Obi L. Griffith, Ph.D.

Associate Professor
Internal Medicine
Oncology
Assistant Director, The Genome Institute
Genetics

Biomedical Informatics and Data Science Program
Cancer Biology Program
Molecular Cell Biology Program
Immunology Program

  • 314-747-9248

  • 314-273-5820

  • 314-286-1810

  • 8501-29-10

  • Mid Campus Center, 4590 Childrens Pl, 10th floor, Room 10116

  • obigriffith@wustl.edu

  • https://griffithlab.org/

  • https://twitter.com/obigriffith

  • bioinformatics, machine learning, cancer, genomics, immunogenomics, precision oncology

  • Development of personalized medicine strategies for cancer using genomic technologies

Research Abstract:

Genome-scale technologies, with next generation sequencing (NGS) leading the field, have begun to inform clinical decision making for a small number of cancer patients. The anecdotal cases currently coming out of major genome centers represent the crest of a wave that will soon spread to many institutes and hospitals. Most will find themselves drastically unprepared for the task of processing and interpreting significant numbers of tumor genomes. Data analysis and interpretation continues to be the major bottleneck. Serious practical, technical and ethical challenges remain when it comes to processing these data sets and transmitting genomic information to clinicians and patients. My research focuses on tackling these challenges in three key areas: (1) Development of tools and technologies to identify cancer-driving genomic events; (2) Development of knowledgebases for improved interpretation of cancer genomics; (3) Training the next generation of cancer informaticians and clinical genomicists.

Mentorship and Commitment to Diversity Statement:
I am committed to all kinds of diversity in my lab and want all trainees to feel welcome and free to express themselves. I truly believe that academic and research enterprises are most effective when they represent a broad diversity of backgrounds, viewpoints, and experiences. I have mentored a number of trainees from under-represented groups. I am committed to understanding and addressing disparities in genomic testing through my own research. I am also working to improve equity, diversity and inclusion through my leadership role in the Cancer Genomics Consortium.

Selected Publications:

Yoon CJ, Kim SY, Nam CH, Lee J, Park JW, Moon J, Park S, Lee S, Yi B, Min KI, Wiley B, Bolton KL, Lee JH, Kim E, Yoo HJ, Jun JK, Choi JS, Griffith M, Griffith OL†, YS Ju†. 2022. Estimation of intrafamilial DNA contamination in family trio genome sequencing using deviation from Mendelian inheritance. Genome Research. Accepted. †Corresponding author.

Barnell EK, Skidmore ZL, Newcomer KF, Chavez M, Campbell KM, Cotto KC, Spies NC, Ruzinova MB, Wang T, Abro B, Kreisel F, Parikh BA, Duncavage EJ, Frater JL, Lee Y, Hassan A, King JA, Kohnen DR, Fiala MA, Welch JS, Uy GL, Vij K, Vij R, Griffith M, Griffith OL†, Wartman LD†. 2022. Distinct clonal identities of B-ALLs arising after Lenolidomide therapy for Multiple Myeloma. Blood Advances. Accepted. †Corresponding author.

Skidmore ZL, Kunisaki J, Lin Y, Cotto KC, Barnell EK, Hundal J, Krysiak K, Magrini V, Trani L, Walker JR, Fulton R, Brunt EM, Miller CA, Wilson RK, Mardis ER, Griffith M†, Chapman W†, Griffith OL†. 2022. Genomic and transcriptomic somatic alterations of hepatocellular carcinoma in non-cirrhotic livers. Cancer Genetics. 2022 Jun;264-265:90-99. †Corresponding author.

Krysiak K†, Danos AM, Kiwala S, McMichael JF, Coffman AC, Barnell EK, Sheta L, Saliba J, Grisdale CJ, Kujan L, Pema S, Lever J, Spies NC, Chiorean A, Rieke DT, Clark KA, Jani P, Takahashi H, Horak P, Ritter DI, Zhou X, Ainscough BJ, Delong S, Lamping M, Marr AR, Li BV, Lin WH, Terraf P, Salama Y, Campbell KM, Farncombe KM, Ji J, Zhao X, Xu X, Kanagal-Shamanna R, Cotto KC, Skidmore ZL, Walker JR, Zhang J, Milosavljevic A, Patel RY, Giles RH, Kim RH, Schriml LM, Mardis ER, Jones SJM, Raca G, Rao S, Madhavan S, Wagner AH, Griffith OL†, Griffith M†. 2022. A community approach to the cancer-variant-interpretation bottleneck. Nature Cancer. 3(5):522-525. †Corresponding author.

