Welcome to Boston, Lauren!
Lauren Kagaler is joining the Meyerson laboratory as a research associate with Elisa Aquilanti. Lauren grew up in Zimbabwe and attended Dickinson College where she worked in Michael Roberts’ laboratory on a project aimed at understanding the role of EGR1 in reprogramming of human leukemia stem cells. She also worked at Loyola University on optimizing transaminase reactions that form amines in order to reduce waste. When she is not in lab, Lauren enjoys spending as much time outdoors as possible and loves hiking, backpacking, camping, and running.
Welcome to Boston, Lauren!
Welcome to Hersh Gupta, our new associate computational biologist, and Blake Sanders, our new post-doctoral fellow! Hersh graduated from Brown with an A.B. in computational biology and chemistry. He will be working with Yvonne Li and Andy Cherniack on clinical sequencing analysis projects, done in conjunction with physicians and scientists across DFCI. Blake recently defended his PhD thesis at Virginia Tech in Blacksburg, in the laboratory of Dan Slade. Blake brings great experience in microbiology to our project on the colorectal cancer microbiome as part of the Cancer Research UK Grand Challenge.
Welcome to the laboratory, Hersh and Blake!
After graduating with a B.Sc. from the University of Puerto Rico, Maria joined the Broad Institute’s Biological Samples Platform in 2011. While in our lab, Maria has made contributions to a broad array of projects including discoveries of chemo-resistance in ovarian cancer and biomarker discovery for the KAT6A project. Maria is joining Merck as a Scientist in the Discovery Oncology Functional Genomics group under the direct supervision of a former Broadie, Elsa Krall. We look forward to hearing of the discoveries that Maria and her team will make in this very exciting new role!
Lindsay joined our team after completing a B.S. in Computer Science and Molecular Biology at MIT. Lindsay worked with Andrew Cherniack for two years on numerous computational projects for the Bayer collaboration and as part of the Genomic Data Analysis Network. Lindsay is leaving our lab to teach underserved junior high school students in Richmond, California as part of Teach for America. We wish Lindsay all the best in her future endeavors!
Carrot-Zhang et al. studied the effects of ancestry on mutation rates, DNA methylation, and mRNA and miRNA expression. Using 10,678 patients across 33 cancer types from The Cancer Genome Atlas, they determined that ancestry effects occur in a tissue-specific manner. They also identified that FBXW7, VHL, and PBRM1 cancer mutation rates differ by ancestry. This work reveals the importance of accounting for ancestry as a potential confounder in understanding cancer and potential treatments.
The Meyerson lab recently discovered a small molecule compound, DNMDP (6-(4-(diethylamino)-3-nitrophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one) that selectively kills cancer cell llnes at nM potency (de Waal et al, 2016). Unlike typical targeted therapies that leverage dependencies in cancer cells created by genomic alterations, DNMDP induces cancer cell death by a gain-of-function mechanism involving the formation of a complex between phosphodiesterase 3A (PDE3A) and schlafen family member 12 (SLFN12). To probe the mechanism of action of DNMDP, Xiaoyun et al. studied the genomic determinants of cancer cell response to DNMDP, finding a linear correlation between DNMDP sensitivity and PDE3A protein levels, and a requirement for expression of SLFN12 and the aryl hydrocarbon receptor-interacting protein, AIP. They further demonstrated that the PDE3A catalytic domain is necessary and sufficient for mediating sensitivity to DNMDP, and that PDE3B can substitute for PDE3A. In the absence of AIP, there is no PDE3A-SLFN12 complex formation and cells no longer respond to DNMDP-induced cancer cell killing. This study provides new insight into how DNMDP, through the PDE3A-SLFN12 complex, mediates cell death.