Stuart Scott, PhD
- ADJUNCT ASSOCIATE PROFESSOR | Genetics and Genomic Sciences
PhD, University of Saskatchewan
Fellowship, Icahn School of Medicine at Mount Sinai
Dr. Harold and Golden Lamport Research Award
Icahn School of Medicine at Mount Sinai
William K. Bowes Jr Award in Medical Genetics
Partners HealthCare Center for Personalized Genetic Medicine, Harvard Medical School
Laboratory website: stuartscottlab.org
Pharmacogenetics and Pharmacogenomics
A major focus of the laboratory is studying genetic determinants of drug response variability, with ongoing collaborative research projects on cardiovascular pharmacogenomics, multi-ethnic pharmacogenetic allele discovery and population profiling, and the development of next-generation sequencing methods for pharmacogenomic research and clinical testing. Our group has made novel discoveries with anticoagulant and antiplatelet pharmacogenetics, characterized several novel CYP450 alleles in various ethnic and racial groups, and participated in the NHLBI-supported COAG warfarin pharmacogenetics trial as a clinical site with the Mount Sinai Genetic Testing Laboratory (MGTL) and Mount Sinai Cardiology. We are currently utilizing exome and/or genome sequencing to identify variants implicated in antiplatelet response variability as well as novel pharmacogenomic variant discovery in unique ethnic subpopulations. In collaboration with next-generation sequencing companies, second and third generation high-throughput sequencing chemistries are being compared to interrogate pharmacogenomic gene panels. In addition, Dr. Scott serves as a Co-Investigator of the Institute for Personalized Medicine's (IPM) PGx program by providing expertise in clinical genetics and implementing pharmacogenetic testing.
Epigenetics and Epigenomics
Another area of focus in the laboratory is the study of epigenetic DNA modifications and their role in disease pathogenesis. Previous studies investigated promoter hypermethylation of mismatch repair and cell cycle genes implicated in leukemia pathogenesis; however, current efforts are aimed at studying germline epigenetic susceptibility to other common diseases and drug response phenotypes. Additionally, we are interested in DNA methylation detection technologies, including microarray and next-generation sequencing chemistries. Our group recently developed single-molecule real-time bisulfite sequencing (SMRT-BS), which is a novel quantitative and multiplexed bisulfite sequencing method for targeted CpG methylation analysis that employs the long read lengths from Pacific Biosciences third-generation sequencing. To facilitate the bioinformatic analysis of amplicon bisulfite next-generation sequencing, we are now in the process of launching HiTMAP: a High Throughput Methylation Analysis Program for targeted bisulfite sequencing analyses.
Yang Y, Sebra R, Pullman BS, Qiao W, Peter I, Desnick RJ, Geyer CR, DeCoteau JF, Scott SA. Quantitative and multiplexed DNA methylation analysis using long-read single-molecule real-time bisulfite sequencing (SMRT-BS). BMC genomics 2015; 16.
Abul-Husn NS, Owusu Obeng A, Sanderson SC, Gottesman O, Scott SA. Implementation and utilization of genetic testing in personalized medicine. Pharmacogenomics and personalized medicine 2014; 7.
Yang Y, Peter I, Scott SA. Pharmacogenetics in Jewish populations. Drug metabolism and drug interactions 2014; 29(4).
Scott SA, Sangkuhl K, Stein CM, Hulot JS, Mega JL, Roden DM, Klein TE, Sabatine MS, Johnson JA, Shuldiner AR. Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. Clinical pharmacology and therapeutics 2013 Sep; 94(3).
Gottesman O, Scott SA, Ellis SB, Overby CL, Ludtke A, Hulot JS, Hall J, Chatani K, Myers K, Kannry JL, Bottinger EP. The CLIPMERGE PGx Program: clinical implementation of personalized medicine through electronic health records and genomics-pharmacogenomics. Clinical pharmacology and therapeutics 2013 Aug; 94(2).
Scott SA. Clinical pharmacogenomics: opportunities and challenges at point of care. Clinical pharmacology and therapeutics 2013 Jan; 93(1).
Martis S, Mei H, Vijzelaar R, Edelmann L, Desnick RJ, Scott SA. Multi-ethnic cytochrome-P450 copy number profiling: novel pharmacogenetic alleles and mechanism of copy number variation formation. The pharmacogenomics journal 2013 Dec; 13(6).
Martis S, Peter I, Hulot JS, Kornreich R, Desnick RJ, Scott SA. Multi-ethnic distribution of clinically relevant CYP2C genotypes and haplotypes. The pharmacogenomics journal 2013 Aug; 13(4).
Scott SA, Martis S, Peter I, Kasai Y, Kornreich R, Desnick RJ. Identification of CYP2C19*4B: pharmacogenetic implications for drug metabolism including clopidogrel responsiveness. The pharmacogenomics journal 2012 Aug; 12(4).
Cayla G, Hulot JS, O'Connor SA, Pathak A, Scott SA, Gruel Y, Silvain J, Vignalou JB, Huerre Y, de la Briolle A, Allanic F, Beygui F, Barthélémy O, Montalescot G, Collet JP. Clinical, angiographic, and genetic factors associated with early coronary stent thrombosis. JAMA 2011 Oct; 306(16).
Scott SA. Personalizing medicine with clinical pharmacogenetics. Genetics in medicine : official journal of the American College of Medical Genetics 2011 Dec; 13(12).
Scott SA, Cohen N, Brandt T, Warburton PE, Edelmann L. Large inverted repeats within Xp11.2 are present at the breakpoints of isodicentric X chromosomes in Turner syndrome. Human molecular genetics 2010 Sep; 19(17).
Lakshmikuttyamma A, Scott SA, DeCoteau JF, Geyer CR. Reexpression of epigenetically silenced AML tumor suppressor genes by SUV39H1 inhibition. Oncogene 2010 Jan; 29(4).
Scott SA, Edelmann L, Kornreich R, Desnick RJ. Warfarin pharmacogenetics: CYP2C9 and VKORC1 genotypes predict different sensitivity and resistance frequencies in the Ashkenazi and Sephardi Jewish populations. American journal of human genetics 2008 Feb; 82(2).