Joseph Lee

Joseph Lee

Joseph Lee

Professor at CUMC
Epidemiology (in the Sergievsky Center) at the Columbia University Medical Center

Office/Address:

630 W. 168th Street, P&S Unit 16, PH19-305
New York NY 10032
Phone:
212-305-6022
Website address: Email:

Biography

Joseph H. Lee, DrPH, studies the biology of aging traits in several unique populations in different parts of the world. To this end, he has four areas of research. First, Dr. Lee and colleagues are studying large Caribbean Hispanic families with multiple affected relatives to identify genes that contribute to Alzheimer disease (AD). Currently, he is focusing on families that carry a founder mutation in the PSEN1 gene to identify protective genetic factors. To identify genetic factors that alter AD risk, he applies genome-wide linkage and association, whole genome/exome sequencing, RNA-sequencing, transcriptomics, and other functional genetic approaches. Second, Dr. Lee and colleagues are examining adults with Down syndrome (DS) to better understand the aging brain. Adults with DS age faster than the general population, and they start developing AD neuropathologies in their 40s. He and his colleagues apply multi-omic approaches (including genomic, proteomic, and metabolomics and phenomics) to examine the disease processes. Third, he and colleagues are conducting a multi-site longitudinal study to determine why some individuals live to exceptionally old age and remain healthy. This study examines genome-phenome relations in several hundred longevous families. Fourth, he and colleagues are studying migrant populations to interrogate gene-environment interaction. By examining individuals who share the same genetic background but are exposed to disparate environments, they will be able to explore the influence of environment on genetic factors. In addition, he and his collaborators are investigating a cohort of inbred American-Indians in Venezuela to identify and characterize genetic and environmental factors that contribute to the relations between dementia and cardio-metabolic risk factors. (modified 2017.05.25)

Topics

Education

Other, 1999, University of Pennsylvania
DrPH, 1996, Columbia University
MPH, 1985, University of California at Berkeley
BS, 1983, University of California at Irvine

Mailman Affiliations

Professor at CUMC, Department of Epidemiology

Editorial Boards

Alzheimer Disease and Associated Disorders

Columbia Affiliations

Professor at CUMC, Sergievsky Center, College of Physicians and Surgeons
Professor at CUMC, Taub Institute, College of Physicians and Surgeons
Professor at CUMC, Department of Neurology, College of Physicians and Surgeons

Other Affiliations

Member, American Society of Human Genetics
Member, International Society of Genetic Epidemiology
Member, Human Genome Organization
Member, American Association of Anthropological Genetics
Member, International Society to Advance Alzheimer Research and Treatment
Member, Trisomy 21 Research Society

Areas of Expertise

Alzheimer's Disease, Healthy Aging and Longevity, Research Design and Methods, Cardiovascular Disease, Neurological Disease / Disorders, Gene-Environment Interactions, Genetic Susceptibility, Genetics, Genomics, Statistical Genetics, Global Health

Select Global Activities

Genetic epidemiology of early onset Alzheimer disease (AD), Colombia, Dominican Republic, Puerto Rico: The goal of this study is to examine families that carry a PSEN1 mutation to identify novel genetic variants that may modify AD-related phenotypes, such as age at onset of AD. Once such modifiers are identified, we will apply the state-of-the-art genomic tools to understand their functions.
Genetic epidemiology of Down syndrome, United Kingdom (England, Wales, Scotland, Northern Ireland): This multi-center study uses multi-omic methods to understand how adults with Down syndrome age cognitively. For this purpose, we will examine genomic, proteomic, metabolomic, brain imaging (MRI & PET), and clinical evaluation data. Particularly, we are interested in adults with DS (who have 3 copies of APP gene) who are resistant to dementia in old age.
Genetic epidemiology of healthy cellular aging: Natural experiments, Kazakhstan, South Korea, Venezuela: Three natural experiments are ongoing. The first study examines how lifestyle influences levels of metabolites in aging cohorts. For this purpose, we compare ethnic Kazakhs in Kazakhstan (urban) vs Kazakhs in China (nomadic). Subsequently, we examine the genome to identify variants that contribute to variation in levels of metabolites. The second study compares ethnic Koreans in Kazakhstan vs those in China and Korea to understand genetic and environmental factors that influence normal variations in aging traits. The third study aims to understand the biology of brain aging by examining brain imaging and genomics of highly inbred Native Indians.

