Christopher A. Maher, PhD

Christopher A. Maher, PhD


Division of Oncology
Mail Stop 8069-0057-07
Washington University
660 South Euclid Avenue
St. Louis, MO 63110

Room 740 Southwest Tower (office)

McDonnell Genome Institute
Room 5133
4444 Forest Park Parkway
St. Louis, MO 63110 (lab)

Research Interests
  • Computational biology
  • Bioinformatics
  • Genomics
  • Cancer
  • Long noncoding RNAs

Long Non-coding RNAs (lncRNAs)

Our lab is currently integrating genomics, bioinformatics, and molecular biology approaches to characterize RNA species, elucidate their function, and assessing their clinical applicability.

  • Understanding the role of long non-coding RNAs in lung cancer
    In our recently published study in Genome Biology (PMID: 25116943) we leveraged three large publically available data collections comprising ~550 lung cancer patients that enable us to detect 111 lung cancer associated lncRNAs, which we refer to as LCALs. We experimentally validated a subset of LCALs in cell lines and an independent tissue cohort as well as confirming their full-length transcripts. A meta-analysis across human cancers revealed that most LCALs that have lung cancer specific expression and therefore may represent putative biomarkers. However, a few LCALs are altered in multiple solid tumors suggesting they may have a common oncogenic role. Furthermore, we have found that the expression of multiple LCALs is associated with poor overall survival in a cohort of 409 stage I/II lung cancer patients suggesting their clinical potential. Lastly, to demonstrate that LCALs may contribute to lung tumorigenesis we silenced and over expressed the most commonly up-regulated lncRNA across lung subtypes, LCAL1, highlighting its role in regulating cellular proliferation. Overall, transcriptomic analysis highlights the lncRNA landscape that may contribute to lung cancer and lays the framework for future studies exploring their mechanism in lung tumorigenesis and potential use as biomarkers. Our lab is currently addressing the challenge of understanding how lncRNAs function using high-throughput assays (i.e., RIP-Seq) within subsets of lung cancer patients with the intent of identifying novel therapeutic strategies.
  • Understanding the biological and clinical significant of Prostate Cancer Associated Transcripts (PCATs)
    Each year, over 180,000 men are diagnosed with prostate cancer in the United States, and over 29,000 will die from this disease. To date prostate cancer research has primarily focused on the deregulation of protein-coding genes to identify oncogenes and tumor suppressors as potential diagnostic and therapeutic targets. We leveraged the unbiased approach of transcriptome sequencing to identify over 1,800 unannotated lncRNAs, with 121 found to be involved in prostate tumorigenesis, referred to as prostate cancer associated transcripts (PCATs). Although originally regarded as transcriptional noise, several well-described examples indicate that lncRNAs may be master regulators in cancer biology, typically facilitating epigenetic gene repression through chromatin-modifying complexes. However, of the thousands of lncRNAs discovered to date, only a few have been functionally characterized in human cancers. Interestingly, PCAT-1 was found to have mutually exclusive expression with EZH2, a core PRC2 protein and prostate cancer biomarker. Subsequent in vitro and in vivo studies demonstrated that PCAT-1 regulates cellular proliferation through an unknown mechanism. Through RNA immunoprecipitation we found that PCAT-1 associates with PRC2, which in turn can bind to the PCAT-1 promoter. Taken together, these results suggest that PCAT-1 biology may exhibit two distinct modalities: one in which PRC2 represses PCAT-1 and a second in which active PCAT-1 promotes cell proliferation. Building upon this, our lab is currently focusing on understanding how additional PCATs promote to prostate cancer and placing them in clinical context (as part of the projects described in the ‘Prostate Cancer Genomics’ section).
  • Understanding the contribution of long non-coding RNAs to metastasis
    As part of a Team Science Award we are exploring the differences in the genome, transcriptome, and epigenome between primary and metastatic colorectal cancer with the intent of revealing novel pathways critical for tumor metastases, identify potential diagnostic/prognostic markers, and unmask new targets for therapeutic intervention. Interestingly, a gene set enrichment analysis of the differentially expressed protein-coding genes from our patient cohort revealed an enrichment of Polycomb Repressive Complex 2 (PRC2) target genes during the progression of mCRC. Consistent with earlier reports, our subsequent preliminary studies demonstrate that ~20% of the known lncRNAs associate with the PRC2, which represses the transcription of pro-differentiation and anti-proliferative genes leading to poorly differentiated and aggressive human tumors. Therefore, we are optimizing novel techniques to systematically identify how lncRNAs interact with PRC2 to modulate chromatin states.
  • Breast cancer
    Estrogen-receptor-positive breast cancer exhibits highly variable prognoses, histological growth patterns and treatment outcomes. The observation that estrogen receptor positive breast cancer growth is stimulated by estrogen led to clinical trials utilizing anti-estrogen therapies prior to surgery. To date multiple clinical trials have focused on aromatase inhibitors, a form of anti-estrogen therapy that blocks the enzyme aromatase from synthesizing estrogen. Despite the successes of using neoadjuvant hormone therapy, only a subset of patients will respond to treatment. Therefore, our lab is focusing on understanding the role of lncRNAs in therapy sensitivity.

