Research Faculty

Address
PS12-420 (Office)
BB1206 (Lab)
630 West 168th Street
New York, NY 10032


Phone: 212-304-5268
Fax: 212-304-5481

lc654@cumc.columbia.edu
Education and Training
B.Sc. (Hons) University of London, UK 1990
Ph.D., University of Manchester, UK 1995

Collaborations
Dr Ellen Sidransky (National Human Genome Research Institute, NIH); Dr Andy Singleton (Laboratory of Neurogenetics, NIA)
Training Activities
Molecular Genetic Pathology Fellowship Program
Pathobiology and Molecular Medicine Graduate Doctoral Program
T35 Predoctoral Research Training (Department of Neurology)
Lorraine N. Clark, Ph.D.
Associate Professor of Clinical Pathology
Director of the Taub Institute Genomics Core
Co-Director in the Division of Personalized Genomic Medicine
Department of Pathology and Cell Biology
Taub Institute for Alzheimer Disease and Aging
Research Summary

Research Interests

• Genetics and Genomics
• SNP genotyping
• GWAS, CNV, whole exome and whole genome sequencing
• Ashkenazi Jewish Genomics
• Glucocerebrosidase and lysosomal storage disorder genes
• Neurodegenerative disease including Parkinson’s disease and Essential Tremor

My research uses genetic and genomic approaches to study the basis of neurodegenerative disease with a focus on common age-related neurodegenerative disorders including Parkinson’s disease and Essential Tremor.

Genomic technologies including microarray and next generation high throughput sequencing platforms together with computational approaches are enabling rapid advances in genetic analysis and human genetics. My laboratory uses this technology to identify variation in both DNA sequence and gene expression levels in families, patient populations and autopsy material to determine the genetic contribution to disease pathogenesis. To identify causal and susceptibility genes we are using a variety of approaches including, exome and whole genome sequencing, SNP analysis and case-control association studies, copy number variation discovery (CNV) and analysis, genome wide association studies (GWAS), fine mapping and gene identification, resequencing and mutation analysis, transcriptomics, miRNA analysis and methylation analysis. These studies require close coordination and collaboration between clinical, statistical and genetics researchers in several research departments and institutes.


Affiliations

Department of Pathology and Cell Biology
Taub Institute for Research on Alzheimer Disease and the Aging Brain
Center for Human Genetics
The Division of Personalized Genomic Medicine


Funded Research Projects

1) The Michael J Fox Foundation 2013-2015
Analysis and Replication of a Genetic Interaction between LRRK2 and PARK16
Role: Principal Investigator

2) R01 NS073872 (Louis/Clark) 9/30/11-8/31/14
Identification of Susceptibility Genes for Essential Tremor
Goals: Linkage Analysis and exome sequencing in early onset families with essential tremor.
Role: Co-Principal Investigator

3) PDF 50611406 (Fahn/Clark) 07/01/13-06/30/14
The Parkinson’s Disease Foundation
Goals: To identify genetic risk factors for Parkinson’s Disease
Role: Principal Investigator

4) 2P50NS038370-11 (Burke) 09/30/09-07/31/14
Mechanisms of dopamine neuron degeneration.
Role: Co-Investigator

5) 5 P50 AG008702 (Shelanski) 08/01/2009-07/31/2014
National Institute on Aging.
Project 3 (Clark) “Glucocerebrosidase Mutations and Dementia with Lewy Bodies”
Role: Principal Investigator

6)P50(Silverman/Schupf) 2010-2015
Genetics of Down’s Syndrome
NIH
Project IV. Genetic epidemiology of Alzheimer’s disease in Down syndrome.
Role: Co-Investigator
Service Activities

Co-director Personalized Genomic Medicine
Selected Publications

1. Hewitt, J. E., Clark, L.N., Ivens, A. and Williamson, R. R. (1991) Structure and sequence of the human homeobox gene HOX7. Genomics. 11: 670-678.

2. Wijmenga, C., Hewitt, J. E., Sandkujl, L. A., Clark, L.N., Wright, T.J., Dauwerse, H. G., Gruter, A-M., Hofker, M. H., Moerer, P., Williamson, R. R., van Ommen, G-J. B., Padberg, G. W. and Frants, R. R. (1992) Chromosome 4q DNA rearrangements associated with facioscapulohumeral muscular dystrophy. Nature Genetics 2: 26-30.

