Matthew Shirley, Ph.D.
|Rare disease and cancer genomics researcher, developer of software for genomics data.||
250 Massachussetts Ave
Cambridge MA 02139
|2013||Ph.D. Biochemistry, Cellular, and Molecular Biology, Johns Hopkins School of Medicine, Baltimore, MD|
|2008||B.S. Biochemistry, University of Missouri, Columbia, MO|
Research & Professional Experience
|May 2021 - current||Chief Scientific Officer for Sturge-Weber Foundation, Houston TX|
|May 2015 - current||Senior Expert II, Novartis Institutes for BioMedical Research, Cambridge MA|
- Developed and support an alignment-free RNA-seq pipeline for processing thousands of internal and external data sets.
- Identified and validated novel pharmacodynamic markers to support multiple oncology drug development programs.
- Interface between wet lab biologists and sequencing facilities to guide experimental design, execution and perform data analysis of multiple NGS assays.
- Designed new tools for validation of CRISPR/Cas9 sgRNA efficiency.
- Mining internal and public data sets to identify or validate new drug targets.
- Organized a global computational research symposium spanning six geographical sites.
- Committee member of a global resource group for Novartis computational biology, bioinformatics and cheminformatics employees.
|Mar 2013 - May 2015||Postdoctoral Fellow, Department of Oncology, Johns Hopkins School of Medicine|
- Developing statistical framework for integrative whole-genome genetic and bisulfite sequence analysis.
- Mining genomic data for epigenetic prostate cancer biomarkers.
- Collaboratively developing and deploying new software tools in the genomics community.
- Mentoring graduate and undergraduate students in computational methods.
- Teaching classes and workshops for computational biology and programming.
|Aug 2008 - Mar 2013||Ph.D. Candidate, Department of Neuroscience, Johns Hopkins School of Medicine|
- Discovered causative Sturge-Weber syndrome somatic mutation using whole genome sequencing.
- Characterized SNP and CNV variability in lymphoblast cell lines using DNA microarrays.
- Supported development of software and method for population-scale genetic relatedness testing.
- Explored the human kinome for novel kinase-substrate interactions using protein microarrays.
- Developed and deployed web-based tool for somatic mosaicism detection.
|Jun 2006 - May 2008||Research Assistant, Department of Biochemistry, University of Missouri-Columbia|
- Studied genetics of heavy metal bioremediation in bacterium Desulfovibrio vulgaris Hildenborough.
- Sequenced transposon insertion mutagenesis library in DvH.
- Characterized metabolites of DvH anaerobic growth using gas chromatography.
- Sequencing Analysis
- Molecular Biology
- Applied Statistics
- Code Version Control
- Continuous Integration Testing
- Cloud Computing
- Software Development
|Matthew S. Crowe, Tatiana Zavorotinskaya, Charles F Voliva, Matthew D. Shirley, Yanqun Wang, David A. Ruddy, Daniel P Rakiec, Jeffrey A. Engelman, Darrin D. Stuart and Alyson K Freeman. RAF-mutant melanomas differentially depend on ERK2 over ERK1 to support aberrant MAPK pathway activation and cell proliferation. Molecular Cancer Research. 2021.|
|Hui Qin Wang, Iain J Mulford, Fiona Sharp, Jinsheng Liang, Sema Kurtulus, Gina Trabucco, David S Quinn, Tyler A Longmire, Nidhi Patel, Roshani Patil, Matthew D. Shirley, Yan Chen, Hao Wang, David A. Ruddy, Claire Fabre, Juliet A. Williams, Peter S. Hammerman, Jennifer Mataraza, Barbara Platzer and Ensar Halilovic. Inhibition of MDM2 promotes anti-tumor responses in p53 wild-type cancer cells through their interaction with the immune and stromal microenvironment. Cancer Research. 2021.|
|Matthew D Shirley, Viveksagar K Radhakrishna, Javad Golji, Joshua M Korn. (Preprint) PISCES: a package for rapid quantitation and quality control of large scale mRNA-seq datasets. bioRxiv. 2020.|