Prostate Cancer Genomics

Our lab also has a long-standing interest in translating genome-based discoveries that to improve prostate cancer treatment. This can be exemplified by two ongoing projects.

  • Identifying molecular biomarkers of long-term response to androgen deprivation therapy and radiation in lethal prostate cancer
    Of the 29,480 men who died from prostate cancer last year, over 80% of these patients presented with localized disease. Thus, a majority of lethal prostate cancers are diagnosed at a potentially curable stage. This presents two critical challenges: determining which patients will benefit from intensified treatment with earlier initiation of anti-androgen therapy, and conversely, identifying which patients will develop resistance and proceed to lethal disease. Therefore, we our lab is using comprehensive genomic approaches to discover biomarkers predictive of treatment resistance and lethal disease. To accomplish this, we will study 771 patients enrolled in a phase III clinical trial. This study is highly unique as these patients were randomized to receive common treatments and have long-term clinical follow-up (>10-years). Therefore, this represents the first study of its kind to discover predictors of prostate cancer cure and death. Successful completion of this study will benefit men fighting metastatic prostate cancer and their families by discovering markers that can predict who will benefit from treatment and who will become resistant resulting in more personalized patient care. This in turn will also reduce putting patients at risk of side effects unnecessarily. The discovery of predictive biomarkers will also help shape the design of future clinical trials and significantly impact the direction of prostate cancer therapy.
  • Molecular predictors of indolent and aggressive disease
    A critical goal in prostate cancer research is determining the molecular underpinnings of aggressive and indolent disease and its subsequent application to patient management and prognosis. At present, one of the best indications of disease aggressiveness is Gleason grade, an indicator of cellular differentiation level, assigned by histopathologic examination of carcinoma in prostate tissue. Tumors with Gleason grade 4 are clinically more aggressive than Gleason grade 3. Therefore, the nucleotide-level characterization of isolated Gleason grade 3 and 4 tumor foci from the same patient are of particular interest in understanding the genomic relatedness of foci and the genetic underpinnings of disease progression. In an effort to better understand the genetic progression of the disease, we will sequence Gleason grade 3 and 4 foci as well as grade 3 and 5 foci from the same patients to permit this comparison. To isolate carcinoma cells of different grades we will use laser capture microdissection, then we will use the small amount of DNA isolated from the cells to produce a whole genome sequence data set from the microdissected-isolated cells. The resulting data will provide a comprehensive comparison of genome-wide somatic alterations in the progression from indolent to aggressive disease, and illustrate the genomic relationship of different tumor grades within the same tumor. Our goal is to identify hallmarks of prostate cancer progression and illustrate the genomic relatedness between shared tumor foci by comparing the mutational landscapes of Gleason grade 3 and 4 cells and Gleason grade 3 and 5 cells.

