The SCOTT LAB acknowledges the continued collaboration with colleagues in the Department of Genetics and Genomic Sciences, the Mount Sinai Genetic Testing Laboratory, the Icahn Institute for Genomics and Multiscale Biology and the Charles Bronfman Institute for Personalized Medicine (IPM). Ongoing research projects frequently involve the laboratories and expertise of Drs. Robert J. DESNICK, Inga PETER, and Jean-Sébastien HULOT at Mount Sinai, Drs. John F. DECOTEAU and C. Ron GEYER at the University of Saskatchewan, Canada, and Dr. James WEISFELD-ADAMS at the University of Colorado School of Medicine in Denver.
Research support has been provided by a KL2 Faculty Scholar Award from the Conduits Program at Mount Sinai, a K23 Translational Scholar Career Award in Pharmacogenomics and Personalized Medicine from the NIH/NIGMS and Pharmacogenomics Research Network (PGRN), and through ongoing and productive collaborations with interested biotechnology companies.
A major focus of the SCOTT LAB 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, together with the Institute for Personalized Medicine (IPM) at Mount Sinai, research projects are in development to interrogate the BioMe biobank and patient electronic health records for pharmacogenomic discovery.
Translating pharmacogenetic discovery to clinical implementation is an ongoing interest in the laboratory. We are members of the Clinical Pharmacogenetics Implementation Consortium (CPIC), participating in authoring guidelines for pharmacogenetic-based drug therapy and other related initiatives. An interdisciplinary group at Mount Sinai is continually assessing the evidence of gene/drug response associations and the potential clinical utility of pharmacogenetic-guided therapy. As such, Dr. SCOTT is a Co-Investigator of the Institute for Personalized Medicine’s (IPM)-PGx and eMERGE-PGx programs by providing expertise in clinical genetics and implementing clinical pharmacogenetic testing at Mount Sinai. Led by Dr. Aniwaa OWUSU OBENG, the clinical pharmacogenetics implementation projects at IPM are preemptively genotyping a panel of pharmacogenetic variants through the Mount Sinai Genetic Testing Laboratory (MGTL) among prospectively enrolled patients at selected Mount Sinai clinics as well as patients enrolled in the BioMe biobank. This program seeks to develop process best practices for successful translation of pharmacogenomics and personalized medicine discoveries into clinical practice.
Another area of focus in the SCOTT LAB 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 open access targeted bisulfite sequencing analyses.
Dr. SCOTT is one of the Directors of the Mount Sinai Genetic Testing Laboratory (MGTL), which is a CLIA and New York State (NYS) approved and College of American Pathologists (CAP) accredited clinical genetics laboratory led by Dr. Lisa EDELMANN with Biochemical Genetics, Cytogenetics and Cytogenomics, Molecular Genetics and Genomics, Pharmacogenomics, and Molecular Oncology subdivisions. In addition to clinical genetic testing, the MGTL has a large American Board of Genetics and Genomics (ABMGG) accredited postdoctoral fellowship training program in clinical laboratory genetics. As such, collaborative research projects with the trainees are always ongoing and often are centered on clinical cytogenomic and/or molecular case reports/studies, new test development and validation, analytical comparisons of genetic testing platforms, and multi-ethnic population screening.
Stuart A. SCOTT, PhD
Stuart SCOTT got his Ph.D. from the University of Saskatchewan, Canada, under the mentorship of hematopathologist Dr. John F. DECOTEAU. His interest in medical genetics and molecular pathology prompted postdoctoral American Board of Medical Genetics and Genomics (ABMGG) training in Clinical Molecular Genetics and Clinical Cytogenetics at the Mount Sinai Genetic Testing Laboratory (MGTL) and Board certification in both specialties. In the MGTL he is involved in high-complexity clinical molecular testing, including microarray-based comparative genomic hybridization (aCGH) and pharmacogenetic targeted genotyping and sequencing. Dr. SCOTT’s research interests are focused on translational molecular biology, particularly in the areas of pharmacogenomics, epigenomics and cytogenomics, and he considers himself fortunate to work with the people that he does.
Yao YANG, PhD
Yao YANG got his Ph.D. in Biomedical Engineering from Southeast University, Nanjing, China, before joining the SCOTT LAB as a postdoctoral fellow in 2011. Dr. YANG became an Instructor in 2015 and his primary research interests involve the application and development of next-generation sequencing workflows and bioinformatic pipelines for discovery in epigenomics and pharmacogenomics. He developed both SMRT-BS, a quantitative and multiplexed DNA methylation detection method using Pacific Biosciences (PacBio) long-read sequencing, and long-read single molecule real-time full gene sequencing of CYP2D6 using PacBio. In addition to other collaborative research projects on multi-ethnic epigenomics and pharmacogenomics, Dr. YANG also is developing novel variant calling pipelines for long-read amplicon sequencing.
Meredith ROSS, BA
Meredith ROSS completed her Bachelor of Arts (B.A.) in Biology/Biological Sciences & Medicine, Health, and Society at Vanderbilt University, and currently is a second year Masters of Science (M.S.) in Genetic Counseling student at the Icahn School of Medicine at Mount Sinai. Meredith’s interest in prenatal genetic counseling prompted her thesis project with the SCOTT LAB, which is aimed at assessing knowledge and attitudes on non-invasive prenatal pharmacogenetic screening among pregnant and preconception women.
Zinira MUNSHI is a summer student from Rutgers University, majoring in Genetics in the School of Arts and Sciences Honors Program, who is expecting to complete her Bachelor of Arts (B.A.) in 2017. Her undergraduate research is centered on studying the role of aurora kinases in cancer, and she is the recipient of Douglass Project stipend from Rutgers University to foster engagement in research. At the SCOTT LAB she is helping build a database of clinically actionable and informative pharmacogenomic variants and studying their multi-ethnic allele frequencies across world-wide populations.
