Genetic differences play an important role in normal human development and disease. These differences can also play a role in the progression of disease and in individual responses to therapy. The research mission of our laboratory is to use of modern genomics to help understand the roles of human genetic variation in these processes.
Genetic variation in human populations. We have characterized genetic variation in a number of human populations (Hispanics and Latinos, Jewish HapMap Project) to understand the origins and migrations of these populations. Currently, we are exploring the role of natural selection in the formation of some of these populations. We are carrying the work forward to understand disease susceptibilities within these groups. A key feature of this work is translating new findings into clinical practice to promote personalized medicine
Human developmental disorders. We study the genetic basis of rare genetic disorders, notably disorders found in isolated populations and disorders of sex development, to indentify not only the mutational basis, but also the molecular mechanisms. Recently, we identified mutations in genes in the MAP kinase pathway in abnormal testicular development and now are investigating the roles of members of this pathway in normal testicular development.
Cancer genetics and genomics. We have explored the roles of low and high-penetrance variants in risk of human cancers and have developed models for predicting risk. Through genome wide association studies, we have identified common variants that increase risk of adverse outcomes (erectile dysfunction, urinary dysfunction, proctitis) for men treated with radiation therapy for prostate cancer. We have also developed a molecular signature based on acquired somatic copy number alterations that is highly predictive of risk of metastasis and may account for this increased risk among African-American men.
Atzmon G, Hao L, Pe'er I, Velez C, Pearlman A, Palamara PF, Morrow B, Friedman E, Oddoux C, Burns E, Ostrer H. Abraham’s children in the Genome Era: Major Jewish Diaspora populations comprise distinct genetic clusters with shared Middle Eastern ancestry. Am J Hum Genet. 86:850-9, 2010.
Kerns SL, Ostrer H, Stock RG, Li W, Moore J, Pearlman A, Campbell CL, Shao Y, Stone N, Kusnetz L, Rosenstein BS. Genome wide association study to identify single nucleotide polymorphisms (SNPs) associated with the development of erectile dysfunction in African-American men following radiotherapy for prostate cancer. Internat J Rad Oncol Biol Phys. 78:1292-1300, 2010.
Pearlman, A. Loke J, Le Caignec, C, White, S, Chin L, Friedman A, Warr N, Willan J, Brauer D, Farmer C, Brooks E, Oddoux C, Riley B, Shajahan S, Camerino G, Homfray T, Crosby A, Couper J, David A, Greenfield A, Sinclair A, Ostrer H. Mutations in MAP3K1 cause 46,XY disorders of sex development and implicate a common signal transduction pathway in human testis determination. Am J Hum Genet. 87:898-904, 2010.
Rose AE, Poliseno L, Wang J, Clark M, Pearlman A, Wang G, Vega Y Saenz de Miera EC, Medicherla R, Christos PJ, Shapiro R, Pavlick A, Darvishian F, Zavadil J, Polsky D, Hernando E, Ostrer H, Osman I. Integrative genomics identifies molecular alterations that challenge the linear model of melanoma progression. Cancer Res. 71:2561-71, 2011.
Moorjani P, Patterson N, Hirschhorn JN, Keinan A, Hao L, Atzmon G, Burns E, Ostrer H, Price AL, Reich D. The history of African gene flow into southern Europeans, Levantines, and Jews. PLoS Genet. 7(4):e1001373, 2011.
Warr N, Bogani D, Siggers P, Brixey R, Tateossian H, Dopplapudi A, Wells S, Cheeseman M, Xia Y, Ostrer H, Greenfield A. Minor abnormalities of testis development in mice lacking the gene encoding the MAPK signalling component, MAP3K1. PLoS One. 6(5):e19572, 2011.
Velez C, Palamara PF, Guevara-Aguirre J, Hao L, Karafet T, Guevara-Aguirre M, Pearlman A, Oddoux C, Hammer M, Burns E, Pe'er I, Atzmon G, Ostrer H. The impact of Converso Jews on the genomes of modern Latin Americans. Hum Genet. 131:251-63, 2012
Loke J, Ostrer H. Rapidly screening variants of uncertain significance in the MAP3K1 gene for phenotypic effects. Clin Genet. 81:272-7, 2012
Campbell CL, Palamara PF, Dubrovsky M, Botigué LR, Fellous M, Atzmon G, Oddoux C, Pearlman A, Hao L, Henn BM, Burns E, Bustamante CD, Comas D, Friedman E, Pe'er I, Ostrer H. North African Jewish and non-Jewish populations form distinctive, orthogonal clusters. Proc Natl Acad Sci U S A. 109:13865-70, 2012
Kerns SL, Stock R, Stone N, Buckstein M, Shao Y, Campbell C, Rath L, DeRuysscher D, Lammering G, Hixson R, Cesaretti J, Terk M, Ostrer H, Rosenstein BS. A 2-stage genome-wide association study to identify single nucleotide polymorphisms associated with development of erectile dysfunction following radiation therapy for prostate cancer. Int J Radiat Oncol Biol Phys 85(1):e21-8, 2013.
Guevara-Aguirre J, Guevara-Aguirre M, Hwa V, Prócel P, Saavedra J, Ostrer H, Fang P, Rosenfeld RG, Kerns S, Rosenbloom AL. Intrauterine and postnatal growth failure with normal GH/IGF1 axis and insulin-resistant diabetes in a consanguineous kinship. Eur J Endocrinol. 166:521-9, 2012.
Kerns SL, Stone NN, Stock RG, Rath L, Ostrer H, Rosenstein BS. A 2-stage genome-wide association study to identify single nucleotide polymorphisms associated with development of urinary symptoms after radiotherapy for prostate cancer. J Urol. 190:102-8, 2013.
Rinella ES, Shao Y, Yackowski L, Pramanik S, Oratz R, Schnabel F, Guha S, LeDuc C, Campbell CL, Klugman SD, Terry MB, Senie RT, Andrulis IL, Daly M, John EM, Roses D, Chung WK, Ostrer H. Genetic variants associated with breast cancer risk for Ashkenazi Jewish women with strong family histories but no identifiable BRCA1/2 mutation. Hum Genet. 132:523-36, 2013.
Ostrer H. Genes: US patent rulings will fuel invention. Nature 499:29, 2013.
Material in this section is provided by individual faculty members who are solely responsible for its accuracy and content.
Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Ullmann Building, Room 817
Bronx, NY 10461
The Wall Street Journal interviews Dr. Harry Ostrer about an historic and unanimous Supreme Court ruling that determined human genes cannot be patented.