BBS Faculty Member - Sekar Kathiresan

Sekar Kathiresan

Department of Medicine

Massachusetts General Hospital
Simches Research Center CPZN 5.252
185 Cambridge St.
Boston, MA 02114
Tel: 617-643-6120
Fax: 617-507-7766
Visit my lab page here.

I am a human geneticist and a clinical cardiologist. I am a genetics researcher at the Center for Human Genetic Research at Massachusetts General Hospital and in the Broad Institute’s Program in Medical and Population Genetics. I direct preventive cardiology at Massachusetts General Hospital.

I seek to discover the genes responsible for inter-individual differences in risk for myocardial infarction (MI) and use this information to understand biologic mechanisms and to improve preventive cardiac care.

The key scientific questions driving my work include the following:
Lipid pathways and MI: Beyond low-density lipoprotein cholesterol, are there any lipid-mediated pathways that cause MI in humans?
Non-lipid pathways and MI: Are there genes and pathways that cause MI but operate outside of known risk factors?
Mechanism: If we identified novel lipid and non-lipid pathways to MI, would this lead to new biologic insights?

The laboratory focuses on gene discovery, understanding biologic mechanism at newly discovered genes, and using discovered gene variants to address clinical questions. We use a range of gene mapping techniques (genome-wide association, exome sequencing, whole genome sequencing), study designs (population-based, Mendelian families, extremes), and analytical approaches to understand the inherited basis for blood lipids and risk for myocardial infarction.

My laboratory’s scientific contributions have been five-fold. First, through genetic studies in populations, we have discovered 45 gene regions related to risk for MI and 95 gene regions related to risk factors for MI including blood cholesterol and triglycerides. Second, through genetic studies in families, we have identified a gene responsible for extremely low levels of LDL cholesterol. Third, at the chromosome 1p13 locus that we first discovered for plasma LDL cholesterol, we identified the causal variant, gene, and mechanism. This work identified a novel regulatory pathway for LDL metabolism and provided the first evidence that common non-coding variants mapped by GWAS may directly influence clinical phenotypes. Fourth, we have utilized gene variants to show that some means of raising HDL cholesterol may not lower risk for MI and that beyond LDL cholesterol, plasma triglyceride-rich lipoproteins likely represent causal factors for MI. Finally, we have identified a panel of gene variants that can be used to assess future risk for MI.

Last Update: 6/18/2014


For a complete listing of publications click here.



Musunuru K*, Pirruccello JP*, Do R*, Peloso GM, Guiducci C, Sougnez C, Garimella KV, Fisher S, Abreu J, Barry AJ, Fennell T, Banks E, Ambrogio L, Cibulskis K, Kernytsky A, Gonzalez E, Rudzicz N, Engert JC, DePristo MA, Daly MJ, Cohen JC, Hobbs HH, Altshuler D, Schonfeld G, Gabriel SB*, Yue P*, Kathiresan S*. Exome sequencing, mutations in ANGPTL3, and familial combined hypolipidemia. N Engl J Med 2010; 363: 2220-2227. PMID: 20942659 (cited by 102)

Teslovich TM*, Musunuru K*, Global Lipids Genetics Consortium Collaborators, Cupples LA*, Sandhu MS*, Ridker PM*, Rader DJ*, van Duijn CM*, Peltonen L*, Abecasis GR*, Boehnke M*,
Kathiresan S*. Biological, clinical, and population relevance of 95 loci for blood lipids. Nature 2010;466: 707-713. PMID: 20686565 (cited by 574)

Musunuru K*, Strong A*, Frank-Kamenetsky M, Lee NE, Ahfeldt T, Sachs KV, Li X, Li H, Kuperwasser N, Ruda VM, Pirruccello JJ, Muchmore B, Prokunina-Olsson L, Hall JL, Schadt EE, Morales CR, Lund-Katz S, Phillips MC, Wong J, Cantley W, Racie T, Ejebe KG, Orho-Melander M, Melander O, Koteliansky V, Fitzgerald K, Krauss RM, Cowan CA,
Kathiresan S* & Rader DJ*. From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus. Nature 2010;466: 714-719. PMID: 20699424 (cited by 191)

Voight* BF, Peloso* GM, Orho-Melander M, Frikke-Schmidt R, Barbalic M, Jensen MK, Hindy G, Hólm H, Ding EL, Johnson T, Schunkert H, Samani NJ,…, Overvad K, Rimm E, Boerwinkle E, Tybjaerg-Hansen A, Cupples LA, Reilly MP, Melander O, Mannucci PM, Ardissino D, Siscovick D, Elosua R, Stefansson K, O’Donnell CJ, Salomaa V, Rader DJ, Peltonen L, Schwartz SM, Altshuler D,
Kathiresan S. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Lancet 2012;280: 572-580. PMID: 22607825. (cited by 73)

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