Structural Variation

Over the last few years, our group has focused on developing methods to discover gene fusions using transcriptome sequencing (RNA-Seq) and understand their biological and clinical significance. This has led to numerous discoveries including a recurrent RNA chimera SLC45A3-ELK4 and a novel class of RAF fusions in prostate cancer (PMID: 20526349), MAST kinase and NOTCH fusions in triple negative breast cancer (PMID: 22101766), ESR1 fusions in ER+ breast cancer (PMID: 24055055), ALK and ROS fusions in lung cancer (PMID: 22980976), and a recurrent RNA chimera in chronic lymphocytic leukemia (PMID: 23382248). To enable other labs to make similar discoveries we have developed and released open source software, ChimeraScan, to detect gene fusions using transcriptome sequencing data. Despite our successes, we are still faced with the critical challenge of ensuring that a casual gene fusion is not only detected, but that it can be prioritized accordingly amongst the increasing number of chimeric mutations in a cancer transcriptome. To address this, our lab is continuing to optimize computational and experimental methods for discovering and prioriziting gene fusions.



  • 2006-2004: PhD in Biomedical Engineering, Cold Spring Harbor Laboratory & Stony Brook University, NY
  • 2004-2000: MS in Biomedical Engineering, Cold Spring Harbor Laboratory & Stony Brook University, NY
  • 2002-1998: BS in Biological and Environmental Engineering, Cornell University, Ithaca, NY

Post-Graduate Training

  • 2009-2007: Research Fellow, Michigan Center for Translational Pathology and Department of Pathology, University of Michigan, Ann Arbor, MI
  • 2007: Postdoctoral Fellow, South African National Bioinformatics Institute, University of Western Cape, Cape Town, South Africa

Academic Positions & Employment

  • present-2018: Associate Professor, Departments of Medicine and Biomedical Engineering, Washington University, St. Louis, MO
  • present-2012: Research Member, Siteman Cancer Center at Washington University, St. Louis, MO
  • present-2011: Assistant Director, The McDonnell Genome Institute (MGI) at Washington University, St. Louis, MO
  • 2018-2013: Assistant Professor, Department of Biomedical Engineering, Washington University, St. Louis, MO
  • 2018-2011: Assistant Professor, Department of Medicine, Division of Oncology, Washington University, St. Louis, MO
  • 2011-2009: Research Investigator, Michigan Center for Translational Pathology (MCTP), Department of Pathology, and Center for Computational Medicine and Bioinformatics (CCMB), University of Michigan, Ann Arbor, MI
  • 2004: Visiting Scientist, South African National Bioinformatics Institute, University of Western Cape, Cape Town, South Africa

University & Hospital Appointments & Committees

  • present-2018: K12 Ad-hoc Reviewer
  • present-2014: American Cancer Society IRG Reviewer
  • present-2014: Siteman Cancer Center, Solid Tumor Therapeutics Program Steering Committee
  • present-2012: Siteman Cancer Center, Breast Cancer Research Program Leadership Team
  • present-2011: Siteman Cancer Center, Genitourinary Oncology Focus Group Co-leader
  • 2020, 2017: Siteman Investment Program Cycle I Ad-hoc Reviewer

Honors & Awards

  • 2021-2017: American Cancer Society, Research Scholar Grant
  • 2018-2016: Prostate Cancer Foundation / Movember Foundation Challenge Award
  • 2017: International Medical Informatics Association (IMIA) Best 2016 Article in the field of ‘Bioinformatics and Translational Informatics’
  • 2017: Lung Cancer Research Foundation Award
  • 2017: William Rippe Award for Distinguished Research in Lung Cancer
  • 2017: Jon Shevell Young Scientist Travel Scholarship
  • 2017-2016: WUSTL Pancreatic SPORE Development Research Project Award
  • 2017-2015: Prostate Cancer Foundation Global Treatment Science Challenge Awardee
  • 2017-2014: Susan G. Komen, Career Catalyst Award
  • 2015-2012: LUNGevity Foundation Career Development Awardee
  • 2015-2010: NIH Pathway to Independence Award
  • 2014-2013: V Foundation V Scholar Award
  • 2014-2013: Cancer Research Foundation Young Investigator Award
  • 2013-2010: Prostate Cancer Foundation Young Investigator Award
  • 2012: Prostate Cancer Foundation Scholar in Residence
  • 2012: Melissa Lumberg Zagon Founders’ Award
  • 2012: American Lung Association Biomedical Research Grant Awardee
  • 2010: Prostate SPORE Meeting, Best Poster Competition, 2nd Place
  • 2010: Genome Technology “Tomorrow’s PIs”
  • 2010-2009: UMCCC Prostate SPORE Pilot Project Awardee
  • 2010-2008: American Cancer Society / Canary Foundation Early Detection Postdoctoral Fellowship (1 of 5 awarded)
  • 2010-2008: American Association for Cancer Research (AACR) Centennial Postdoctoral Research Fellowship in Cancer Research (declined)
  • 2009: American Association for Cancer Research Aflac, Incorporated Scholar-in-Training Award
  • 2009-2008: American Association for Cancer Research and Amgen Fellowship in Clinical/Translational Research (1 awarded)
  • 2007: NIH Ruth L. Kirschstein National Research Service Award
  • 2005: Best Talk 2nd Annual Biomedical Engineering Graduate Student Research Symposium
  • 2004: NSF Plant Genome Program, Biological Sciences travel stipend