|Florencia Rago, GiNell Elliott, Ailing Li, Kathleen Sprouffske, Grainne Kerr, Aurore Desplat, Dorothee Abramowski, Julie T. Chen, Ali Farsidjani, Kay X. Xiang, Geoffrey Bushold, Yun Feng, Matthew D. Shirley, Anka Bric, Anthony Vattay, Henrik Möbitz, Katsumasa Nakajima, Christopher D. Adair, Simon Mathieu, Rukundo Ntaganda, Troy Smith, Julien P.N. Papillon, Audrey Kauffmann, David A. Ruddy, Hyo-eun C. Bhang, Deborah Castelletti and Zainab Jagani. The Discovery of SWI/SNF Chromatin Remodeling Activity as a Novel and Targetable Dependency in Uveal Melanoma. Molecular Cancer Therapeutics. 2020.|
|Huai-Xiang Hao, Hongyun Wang, Chen Liu, Steven Kovats, Roberto Velazquez, Hengyu Lu, Bhavesh Pant, Matthew Shirley, Matthew J Meyer, Minying Pu, Joanne Lim, Michael Fleming, LeighAnn Alexander, Ali Farsidjani, Matthew J. LaMarche, Susan Moody, Serena J Silver, Giordano Caponigro, Darrin D. Stuart, Tinya J Abrams, Peter S. Hammerman, Juliet Williams, Jeffrey A. Engelman, Silvia Goldoni and Morvarid Mohseni. Tumor intrinsic efficacy by SHP2 and RTK inhibitors in KRAS mutant cancers. Molecular Cancer Therapeutics. 2019.|
|Zainab Jagani, Gregg Chenail, Kay Xiang, Geoffrey Bushold, Hyo-Eun C. Bhang, Ailing Li, GiNell Elliott, Jiang Zhu, Anthony Vattay, Tamara Gilbert, Anka Bric, Rie Kikkawa, Valérie Dubost, Rémi Terranova, John Cantwell, Catherine Luu, Serena Silver, Matt Shirley, Francois Huet, Rob Maher, John Reece-Hoyes, David Ruddy, Daniel Rakiec, Joshua Korn, Carsten Russ, Vera Ruda, Julia Dooley, Emily Costa, Isabel Park, Henrik Moebitz, Katsumasa Nakajima, Christopher D. Adair, Simon Mathieu, Rukundo Ntaganda, Troy Smith, David Farley, Daniel King, Xiaoling Xie, Raviraj Kulathila, Tiancen Hu, Xuewen Pan, Qicheng Ma, Katarina Vulic, Florencia Rago, Scott Clarkson, Robin Ge, Frederic Sigoillot, Gwynn Pardee, Linda Bagdasarian, Margaret McLaughlin, Kristy Haas, Jan Weiler, Steve Kovats, Mariela Jaskelioff, Marie Apolline-Gerard, Johanna Beil, Ulrike Naumann, Pascal Fortin, Frank P. Stegmeier, Michael G. Acker, Juliet Williams, Matthew Meyer, James E. Bradner, Nicholas Keen, William R. Sellers, Francesco Hofmann, Jeffrey A. Engelman, Darrin Stuart, Julien P.N. Papillon. (Preprint) In-Depth Characterization and Validation in BRG1-Mutant Lung Cancers Define Novel Catalytic Inhibitors of SWI/SNF Chromatin Remodeling. BioRxiv. 2019.|
|Grace P Leung, Tianshu Feng, Frederic D Sigoillot, Felipe Correa Geyer, Matthew D Shirley, David A Ruddy, Daniel Rakiec, Alyson K Freeman, Jeffrey A Engelman, Mariela Jaskelioff, Darrin D Stuart. Hyperactivation of MAPK Signaling is Deleterious to RAS/RAF Mutant Melanoma. Molecular Cancer Research. 2018.|
|Munoz DM, Cassiani PJ, Li L, Billy E, Korn JM, Jones MD, Golji J, Ruddy DA, Yu K, McAllister G, DeWeck A, Abramowski D, Wan J, Shirley MD, Neshat SY, Rakiec D, de Beaumont R, Weber O, Kauffmann A, McDonald ER, Keen N, Hofmann F, Sellers WR, Schmelzle T, Stegmeier F, Schlabach MR. CRISPR screens provide a comprehensive assessment of cancer vulnerabilities but generate false-positive hits for highly amplified genomic regions. Cancer Discovery. 2016.|
|Matthew D Shirley, Laurence Frelin , José Soria López , Anne Jedlicka , Amanda Dziedzic , Michelle A. Frank-Crawford , Wayne Silverman , Louis Hagopian , Jonathan Pevsner. Copy Number Variants Associated with 14 Cases of Self-Injurious Behavior. PLOS ONE. 2016.|
|Shirley MD, Ma Z, Pederson B, Wheelan S. Efficient "pythonic" access to FASTA files using pyfaidx. PeerJ PrePrints. 2015.|
|Shirley MD, Tang H, Gallione CJ, Baugher JD, Frelin LP, Cohen B, North PE, Marchuk DA, Comi AM, Pevsner J. Sturge–Weber Syndrome and Port-Wine Stains Caused by Somatic Mutation in GNAQ. New England Journal of Medicine. 2013.|
|Baugher JD, Baugher BD, Shirley MD, Pevsner J. Sensitive and specific detection of mosaic chromosomal abnormalities using the Parent-of-Origin-based Detection (POD) method. BMC Genomics. 2013.|
|R.H. Newman, J. Hu, H. Rho, Z. Xie, C. Woodard, J. Neiswinger, C. Cooper, M. Shirley et al. Construction of human activity-based phosphorylation networks. Molecular Systems Biology. 2013.|
|Stevens EL, Baugher JD, Shirley MD, Frelin LP, Pevsner J. Unexpected Relationships and Inbreeding in HapMap Phase III Populations. PLOS ONE. 2012.|
|Shirley MD, Baugher JD, Stevens EL, Tang Z, Gerry N, Beiswanger CM, Berlin DS, Pevsner J. Chromosomal variation in lymphoblastoid cell lines. Human Mutation. 2012.|