Skidmore ZL, Campbell KM, Cotto KC, Griffith M†, Griffith OL†. 2021. Exploring the genomic landscape of cancer patient cohorts with GenVisR. Current Protocols. 1(9):e252. †Corresponding author.

Mudianto T*, Campbell K*, Webb J, Zolkind P, Skidmore ZL, Riley R, Barnell EK, Ozgenc I, Giri T, Dunn G, Adkins D, Griffith M, Egloff AM+, Griffith OL+, Uppaluri R+. 2021. YAP1 Mediates Trametinib Resistance in Head and Neck Squamous Cell Carcinomas. *These authors contributed equally to this work. +Co-senior authors. Clinical Cancer Research. 27(8):2326-2339.

Barnell EK, Newcomer KF, Skidmore ZL, Krysiak K, Anderson SR, Wartman LD, Oh ST, Welch JS, Stockerl-Goldstein KE, Vij R, Cashen AF Pusic I, Westervelt P, Abboud CN, Ghobadi A, Uy GL, Schroeder MA, Dipersio JF, Politi MC, Spencer DH, Duncavage EJ, Ley TJ, Griffith M, Jacoby MA, Griffith OL. 2021. Impact of a 40-Gene Targeted Panel Test on Physician Decision Making for Patients With Acute Myeloid Leukemia. JCO Precision Oncology. 5:PO.20.00182.

Freshour SL, Kiwala S, Cotto KC, Coffman AC, McMichael JF, Song JJ, Griffith M†, Griffith OL†, Wagner AH†. 2021. Integration of the Drug-Gene Interaction Database (DGIdb 4.0) with open crowdsource efforts. Nucleic Acids Research. 49(D1):D1144-D1151. †Corresponding author.

Uppaluri R*, Campbell KM*, Egloff AM, Zolkind P, Skidmore ZL, Nussenbaum B, Paniello RC, Rich JT, Jackson R, Pipkorn P, Michel LP, Ley J, Oppelt P, Dunn GP, Barnell EK, Spies NC, Lin T, Li T, Mulder DT, Hanna Y, Cirlan I, Pugh TJ, Mudianto T, Riley R, Zhou L, Jo V, Stachler M, Hanna GJ, Kass J, Haddad R, Schoenfeld J, Gjini E, Lako A, Thorstad W, Gay HA, Daly M, Rodig SJ, Hagemann IS, Kallogjeri D, Piccirillo JF, Chernock RD, Griffith M, Griffith OL+, Adkins DR+. 2020. Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase 2 Trial. Clinical Cancer Research. 26(19):5140-5152. Online ahead of print. *These authors contributed equally to this work. +Co-senior authors.

Wagner AH, Walsh B, Mayfield G, Tamborero D, Sonkin D, Krysiak K, Pons JD, Duren R, Gao J, McMurry J, Patterson S, Vecchio Fitz CD, Sezerman OU, Warner J, Rieke DT, Aittokallio T, Cerami E, Ritter D, Schriml LM, Haendel M, Raca G, Madhavan S, Baudis M, Beckmann JS, Dienstmann R, Chakravarty D, Li XS, Mockus S, Elemento O, Schultz N, Lopez-Bigas N, Lawler M, Goecks J, Griffith M†, Griffith OL†, Margolin AA. Variant Interpretation for Cancer Consortium. 2020. A harmonized meta-knowledgebase of clinical interpretations of cancer genomic variants. Nature Genetics. 52(4):448-457. †Corresponding author.

Wagner AH, Kiwala S, Coffman AC, McMichael JF, Cotto KC, Mooney TB, Barnell EK, Krysiak K, Danos AM, Griffith OL+,†, Griffith M+. 2020. CIViCpy: a Python software development and analysis toolkit for the CIViC knowledgebase. JCO Clinical Cancer Informatics. 4:245-253. †Corresponding author. +Co-senior authors.

Hundal J, Kiwala S, McMichael J, Miller CA, Xia H, Wollam AT, Liu CJ, Zhao S, Feng YY, Graubert AP, Wollam AZ, Neichin J, Neveau M, Walker J, Gillanders WE, Mardis ER, Griffith OL†, Griffith M†. 2020. pVACtools: a computational toolkit to identify and visualize cancer neoantigens. Cancer Immunology Research. 8(3):409-420. †Corresponding author. **Most-Cited Article Published in 2020

Lever J, Jones MR, Danos AM, Krysiak K, Bonakdar M, Grewal JK, Culibrk L, Griffith OL†, Griffith M†, Jones SJM†. 2019. Text-mining clinically relevant cancer biomarkers for curation into the CIViC database. Genome Medicine. 11(1):78. †Corresponding author.