Kevin SANAYCELA is a summer student from the Dalton School in New York City, who will be completing his high school program in 2017. His interest in getting first hand exposure to science and research lead him to a volunteer position at the SCOTT LAB through the Dalton Science Research Program. He currently is working on validating computational strategies for haplotype phasing from long read third-generation (PacBio) sequencing data, interrogating the CYP2D6 gene in selected ethnic subpopulations.
James WEISFELD-ADAMS, MB, ChB
James WEISFELD-ADAMS is an Assistant Professor at the Children’s Hospital Colorado, University of Colorado School of Medicine in Denver. Board certified in pediatrics and clinical genetics, Dr. WEISFELD-ADAMS has a clinical practice centered on pediatric and adult patients with rare inherited metabolic and neurogenetic diseases. The SCOTT LAB collaborates directly with Dr. WEISFELD-ADAMS on research studies aimed at identifying rare variants implicated in primary progressive multiple sclerosis, as well as other informative clinical genomic case studies.
Benjamin S. PULLMAN, BA
Ben PULLMAN completed his Bachelor of Arts (B.A.) in Computer Science and Music at Amherst College in 2013, including an honors thesis entitled Machine Learning Methods for Detecting Code Obfuscation. He volunteered in the SCOTT LAB from 2014 to 2015 while working as a developer for the social campaign around the film Girl Rising. During that time he spearheaded our High Throughput Methylation Analysis Program (HiTMAP) project, which is a quantitative online tool for amplicon bisulfite sequencing DNA methylation analyses. Although he will always be involved with HiTMAP, Ben currently is pursuing a Ph.D. in Computer Science and Engineering at the University of California, San Diego (UCSD) in the Center for Computational Mass Spectrometry.
Hetanshi NAIK, MS, CGC
Hetanshi NAIK completed her Masters of Science (M.S.) in Genetic Counseling at the Icahn School of Medicine at Mount Sinai in 2010 and currently is a Project Manager and Genetic Counselor in Dr. Robert J. DESNICK’s laboratory where she oversees the NIH-supported Rare Diseases Clinical Research Network’s Porphyrias Consortium. In addition to pursuing her Ph.D. in Clinical Research at Mount Sinai, Hetanshi also is involved in cardiovascular and prenatal pharmacogenomics projects with the SCOTT LAB.
Noura ABUL-HUSN, MD, PhD
Noura ABUL-HUSN is an Associate Director of Translational Genetics at the Regeneron Genetics Center, and an Adjunct Assistant Professor in Medicine and Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai. Dr. ABUL-HUSN is using large-scale sequencing data to identify clinically relevant disease-gene associations and advance genetics-driven drug discovery. The SCOTT LAB collaborates directly with Dr. ABUL-HUSN on pharmacogenomics discovery and genomic medicine implementation projects.
Irene L. FENG
Irene FENG is an undergraduate student at Dartmouth College doing a Bachelor of Arts (B.A.) in Computer Science/Biology. She has been volunteering in the laboratory since February 2015, and under the direction of Ben PULLMAN, has focused her time on programming the user interface of our High Throughput Methylation Analysis Program (HiTMAP) for amplicon bisulfite sequencing data analysis.
Jeff SLOAD initially volunteered in the SCOTT LAB in 2012 in conjunction with the Authentic Science Research (ASR) program at Darien High School, which aimed at getting high school students first-hand scientific research experience. Following completion of the program and graduation from Darien High School in 2013, he continued working in the SCOTT LAB on cardiovascular pharmacogenomics projects as a summer student. Jeff currently is studying Biology at Williams College and enjoys ultimate frisbee, jazz trombone, and the New York Rangers.
Suparna MARTIS, PhD
Suparna MARTIS got her Ph.D. form the University of Delhi in Peptide Chemistry and subsequently pursued postdoctoral research at the Institute of Genomics & Integrative Biology (CSIR) and several Senior Scientist positions at genetics/genomics companies in Asia and North America, eventually landing at Mount Sinai as a postdoctoral fellow in 2010. With a strong background in population pharmacogenetics, Dr. MARTIS lead a number of projects in the SCOTT LAB on multi-ethnic pharmacogenetic allele profiling where she discovered several novel CYP450 variant alleles, including copy-number variants.
Manishkumar PATEL, MS
Manishkumar PATEL was a graduate student at the University of New Haven, CT, who did his M.S. thesis research project with the SCOTT LAB in 2009 entitled: ‘Warfarin Pharmacogenetics: Copy-Number Variation and Novel CYP2C9 Alleles in a Multi-ethnic Population.’ Following successful completion of his M.S. degree, Manish joined Mount Sinai as a Research Associate in a laboratory within the Department of Hematology & Medical Oncology.
Johnson JA, Caudle K, Gong L, Whirl-Carrillo M, Stein CM, Scott SA, Lee MT, Gage BF, Kimmel SE, Perera MA, Anderson JL, Pirmohamed M, Hines R, Klein TE, Limdi N, Cavallari LH, Wadelius M. Clinical Pharmacogenetics Implementation Consortium (CPIC®) guidelines for warfarin dosing: 2017 update. Clin Pharmacol Ther. [Epub 2017 Feb 15.]
Karger L*, Khan WA*, Calabio R, Singh R, Xiang B, Babu A, Cohen N, Yang A, Scott SA. Maternal uniparental disomy of chromosome 15 and concomitant STRC and CATSPER2 deletion-mediated deafness-infertility syndrome. Am J Med Genet A, in press. (* equal contribution)
Stillitano F, Hansen J, Kong CW, Karakikes I, Funck-Brentano C, Scott SA, Reynier S, Ma W, Valogne Y, Desseaux C, Salem JE, Jeziorowska D, Zahr N, Li R, Ivengar R, Hajjar R, Hulot JS. Modeling susceptibility to drug-induced long QT with a panel of subject-specific iPS cells. eLife, 2017;6:e19406.
