Christopher E. Mason, Ph.D.
Assistant Professor of Computational Genomics and Neuroscience
Our laboratory utilizes experimental and computational methodologies to identify and characterize the essential genetic elements that guide the function of the human genome
Noah Alexander, Technician
Marjan Bozinoski, Graduate Student
Sagar Chhangawala, Programmer
Jorge Gandara, Technician
Francine Garrett-Bakelman, Instructor
Sheng Li, Graduate Student
Lenore Pipes, Graduate Student
Darryl Reeves, Graduate Student
Yogesh Saletore, Graduate Student
Paul Zumbo, Senior Staff
Priyanka Vijay, Graduate Student
Dhruva Chandramohan, Graduate Student
Cem Meyden, Post-doctoral Associate
Dyala Jaroudi, Visiting Scholar
We perform research in three principal areas: (1) molecular profiling in patients with extreme phenotypes, including brain malformations, aggressive cancers, and undiagnosed diseases, (2) longitudinal monitoring of expression changes that orchestrate the development of the human brain and their evolutionary changes, and (3) the development of bioinformatics models for systems and synthetic biology. We use high-throughput sequencing-based methods to generate cell-specific molecular maps of genetic, epigenetic, and transcriptional activity, which give us multi-dimensional molecular portraits of development and disease. We then develop algorithms to leverage these data for detecting, cataloging and functionally annotating interactions between these molecular changes and also connect them to larger datasets (ENCODE, TCGA, ICGC) for replication and contextualization.
In the very long term, we hope these systems-based methods will enable such a rich understanding of the functional elements of the human genome that we can begin to repair or re-engineer these genetic networks for ameliorating or attenuating disease.
For examining molecular changes in tumors, we have pioneered several new approaches in concert with passionate clinical collaborators. First, we developed a novel, genome-wide approaches (eRRBS, mRRBS) and open-source algorithms (Methylkit, eDMR, methclone) for delineating DNA methylation changes, and these methods revealed separate genetic and epigenetic signatures in leukemia patients that clearly stratified tumor sub-type and severity. Second, we published a new, single-cell sequencing method that can capture full-length RNAs, which enables low-input, single-cell RNA-Sequencing (scRNA-Seq) that is essential for limited, clinical samples. Finally, we used our RNA-Seq methods in pediatric leukemia patients to detect chemo-resistant cells that emerge after chemotherapy. Importantly, our work has found mutations and molecular changes that can serve as signatures of chemo-resistance, which can then be used to modify and personalize appropriate treatments for patients within a day of having blood drawn. We have also developed novel method for RNA methylation discovery (MeRIP-seq), and our work has been hailed as a “wonderful revision the central dogma” of molecular biology and also opened an entirely novel area of research called the “epitranscriptome.” Specifically, we discovered that an RNA modification called methyl-6-adenosine (m6A) is a highly conserved modification in mRNAs and non-coding RNAs in both humans and mice.
(1) Stolc V*, Gauhar Z*, Mason C*, Halasz G, van Batenburg MF, Rifkin SA, Hua S, Herreman T, Tongprasit W, Barbano PE, Bussemaker HJ, White KP. A gene expression map for the euchromatic genome of Drosophila melanogaster. Science. Oct 22;306(5696):655-60. 2004. This was the first demonstration of widespread non-coding RNA activity in an invertebrate system and demonstrated that the active areas of the genome are far more widespread than just the coding exons of genes.
(2) Marioni JC*, Mason CE*, Mane SM, Stephens M, Gilad Y. RNA-seq: an assessment of technical reproducibility and comparison with gene expression arrays. Genome Research. 18(9), 1509-1517. 2008. This is one of the foundational articles ever published on RNA-Sequencing and established principles and metrics for an entirely novel sequencing method for examining changes in RNA splicing and expression profiling. It remains one of the highest cited papers in the field (608 times to date).
