RESEARCH | The Mason Lab

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Our Mission

The Mason laboratory is working on a ten-phase, 500-year plan for the survival of the human and other species on Earth, in space, and on other planets. To that end, we develop and deploy new biochemical and computational methods in functional genomics to elucidate the genetic basis of human disease and human physiology. We focus on novel techniques in next-generation sequencing and algorithms for tumor evolution, genome evolution, DNA and RNA modifications, and genome/epigenome engineering. We work closely with NIST/FDA to build international standards for these methods and ensure clinical-quality genome measurements and editing. We also collaborate with NASA, SpaceX, and other agencies to build integrated molecular portraits of genomes, epigenomes, transcriptomes, and metagenomes for astronauts, which help establish molecular foundations and genetic defenses for long-term human spaceflight.

Our Philosophy

At the core of the Mason lab lies an unwavering commitment to scientific rigor, transparency, and innovation. We embrace skepticism and welcome scrutiny, recognizing that robust science thrives in an environment where claims are tested and validated through rigorous experimentation. We are committed to openness in all facets of our work to not only promote accountability, but also facilitate collaboration and constructive critique that will ultimately enrich the scientific discourse. We aim to constantly push the boundaries of conventional wisdom through pioneering new methodologies, discovering novel phenomena, or reimagining existing paradigms. In our lab, we amplify our capacity for innovation to tackle complex scientific challenges by cultivating an inclusive environment that fosters collaboration across diverse perspectives, disciplines, and institutions.

These principles serve as guiding stars that illuminate our path towards meaningful discovery, societal impact, and advancement in the realm of science. As stewards of scientific inquiry, we recognize that the pursuit of knowledge is a noble endeavor and are committed to upholding these principles with unwavering dedication and integrity.

"The only limiting factors are sleep and determination."

Dr. Chris Mason, Laboratory Leader

Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)

Using single-cell and spatial genomics technolgoies, our team is identifying stem cell populations and their underlying biological mechanisms contributing to disease progression and treatment resistance of AML and MDS.

B-cell Lymphoma 3D Genome Architecture

The majority of B-cell lymphomas arise from B-cells transiting the germinal center (GC) reaction, a dynamic system in which B-cells undergo continuous dramatic phenotypic shifts and multilayered alterations in 3D genomic architecture. This project, a collaboration with the Melnick lab, focuses on investigating discrete networks of interacting regulatory elements and genes from the context of regulatory hubs.

Circulating Epigenetic Marks in Lymphoma

B-cell lymphoma's epigenetic landscape offers unique insight into disease onset, progression, and treatment outcomes. Thus, there is a significant interest in developing epigenetic therapies aimed at correcting alterations of epigenetic patterning present in the most prevalent types of lymphoma, including DLBCL and FL. This project, in collaboration with the Melnick lab, seeks to leverage recent advances in the liquid biopsy field to develop new methods that can be utilized in clinical environments to evaluate the efficacy of such therapies.

Role of H1 Deficiency in Progression of Malignant Phenotypes

In a collaboration with the Melnick lab, we showed that histone H1 mutations, which are highly recurrent in germinal center-derived B-cell lymphomas, result in chromatin decompaction, gain of H3K36me2, and expression of normally silenced stem cell genes. These changes are associated with gain of stem-like features, such as self-renewal and phenotypic plasticity. Currently, we are in examining the process of enhancer hijacking by reactivated stem cell promoters due to genome-wide chromatin decompaction.

The Microbe Directory

The Microbe Directory is a collective research effort to profile and annotate more than 7,500 unique microbial species from the MetaPhIAn2 database that includes bacteria, archaea, viruses, fungi, and protozoa. By collecting and summarizing data on various microbes' characteristics, the project comprises a database that can be used downstream of large-scale metagenomic taxanomic analyses, allowing one to interpret and explore their taxanomic classifications to have a deeper understanding of the microbial ecosystem they are studying.

The Microbe Directory has an online counterpart (https://microbe.directory/) that provides a user-friendly interface for storage, retrieval, and analysis into which other microbial database projects could be incorporated.

The Microbe Directory was primarily designed to serve as a resource for researchers conducting metagenomic analyses, but its online web interface should also provide useful to any individual who wishes to learn more about a particular microbe.

SUMMA Genome

Building database for extremophile genomes and metagenomes, extremophile-specific characteristics to find associations with various genes (i.e. cold temperatures, high salinity, etc.)

GLOW Database

The Genomic Library of Ocean Worlds (GLOW) is an ongoing initiative to construct the most comprehensive database of extremophiles in analog environments to ocean worlds. We aim to create a spectral catalog to understand how factors like radiation, gravity, and salinity affect biosignatures, supporting the search for life on other worlds.

For a more comprehensive list of databases the Mason Lab has been involved in, check out our data page here.