Moriyama B, Owusu Obeng A, Barbarino JM, Penzak SR, Henning SA, Scott SA, Agúndez JAG, Wingard JR, McLeod HL, Klein TE, Cross S, Caudle KE, Walsh TJ. Clinical Pharmacogenetics Implementation Consortium (CPIC®) guideline for CYP2C19 and voriconazole dosing. Clin Pharmacol Ther. [Epub 2016 Dec 16.]
Reiner J, Karger L, Cohen N, Mehta L, Edelmann L, Scott SA. Chromosomal microarray detection of constitutional copy number variation using saliva DNA. J Mol Diagn, in press.
Owusu Obeng A, Kaszemacher T, Abul-Husn NS, Gottesman O, Vega A, Waite E, Myers K, Cho J, Bottinger EP, Ellis SB, Scott SA. Implementing algorithm-guided warfarin dosing in an ethnically diverse patient population using electronic health records and pre-emptive CYP2C9 and VKORC1 genetic testing. Clin Pharmacol Ther. 2016;100:427-430. [Epub 2016 Jul 9.]
Caudle KE, Dunnenburger HM, Freimuth RR, Peterson JF, Burlison JD, Whirl-Carrillo M, Scott SA, Rehm HL, Williams MS, Klein TE, Relling MV, Hoffman JM. Standardizing terms for clinical pharmacogenetic test results: The Clinical Pharmacogenetics Implementation Consortium (CPIC) term standardization project. Genet Med. [Epub 2016 Jul 21.]
Scott SA, Collet JP, Baber U, Yang Y, Peter I, Linderman M, Sload J, Qiao W, Kini AS, Sharma SK, Desnick RJ, Fuster V, Hajjar RJ, Montalescot G, Hulot JS. Exome Sequencing of extreme clopidogrel response phenotypes identifies B4GALT2 as a determinant of on-treatment platelet reactivity. Clin Pharmacol Ther. 2016;100:287-94. [Epub 2016 May 23.]
Weisfeld-Adams JD, Tkachuk A, Maclean KN, Meeks N, Scott SA. A de novo 2.78 Mb duplication on chromosome 21q22.11 implicates candidate genes in the partial trisomy 21 phenotype. npj Genomic Medicine. 2016;1: 16003.
Ruderfer DM, Charney AW, Readhead B, Kidd BA, Kähler AK, Kenny PJ, Keiser MJ, Moran JL, Hultman CM, Scott SA, Sullivan PF, Purcell SM, Dudley JT, Sklar P. Polygenic overlap between schizophrenia risk and antipsychotic response: a genomic medicine approach. Lancet Psychiatry. 2016;3:350-7. [Epub 2016 Feb 22.]
Bush WS, Crosslin DR, Owusu Obeng A, Wallace J, Almoguera B, Basford MA, Bielinski SJ, Carrell DS, Connolly JJ, Crawford D, Doheny KF, Gallego CJ, Gordon AS, Keating B, Kirby J, Kitchner T, Manzi S, Mejia AR, Pan V, Perry CL, Peterson JF, Prows CA, Ralston J, Scott SA, Scrol A, Smith M, Stallings SC, Veldhuizen T, Wolf W, Volpi S, Wiley K, Li R, Manolio T, Bottinger E, Brilliant MH, Carey D, Chisholm RL, Chute CG, Haines JL, Hakonarson H, Harley JB, Holm IA, Kullo IJ, Jarvik GP, Larson EB, McCarty CA, Williams MS, Denny JC, Rasmussen-Torvik LJ, Roden DM, Ritchie MD. Genetic variation among 82 pharmacogenes: The PGRN-Seq data from the eMERGE Network. Clin Pharmacol Ther. 2016;100:160-9. [Epub 2016 Feb 9.]
Qiao W, Wang J, Pullman BS, Chen R, Yang Y, Scott SA. The CYP2D6 VCF translator. Pharmacogenomics J, 2016. [Epub 2016 Mar 15.]
Zhang J*, Fedick A*, Wasserman S, Zhao G, Edelmann L, Bottinger EP, Kornreich R, Scott SA. Analytical validation of a personalized medicine APOL1 genotyping assay for non-diabetic chronic kidney disease risk assessment. J Mol Diagn. 2016;18:260-6. [Epub 2016 Jan 7.] (* equal contribution)
Van Driest SL, Wells QS, Stallings S, Bush WS, Gordon A, Nickerson DA, Kim JH, Crosslin DR, Jarvik GP, Carrell DS, Ralston JD, Larson EB, Bielinski SJ, Olson JE, Ye Z, Kullo IJ, Abul-Husn NS, Scott SA, Bottinger E, Almoguera B, Connolly J, Chiavacci R, Hakonarson H, Rasmussen-Torvik LJ, Pan V, Persell SD, Smith M, Chisholm RL, Kitchner TE, He MM, Brilliant MH, Wallace JR, Doheny KF, Shoemaker MB, Li R, Manolio TA, Callis TE, Macaya D, Williams MS, Carey D, Kapplinger JD, Ackerman MJ, Ritchie MD, Denny JC, Roden DM. Association of Arrhythmia-Related Genetic Variants With Phenotypes Documented in Electronic Medical Records. JAMA, 2016;315:47-57.