Editorial Boards

  • present-2019: Biology Open (Editor)
  • present-2018: BMC Genomics
  • present-2016: Genes, Chromosomes, and Cancer
  • present-2014: Medical Oncology
  • present-2014: Molecular Cancer Research

National Scientific Panels

  • present-2018: American Cancer Society, RNA Mechanisms in Cancer Peer Review Committee
  • present-2015: Prostate Cancer Foundation (PCF) Stupski Prize in Precision Oncology Committee
  • present-2014: GBC Genomic and Informed Consent Working Group
  • present-2012: RTOG Translation Oncology Scientific Review Committee
  • present-2012: LUNGevity Scientific Advisory Board (ex-officio member)
  • present-2010: Prostate Cancer Foundation Grant Reviewer
  • 2020: National Institutes of Health (NIH) Cancer Genetics Study Section, Ad-hoc Reviewer
  • 2020: National Institutes of Health (NIH) Cancer Biomarkers (CAMP) Study Section, Ad-hoc Reviewer
  • 2019, 2018: National Institutes of Health (NIH) Cancer Molecular Pathobiology (CAMP) Study Section, Ad-hoc Reviewer
  • 2018-2017: AACR Annual Meeting, microRNAs and Other Noncoding RNAs Section of the Molecular and Cellular Biology, Genetics Subcommittee
  • 2016: American Association for Cancer Research (AACR) Annual Meeting Education Committee
  • 2016: Medical Research Council Grant Reviewer
  • 2016: National Institutes of Health (NIH) Cancer Genetics Study Section (ad hoc reviewer)
  • 2015: Ralph E. Powe Junior Faculty Award
  • 2015: National Science Foundation (NSF) Molecular and Cellular Biology – Genetic Mechanisms (NSF 13-510)
  • 2015: Department of Defense (DOD) Prostate Cancer Research Program (PCRP) Health Disparities (HDA) Study Section
  • 2013: Prostate Cancer UK Reviewer
  • 2013: Longer Life Foundation Reviewer
  • 2013: American Association for Cancer Research (AACR) Annual Meeting Methods Workshop Organizer
  • 2012: Workshop on Data Mining of Next Generation Sequencing (WDNS)
  • 2012-2011: DOD Prostate Cancer Research Program (PCRP) CBY-MBG Panel Review
  • 2011: Great Lakes Bioinformatics Conference (GLBIO), Ohio University
  • 2011: Cancer UK, Biomarkers and Imaging Discovery (BIDD) Development Committee, Genomics Initiative, London, UK
  • 2011: Prostate Cancer UK Reviewer
  • 2010: Experimental Biology, Session chair, Bioinformatics and Next Generation Sequencing
  • 2010: AACR 101st Annual Meeting, Cellular and Molecular Biology (CB) Subcommittee focusing on Bioinformatics and Computational Molecular Biology
  • 2009: AACR 100th Annual Meeting, WICR Careen Mentoring Forum Facilitator

Professional Societies & Organizations

  • present-2016: Academy of Science St. Louis
  • present-2012, 2004, 2002: International Society for Computational Biology
  • present-2010: American Association of the Advancement of Science
  • present-2008: American Association for Cancer Research
  • 2010-2009: American Society for Investigative Pathology
  • 2010-2009: Society of Genome Biology and Technology
  • 2004-2002: American Society of Plant Biologists