We work closely with cancer laboratories and researchers from New York Presbyterian Hospital, Memorial Sloan-Kettering Cancer Center, and New York University Medical School, including Drs. Ari Melnick, Gail Roboz, Ross Levine, Selina Chen-Kiang, Christina Leslie, Olivier Elemento, and William Carroll. Through careful patient selection and monitoring, we are working to create genetic sub-classification of response to clinical trials for new therapeutic agents in brain tumors such as glioblastoma and hematological malignancies such acute myeloid leukemia, acute lymphocytic leukemia, and mantle cell lymphoma. For certain tumors, we examine sub-populations of cells during the progression of the tumors to search for the chemo-resistant clones which have been selected during the harsh treatments, with a goal to narrow our treatments to targets which can simplify and shorten treatment regimens for these patients. We examine genetic, epigenetic, transcriptional, and metabolic changes before, during, and after treatments, in humans as well as mouse models.
We work with Dr. William Gahl and researchers at the NIH’s UDP to look for mutations and molecular changes that may explain the mysterious phenotypes of no known etiology. Genome and transcriptome sequencing of these extreme phenotypes has the potential to reveal the effect of severely deleterious mutations in the human genome.
Methyl-6-Adenosine, or m6A, is an RNA modification that was discovered originally in the 1970s. Working in collaboration with Dr. Samie Jaffrey, we developed MeRIP-Seq (Methylated RNA ImmunoPrecipitation Sequencing) to use an antibody specific for m6A sites in an immunoprecipitation (IP) protocol (similar to ChIP-Seq) to enrich RNA fragments that contain m6A sites, coupled with next-generation high-throughput sequencing (NGS/HTS) and a computational pipeline, MeRIPPeR, to localize these sites throughout the transcriptome. In the Mason Lab, we are now studying to further elucidate the functional significance and role of m6A and what roles it may play in specific clinical applications.
Our lab leads the computational analysis of the NHPRT Project, where we work to perfect the de novo assembly of transcriptomes for various human tissues and primates and comparison of tissue-specific or species-specific transcriptomes against each other. Also, we create draft assemblies of various primates, if they are not available. This work is carried out in collaboration with ENSEMBL, Merck, Illumina, Baylor, the Katze Lab at the University of Washington and the Thierry-Mieg lab at NCBI.
Personalized medicine starts with the first cell. We use NGS methods and mouse models to examine the risk factors for NTDs, especially genes involved in the folic acid (FA) metabolic pathway, which is the primary source of methyl donor for nucleic acids. We have shown in preliminary experiments with Dr. Betsy Ross that there exist some genotype-specific risk and protective alleles for NTDs in response to FA, and we are expanding these studies to tease out the mechanisms of NTDs. We test certain candidates in Zebrafish models with Dr. Todd Evans, and also examine zebrafish developmental questions with NGS methods.
Working with Dr. Samie Jaffrey, we look at the transcription of specific sub-regions of neurons and leverage the brain RNA-Seq data from the NHPRT, where, among the list of 20 tissues, we are comparing the expression profiles of orthologous brain regions between the primates. We aim to construct the cross-species and cross-regional motifs and base modifications that regulate the transcriptional landscape of the brain and neurons, for improved annotation in understanding neurogenetics disorders.
Our lab is founding member of the SEQC, which is an evolution of the previous Microarray Quality Control (MAQC) Consortium. We are an official Illumina test site for the Federal Drug Administration (FDA)-led study, which aims to perfect the detection of molecules using NGS methods across all platforms, improving both QC steps and analytical methods for use in clinical, diagnostic, and personalized medicine. We also coordinate the scientific design and execution for a related study with the Association of Biomolecular Resource Facilities (ABRF). We use the extremely deep data from the SEQC to further annotate and define functional regions of the human genome and to identify transcriptional active regions (TARs) that are of unknown function.
We use chemical and physical separation methods to examine single cell differences within tumors, as well as novel methods for full-length cDNA amplification within a single cell or few cells. We also test new protocols for amplification of RNA and cDNA, working with the Weissman Laboratory at Yale.