Qiao W*, Yang Y*, Sebra R, Mendiratta G, Gaedigk A, Desnick RJ, Scott SA. Long-read single-molecule real-time (SMRT) full gene sequencing of cytochrome P450-2D6 (CYP2D6). Hum Mut. 2016;37:315-23. [Epub 2015 Nov 25.] (* equal contribution)
Kalman LV, Agúndez JAG, Appell MLA, Black JL, Bell G, Boukouvala S, Bruckner C, Bruford E, Bruckner C, Caudle K, Coulthard S, Daly AK, Del Tredici AL, den Dunnen JT, Drozda K, Everts R, Flockhart D, Freimuth R, Gaedigk A, Hachad H, Hartshorne T, Ingelman-Sundberg M, Klein TE, Lauschke VM, Maglott DR, McLeod HL, McMillin GA, Meyer UA, Müller DJ, Nickerson DA, Oetting WS, Pacanowski M, Pratt VM, Relling MV, Roberts A, Rubinstein WS, Sangkuhl K, Schwab M, Scott SA, Sim SC, Thirumaran RK, Toji LH, Tyndale R, van Schaik RHN, Whirl-Carrillo M, Yeo K-TJ, Zanger UM. Pharmacogenetic allele nomenclature: International workgroup recommendations for test result reporting. Clin Pharmacol Ther. 2016;99:172-85. [Epub 2015 Nov 20.]
Pratt VM, Everts RE, Aggarwal P, Beyer BN, Broeckel U, Epstein-Baak R, Hujsak P, Kornreich R, Liao J, Lorier R, Scott SA, Smith CH, Toji LH, Turner A, Kalman LV. Characterization of 137 genomic DNA reference materials for 28 pharmacogenetic genes: A GeT-RM collaborative project. J Mol Diagn. 2016;18:109-23. [Epub 2015 Nov 24.]
Yang Y, Lewis JP, Hulot JS, Scott SA. The pharmacogenetic control of antiplatelet response: Candidate genes and CYP2C19. Expert Opin Drug Metab Toxicol. 2015;11:1599-617. [Epub 2015 Jul 14.] (Invited review)
Hicks JK, Bishop JR, Sangkuhl K, Müller DJ, Ji Y, Leckband SG, Leeder JS, Graham RL, Chiulli DL, LLerena A, Skaar TC, Scott SA, Klein TE, Caudle KE, Gaedigk A. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clin Pharmacol Ther, 2015;98:127-34. [Epub 2015 Jun 29.]
Yang Y, Sebra R, Pullman B, 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;16:350.
Termsarasab P, Yang AC, Reiner J, Mei H, Scott SA, Frucht SJ. Paroxysmal kinesigenic dyskinesia caused by 16p11.2 microdeletion. Tremor Other Hyperkinet Mov (N Y), 2014;4:274.
Rasmussen-Torvik LJ, Stallings SC, Gordon AS, Almoguera B, Basford MA, Bielinski SJ, Brautbar A, Brilliant M, Carrell DS, Connolly J, Crosslin DR, Doheny KF, Gallego CJ, Gottesman O, Kim DS, Leppig KA, Li R, Lin S, Manzi S, Mejia AR, Pacheco JA, Pan V, Pathak J, Perry CL, Peterson JF, Prows CA, Ralston J, Rasmussen LV, Ritchie MD, Sadhasivam S, Scott SA, Smith M, Vega A, Vinks A, Volpi S, Wolf W, Bottinger E, Chisholm RL, Chute CG, Haines JL, Harley JB, Keating B, Holm IA, Kullo IJ, Jarvik GP, Larson EB, Manolio T, McCarty CA, Nickerson DA, Scherer SE, Williams MS, Roden DM, Denny JC. Design and anticipated outcomes of the eMERGE-PGx project: A multi-center pilot for pre-emptive pharmacogenomics in electronic health record systems. Clin Pharmacol Ther, 2014;96:482-489. [Epub 2014 Jun 24.]
Abul-Husn NS, Owusu Obeng A, Sanderson SC, Gottesman O, Scott SA. Implementation and utilization of genetic testing in personalized medicine. Pharmgenomics Pers Med, 2014;7:227-240. (Invited review)
Jaja C, Patel N, Scott SA, Gibson R, Kutlar A. CYP2C9 allelic variants and frequencies in pediatric sickle cell disease cohort: Implications for NSAIDs pharmacotherapy. Clin Transl Sci, 2014;7:396-401. [Epub 2014 May 29.]
Yang Y, Peter I, Scott SA. Pharmacogenetics in Jewish populations. Drug Metabol Drug Interact, 2014;29:221-233. [Epub May 27 2014] (Invited review)
Overby CL, Ludtke A, Abul-Husn NS, Ellis S, Scott SA, Owusu Obeng A, Kannry JL, Hripcsak G, Bottinger EP, Gottesman O. Physician attitudes toward adopting genome-guided prescribing through clinical decision support. J Pers Med, 2014;4:35-49.
Scott SA and Lubitz SA. Warfarin pharmacogenetic trials: Is there a future for pharmacogenetic-guided dosing? Pharmacogenomics, 2014;15:719-722. (Invited editorial)
Scott SA, Owusu Obeng A, Hulot JS. Antiplatelet drug interactions with proton pump inhibitors. Expert Opin Drug Metab Toxicol, 2014;10:175-189. [Epub 2013 Nov 9.] (Invited review)
Caudle KE, Klein TE, Hoffman JM, Müller DJ, Whirl-Carrillo M, McDonagh EM, Sangkuhl K, Thorn CF, Schwab M, Agúndez JAG, Freimuth RR, Huser V, Lee MTM, Iwuchukwu OF, Crews KR, Scott SA, Wadelius M, Swen JJ, Tyndale RF, Stein CM, Roden D, Relling MV, Williams MS, Johnson SG. Incorporation of pharmacogenomics into routine clinical practice: The Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline development process. Curr Drug Metab, 2014;15:209-217. [Epub 2014 Jan 30.]