Wastewater Monitoring and Global K-mer maps

The University of Miami and Weill Cornell Medicine have collaborated on a study for human and environmental surveillance of SARS-CoV-2, called South Florida RADx-rad, utilizing resources like shared research facilities and extensive surveillance systems for both human and wastewater samples, aiming to predict and understand the spread of COVID-19. This partnership integrates various sampling and analysis approaches to develop predictive models for local and community spread of COVID-19 and other pathogens, while also aiming to improve the sensitivity and specificity of wastewater measurements through innovative methods. The research outcomes not only enhance local and community level public health strategies, but also have broader implications for national and international public health initiatives, demonstrating the significance of collaborative efforts and shared resources in combating infectious diseases. To learn more, click here.

The Two Frontiers Project

We are devoted to advancing human and environmental health by expanding humanity's greatest frontiers: the oceans and space. By studying how life thrives in humanity's greatest frontiers, we can receive the tools we need to protect - and survive in - extreme environments. Click here to learn more.

CRISPRa/i Reprogramming

With CRISPRa/i reprogramming technology, it is able to modulate a specific gene expression in a programmable manner. Our team is utilizing programmable gene modulating systems for humans in space, to cure diseases, and to perform functional genomics research (e.g. single cell CRISPR screens).

DSUP

Our team is elucidating the radioprotective role of DSUP, a radioactive protein identified from tardigrade, in human cells with multi-omics analysis - including the epigenome, transcriptome, and proteome. We aim to utilize this exogenous protein to engineer humans to adapt to life in space.

Xeroderma Pigmentosa (XP)

Our team is modeling XP by CRISPR technologies. We will utilize the XP cell lines to elucidate the XP biological mechanism and the potential therapy.

Genome in a Bottle (GIAB)

The Genome in a Bottle Consortium, hosted by NIST, aims to build technical infrastructure for human whole genome sequencing, with a focus on enabling its translation into clinical practice and fostering technological innovations. Within the Mason lab, contributions involve developing and refining standards and reference methods through diverse sequencing and analysis approaches.

Spatial Atlas of Human Anatomy (SAHA)

SAHA aims to collect and characterize 30 normal human organs capturing the diversity of gender, age, and ancestry, using state-of-the art, highest resolution spatial and multi-omics platforms such as 10X Xenium and NanoString CosMx SMI, coupled with single-cell profiling.

Single-cell/Spatial Technologies

We are continually testing, building, and benchmarking new single-cell and spatial technologies.

The Sequencing Quality Control (SEQC) Consortium

Our lab is a 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).

In 2021, the results of the SEQC Phase 2 (SEQC2) project was released. SEQC2 - a final five-year effort by a coalition of >300 participants and >150 organizations - reports its efforts to benchmark sequencing platforms in several applications, including somatic and germline mutation analysis, single-cell RNA-seq, copy number variation, oncopanel sequencing, and liquid biopsies of tumor samples.

Metagenomics and Metadesign of the Subway of Urban Biomes (MetaSub)

MetaSub is a novel, interdisciplinary initiative made up of experts across many fields, including genomics, data analysis, engineering, public health, and design. Just as there is a standard measurement of temperature, air pressure, wind currents - all of which are considered in the design of the built environment - the microbial ecosystem is just as dynamic and just as integral and should be integrated into the design of cities. By developing and testing standards for the field and optimizing methods for urban sample collection, DNA/RNA isolation, taxa characterization, and data visualization, the MetaSub consortium is undertaking an unprecedented study of urban mass-transit systems and cities around the world. This data will benefit city planners, public health officials, and designers, as well as discover new species, biological systems, and biosynthetic gene clusters (BGCs), thus enabling an era of more quantified, responsive, and "smarter cities".

MetaCats

The project, launched in 2020, aims at investigating the prevalence of SARS-CoV-2 and other coronaviruses in domestic cats, along with their microbial communities or microbiomes.

Diet Influence on the Microbiome and Host Biology

This project interrogates the role of high fat diets in modulating and mitigating cancer risk.

Superfund Sites

The Gowanus Canal is undergoing dredging and sub-aquatic capping as part of the USEPA Superfund Cleanup plan, first started in 2016. We are studying the canal to discover new communities of microorganisms capable of biologically processing pollutants. Since 2015, we have engaged in a microbiome analysis of sediment samples to ensure the taxonomy and potentially unique cellular functions of microbial communities in the Gowanus Canal are catalogued and studied before dredging operations eliminate access.

Space Omics and Medical Atlas (SOMA)

The SpaceX Inspiration4 mission provided a unique opportunity to study the impact of spaceflight on the human body. We collected biospecimen samples from the crew at different stages of the mission and created the SOMA initiative. This details a robust framework for obtaining and preserving high-quality human, microbial, and environmental samples for aerospace medicine.