PathoMap is a molecular profiling initiative launched in the summer of 2013 with the help of undergraduates from Weill Cornell Medicine and the Macaulay Honors College. The study's objective is to study the microbiome of New York City's urban, metropolitan environment. This is the first study of its kind to be launched at such a large scale and to comprehensively map the microbiome and metagenome on the surfaces of the city. The study also aims to develop a seasonal pathogen monitoring “weather map”. We envision that the map will be able to monitor the city and send alerts whenever a potential outbreak is detected. The map will also serve as a long-term study of the dynamics and health of the city at the molecular level.
The MetaSUB International Consortium was launched in June of 2015 to help address the gap in our knowledge of the built environment, where researchers world-wide are working to establish a "DNA map" of microbiomes in mass-transit systems. Mass-transit systems represent unique urban biomes, microbiomes, and metagenomes. These subterranean and above-ground structures are ubiquitous and the interactions between passengers and the subway surfaces define perhaps one of the world’s largest, high-traffic, and universal built environments. Also, these subway surfaces define the daily commute for millions of people every single day and billions of people each year. The microbiome constitutes an important element of our environment: bacterial cells in and on our bodies outnumber human cells by a 10:1 ratio, contribute as much as 36% of the active molecules present in the human bloodstream, and serve as a key mediator of human health. Yet, how humans may interact with (or acquire) new species of bacteria depends on the environment they are exposed to, the types of surfaces they touch, and the physical dynamics of their environment. This is especially true in dense, built environments such as cities, wherein the majority of the world’s population (54%) currently live.
Professor: Christopher E. Mason
Description: The rapid advancement of Next-Generation Sequencing (NGS) has opened a wealth of opportunities for research in many fields: cancer biology, epigenetics, tumor evolution, microbiome and infectious disease dynamics, neuro-degeneration, personalized medicine, and improved diagnosis and risk assessment for patients. Moreover, there are emerging, faster NGS technologies that promise comprehensive molecular portraits of disease and actionable clinical results for doctors within a single day. Scientists and physicians will be better equipped to design studies and help patients if they possess an intricate knowledge of these molecular-profiling methods, their biological context, and their applicability to specific cases and diseases. Finally, a rich understanding of the complexity of the human genome is essential for the proper annotation of characterization of any new mutations/modifications found, since large-scale efforts at tumor and normal genome sequencing have dramatically altered our view of the normal genome and epigenome.
Thus, in this 10-week course, students will build a strong foundation of knowledge of NGS technologies (both existing and emerging), learn the applications of these technologies for basic and clinical research, and finally learn the essential tools for the analysis, integration, and application of these data relative to other public databases and phenotype repositories. We have a broad range of expertise being contributed from many leaders in the field.
Professor: Christopher E. Mason
Description: This course will introduce participants to the biochemical background, data collection, and data analysis frameworks for next-gen sequencing (NGS). Over the course of this workshop, they will learn how to handle the enormous amounts of data that are generated by these methods, and how to approach their analysis, from re-sequencing, RNA-Seq, ChIP-Seq, or other NGS datasets.
Prerequisites: Participants should be comfortable with using the UNIX command line, and should have a good knowledge of the UCSC genome browser.
Professors: Carl Blobel and Christopher E. Mason
Description: This course is required for all 1st and 2nd year PBSB graduate students, but is open to all WGSMS students. It is designed to train students in scientific presentation and critique. The structure is a formalized, in depth "journal club". Each 1st year student will choose a paper from a list provided by the Course Directors. Each 2nd year student will select a paper in their thesis field, subject to approval of the Course Directors. Each session will consist of a student formally presenting their selected paper to the class, which is expected to serve as a critical audience. The presentation should consist of an introduction of the relevant background literature, an objective presentation of the study, a subjective analysis/critique of the work, and suggestions for future work. Presentations by 2nd year students will be scheduled first, giving the 1st year students the opportunity to learn from their more senior colleagues. Grading will be based on presentation quality and contribution to constructive feedback.
Undergraduate Research Scholars Program in Bioengineering
Description: This is a pilot independent study research program that enables students to work on a bioengineering related project with a participating faculty member for up to two semesters. Students selected to participate in the program will be eligible to receive funding to support project costs as well as conference travel. The program is generously funded by the Rose Sandholm grant.