Inga Peter, PhD Email Inga Peter

Research

My research focus is in identifying genes involved in complex disorders that include hypertension, cardiovascular disease, obesity, diabetes, and Crohn's disease. I am particularly interested in genetic control of estrogen metabolism and action. My colleagues and I identified genetic variations in estrogen receptor genes (ESR1 and ESR2) that are associated with increased prevalence of myocardial infarction and other cardiovascular risk factors. In addition, I am interested in finding genes that influence vascular reactivity, arterial stiffness and are associated with the risk of atherosclerosis and hypertension. My general approach is to apply candidate gene and genome-wide association studies, or GWAS, to detect genotype-phenotype associations in large cohorts of individuals.

Most recently, I started to investigate genetic influences on responsiveness to treatments. I lead a pharmacogenetic study of an ongoing randomized clinical trial aimed to provide myocardial metabolic support in the form of intravenous Glucose-Insulin-Potassium (GIK) therapy to individuals with acute coronary syndrome. IMMEDIATE (Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care) Trial is currently in the process of recruiting patients nation-wide and comparing immediate and long-term response to treatment versus placebo with regard to myocardial function. Given accumulating evidence strongly suggesting that mutations in genes encoding drug targets can be linked to drug responses, we hypothesize that variations in genes encoding common pathways related to GIK response in the heart will be associated with the immediate and long-term response to GIK therapy. Another project is aimed to identify variation in genes that are members of the G-coupled protein receptor (GPCR) family associated with diabetes and obesity. The major study cohort isthe Look AHEAD study (Action for HEAlth in Diabetes), a clinical trial conducted in 16 centers in the US investigating the long-term health impact of an intensive lifestyle intervention in overweight and obese adults with type 2 diabetes. So far, the trial completed its 1-year follow-up that showed that intensive lifestyle intervention resulted in clinically significant weight loss, which was associated with improved diabetes control and CVD risk factors. The next step will be to investigate whether these phenotypes correlate with GPCR genotype data. We expect to see that carriers of certain genotypes will be more likely to lose and maintain low weight over time.

Finding genes associated with complex disorders may help elucidate mechanisms of disease pathogenesis and enhance our ability to postpone and treat these conditions in genetically susceptible individuals before irreversible clinical manifestations occur.

I also serve as the Principal and co-Investigator on a number of projects that involve Mount Sinai Biobank participants.

I am the co-Investigator of the NHGRI-funded U01 grant ‘Biorepositories for Genomic Medicine in Diverse Communities’ (eMERGE) and the Institute of Personalized Medicine - funded grant ‘Evaluating Information Needs to Generate Community Engagement and Genomics Education’ (ENGAGE). I also lead two pilot studies focused on the Mount Sinai Biobank population: 1) to determine genetic variants associated with type 2 diabetes in the absence of obesity and 2) to identify differences in microbial content between obese and lean diabetics. In addition, I am the Principal Investigator of the National Heart, Lung and Blood Institute - funded R01 grant aimed to identify genetic factors associated with response to metabolic therapy in a setting of acute coronary syndrome. Furthermore, I am leading the laboratory research on mechanisms of Crohn’s disease.

Research Interests:

• Genetics of complex diseases through next generation sequencing
• Pharmacogenetics and genetic risk modification by means of lifestyle intervention
• Microbiome studies of Crohn’s disease, type 2 diabetes, and obesity
• Population genetics of Ashkenazi Jews

Peter I, Tighiouart H, Lapaire O, Johnson KL, Bianchi DW, Terrin N. Cell free DNA fragmentation patterns in amniotic fluid identify genetic abnormalities and changes due to storage. Diag Mol Pathol 2008 Sep; 17(3): 185-190.

Kelley-Hedgepeth A, Peter I, Kip KE, Montefusco MC, Kogan S, Cox D, Ordovas JM, Levy D, Reis SE, Mendelsohn ME, Housman D, Huggins GS. The protective effect of KCNMB1 E65K against hypertension is restricted to blood pressure treatment with beta-blockade. J Hum Hypertens 2008 Jul; 22(7): 512-515.

Peter I, Kelley-Hedgepeth A, Fox CS, Cupples LA, Huggins GS, Housman DE, Karas RH, Mendelsohn ME, Levy D, Murabito JM. Variation in Estrogen-Related Genes Associated with Cardiovascular Phenotypes and Circulating Estradiol, Testosterone, and Dehydroepiandrosterone Sulfate Levels. J Clin Endocrinol Metab 2008 Jul; 93(7): 2779-2785.

Peter I, Huggins GS, Shearman AM, Pollak A, Schmid CH, Cupples LA, Demissie S, Patten RD, Karas RH, Housman DE, Mendelsohn ME, Vasan RS, Benjamin EJ. Age-related Changes in Echocardiographic Measurements: Association with Variation in the Estrogen Receptor-a Gene. Hypertension 2007 May; 49(5): 1000-1006.

Lapaire O, Bianchi DW, Peter I, O'Brien B, Stroh H, Cowan JM, Tantravahi U, Johnson KL. Cell-Free Fetal DNA in Amniotic Fluid: Unique Fragmentation Signatures in Euploid and Aneuploid Fetuses. Clin Chem 2007 Mar; 53(3): 405-411.

Peter I, Chin K. An overview of genetic testing in cancer. Personalized Medicine 2006; 3(3): 325-333.

Shearman AM, Demissie S, Cupples LA, Peter I, Schmid CH, Ordovas JM, Mendelsohn ME, Housman DE. Tobacco smoking, estrogen receptor a gene variation and small low-density lipoprotein level. Human Molecular Genetics 2005; 14(16): 2405-2413.

Peter I, Shearman AM, Vasan RS, Zucker DR, Schmid CH, Demissie S, Cupples LA, Kuvin JT, Karas RH, Mendelsohn ME, Housman DE, Benjamin AJ. Association of estrogen receptor beta gene polymorphisms with left ventricular mass and wall thickness in women. Am J Hypertens 2005; 18(11): 1388-1395.

Peter I, Shearman AM, Zucker DR, Schmid CH, Demissie S, Cupples LA, Larson MG, Vasan RS, D'Agostino RB, Karas RH, Mendelsohn ME, Housman DE, Levy D. Variation in estrogen-related genes and cross-sectional and longitudinal blood pressure in the Framingham Heart Study. J Hypertens 2005; 23(12): 2193-2200.

Shearman A, Cupples A, Demissie S, Peter I, Schmid C, Karas R, Mendelsohn M, Housman D, Levy D. Estrogen Receptor a Gene Variation is Associated with Susceptibility to Myocardial Infarction. JAMA 2003; 290: 2263-2270.