Kadian-Dodov D, van der Zee S, Scott SA, Peter I, Martis S, Doheny DO, Rothlauf EB, Lubitz SA, Desnick RJ, Halperin JH. Warfarin pharmacogenetics: A controlled dose response study in healthy subjects. Vasc Med, 2013;18:290-297. [Epub 2013 Sep 12.]
Scott SA, Tan Q, Baber U, Martis S, Yang Y, Bander J, Kornreich R, Hulot J-S, Desnick RJ. An allele-specific PCR system for rapid detection and discrimination of the CYP2C19*4A, *4B, and *17 alleles: Implications for clopidogrel response testing. J Mol Diagn, 2013;15:783-789. [Epub 2013 Sep 4.]
Scott SA, Sangkuhl K, Stein CM, Hulot J-S, Mega JL, Roden DM, Klein TE, Sabatine MS, Johnson JA, Shuldiner AR. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for cytochrome P450-2C19 (CYP2C19) genotype and clopidogrel therapy: 2013 Update. Clin Pharmacol Ther, 2013;94:317-323. [Epub 2013 May 22.]
Luo M, Liu L, Peter I, Scott SA, Eversley C, Kornreich R, Desnick RJ, Edelmann L. Spinal muscular atrophy: Improved detection of silent (2+0) carriers by identification of SMN1 founder alleles. Genet Med, 2014;16:149-156. [Epub 2013 Jun 20.]
Baber U, Bander J, Karajgikar R, Abraham B, Yadav K, Hadi A, Theodoropolous K, Gukathasan N, Thapi R, Roy S, Sayeneni S, Scott SA, Palkhiwala S, Suleman J, Kovacic J, Yu J, Sartori S, Dangas G, Mehran R, Uribarri J, Badimon J, Muntner P, Moreno P, Kini AS, Sharma SK. Combined and independent impact of diabetes mellitus and chronic kidney disease on residual platelet reactivity. Thromb Haemost, 2013;110:118-123. [Epub 2013 May 16.]
Gottesman O, Scott SA, Ellis SB, Overby CL, Ludtke A, Hulot J-S, 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. Clin Pharmacol Ther, 2013;94:214-217. [Epub 2013 Apr 3.]
Perera MA, Cavallari LH, Limdi NA, Gamazon ER, Konkashbaev A, Daneshjou R, Pluzhnikov A, Crawford DC, Wang J, Liu N, Tatonetti NJ, Bourgeois S, Takahashi H, Bradford Y, Burkley BM, Desnick RJ, Halperin JL, Khalifa SI, Langaee TY, Lubitz SA, Nutescu EA, Oetjens M, Shahin MH, Shitalben RP, Tector M, Rieder MJ, Scott SA, Wu AHB, Burmester JK, Deloukis P, Wagner MJ, Mushiroda T, Kubo M, Roden DM, Cox NJ, Altman RB, Klein TE, Nakamura Y, Johnson JA. Genetic variants associated with warfarin dose in African-American individuals: a genome-wide association study. Lancet, 2013;382:790-796. [Epub 2013 Jun 4.]
Scott SA*, Liu B*, Nazarenko I*, Martis S, Kozlitina J, Yang Y, Ramirez C, Kasai Y, Hyatt T, Peter I, Desnick RJ. Frequency of the Cholesteryl Ester Storage Disease common LIPA E8SJM mutation (c.894G>A) in various racial and ethnic groups. Hepatology, 2013;58:958-965. [Epub 2013 Feb 19.] (* equal contribution)
Scott SA. Clinical pharmacogenomics: Opportunities and challenges at point-of-care. Clin Pharmacol Ther, 2013;93:33-35. [Epub 2012 Dec 5.] (Invited manuscript)
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. Pharmacogenomics J, 2013;13:558-566. [Epub 2012 Nov 20.]
Danese E, Montagnana M, Johnson JA, Rettie A, Zambon CF, Lubitz SA, Suarez-Kurtz G, Cavallari LH, Zhao L, Huang M, Nakamura Y, Mushiroda T, Kringen MK, Borgiani P, Ciccacci C, Rieder MJ, Langaee TJ, Siguret V, Loriot MA, Sagreiya H, Altman RB, Shahin MHA, Scott SA, Khalifa SI, Chowbay B, Suriapranata IM, Teichert M, Taljaard M, Botton MR, Zhang JE, Pirmohamed M, Zhang X, Carlquist JF, Horne BD, Lee MTA, Pengo V, Guidi GC, Minuz P, Fava C. Impact of the CYP4F2 p.V433M polymorphism on coumarin dose requirement: a systematic review and meta-analysis. Clin Pharmacol Ther, 2012;92:746-756.
Lyon E, Foster JG, Palomaki GE, Pratt VM, Reynolds K, Sabato F, Scott SA, Vitaska P. A working group of the Molecular Genetics Subcommittee on behalf of the American College of Medical Genetics and Genomics (ACMG) Laboratory Quality Assurance Committee. Laboratory testing of CYP2D6 alleles in relation to tamoxifen therapy. Genet Med, 2012;14:990-1000. [Epub 2012 Sept 6.]
Takahashi N, Miura M, Scott SA, Niioka T, Sawada K. Pharmacokinetics of dasatinib for Philadelphia chromosome-positive acute lymphocytic leukemia with acquired T315I mutation. J Hematol Oncol, 2012;5:23.
Martis S, Peter I, Hulot J-S, Kornreich R, Desnick RJ, Scott SA. Multi-ethnic distribution of clinically relevant CYP2C genotypes and haplotypes. Pharmacogenomics J, 2013;13:369-377. [Epub 2012 Apr 10.]
