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Andrew Sharp

  • ASSOCIATE PROFESSOR Genetics and Genomic Sciences
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Education

  • BSc, University of Exeter
    Biological Sciences

  • PhD, University of Southampton
    Human Genetics

Biography

    Mar 2010 - present – Associate Professor, Department of Genetics and Genomics, Mount Sinai School of Medicine, New York, USA

    October 2007 - March 2010: Marie Curie Fellow in laboratory of Stylianos Antonarakis, Department of Genetic Medicine, University of Geneva, Switzerland

    January 2004 - September 2007: Senior Fellow in laboratory of Evan Eichler, Department of Genome Sciences, University of Washington, Seattle. Studying structural variation of the human genome and genomic disorders

    October 2002 - December 2003: Research Assistant, Wessex Regional Genetics Laboratory, Salisbury, UK

    September 1997 - September 2002: PhD Student, University of Southampton, England. Supervisor Prof. Patricia Jacobs. Thesis entitled ‘Molecular Studies of X Chromosome Inactivation in Humans’, Division of Human Genetics,

    January 1997 - October 1999: Research Technician, Wessex Regional Genetics Laboratory, Salisbury, UK

Awards

  • 2009 -
    Young Investigator Award for Outstanding Science
    European Society of Human Genetics

  • 2006 -
    Trainee Award (postdoctoral)
    American Society of Human Genetics

  • 2002 -
    Trainee Award (predoctoral)
    American Society of Human Genetics

Research

The Sharp lab is an integrated research environment combining both experimental and bioinformatic approaches. My research uses genomic approaches to study the human genome and disease, utilizing a strategy that can be described as 'reverse genetics'. The theory behind this idea is that rather than studying a specific condition, we use a bottom-up approach using high-throughput techniques to study various aspects of the human genome, and then link these observations to different diseases.

            My lab therefore performs global analyses of structural variation, epigenetics, and gene expression combining innovative experimental and bioinformatic approaches. We use both wet lab technologies such as DNA microarrays and high-massively parallel sequencing in addition to performing computational analyses of the human genome, and large datasets produced by high-throughput technologies.

            What can this approach do? During my postdoctoral work, I developed custom microarrays to study structural variation of the human genome. By first analyzing the human genome computationally, we identified regions that had a structure that suggested they might render them unstable and prone to frequent rearrangement. By focusing our studies on these regions, we were then able to identify many new genetic syndromes that together account for ~2% of cases of mental retardation worldwide, and also act as susceptibility factors for autism, schizophrenia and diabetes. One also represents the most common genetic risk factor for epilepsy identified to date.

            More recently we have developed genome-wide technologies for analyzing DNA methylation, an epigenetic modification that controls how genes are switched on and off. By comparing methylation patterns in healthy and diseased patients, we can discover what parts of the genome regulate patterns of gene expression, hence identifying the important functional elements that are now excellent candidates for human disease. Other projects I am developing seek to study the role of tandem repeat DNA in the human genome, utilize patterns of gene expression as a tool to uncover genes regulating human phenotypes, and investigate epigenetic changes in diseases including multiple sclerosis, Alzheimer's disease, and neural tube defects.

            My work has been published repeatedly in top journals such as Nature Genetics and The New England Journal of Medicine. I also have the unique achievement of receiving the Young Investigator Award for Outstanding Science from the European Society of Human Genetics, and the Trainee Award from the American Society of Human Genetics on two different occasions.

I am a co-Director of the Graduate Program in Genetics and Genomic Sciences, and also course director for two graduate courses: BSR2400, a 2-credit course entitled “Translational Genomics” that gives an overview of diverse topics in modern genetics/genomics, and BSR4401, the “Genetics andGenomics Journal Club”.

            I welcome the opportunity to teach bright students with an interest in learning novel approaches to the study of the human genome. I can offer a diverse environment and the opportunity to gain exposure to many productive and innovative areas of research in human genetics and genomics. Computational skills are a definite advantage, but are not required. If you are interested in learning more about my research please contact me at andrew.sharp@mssm.edu

 

Publications

Huynh JL, Garg P, Thin TH, Yoo S, Dutta R, Trapp BD, Haroutunian V, Zhu J, Donovan MJ, Sharp AJ, Casaccia P. Epigenome-wide differences in pathology-free regions of multiple sclerosis-affected brains. Nature neuroscience 2013 Nov;.