|PISCES: a package for rapid quantitation and quality control of large scale mRNA-seq datasets|
|pyfaidx: efficient & pythonic random access to fasta subsequences|
|simplesam: Simple pure Python SAM parser and objects for working with SAM records|
|fastqp: Python FASTQ and SAM read quality assessment and plotting|
|sra-tools-galaxy: NCBI SRA toolkit Galaxy package and tool wrappers|
|hamstring: Python module for Hamming7,4 error-correcting DNA barcodes|
|tripod: web interface for the triPOD mosaicism analysis|
|Jonathan Pevsner, Anne Comi, Douglas Marchuk, Matthew Shirley Diagnostic and prognostic test for Sturge-Weber syndrome, Klippel-Trenaunay-Weber syndrome, and port-wine stains (PWSS). USPTO. 2020.|
|2013||Amazon Web Services in Education Grant, supporting Introduction to Python|
|2013||Center for Computational Genomics, Johns Hopkins School of Medicine, Baltimore MD|
|2013||Bioinformatics & Computational Biology Department, Foundation for Advanced Education in the Sciences, Bethesda MD|
- PISCES: alignment free RNA-seq quantiation and QC pipeline, February 16 2017, MIT BIG meeting, MIT, Cambridge MA (video)
- Deep amplicon sequencing reveals GNAQ 548G>A as the causal somatic mutation in Sturge-Weber syndrome and common port-wine stains, October 17 2013, Center for Computational Genomics, Johns Hopkins School of Medicine, Baltimore MD
- Chromosomal Variation in Lymphoblastoid Cell Lines, December 10 2012, Department of Biochemistry, Cellular, and Molecular Biology, Johns Hopkins School of Medicine, Baltimore MD
Abstracts and Posters
- Shirley MD, Korn JM, Bitter H. PISCES: a package for quantitation and QC of big mRNA-seq datasets, Genome Informatics. Cold Spring Harbor Laboratories. November 2017
- Grace P. Leung, Tianshu Feng, Matthew D. Shirley, Alyson K. Freeman, Mariela Jaskelioff, and Darrin D. Stuart. Deleterious effects of MAPK pathway hyperactivation in BRAF-mutant melanoma, Kinases: Next-Generation Insights and Approaches. Breckenridge, Colorado USA. March 2017
- Shirley MD et al. A Somatic Mosaic Mutation in GNAQ causes Sturge-Weber syndrome and Isolated Port-wine Birthmarks, 42nd Annual Meeting of the Child Neurology Society. November 2013
- Shirley MD et al. Chromosomal Variation in Lymphoblastoid Cell Lines, April 25 2012, Johns Hopkins School of Medicine, Baltimore MD
- Shirley MD et al. Rapid Automated Characterization of Transposon Insertion Mutants in Desulfovibrio vulgaris Hildenborough by srnPCR, Undergraduate Research and Creative Achievements Forum, 2007, University of Missouri, Columbia MO
- Shirley MD et al. Rapid Automated Characterization of Transposon Insertion Mutants in Desulfovibrio vulgaris Hildenborough by srnPCR, Virtual Institute for Microbial Stress and Survival, 2007, Lawrence Berkeley National Laboratories, Berkeley CA
Titles of talks link to slides.
- BIOF309: Introduction to Python Working with Pandas, May 1, 2014, FAES
- BIOF309: Introduction to Python Sequence alignment with Biopython, April 24, 2014, FAES
- Biotrac45: Bioinformatic Analysis of Next Generation Sequencing Data, Galaxy for Next Generation Sequencing Analysis, April 8, 2014, FAES
- Introduction to Python: data structures and flow control, October 28 2013, CCG
- Introduction to Python: functions, classes, and I/O, October 30 2013, CCG
- BIOF503: Make Striking Figures and Analyze Data with R, Spoon-Fed R, October 24 2013, FAES
- BIOF309: Introduction to Python, Interfacing R and Python using Rpy2, May 2 2013, FAES
- BIOF309: Introduction to Python, Hello web: Accessing databases and APIs using Biopython, April 25 2013, FAES
- BIOF309: Introduction to Python, Reading, processing, and writing high throughput sequencing data, April 18 2013, FAES
- BIOF521: Bioinformatics for analysis of data generated by NGS, Galaxy for Next Generation Sequencing Analysis, February 6 2013, FAES
- Biotrac45: Bioinformatic Analysis of Next Generation Sequencing Data, Galaxy for Next Generation Sequencing Analysis, July 9 2013, FAES
- Biotrac45: Bioinformatic Analysis of Next Generation Sequencing Data, Galaxy for Next Generation Sequencing Analysis, November 12 2012, FAES