Danos AM*, Krysiak K*, Barnell EK*, Coffman AC, McMichael JF, Kiwala S, Spies NC, Sheta LM, Pema S, Kujan L, Clark KA, Wollam AZ, Rao S, Ritter DI, Sonkin D, Raca G, Kim RH, Wagner AH, Madhavan S, Griffith M†, Griffith OL†. 2019. Standard operating procedure for curation and clinical interpretation of variants in cancer. Genome Medicine. 11(1):76. *These authors contributed equally to this work. †Corresponding author.

Barnell EK, Waalkes A, Mosior MC, Penewit K, Cotto KC, Danos AM, Sheta LM, Campbell KM, Krysiak K, Rieke D, Spies NC, Skidmore ZL, Pritchard CC, Fehniger TA, Uppaluri R, Govindan R, Griffith M, Salipante SJ†, Griffith OL†. 2019. Open-Sourced CIViC Annotation Pipeline to Identify and Annotate Clinically Relevant Variants Using Single-Molecule Molecular Inversion Probes. JCO Clinical Cancer Informatics. 3:1-12. †Corresponding author.

Barnell E, Kang Y, Wurtzler E, Griffith M, Chaudhuri AA†, Griffith OL†; Geneoscopy Scientists. 2019. Noninvasive Detection of High-risk Adenomas Using Stool-derived Eukaryotic RNA Sequences as Biomarkers. Gastroenterology. 157(3):884-887. †Corresponding author.

Campbell KM, O’Leary KA, Rugowski DE, Mulligan WA, Barnell EK, Skidmore ZL, Krysiak K, Griffith M, Schuler LA†, Griffith OL†. 2019. Spontaneous aggressive ERα+ mammary tumor model is driven by Kras activation. Cell Reports. 28(6):1526-1537. †Corresponding author.

Barnell EK, Ronning P, Campbell KM, Krysiak K, Ainscough BJ, Sheta LM, Pema SP, Schmidt AD, Richters M, Cotto KC, Danos AM, Ramirez C, Skidmore ZL, Spies NC, Hundal J, Sediqzad MS, Kunisaki J, Gomez F, Trani L, Matlock M, Wagner AH, Swamidass SJ, Griffith M†, Griffith OL†. 2019. Standard operating procedure for somatic variant refinement of sequencing data with paired tumor and normal samples. Genetics in Medicine. 21(4):972-981. †Corresponding author.

Ainscough BJ*, Barnell EK*, Ronning P, Campbell KM, Wagner AH, Fehniger TA, Dunn GP, Uppaluri R, Govindan R, Rohan TE, Griffith M, Mardis ER, Swamidass SJ†, Griffith OL†. 2018. A deep learning approach to automate refinement of somatic variant calling from cancer sequencing data. Nature Genetics. 50(12):1735-1743. *These authors contributed equally to this work. †Corresponding author.

Danos AM*, Ritter DI*, Wagner AH, Krysiak K, Sonkin D, Micheel C, McCoy M, Rao S, Raca G, Boca SM, Roy A, Barnell EK, McMichael JF, Kiwala S, Coffman AC, Kujan L, Kulkarni S†, Griffith M†, Madhavan S†, Griffith OL†. 2018. Crowdsourced and community-driven standards for curation and submission of somatic cancer variants. Human Mutation. 39(11):1721-1732. *These authors contributed equally to this work. †Corresponding author.

Wagner AH*, Devarakonda S*, Griffith M*, Skidmore ZL, Krysiak K, Ramu A, Trani L, Kunisaki J, Masood A, Waqar SN, Morgensztern D, Fulton RS, Maggi LB, Weber J, Watson MA, Mukhopadhyay A, Can I, Cessna MH, Oliver TG, Mardis ER, Wilson RK†, Griffith OL†, Govindan R†. 2018. Recurrent APC and WNT Pathway Alterations Are Frequent in Chemoresistant, Relapsed Small Cell Lung Cancer. Nature Communications. 9(1):3787. *These authors contributed equally to this work. †Corresponding author.