(3) Mason CE, Shu FJ, Wang C, Session RM, Kallen RG, Sidell N, Yu T, Liu MH, Cheung E, Kallen CB. “Location analysis for the estrogen receptor-a reveals binding to diverse ERE sequences and widespread binding within repetitive DNA elements.” Nucleic Acids Research. Apr;38(7):2355-68. 2010. This paper showed active and functional regulatory elements present within repetitive areas of the genome, which are often overlooked. But, in light of recent ENCODE data, it is now well-recognized that many noncoding areas of the genome have regulatory and functional potential and roles.
(4) Meyer KD, Saletore Y, Zumbo P, Elemento O, Mason CE*, Jaffrey SJ*. Comprehensive Analysis of mRNA Methylation Reveals Pervasive Adenosine Methylation in 3’ UTRs. Cell. 2012. Jun 22;149(7):1635-46. This work showed the importance of a new kind of RNA modification (m6A) and was prominently featured in many news and scientific organizations (Appendix 1), being hailed as work that “revolutionizes our understanding of gene expression.” Methods are Patent Pending (L29543.7070).
(5) Saletore Y, Meyer KD, Korlach J, Vilfan I, Jaffrey S, Mason CE. The Birth of the Epitranscriptome: Deciphering the Function of RNA Modifications. Genome Biology. 31;13(10):175. 2012. The work from the Mason Lab was featured in Genome Biology article that detailed the pioneering work that opened an entirely novel realm of regulation in biology, dubbed as “The Epitranscriptome.” This work also showed the very first detection of RNA modifications with a single-molecule sequencing technology.
(6) Pan X, Durrett RE, Zhu H, Tanaka Y, Li Y, Zi X, Marjani SL, Euskirchen G, Ma C, LaMotte RH, Park I-H, Snyder M, Mason CE, Weissman SM. Two methods for full-length RNA-seq for low quantities of cells and single cells. Proceedings of the National Academies of Sciences. This paper describes novel methods for full-length RNA Sequencing of single cells or low input RNA from clinical samples. This represents the first complete, full-length cDNA amplification method for RNA Sequencing.
(7) Pipes L, Li S, Bozinoski M, Palermo R, Peng X, Blood P, Kelly S, Weiss JM, Thierry-Mieg J, Thierry-Mieg D, Zumbo P, Chen R, Schroth GP, Mason CE, Katze MG. The Nonhuman Primate Reference Transcriptome Resource (NHPRTR) for Comparative Functional Genomics. Nucleic Acids Research. 2013 Jan 1;41(D1):D906-D914. PMID: 23203872. This paper details the large-scale resources for 14 primates and 21 tissues to establish references and gene models across all primates.
(8) Meyer JA, Wang J, Hogan LE, Dandekar S, Patel JA, Tang Z, Zumbo P, Li S, Zavadil J, Levine RL, Cardozo T, Hunger SP, Raetz EA, Morrison DJ, Mason CE, and Carroll WL. Relapse Specific Mutations in Cytosolic 5’-Nucleotidase II in Childhood Acute Lymphoblastic Leukemia. Nature Genetics. 2013 Mar;45(3):290-4. This paper used RNA-Seq in ALL patients to find relapse-specific mutations that emerged after chemotherapy and found that these chemo-resistant variants can predict the aggressive type of the leukemia.
(9) Saletore Y, Chen-Kiang S, Mason CE. Novel RNA regulatory mechanisms revealed in the epitranscriptome. RNA Biology. 2013 Feb 22;10(3). This invited submission points out the likely roles for RNA modifications, including methyl-6-adenosine, which includes RNA degradation rates, RNA editing prevention, translation efficiency, miRNA interactions, and many RNA-binding roles for the epitranscriptome.
(10) Rosenfeld J and Mason CE. Pervasive gene patents cover the entire human genome. Genome Medicine. 2013. Mar 25; 5(3)27. This paper shows how small patent claims on short sequence fragments from genes, such 15mers in BRCA1, also inadvertently patent hundreds of other genes, and that using an analysis of all known patents indicate that the majority of the genes in the genome are already patented. This work was cited by the Supreme Court and has influenced national standards in intellectual property.
Physiology and Biophysics