Physiology and Biophysics
Weill Cornell Medicine
Our vision is to identify each genetic and epigenetic site of evolution in cancer so we can then reach into cells and edit the genes and loci that have gone awry. Our ultimate goal is to fix patients with their own cells, using methods that can re-write and fix parts of the genome and epigenome.
Christopher Mason completed his dual B.S. in Genetics and Biochemistry from University of Wisconsin-Madison (2001) and his Ph.D. in Genetics from Yale University (2006). He completed his dual post-doctoral training at Yale Medical School in genetics and a fellowship at Yale Law School (2009). He is currently an Associate Professor at Weill Cornell Medicine, with appointments at the Tri-Institutional Program on Computational Biology and Medicine between Cornell, Memorial Sloan-Kettering Cancer Center and Rockefeller University, the Sandra and Edward Meyer Cancer Center, and the Feil Family Brain and Mind Research Institute.
The Mason laboratory develops and deploys new biochemical and computational methods in functional genomics to elucidate the genetic basis of human disease and human physiology and publishes novel techniques in next-generation sequencing and algorithms for: tumor evolution, genome evolution, DNA and RNA modifications, and genome/epigenome engineering. The Mason laboratory also work closely with NASA to tie together these myriad research areas into an integrated molecular portrait of human genetics, epigenetics, transcriptomics, and metagenomics, which help establish the molecular foundations and genetic defenses for enabling long-term human space travel.
Dr. Mason has won the NIH’s Transformative R01 Award, the Hirschl-Weill-Caulier Career Scientist Award, the Vallee Foundation Young Investigator Award, the CDC Honor Award for Standardization of Clinical Testing, and the WorldQuant Foundation Research Scholar Award.
Single-Cell Resolution of Leukemia’s Epigenetic Evolution During Therapy
The central dogma of molecular biology (DNAàRNAàprotein) is the key guiding framework for almost all organisms. Yet, this is an incomplete dogma, about which we are still learning key components. Specifically, since the same DNA is present in all cells of a person’s body, other mechanisms must regulate how and when genes (portions of DNA) are turned on and off, which then guide the cells’ activities. Collectively, this is called the “epigenome,” which fine-tunes the activity of DNA in each cell and enables a single set of DNA instructions in the embryo to blossom into the trillions of specialized cells that comprise the human body.
“This grant will enable us to rapidly move from detecting evolving epigenetic hotspots in cancer to actually reaching into cells and fixing the problem.”
The importance of the epigenome is also evident in several cancers, including acute myeloid leukemia (AML). Despite the widespread use of chemotherapy in AML, it remains a mostly fatal disease, where the majority of patients relapse after therapy. Upon relapse, patients often develop chemo-resistant AML; yet in many cases the tumor shows no genetic differences. Instead, it is the epigenetic changes that are relapse-specific, and we have shown that they are associated with AML pathogenesis and relapse.
“Innovation is propelled by a fearlessness of all ideas and an endless passion for technology, both of which open up new realms of previously unseen biology.”
Since adaptation and survival of AML cells can be mediated through the epigenome, we will use new computational and biochemical methods to define and then target these epigenetic sub-types, which can further separate AML patients previously labeled as “intermediate”. We will also use new methods to target and re-program the specific sites of epigenetic aggressiveness of a person’s cancer, which can improve the clinical outcomes in AML.