3. Hewitt, J. E., Lyle, R., Clark, L.N., Valleley, E. M., Wright, T. J.,Wijmenga, C., van Deutekom, J. C. T., Francis, F., Sharpe, P. T., Hofker, M., Frants, R. R. and Williamson, R. (1994) Analysis of the tandem repeat locus D4Z4 associated with facioscapulohumeral muscular dystrophy. Human Molecular Genetics 3:1287-1295.

4. Lyle, R., Wright, T. J., Clark, L.N. and Hewitt, J. E. The facioscapulohumeral muscular dystrophy associated repeat, D4Z4, is a member of a dispersed family of homeobox-containing repeats, subsets of which are clustered on the short arms of the acrocentric chromosomes (1995) Genomics 28: 389-397

5. Clark, L.N., Poorkaj, P., Wszolek, Z., Geschwind, D. H., Nasreddine, Z. S., Miller, B., Payami, H., Awert, F., Markopoulou, K., D’Souza, I., M.-Y. Lee, V., Reed, L., Trojanowski, J. Q., Zhukareva, V., Bird, T., Schellenberg, G. and Wilhelmsen, K. C. (1998) Pathogenic implications of mutations in the tau gene in Pallido-Ponto-Nigral degeneration and related chromosome 17-linked neurodegenerative disorders. Proceedings of The National Academy of Sciences of the United States of America 95: 13103-13107.

6. Clark, L.N., Levy G, Tang MX, Mejia-Santana H, Ciappa A, Tycko B, Cote LJ, Louis ED, Mayeux R, Marder K. (2003). The Saitohin 'Q7R' polymorphism and tau haplotype in multi-ethnic Alzheimer disease and Parkinson's disease cohorts. Neurosci Lett. 14;347:17-20.

7. Chih B, Afridi S, Clark, L.N. and Scheiffele P (2004) Disorder-Associated Mutations Lead to Functional Inactivation of Neuroligins Hum Mol Genet. 2004 Jul 15;13(14):1471-7.

8. Clark, L.N., Hammer E, Mejia-Santana H et al. Construction and validation of a PD mutation Genotyping Array for the Parkin Gene Mov Disord. 2007 May 15;22(7):932-7.

9. Clark, L.N., Ross B, Wang Y, Mejia-Santana H, Harris J, Louis ED, Cote L, Andrews H , Fahn S, Waters C, Ford B, Frucht S, Ottman R, Marder K. Mutations in the Glucocerebrosidase Gene are associated with Early-Onset Parkinson’s disease. Neurology. 2007 Sep 18; 69(12):1270-7.

10. Clark, L.N., Kartsaklis LA, Gilbert RW, Dorado B, Ross BM, Kisselev S, Verbitsky M, Mejia-Santana H, Cote LJ, Andrews H, Vonsattel J-P, Fahn S, Mayeux R, Honig L, Marder K, Glucocerebrosidase Mutations are Associated with Dementia with Lewy Bodies. Arch Neurol. 2009;66(5):578-583.

11. Sidransky E, Aharon-Peretz J, Annesi G, Barbosa ER, Bar-Shira A, Berg D, Bras J, Brice A, Chen C-M, Clark, L.N.,Condroyer C, De Marco VE, Dürr A, Eblan MJ, Fahn S, Farrer M, Fung H-C, Gan-Or Z, Gasser T, Gershoni R, Giladi N, Griffith A, Gurevich T, Januario C, Kropp P, Lang AE, Lee-Chen G-J, Lesage S, Karen Marder K, Mata IF, Mirelman A, Mitsui J, Mizuta I, Nalls MA, Nicoletti G, Oliveira C, Orr-Urtreger A, Pereira L de Veiga, Quattrone A, Rogaeva E, Rolfs A, Rosenbaum H, Rozenberg R, Samii A, Sammadar T, Schulte C, Manu Sharma M, Singleton A, Spitz M, Tan E-K, Tayebi N, Toda T, Troiano A, Tsuji S, Wolfsburg T, Wu Y-R, Zabetian CP, Ziegler SG. Mutations in the glucocerebrosidase gene confer a six fold increased risk of developing Parkinson disease: Results of an international multi-center collaborative study of 5691 patients. N Engl J Med. 2009 Oct 22;361(17):1651-61.