Spaceflight on Mouse and Human Gut-Brain-Axis

CAMbank

The Cornell Aerospace Medicine Biobank or "CAMbank" is a cutting-edge repository dedicated to the preservation of specimens obtained during spaceflight experiments. These invaluable samples are meticulously cataloged for molecular profiling and sequencing, offering a treasure trove of data for the next frontier of aerospace medical research.

This study is investigating biomarkers (short-chain fatty acids - SCFAs, cytokines, neurotransmitters) of cognitive and metabolic dysfunction in astronauts and mice, understanding the dysbiosis-cognition connection through irradiated and microgravity-simulating hind-limb unloading (HU) murine models, and exploring cognitive impairment interventions by targeting the gut microbiome.

8-oxoG Prediction Model using Nanopore Sequencing Data

Space Exploration & Research Agency
(SERA)

SERA was founded to build a global community dedicated to space exploration and research. Its mission is to create a space agency for everyone.

Learn more here!

This project focuses on optimizing the protocol to produce a training dataset that covers 8-oxoG modifications in all contexts to call the modification with single-nucleotide resolution. Using the sequencing data, train a model to detect the modification with high sensitivity and specificity.

Clinical Trials

We are honored to work with passionate clinical collaborators at New York Presbetyrian Hospital, Memorial Sloan Kettering Cancer Center, and Rockefeller University. This leads us to have a range of active clinical trials in the laboratory, including:

1) Multi-Omics, Physiological, and Clinical Analysis of Human Spaceflight. This protocol underlines the Space Omics and Medical Atlas (SOMA), which recruit subjects from government and commercial space missions (e.g. SpaceX, Axiom, Sierra Space), as well as controls, to further examine the impacts of short-term and long-term spaceflight on the human body, physiology, and health and to put them into the context of normal human variability.

2) The Impact of Spaceflight and Radiation on Clonal Hematopoiesis. This study examines the long-term impact of spaceflight on the human body and metrics for clones that may carry novel mutations.

3) Early Risk Assessment for COVID-19 Patients Using Clinical Care Data. This study builds models from EMR data and molecular data to better understand long-term genetic risk factors and outcomes.

4) A cohort study of COVID-19-vaccinated healthcare workers to determine rate of asymptomatic SARS-CoV-2 shedding. This study aims to describe the rates of SARS-CoV-2 asymptomatic shedding and infection in COVID-19-vaccinated healthcare workers. This will help inform policies regarding personal protective equipment and social distancing and will serve as a sentinel cohort for the emergence of SARS-CoV-2 variants that may not be adequately prevented by current vaccines

5) Rapid Diagnosis of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV- 2). The purpose of this study will be to assess the performance of the various Covid-19 tests in a real-world clinical setting.

6) Precision Metagenomics. We hypothesize that i) microbe identification and antibiotic resistance testing via NGS will correlate greater than 80% with results obtained by conventional methods, ii) results from sequencing of samples negative by conventional methods will unmask infectious agents within a timeframe to inform decisions in antibiotic coverage and patient management, and iii) microbial enrichment will significantly increase NGS sensitivity for pathogens in clinical specimens compared to no microbial enrichment.

Black-footed Ferret

Through collaboration with the Smithsonian Institute, we have characterized the genome of the endangered black-footed ferret. In 1981, the Smithsonian discovered the last 18 wild black-footed ferrets and established a breeding program. However, due to inbreeding and reduced genetic variation, the species were again at risk. So a female ferret was born in 2020 - cloned from cells from a female ferret that died years prior. We have systematically sequenced samples from these offspring and other generations to characterize their whole genome.

Coral Genomics and Metagenomics

Using conservation genomics, we've pinpointed methods to profile the genomes of various coral species and discern characteristics of both thriving and ailing corals, crucial for disease management. Our team is employing advanced techniques to extract pure DNA from coral hosts and their symbiotic microorganisms, preparing it for next-generation sequencing.

Our aim is twofold: 1) to classify endangered reef coral species and 2) to devise strategies for shielding them against bleaching and disease (such as stony-coral tissue loss disease).

Cultural Heritage

In collaboration with the Metropolitan Museum of Art, we are utilizing a genomic approach to analyze the biological components used in the making of artifacts of cultural significance and how microbes modify the ecoystem in old artifacts. By leveraging next generation sequencing and qPCR technologies, we are striving to definitively identify the use of chia oil in the making of the 18th century Mexican Lacquerware. The goal is to use chia oil as a proof of concept for a methodology that could be applied to other biologicals used in the making of objects significant to other cultures and time periods.

Genetically-guided artifact reconstruction

We work with Oded Rechavi on a range of fun projects, but one of our favorites is the metagenomic analysis of the Dead Sea Scrolls. Our paper in 2020 showed that the cow hide in two distinct parts of the Scrolls was not likely processed in the desert, but rather was brought from another place. These results indicated that the fragments found in the cages were from two different copies of the Book of Jeremiah, reflecting different versions of the book, which stray from the biblical text.

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