Research

Current Research

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

I'm currently working as an Instructor in the Division of Oncology at the Washington University School of Medicine, under the mentorship of Drs. Obi and Malachi Griffith. I also serve as a co-lead for the Global Alliance for Genomics and Health (GA4GH) Variant Representation group, and as co-director of the Variant Interpretation for Cancer Consortium (VICC)

I am the project lead for the VICC meta-knowledgebase project. In this project, harmonized the elements comprising clinical interpretations of cancer variants (genes, variants, diseases, drugs, and evidence) to enable comparative analyses and develop standards and best practices for curating and representing these interpretations. I am translating this work into global standards for variant representation through my role with the GA4GH.

I have also led and/or developed multiple other open-source tools enabling precision medicine. Among these are:

  • The Clinical Interpretations of Variants in Cancer Database (CIViC) - community-sourced curation tool for clinical interpretations of cancer variants.
  • The Drug-Gene Interaction Database (DGIdb) - consolidates disparate data sources describing drug-gene interactions and gene druggability.
  • 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 in R (GenVisR).

Finally, I led the analysis of relapsed and chemoresistant 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 chemoresistant SCLCs, and point to WNT-signaling activation as a recurrent mechanism for chemoresistance in this lethal class of disease (Wagner and Devarakonda, et al.Nature Communications (2018)).


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 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 (unpublished) 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.
Denotes co-first authorship

AM Danos, DI Ritter, AH Wagner, ..., S Madhavan, OL Griffith (2018) "Adapting crowdsourced clinical cancer curation in CIViC to the ClinGen minimum variant level data community‐driven standards". Human Mutation. doi: 10.1002/humu.23651.

AH Wagner, S Devarakonda, ..., OL Griffith, R Govindan (2018) "Recurrent WNT pathway alterations are frequent in relapsed small cell lung cancer". Nature Communications. doi: 10.1038/s41467-018-06162-9.

K Cotto, AH Wagner, YY Feng, S Kiwala, AC Coffman, G Spies, A Wollam, NC Spies, OL Griffith, M Griffith (2017) "DGIdb 3.0: a redesign and expansion of the drug-gene interaction database". Nucleic Acids Research. doi: 10.1093/nar/gkx1143.

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

Download the PDF here

Bio

Born in Long Beach, California, I spent the latter years of my childhood growing up in Roscoe, 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.

I then spent 4.5 years as a graduate student at the University of Iowa working with Dr. Terry Braun, which is outlined in more detail above.

Currently I'm living in Saint Louis with my wife and two young children. In my spare time, I enjoy a variety of sports and activities, including bicycling, racquetball, coding, political activism, and gaming with friends. Since 2015, I primarily spend my non-work hours playing with my kids and taking them to our favorite St. Louis destinations: the zoo, Science Center, and Magic House.

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