Scott SA*, Patel M*, Martis S, Lubitz SA, van Der Zee S, Edelmann L, Yoo C, Halperin JL, Desnick RJ. Copy number variation and warfarin dosing: evaluation of CYP2C9, VKORC1, CYP4F2, GGCX, and CALU. Pharmacogenomics, 2012;13:297-307. [Epub 2011 Dec 21.] (* equal contribution)
Scott SA. Personalizing medicine with clinical pharmacogenetics. Genet Med, 2011;13:987-995. (Invited review)
Cayla G, Hulot J-S, O’Connor S, Pathack A, Scott SA, Gruel Y, Silvain J, Vignalou JB, Huerre Y, de la Briolle A, Allanic F, Beygui F, Barthelemy O, Montalescot G, Collet JP. Clinical, angiographic and genetic determinants of early coronary stent thrombosis: the ONASSIST study. JAMA, 2011;306:1765-1774.
Scott SA, Sangkuhl K, Shuldiner AR, Hulot J-S, Thorn CF, Altman RB, Klein TE. PharmGKB summary: very important pharmacogene information for cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19). Pharmacogenet Genomics, 2012;22:159-165. [Epub 2011 Oct 24.]
Hulot JS, Collet JP, Cayla G, Silvain J, Allanic F, Bellemain-Appaix A, Scott SA, Montalescot G. CYP2C19 but not PON1 genetic variants influence clopidogrel pharmacokinetics, pharmacodynamics and clinical efficacy in post-myocardial infarction patients. Circ Cardiovasc Interv, 2011;4:422-428.
Johnson JA, Gong L, Carrillo M, Gage BF, Scott SA, Stein CM, Anderson JL, Kimmel SE, Lee MT, Pirmohamed M, Wadelius M, Klein TE, Altman RB. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing. Clin Pharmacol Ther, 2011;90:625-629.
Varricchio L, Goldbold J, Scott SA, Whitsett C, Da Costa L, Pospisilova D, Garelli E, Quarello P, Ramenghi U, Migliaccio AR. Increased frequency of the glucocorticoid receptor A3669G (rs6198) polymorphism in patients with Diamond-Blackfan Anemia. Blood, 2011;118:473-474.
Scott SA, Sangkuhl K, Gardner EE, Stein CM, Hulot J-S, Johnson JA, Roden DM, Klein TE, Shuldiner AR. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for cytochrome P450-2C19 (CYP2C19) genotype and clopidogrel therapy. Clin Pharmacol Ther, 2011;90:328-332.
Scott SA, Martis S, Peter I, Kasai Y, Kornreich R, Desnick RJ. Identification of CYP2C19*4B: pharmacogenetic implications for drug metabolism including clopidogrel responsiveness. Pharmacogenomics J, 2012;12:297-350. [Epub 2011 Mar 1.]
Takahashi N, Wakita H, Miura M, Scott SA, Nishii K, Masuko M, Sakai M, Maeda Y, Ishige K, Kashimura M, Fujikawa K, Fukazawa M, Katayama T, Monna F, Narita M, Katayama N, Furukawa T, Miyazaki Y, Urase F, Sawada K. Correlation of imatinib pharmacokinetics with clinical response in Japanese patients with chronic phase chronic myeloid leukemia. Clin Pharmacol Ther, 2010;88:809-813.
Takahashi N, Miura M, Scott SA, Kagaya H, Kameoka Y, Tagawa H, Fujishima N, Saito H, Yoshioka T, Hirokawa M, Sawada K. Influence of CYP3A5 and drug transporter polymorphisms on imatinib trough concentration and clinical response among patients with chronic-phase chronic myeloid leukemia. J Hum Genet, 2010;55:731-737.
Scott SA, Edelmann L, Liu L, Luo M, Desnick RJ, Kornreich R. Experience with carrier screening and prenatal diagnosis for sixteen Ashkenazi Jewish genetic diseases. Hum Mut, 2010;31:1240-1250.
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. Hum Mol Genet, 2010;19:3383-3393. (* equal contribution)
Scott SA, Khasawneh R, Peter I, Kornreich R, Desnick RJ. Combined CYP2C9, VKORC1, and CYP4F2 allele frequencies among racial and ethnic groups. Pharmacogenomics, 2010;11:781-791.
Lubitz SA*, Scott SA*, Rothlauf E, Agarwal A, Peter I, Doheny D, van Der Zee S, Jaremko M, Desnick RJ, Halperin JL. Comparative performance of gene-based warfarin dosing algorithms in a multiethnic population. J Thromb Haemost. 2010;8:1018-1026. (* equal contribution)
Scott SA, Cohen N, Brandt T, Desnick RJ, Toruner G, Edelmann L. Detection of low-level mosaicism and placental mosaicism by oligonucleotide array comparative genomic hybridization. Genet Med. 2010;12:85-92.
Lakshmikuttyamma A, Scott SA, DeCoteau JF, Geyer CR. Reexpression of epigenetically silenced AML tumor suppressor genes by SUV39H1 inhibition. Oncogene. 2010;29:576-588.
Scott SA, Jaremko M, Lubitz SA, Kornreich R, Halperin JL, Desnick RJ. CYP2C9*8 is prevalent among African-Americans: implications for pharmacogenetic dosing. Pharmacogenomics. 2009;10:1243-1255.
Takahashi N, Kameoka Y, Yamanaka Y, Ubukawa K, Saito K, Fujishima M, Fujishima N, Saito H, Hirokawa M, Scott SA, Sawada K. Itraconazole oral solution enhanced vincristine neurotoxicity in five patients with malignant lymphoma. Intern Med. 2008;47:651-653.
Yu WP, Scott SA, Dong WF. Induction of ID1 expression and apoptosis by the histone deacetylase inhibitor (trichostatin A) in human acute myeloid leukaemic cells. Cell Prolif. 2008;41:86-97.