Bala Tannan N, Brahmachary M, Garg P, Borel C, Alnefaie R, Watson CT, Thomas NS, Sharp AJ. DNA methylation profiling in X;autosome translocations supports a role for L1 repeats in the spread of X chromosome inactivation. Human molecular genetics 2013 Nov;.

Garg P, Ludwig KU, Böhmer AC, Rubini M, Steegers-Theunissen R, Mossey PA, Mangold E, Sharp AJ. Genome-wide analysis of parent-of-origin effects in non-syndromic orofacial clefts. European journal of human genetics : EJHG 2013 Oct;.

Tyson C, Sharp AJ, Hrynchak M, Yong SL, Hollox EJ, Warburton P, Barber JC. Expansion of a 12-kb VNTR containing the REXO1L1 gene cluster underlies the microscopically visible euchromatic variant of 8q21.2. European journal of human genetics : EJHG 2013 Sep;.

Hernando-Herraez I, Prado-Martinez J, Garg P, Fernandez-Callejo M, Heyn H, Hvilsom C, Navarro A, Esteller M, Sharp AJ, Marques-Bonet T. Dynamics of DNA methylation in recent human and great ape evolution. PLoS genetics 2013 Sep; 9(9).

Guilmatre A, Highnam G, Borel C, Mittelman D, Sharp AJ. Rapid multiplexed genotyping of simple tandem repeats using capture and high-throughput sequencing. Human mutation 2013 Sep; 34(9).

Watson CT, Garg P, Sharp AJ. Comment on . PLoS genetics 2013 Feb; 9(2).

Borel C, Cheung F, Stewart H, Koolen DA, Phillips C, Thomas NS, Jacobs PA, Eliez S, Sharp AJ. Evaluation of PRDM9 variation as a risk factor for recurrent genomic disorders and chromosomal non-disjunction. Human genetics 2012 Sep; 131(9).

Garg P, Borel C, Sharp AJ. Detection of parent-of-origin specific expression quantitative trait loci by cis-association analysis of gene expression in trios. PloS one 2012; 7(8).

Béna F, Gimelli S, Migliavacca E, Brun-Druc N, Buiting K, Antonarakis SE, Sharp AJ. A recurrent 14q32.2 microdeletion mediated by expanded TGG repeats. Human molecular genetics 2010 May; 19(10).

Sharp AJ. Whole genome methylation profiling by immunoprecipitation of methylated DNA. Methods in molecular biology (Clifton, N.J.) 2012; 925.

Helbig I, Mefford HC, Sharp AJ, Guipponi M, Fichera M, Franke A, Muhle H, de Kovel C, Baker C, von Spiczak S, Kron KL, Steinich I, Kleefuss-Lie AA, Leu C, Gaus V, Schmitz B, Klein KM, Reif PS, Rosenow F, Weber Y, Lerche H, Zimprich F, Urak L, Fuchs K, Feucht M, Genton P, Thomas P, Visscher F, de Haan GJ, Møller RS, Hjalgrim H, Luciano D, Wittig M, Nothnagel M, Elger CE, Nürnberg P, Romano C, Malafosse A, Koeleman BP, Lindhout D, Stephani U, Schreiber S, Eichler EE, Sander T. 15q13.3 microdeletions increase risk of idiopathic generalized epilepsy. Nature genetics 2009 Feb; 41(2).

Sharp AJ. Emerging themes and new challenges in defining the role of structural variation in human disease. Human mutation 2009 Feb; 30(2).

Borel C, Migliavacca E, Letourneau A, Gagnebin M, Béna F, Sailani MR, Dermitzakis ET, Sharp AJ, Antonarakis SE. Tandem repeat sequence variation as causative cis-eQTLs for protein-coding gene expression variation: the case of CSTB. Human mutation 2012 Aug; 33(8).