Campbell KM*, Lin T*, Zolkind P*, Barnell EK, Skidmore ZL, Winkler AE, Law JH, Mardis ER, Wartman LD, Adkins DR, Chernock RD, Griffith M, Uppaluri R, Griffith OL†. 2018. Oral Cavity Squamous Cell Carcinoma Xenografts Retain Complex Genotypes and Intertumor Molecular Heterogeneity. Cell Reports. 24(8):2167-2178. *These authors contributed equally to this work. †Corresponding author.

Griffith OL, Spies NC, Anurag M, Griffith M, Luo J, Tu D, Yeo B, Kunisaki J, Miller CA, Krysiak K, Hundal J, Ainscough BJ, Skidmore ZL, Campbell K, Kumar R, Fronick C, Cook L, Snider JE, Davies S, Kavuri SM, Chang EC, Magrini V, Larson DE, Fulton RS, Liu S, Leung S, Voduc D, Bose R, Dowsett M, Wilson RK, Nielsen TO, Mardis ER, Ellis MJ. 2018. The prognostic effects of somatic mutations in ER-positive breast cancer. Nature Communications. 9(1):3476.

Cotto KC, Wagner AH, Feng YY, Kiwala S, Coffman AC, Spies G, Wollam A, Spies NC, Griffith OL†, Griffith M†. 2018. DGIdb 3.0: a redesign and expansion of the drug-gene interaction database. Nucleic Acids Research. 46(D1):D1068-D1073.

Griffith M*,†, Spies NC*, Krysiak K*, McMichael JF, Coffman AC, Danos AM, Ainscough BJ, Ramirez CA, Rieke DT, Kujan L, Barnell EK, Wagner AH, Skidmore ZL, Wollam A, Liu CJ, Jones MR, Bilski RL, Lesurf R, Feng YY, Shah NM, Bonakdar M, Trani L, Matlock M, Ramu A, Campbell KM, Spies GC, Graubert AP, Gangavarapu K, Eldred JM, Larson DE, Walker JR, Good BM, Wu C, Su AI, Dienstmann R, Margolin AA, Tamborero D, Lopez-Bigas N, Jones SJ, Bose R, Spencer DH, Wartman LD, Wilson RK, Mardis ER, Griffith OL†. 2017. CIViC is a community knowledgebase for expert crowdsourcing the clinical interpretation of variants in cancer. Nature Genetics. 49(2):170-4. *These authors contributed equally to this work. †Corresponding author.

Krysiak K, Gomez F, White BS, Matlock M, Miller CA, Trani L, Fronick CC, Fulton RS, Kreisel F, Cashen AF, Carson KR, Berrien-Elliott MM, Bartlett NL, Griffith M†, Griffith OL†, Fehniger TA†. 2017. Recurrent Somatic Mutations Affecting B-Cell Receptor Signaling Pathway Genes in Follicular Lymphoma. Blood. 129(4):473-483. †Corresponding author.

Griffith OL*, Chan SR*, Griffith M, Krysiak K, Skidmore ZL, Hundal J, Allen JA, Arthur CD, Runci D, Bugatti M, Miceli AP, Schmidt H, Trani L, Kanchi KL, Miller CA, Larson DE, Fulton RS, Vermi W, Wilson RK, Schreiber RD, Mardis ER. 2016. Truncating Prolactin Receptor Mutations Promote Tumor Growth in Murine Estrogen Receptor-Alpha Mammary Carcinomas. Cell Reports. 17(1):249-60. *These authors contributed equally to this work.

Ainscough BJ, Griffith M†, Coffman AC, Wagner AH, Kunisaki J, Choudhary MNK, McMichael JF, Fulton RS, Wilson RK, Griffith OL†, Mardis ER. 2016. DoCM: a database of curated mutations in cancer. Nature Methods. 13(10):806-7. †Corresponding author.

Skidmore ZL, Wagner AH, Lesurf R, Campbell KM, Kunisaki J, Griffith OLϮ, Griffith MϮ. (2016). GenVisR: Genomic Visualizations in R. Bioinformatics. pii: btw325. [Epub ahead of print]. PMID: 27288499. ϮCorresponding author.