12. Clark, LN, Park N, Kisselev S, Rios E, Lee JH, Louis ED.Replication of the LINGO1 gene association with essential tremor in a North American population. Eur J Hum Genet. 2010 Jul;18(7):838-43

13. Liu X, Cheng R, Verbitsky M, Kisselev S, Browne A, Mejia-Sanatana H, Louis ED, Cote LJ, Andrews H, Waters C, Ford B, Frucht S, Fahn S, Marder K, Clark, L.N., Lee JH.
Genome-wide association study identifies candidate genes for Parkinson's disease in an Ashkenazi Jewish population. BMC Med Genet. 2011 Aug 3;12:104.PMID: 21812969

14. Kenny EE, Pe'er I, Karban A, Ozelius L, Mitchell AA, Ng SM, Erazo M, Ostrer H, Abraham C, Abreu MT, Atzmon G, Barzilai N, Brant SR, Bressman S, Burns ER, Chowers Y, Clark, L.N., Darvasi A, Doheny D, Duerr RH, Eliakim R, Giladi N, Gregersen PK, Hakonarson H, Jones MR, Marder K, McGovern DP, Mulle J, Orr-Urtreger A, Proctor DD, Pulver A, Rotter JI, Silverberg MS, Ullman T, Warren ST, Waterman M, Zhang W, Bergman A, Mayer L, Katz S, Desnick RJ, Cho JH, Peter I. A genome-wide scan of Ashkenazi Jewish Crohn's disease suggests novel susceptibility loci. PLoS Genet. 2012;8(3):e1002559. PMCID: PMC3297573.

15. Pankratz N, Beecham GW, DeStefano AL, Dawson TM, Doheny KF, Factor SA, Hamza TH, Hung AY, Hyman BT, Ivinson AJ, Krainc D, Latourelle JC, Clark, LN., Marder K, Martin ER, Mayeux R, Ross OA, Scherzer CR, Simon DK, Tanner C, Vance JM, Wszolek ZK, Zabetian CP, Myers RH, Payami H, Scott WK, Foroud T; PD GWAS Consortium.Meta-analysis of Parkinson's disease: identification of a novel locus, RIT2. Ann Neurol. 2012;71(3):370-84. PMCID: PMC3354734

16. Parmalee N, Mirzozoda K, Kisselev S, Merner N, Dion P, Rouleau G, Clark, L, Louis ED.
Genetic analysis of the FUS/TLS gene in essential tremor. Eur J Neurol. 2012 Nov 1. doi: 10.1111/ene.12023. [Epub ahead of print] PMID: 23114103.

17. Macleod D, Rhinn H, Kuwahara T, Zolin A, MacCabe B, Clark, L, Small S and Abeliovich A. The Park16 locus gene RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting as well as Parkinson’s disease risk. Neuron. 2013; 77:425-39. NIHMS ID: NIHMS440904

18. X. Liu, R. Cheng, S. Kisselev, H. Mejia-Santana, E. Louis, L. Cote, H. Andrews, C. Waters, B. Ford, S. Frucht, S. Fahn, K. Marder, J. Lee, L. Clark Increased Rate of Rare Genic Copy Number Variants in Parkinson’s Disease Among Ashkenazi Jews. Mol Genet Genomic Med. 2013 Sep;1(3):142-154.

19. Carmi S, Hui KY, Kovach E, Liu X, Xue J, Grady F, Guha S, Upadhyay K, Ben-Avraham D, Mukherjee S, Bowen MB, Vijai J, Barzilai N, Darvasi A, Offit K, Ozelius LJ, Peter I, Cho JH, Ostrer H, Atzmon G, Clark LN, Lencz T, Pe’er T. Whole Genome Sequencing of an Ashkenazi Jewish Reference panel support population-targeted personal genomics and illuminates Jewish and European origins. Submitted to Nature.

Committees , Council, and Professional Society Memberships

American Society of Human Genetics
Committee member/Reviewer for the Parkinson’s Disease Foundation
Keywords

Genetics, Genomics, Clinical Genetics

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