Guilmatre A, Sharp AJ. Parent of origin effects. Clinical genetics 2012 Mar; 81(3).

Mefford HC, Sharp AJ, Baker C, Itsara A, Jiang Z, Buysse K, Huang S, Maloney VK, Crolla JA, Baralle D, Collins A, Mercer C, Norga K, de Ravel T, Devriendt K, Bongers EM, de Leeuw N, Reardon W, Gimelli S, Bena F, Hennekam RC, Male A, Gaunt L, Clayton-Smith J, Simonic I, Park SM, Mehta SG, Nik-Zainal S, Woods CG, Firth HV, Parkin G, Fichera M, Reitano S, Lo Giudice M, Li KE, Casuga I, Broomer A, Conrad B, Schwerzmann M, Räber L, Gallati S, Striano P, Coppola A, Tolmie JL, Tobias ES, Lilley C, Armengol L, Spysschaert Y, Verloo P, De Coene A, Goossens L, Mortier G, Speleman F, van Binsbergen E, Nelen MR, Hochstenbach R, Poot M, Gallagher L, Gill M, McClellan J, King MC, Regan R, Skinner C, Stevenson RE, Antonarakis SE, Chen C, Estivill X, Menten B, Gimelli G, Gribble S, Schwartz S, Sutcliffe JS, Walsh T, Knight SJ, Sebat J, Romano C, Schwartz CE, Veltman JA, de Vries BB, Vermeesch JR, Barber JC, Willatt L, Tassabehji M, Eichler EE. Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes. The New England journal of medicine 2008 Oct; 359(16).

Sharp AJ, Stathaki E, Migliavacca E, Brahmachary M, Montgomery SB, Dupre Y, Antonarakis SE. DNA methylation profiles of human active and inactive X chromosomes. Genome research 2011 Oct; 21(10).

Koolen DA, Sharp AJ, Hurst JA, Firth HV, Knight SJ, Goldenberg A, Saugier-Veber P, Pfundt R, Vissers LE, Destrée A, Grisart B, Rooms L, Van der Aa N, Field M, Hackett A, Bell K, Nowaczyk MJ, Mancini GM, Poddighe PJ, Schwartz CE, Rossi E, De Gregori M, Antonacci-Fulton LL, McLellan MD, Garrett JM, Wiechert MA, Miner TL, Crosby S, Ciccone R, Willatt L, Rauch A, Zenker M, Aradhya S, Manning MA, Strom TM, Wagenstaller J, Krepischi-Santos AC, Vianna-Morgante AM, Rosenberg C, Price SM, Stewart H, Shaw-Smith C, Brunner HG, Wilkie AO, Veltman JA, Zuffardi O, Eichler EE, de Vries BB. Clinical and molecular delineation of the 17q21.31 microdeletion syndrome. Journal of medical genetics 2008 Nov; 45(11).

Hannes FD, Sharp AJ, Mefford HC, de Ravel T, Ruivenkamp CA, Breuning MH, Fryns JP, Devriendt K, Van Buggenhout G, Vogels A, Stewart H, Hennekam RC, Cooper GM, Regan R, Knight SJ, Eichler EE, Vermeesch JR. Recurrent reciprocal deletions and duplications of 16p13.11: the deletion is a risk factor for MR/MCA while the duplication may be a rare benign variant. Journal of medical genetics 2009 Apr; 46(4).

Sharp AJ, Migliavacca E, Dupre Y, Stathaki E, Sailani MR, Baumer A, Schinzel A, Mackay DJ, Robinson DO, Cobellis G, Cobellis L, Brunner HG, Steiner B, Antonarakis SE. Methylation profiling in individuals with uniparental disomy identifies novel differentially methylated regions on chromosome 15. Genome research 2010 Sep; 20(9).