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. Am J Hum Genet, 2008;82:495-500.
Scott SA, Edelmann L, Kornreich R, Erazo M, Desnick RJ. CYP2C9, CYP2C19 and CYP2D6 allele frequencies in the Ashkenazi Jewish population. Pharmacogenomics. 2007;8:721-730.
Scott SA, Lakshimikuttysamma A, Sheridan DP, Sanche SE, Geyer CR, DeCoteau JF. Zebularine inhibits human acute myeloid leukemia cell growth in vitro in association with demethylation and reexpression of p15INK4B. Exp Hematol. 2007;35:263-273.
Scott SA, Dong W, Ichinohasama R, Hirsch C, Sheridan D, Sanche S, Geyer CR, DeCoteau JF. 5-aza-2’-deoxycytidine (decitabine) can relieve p21WAF1 repression in human acute myeloid leukemia by a mechanism involving release of histone deacetylase 1 (HDAC1) without requiring p21WAF1 promoter demethylation. Leuk Res. 2006;30:69-76.
Scott SA, Kimura T, Dong WF, Ichinohasama R, Bergen S, Kerviche A, Sheridan D, DeCoteau JF. Methylation status of cyclin-dependent kinase inhibitor genes within the transforming growth factor beta pathway in human T-cell lymphoblastic lymphoma/leukemia. Leuk Res. 2004;28:1293-1301.
Scott SA, Kimura T, Ichinohasama R, Bergen S, Magliocco A, Reimer C, Kerviche A, Sheridan D, DeCoteau JF. Microsatellite mutations of Transforming growth factor- receptor type II and Caspase-5 occur in human precursor T-cell lymphoblastic lymphomas/leukemias in vivo but are not associated with hMSH2 or hMLH1 promoter hypermethylation. Leuk Res. 2003;27:23-34.
Lowsky R, Magliocco A, Ichinohasama R, Reitmair A, Scott SA, Henry M, Kadin ME, DeCoteau JF. MSH2-deficient murine lymphomas harbor insertion/deletion mutations in the transforming growth factor beta receptor type 2 gene and display low not high frequency microsatellite instability. Blood. 2000;95:1767-1772.
Rehm HL, Berg JS, Brooks LD, Bustamante CD, Evans JP, Landrum MJ, Ledbetter DH, Maglott DR, Martin CL, Nussbaum RL, Plon SE, Ramos EM, Sherry ST, Watson MS; ClinGen. ClinGen–the Clinical Genome Resource. N Engl J Med. 2015;372:2235-42.
Kimmel SE, French B, Kasner SE, Johnson JA, Anderson JL, Gage BF, Rosenberg YD, Eby CS, Madigan RA, McBane RB, Abdel-Rahman SZ, Stevens SM, Yale S, Mohler ER 3rd, Fang MC, Shah V, Horenstein RB, Limdi NA, Muldowney JA 3rd, Gujral J, Delafontaine P, Desnick RJ, Ortel TL, Billett HH, Pendleton RC, Geller NL, Halperin JL, Goldhaber SZ, Caldwell MD, Califf RM, Ellenberg JH; COAG Investigators. A pharmacogenetic versus a clinical algorithm for warfarin dosing. N Engl J Med. 2013;369:2283-2293. [Epub 2013 Nov 19.]
Gottesman O, Kuivaniemi H, Tromp G, Faucett WA, Li R, Manolio TA, Sanderson SC, Kannry J, Zinberg R, Basford MA, Brilliant M, Carey DJ, Chisholm RL, Chute CG, Connolly JJ, Crosslin D, Denny JC, Gallego CJ, Haines JL, Hakonarson H, Harley J, Jarvik GP, Kohane I, Kullo IJ, Larson EB, McCarty C, Ritchie MD, Roden DM, Smith ME, Böttinger EP, Williams MS; eMERGE Network. The Electronic Medical Records and Genomics (eMERGE) Network: past, present, and future. Genet Med. 2013;15:761-771. [Epub 2013 Jun 6.]
Yang Y and Scott SA. DNA Methylation profiling using long-read single-molecule real-time bisulfite sequencing (SMRT-BS). In: Functional Genomics, 3rd Edition. Methods in Molecular Biology. Kaufmann M, Klinger C, Savelsbergh A, eds. Springer, New York, NY. In press.
Pratt VM and Scott SA. Personalized medicine in cancer treatment. In: Diagnostic Molecular Pathology. Coleman WB, and Tsongalis G, eds. Academic Press, New York, NY. pp. 503-513, 2016.
Obeng AO and Scott SA. Pharmacogenetics of antiplatelet drugs. In: Pharmacogenomics: Applications to Patient Care, 3rd Edition. Johnson JA, Ellingrod V, Kroetz D, and Kuo G, eds. American College of Clinical Pharmacy, Lenexa, KS. pp. 65-78, 2014.
Scott SA and Lyon E. Pharmacogenetics. In: Molecular Pathology in Clinical Practice, 2nd Edition. Leonard DGB, ed. Springer Publishing Company, New York, NY. pp. 301-312, 2016.
Scott SA. Implementing clinical pharmacogenetics: Point-of-care and pre-emptive testing. In: Handbook of Pharmacogenomics and Stratified Medicines. Padmanabdhan S, ed. Elsevier, Oxford, UK. pp. 921-929, 2014.
Scott SA and Desnick RJ. Pharmacogenetics of warfarin. In: Clinical Genomics: Practical Applications in Adult Patient Care. Murray MF, Giovanni MA, and Babyatsky M, eds. McGraw Hill Publishers, Columbus, OH. pp. 24-29, 2013.
