
Campus Box 8501
4444 Forest Park Ave