Sharp AJ, Mefford HC, Li K, Baker C, Skinner C, Stevenson RE, Schroer RJ, Novara F, De Gregori M, Ciccone R, Broomer A, Casuga I, Wang Y, Xiao C, Barbacioru C, Gimelli G, Bernardina BD, Torniero C, Giorda R, Regan R, Murday V, Mansour S, Fichera M, Castiglia L, Failla P, Ventura M, Jiang Z, Cooper GM, Knight SJ, Romano C, Zuffardi O, Chen C, Schwartz CE, Eichler EE. A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures. Nature genetics 2008 Mar; 40(3).

Mefford HC, Clauin S, Sharp AJ, Moller RS, Ullmann R, Kapur R, Pinkel D, Cooper GM, Ventura M, Ropers HH, Tommerup N, Eichler EE, Bellanne-Chantelot C. Recurrent reciprocal genomic rearrangements of 17q12 are associated with renal disease, diabetes, and epilepsy. American journal of human genetics 2007 Nov; 81(5).

Sharp AJ, Itsara A, Cheng Z, Alkan C, Schwartz S, Eichler EE. Optimal design of oligonucleotide microarrays for measurement of DNA copy-number. Human molecular genetics 2007 Nov; 16(22).

Sharp AJ, Selzer RR, Veltman JA, Gimelli S, Gimelli G, Striano P, Coppola A, Regan R, Price SM, Knoers NV, Eis PS, Brunner HG, Hennekam RC, Knight SJ, de Vries BB, Zuffardi O, Eichler EE. Characterization of a recurrent 15q24 microdeletion syndrome. Human molecular genetics 2007 Mar; 16(5).

Sharp AJ, Hansen S, Selzer RR, Cheng Z, Regan R, Hurst JA, Stewart H, Price SM, Blair E, Hennekam RC, Fitzpatrick CA, Segraves R, Richmond TA, Guiver C, Albertson DG, Pinkel D, Eis PS, Schwartz S, Knight SJ, Eichler EE. Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome. Nature genetics 2006 Sep; 38(9).

Locke DP, Sharp AJ, McCarroll SA, McGrath SD, Newman TL, Cheng Z, Schwartz S, Albertson DG, Pinkel D, Altshuler DM, Eichler EE. Linkage disequilibrium and heritability of copy-number polymorphisms within duplicated regions of the human genome. American journal of human genetics 2006 Aug; 79(2).

Sharp AJ, Cheng Z, Eichler EE. Structural variation of the human genome. Annual review of genomics and human genetics 2006; 7.

Sharp AJ, Locke DP, McGrath SD, Cheng Z, Bailey JA, Vallente RU, Pertz LM, Clark RA, Schwartz S, Segraves R, Oseroff VV, Albertson DG, Pinkel D, Eichler EE. Segmental duplications and copy-number variation in the human genome. American journal of human genetics 2005 Jul; 77(1).

Tuzun E, Sharp AJ, Bailey JA, Kaul R, Morrison VA, Pertz LM, Haugen E, Hayden H, Albertson D, Pinkel D, Olson MV, Eichler EE. Fine-scale structural variation of the human genome. Nature genetics 2005 Jul; 37(7).

Sharp AJ, Spotswood HT, Robinson DO, Turner BM, Jacobs PA. Molecular and cytogenetic analysis of the spreading of X inactivation in X;autosome translocations. Human molecular genetics 2002 Dec; 11(25).

Thomas NS, Ennis S, Sharp AJ, Durkie M, Hassold TJ, Collins AR, Jacobs PA. Maternal sex chromosome non-disjunction: evidence for X chromosome-specific risk factors. Human molecular genetics 2001 Feb; 10(3).

Thomas NS, Sharp AJ, Browne CE, Skuse D, Hardie C, Dennis NR. Xp deletions associated with autism in three females. Human genetics 1999 Jan; 104(1).

James RS, Coppin B, Dalton P, Dennis NR, Mitchell C, Sharp AJ, Skuse DH, Thomas NS, Jacobs PA. A study of females with deletions of the short arm of the X chromosome. Human genetics 1998 May; 102(5).

Industry Relationships

Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.

Dr. Sharp did not report having any of the following types of financial relationships with industry during 2012 and/or 2013: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.

Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.

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