Despite the recent identification of numerous somatic, driving mutations in Acute Myeloid Leukemia (AML), these cancers remain very difficult to treat and have a poor prognosis and high relapse rate. Ineffectiveness of pharmacologic strategies in treating AML is primarily due to their inability to effectively target the cells responsible for disease maintenance (i.e. stem cells), which have recently been shown as the hematopoietic stem cells (HSCs) (Pang et al., 2013). While analysis of the gene expression patterns in AML HSCs or other cell types has yielded important insights into disease biology, the recent demonstration (by our group and others) of the mutational heterogeneity in AML and other malignancies (Ding et al., 2012; Bejar et al., 2011; Meyer et al., 2013, Walter et al., 2012) has demonstrated that pooled cells are insufficient for understanding the unique biology or therapeutic responses of individual AML clones – thus hiding a key aspect of disease progression. We will examine tumor evolution with our recently optimized single-cell RNA-sequencing protocols and cell-purification techniques to investigate the genetic and functional heterogeneity of AML HSCs in a carefully selected group of AML patients before, during, and after therapy. This will reveal the precise, cell-by-cell molecular portrait of clonal evolution that drives chemoresistance in AML and help improve future therapies by pinpointing the adaptive, dangerous genetic and transcriptional changes of these tumors.

Dr Christopher Mason is a Professor of Genomics, Physiology, and Biophysics at Weill Cornell Medicine. He completed a dual BS in Genetics & Biochemistry at University of Wisconsin-Madison (2001), a PhD in Genetics from Yale University (2006), Post-doctoral Fellowship in Clinical Genetics at Yale Medical School (2009) while also serving as the first Visiting Fellow of Genomics, Ethics, and Law at the Information Society Project at Yale Law School (2006-2009). In 2010, he became an Assistant Professor of Genomics, Physiology, and Biophysics at Weill Cornell Medicine, then promoted to Associate Professor in 2015, made the Director of the WorldQuant Initiative for Quantitative Prediction in 2017, and promoted to Full Professor in 2021. He also holds appointments at Tri-Institutional Program on Computational Biology and Medicine (Cornell, Memorial Sloan-Kettering Cancer Center and Rockefeller University), the Sandra and Edward Meyer Cancer Center, the Feil Family Brain and Mind Research Institute, (BMRI), and is an affiliate fellow of the Information Society Project (ISP) at Yale Law School, affiliate faculty of the Consortium for Space Genetics at Harvard Medical School, and a Core Faculty Member of New York Genome Center (NYGC). He was named as one of the “Brilliant Ten” Scientists by Popular Science, featured as a TEDMED speaker, and called “The Genius of Genetics” by 92Y. He has >300 peer-reviewed papers and scholarly works that have been featured on the covers of Nature, Science, Cell, Nature Biotechnology, Nature Microbiology, and Neuron, as well as legal briefs cited by the US District Court and US Supreme Court. He is an inventor on four patents, co-founder of five biotechnology start-up companies, and serves as an advisor to 21 others as well as 3 non-profits.

The Mason Lab