Edelmann L, Scott SA, Liu L, Kornreich R. Molecular medical genetics. In: Molecular Genetic Pathology, 1st and 2nd Editions. Cheng L and Zhang D, eds. Humana Press Inc., Totowa, NJ, pp. 415-440, 2008.
10/11/2016: Long-Read CYP2D6 Sequencing Enables Full Gene Characterization and Novel Allele Discovery. Stuart A. Scott, Ph.D. and Yao Yang, Ph.D.; Drug Discovery & Development, http://www.dddmag.com/article/2016/10/long-read-cyp2d6-sequencing-enables-full-gene-characterization-and-novel-allele-discovery.
9/26/2016: Researchers Hope PharmCAT Tool Will Help Improve Clinical Implementation of Pharmacogenomics. Julia Karow; GenomeWeb, https://www.genomeweb.com/molecular-diagnostics/researchers-hope-pharmcat-tool-will-help-improve-clinical-implementation.
9/8/2016: Pharmacogenetics: The Right Drug for You. Liam Drew; Nature, 537, S60–S62 (08 September 2016) doi:10.1038/537S60a0.
9/1/2016: Pharmacogenetics Informs Clinical Practice. DeeAnn Visk, Ph.D.; GEN News, http://www.genengnews.com/gen-articles/pharmacogenetics-informs-clinical-practice/5816/.
6/15/2016: Determining a Drug Response. Sonya Collins; Genome Magazine, http://genomemag.com/pharmacogenomics/#.V5NbPY4pOt8.
3/19/2015: The Right Drug the First Time. Aaron Krol; Bio-IT World & Clinical Informatics News, http://www.bio-itworld.com/2015/3/19/right-drug-first-time.html.
3/5/2015: Copy Number Variations’ Effect on Drug Response Still Overlooked. Cassandra Willyard; Nature Medicine, 21, 206 (2015) doi:10.1038/nm0315-206.
3/12/2013: Mount Sinai Group Publishes Allele-Specific PCR Assay for Novel CYP2C19 Variants. Ben Butkus; GenomeWeb, https://www.genomeweb.com/pcrsample-prep/mount-sinai-group-publishes-allele-specific-pcr-assay-novel-cyp2c19-variants.
8/15/2012: Without Tests, Heart Drug May Not Work. Elie Dolgin; The Jewish Daily FORWARD, http://forward.com/articles/160778/without-tests-heart-drug-may-not-work/.
2010-present: Medical Genetics
1st year genetic counseling students and ABMGG clinical genetics fellows; Lecturer.
2010-present: Molecular Cellular and Genomic Foundations
1st year medical students; Lecturer.
2012-present: Spectrum of Methods in Clinical Research 3
Clinical Research Training Program; Lecturer.
2013-present: Introduction to Human Genome Sequencing, BSR2401
Elective graduate course; Lecturer.
2013-present: Practical Analysis of Your Human Genome, BSR6402
Elective graduate course; Lecturer.
To address the need for a stand-alone program capable of analyzing data from targeted bisulfite sequencing technologies, we developed HiTMAP: a High Throughput Methylation Analysis Program. HiTMAP is a web tool that takes raw amplicon bisulfite sequence data and demultiplexes against sample barcodes, aligns sequencing reads to in silico converted genomic reference sequences, quantitates CpG methylation levels, and exports resulting methylation data for both individual CpG sites and amplicon regions. The user-facing side of HiTMAP provides an online interface for uploading raw sequence and reference files, setting alignment and methylation quantitation parameters, and for retrieving and saving analysis output data and result figures. HiTMAP eliminates the need for manual data manipulation, local computational resources and expertise, and provides an efficient mechanism to measure CpG methylation from high-throughput next-generation bisulfite sequencing data.
Please note that the HiTMAP manuscript is currently in preparation. Questions or comments can be sent here.
The CYP2D6 variant call format (VCF) Translator v1.0 converts CYP2D6 sequence variants from a .vcf file with GRCh37/hg19 coordinates to the M33388.1 and AY545216.1 GenBank reference sequence coordinates used for CYP2D6 star (*) allele conversion by the Human Cytochrome P450 (CYP) Allele Nomenclature Committee.
Additional details on the CYP2D6 VCF Translator can be found at Qiao W, et al. Pharmacogenomics J, 2016 [Epub 2016 March 15.]
Questions or comments can be sent here.
Amplicon Long-read Error Correction (ALEC) was developed to correct sequencing and alignment errors [insertion/deletions (indels) and mismatches] generated by targeted amplicon sequencing derived from the PacBio RS platform. The ALEC script with additional details on its functionality is accessible at Github: https://github.com/scottlab/ALEC.git
For additional information on the development and validation of ALEC with the CYP2D6 gene, see Qiao W and Yang Y, et al. Hum Mut. [Epub 2015 Nov 25.]
A manuscript detailing and evaluating the functionality of ALEC is currently in preparation. Questions or comments can be sent here.
There are currently no openings for graduate students or postdoctoral fellows in the laboratory. However, we are happy to endorse any scholarship applications for external funding for applicants, particularly for those individuals with shared research interests in genetics and genomics. Please email if interested in pursuing.
Creative and eager summer students, international rotation students, and undergraduate students with independent funding or who are interested in volunteering are welcome to enquire about potential opportunities. If that is you, please email your updated CV directly and include a summary of your research interests, goals, and timeline.
Stuart A. SCOTT, PhD
Department of Genetics and Genomic Sciences
Icahn School of Medicine at Mount Sinai
Atran Berg Laboratory Building
1428 Madison Avenue
2nd Floor, Room B2-14
New York, NY 10029
Department of Genetics and Genomic Sciences
Icahn School of Medicine at Mount Sinai Icahn Medical Institute
1425 Madison Avenue
14th Floor, Room 14-52D
New York, NY 10029