| Lab
Overview
Altered blood lipids predict risk of myocardial
infarction and myocardial infarction is
the leading cause of death worldwide. Both
blood lipid levels and myocardial infarction
are heritable phenotypes. The genes underlying
the variability in blood lipids and risk
of myocardial infarction are largely unknown.
Genes validated in the human population
to relate to blood lipids and to risk of
myocardial infarction may provide novel
diagnostics and new therapeutic targets.
My laboratory seeks to define the genetic
basis for blood lipids (high-density lipoprotein
cholesterol, low-density lipoprotein cholesterol,
and triglycerides) and myocardial infarction
(MI). We are focused on three goals: 1)
mapping of genetic loci related to lipids
and/or myocardial infarction and identifying
the causal variants and genes; 2) developing
a molecular understanding of how the causal
variants and genes lead to phenotype; and
3) applying genetic and functional insights
to improve preventive cardiac care. To address
the above goals, my laboratory uses a variety
of research methodologies and reagants including
population genetics, large patient sample
collections, genetic association, functional
analysis in model organisms, and genetic
studies in clinical trials and prospective
cohort studies.
Post-doctoral positions are available.
Please email Dr. Kathiresan at his MGH
or Broad
Institute email addresses.
Science
The goals of our laboratory
are to:
1. Map genetic loci and the causal
genes associated with blood lipid
traits and risk of myocardial
infarction (MI).
2. Develop a molecular understanding
how causal variants and genes
lead to phenotype .
3. Translate genetic
discoveries to improve preventive
cardiac care . |
The following are current
research projects focused on the above goals:
1. Myocardial
Infarction Genetics Consortium (MIGen).
With collaborators, we have identified
9 genetic loci related to early-onset
myocardial infarction (Nature Genetics
2009a). We seek to identify the
full spectrum of allelic variation
at each locus related to MI and
at several of the novel loci, define
the mechanisms by which the genes
lead to atherosclerotic cardiovascular
disease. |
Figure
1. MIGen in an international consortium
composed of collaborators from 16 sites
across the United States and Europe.
2. Genetics of blood lipids.
Using genome-wide association
methodology, we have identified
30 genetic loci related to
blood LDL cholesterol, HDL
cholesterol, or triglycerides
(Nature Genetics 2008, Nature
Genetics 2009b). Using mouse
models, we are now focused
on developing a molecular
understanding of how the newly
discovered genes influence
plasma lipids.
3. Clinical application of
genetic discoveries. We reported
proof of concept that a panel
of genetic polymorphisms may
aid in predicting risk for
cardiovascular disease (N
Engl J Med 2008). We are now
extending this work to include
a more complete panel of risk
variants and testing the external
generalizability of our initial
findings.
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About
Dr. Sekar Kathiresan
graduated from North Allegheny High
School in Pittsburgh, PA and received
his B.A. in history summa cum laude
from the University of Pennsylvania
in 1992. He received his M.D. from Harvard
Medical School in 1997. He completed
his clinical training in internal medicine
and cardiology at Massachusetts General
Hospital. He served as Chief Resident
in Internal Medicine at MGH in 2002-2003.
Subsequently, he pursued research training
in cardiovascular genetic epidemiology
through a combined experience at the
Framingham Heart Study and the Broad
Institute of Harvard/MIT, mentored jointly
by Drs. Christopher J. O’Donnell
and Joel N. Hirschhorn. In addition
to his research efforts, Dr. Kathiresan
is Director of Preventive Cardiology
at MGH and has a clinic focused on primary
prevention of myocardial infarction
in individuals with a family history
of heart attack.
Email Dr. Kathiresan at his MGH
or Broad
Institute email addresses.
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