Griffith M*, Griffith OL*, Krysiak K, Skidmore ZL, Christopher MJ, Klco JM, Ramu A, Lamprecht TL, Wagner AH, Campbell KM, Lesurf R, Hundal J, Zhang J, Larson DE, Heath S, Fronick C, O`Laughlin S, Fulton RS, Magrini V, McGrath S, Smith SM, Miller CA, Maher CA, Payton JE, Walter MJ, Link DC, Graubert TA, Westervelt P, Kulkarni S, DiPersio JF, Mardis ER, Wilson RK, Ley TJ. (2016). Comprehensive genomic analysis reveals FLT3 activation and a therapeutic strategy for a patient with relapsed adult B-lymphoblastic leukemia. Experimental Hematology. 44(7):603-13. PMCID: PMC4914477. *These authors contributed equally to this work.

Griffith OL*Ϯ, Griffith M*, Krysiak K*, Magrini V, Ramu A, Skidmore ZL, Kunisaki J, Austin R, McGrath S, Zhang J, Demeter R, Graves T, Eldred JM, Walker J, Larson DE, Maher CA, Lin Y, Chapman W, Mahadevan A, Miksad R, Nasser I, Hanto DWϮ, Mardis ERϮ. (2016). A genomic case study of mixed fibrolamellar hepatocellular carcinoma. Annals of Oncology. 27(6):1148-54. PMCID: PMC4880064. *These authors contributed equally to this work. ϮCorresponding author.

Krysiak K, Christopher MJ, Skidmore ZL, Demeter RT, Magrini V, Kunisaki J, O’Laughlin M, Duncavage EJ, Miller CA, Ozenberger BA, Griffith M, Wartman LDϮ, Griffith OLϮ. (2016). A genomic analysis of Philadelphia chromosome-negative AML arising in patients with CML. Blood Cancer Journal. 6:e413. PMCID: PMC4855253. ϮCorresponding author.

Lesurf R, Cotto KC, Wang G, Griffith M, Kasaian K, Jones SJM, Montgomery SBϮ, Griffith OLϮ. (2016). ORegAnno 3.0: a community-driven resource for curated regulatory annotation. Nucleic Acids Research. 44(D1):D126-32. PMCID: PMC4702855. ϮCorresponding author.

Wagner AH, Coffman AC, Ainscough BJ, Spies NC, Skidmore ZL, Campbell KM, Krysiak K, Pan D, McMichael JF, Eldred JM, Walker JR, Wilson RK, Mardis ER, Griffith MϮ, Griffith OLϮ. (2016). DGIdb 2.0: a drug-dene resource for precision medicine hypothesis generation. Nucleic Acids Research. 44(D1):D1036-44. PMCID: PMC4702839. ϮCorresponding author.

Griffith MϮ, Walker JR, Spies N, Ainscough BJ, Griffith OLϮ. (2015). Informatics for RNA-seq: A web resource for analysis on the cloud. PLoS Computational Biology. 11(8):e1004393. PMCID: PMC4527835. ϮCorresponding author.

Griffith M*Ϯ, Griffith OL*Ϯ, Smith SM*, Ramu A, Callaway MB, Brummett AM, Kiwala M, Coffmann AC, Regier AA, Oberkfell BJ, Sanderson GE, Mooney TP, Nutter N, Belter EA, Du F, Long RL, Abbott TE, Ferguson I, Morton D, Burnett M, Weible JV, Peck JB, Dukes A, McMichael JF, Lolofie JT, Derickson BR, Hundall J, Skidmore ZL, Ainscough BJ, Dees ND, Schierding WS, Kandoth C, Kim K, Lu C, Harris CC, Maher N, Maher CA, Magrini VJ, Abbott BS, Chen K, Clark E, Das I, Fan X, Hawkins AE, Hepler TG, Wylie TN, Leonard S, Schroeder WE, Shi X, Carmichael KL, Weil M, Wohldstadter RW, Stiehr G, McLellan MD, Pohl CS, Miller CA, Koboldt DC, Walker JR, Eldred JM, Larson DE, Dooling DJ, Ding L, Mardis ER, Wilson RK. (2015). Genome Modeling System: A Knowledge Management Platform for Genomics. PLoS Computational Biology. 11(7): e1004274. PMCID: PMC4497734. *These authors contributed equally to this work and are listed in alphabetical order. ϮCorresponding author.

Good BM, Ainscough BJ, McMichael JF, Su AIϮ, Griffith OLϮ. (2014). Organizing knowledge to personalize medicine in cancer. Genome Biology. 15(8):438. PMCID: PMC4281950. ϮCorresponding author.

Last Updated: 11/8/2022 4:01:11 PM

The informatics and interpretation bottleneck of precision medicine. (Good et al. 2014. Genome Biology. 15(8):438)
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