Select Publications

Lee JH, Cheng R, Vardarajan B, Lantigua R, Reyes-Dumeyer D, Ortmann W, Graham R, Bhangale T, Behrens T, Medrano M, Jimenez-Velazquez IZ, Mayeux R. Genetic modifiers of age at onset in carriers of the G206A mutation in PSEN1 with familial Alzheimer disease in Caribbean Hispanics. JAMA Neurology. 2015 Jul 27. doi: 10.1001/jamaneurol.2015.1424
Lee JH, Kahn A, Cheng R, Reitz C, Vardarajan B, Lantigua R, Medrano M, Jimenez-Velazquez IZ, Williamson J, Nagy PL, Mayeux R. Disease-related mutations among Caribbean Hispanics with familial dementia. Molecular Genetics and Genomic Medicine doi:10.1002/mgg3.85
Rogaeva E, Meng Y, Lee JH, Gu Y, Kawarai T, Zou F, Katayama T, Baldwin CT, Cheng R, Hasegawa H, Chen F, Shibata N, Lunetta KL, Pardossi-Piquard R, Bohm C, Wakutani Y, Cupples LA, Cuenco KT, Green RC, Pinessi L, Rainero I, Sorbi S, Bruni A, Duara R, Friedland R, Inzelberg R, Hampe W, Bujo H, Song Y, Andersen O, Willnow TE, Graff-Radford N, Petersen R, Dickson D, Der SD, Fraser PE, Schmitt-Ulms G, Younkin S, Mayeux R, Farrer LA, St George-Hyslop P. The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimers Disease. Nature Genetics 2007;39(2): 168-177. PMC2657343
Schupf N, Lee AJ, Park N, Dang L-H, Pang D, Yale A, Krinsky-McHale S, Jenkins E, Luchsinger J, Zigman W, Silverman W, Tycko B, Kisselev S, Clark LN, Lee JH. Candidate genes for Alzheimer's disease are associated with individual differences in plasma levels of beta amyloid peptides in adults with Down syndrome. Neurobiology of Aging. 2015 Jun 19. pii: S0197-4580(15)00331-0. doi: 10.1016/j.neurobiolaging.2015.06.020
Lee JH, Cheng R, Honig LS, Feitosa M, Kammerer C, Kang MS, Schupf N, Lin R, Sanders J, Bae H, Druley T, Perls T, Christensen K, Province M, Mayeux R. Genetic variants on 17q23.2 and 10q11.21 are associated with variation in telomere length: The Long Life Family Study. Frontiers in Genetics of Aging. doi: 10.3389/fgene.2013.00310.
Honig LS, Schupf N, Lee JH, Tang MX, Mayeux R. Short telomere length is associated with mortality in those with APOE4 and those with dementia. Annals of Neurology 60 181-187 2006
Terwilliger JD, Lee JH. Natural Experiments in Human Gene Mapping: The intersection of Anthropological Genetics and Genetic Epidemiology. In: Anthropological genetics: Theory, methods and applications. Crawford MH (Ed.), Cambridge: University of Cambridge Press, 2006, pp. 38-76.
Yan W, Li X, Wang Q, Huang Y, Cao F, Zhang W, Lee JH. Overweight, High Blood Pressure and Impaired Fasting Glucose in Uyghur, Han and Kazakh Chinese Children and Adolescents. Ethnicity and Health. (in press)
Luukkonen T, Poyhonen M, Palotie A, Ellonen P, Lagstrom S, Lee JH, Terwilliger JD, Salonen R, Varilo T. A balanced translocation truncates Neurotrimin in a family with intracranial and thoracic aortic aneurysm. Journal of Medical Genetics. 2012;49(10):621-9. doi: 10.1136/jmedgenet-2012-100977. PMID: 23054244

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