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. We have developed functional variant assays to understand the phenotypic effects of genetic variants.
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. A similar model is being developed for breast cancer.
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.
Cespedes MS, Kerns SL, Holzman RS, McLaren PJ, Ostrer H, Aberg JA. Genetic predictors of cervical dysplasia in African American HIV-infected women: ACTG DACS 268. HIV Clin Trials. 14:292-302, 2013.
Kerns SL, de Ruysscher D, Andreassen CN, Azria D, Barnett GC, Chang-Claude J, Davidson S, Deasy JO, Dunning AM, Ostrer H, Rosenstein BS, West CM, Bentzen SM. STROGAR - STrengthening the Reporting Of Genetic Association studies in Radiogenomics. Radiother Oncol. 110:182-8, 2014.
Isakov O, Rinella ES, Olchovsky D, Shimon I, Ostrer H, Shomron N, Friedman E. Missense mutation in the MEN1 gene discovered through whole exome sequencing co-segregates with familial hyperparathyroidism. Genet Res (Camb). 2013
Aug;95(4):114-20. doi: 10.1017/S0016672313000141. PubMed PMID: 24074368.
Vacic V, Ozelius LJ, Clark LN, Bar-Shira A, Gana-Weisz M, Gurevich T, Gusev A, Kedmi M, Kenny EE, Liu X, Mejia-Santana H, Mirelman A, Raymond D, Saunders-Pullman R, Desnick RJ, Atzmon G, Burns ER, Ostrer H, Hakonarson H, Bergman A, Barzilai N, Darvasi A, Peter I, Guha S, Lencz T, Giladi N, Marder K, Pe'er I, Bressman SB, Orr-Urtreger A. Genome-wide mapping of IBD segments in an Ashkenazi PD cohort identifies associated haplotypes. Hum Mol Genet. 23:4693-702, 2014.
Loke J, Pearlman A, Radi O, Zuffardi O, Giussani U, Pallotta R, Camerino G, Ostrer H. Mutations in MAP3K1 tilt the balance from SOX9/FGF9 to WNT/β-catenin signaling. Hum Mol Genet. 23:1073-83, 2014.
Ostrer H. Disorders of sex development (DSDs): an update. J Clin Endocrinol Metab. 99:1503-9, 2014.
Kerns SL, Ostrer H, Rosenstein BS. Radiogenomics: using genetics to identify cancer patients at risk for development of adverse effects following radiotherapy. Cancer Discov. 4:155-65, 2014.
Hiraki S, Rinella ES, Schnabel F, Oratz R, Ostrer H. Cancer risk assessment using genetic panel testing: considerations for clinical application. J Genet Couns. 23:604-17, 2014.
Rosenstein BS, West CM, Bentzen SM, Alsner J, Andreassen CN, Azria D, Barnett GC, Baumann M, Burnet N, Chang-Claude J, Chuang EY, Coles CE, Dekker A, De Ruyck K, De Ruysscher D, Drumea K, Dunning AM, Easton D, Eeles R, Fachal L, Gutiérrez-Enríquez S, Haustermans K, Henríquez-Hernández LA, Imai T, Jones GD, Kerns SL, Liao Z, Onel K, Ostrer H, Parliament M, Pharoah PD, Rebbeck TR, Talbot CJ, Thierens H, Vega A, Witte JS, Wong P, Zenhausern F; Radiogenomics Consortium. Radiogenomics: radiobiology enters the era of big data and team science. Int J Radiat Oncol Biol Phys. 89:709-13, 2014
Kerns SL, Guevara-Aguirre J, Andrew S, Geng J, Guevara C, Guevara-Aguirre M, Guo M, Oddoux C, Shen Y, Zurita A, Rosenfeld RG, Ostrer H, Hwa V, Dauber A. A novel variant in CDKN1C is associated with intrauterine growth restriction, short stature, and early-adulthood onset diabetes. J Clin Endocrinol Metab. 99:E2117-22. doi: 10.1210/jc.2014-1949, 2014
Carmi S, Hui KY, Kochav E, Liu X, Xue J, Grady F, Guha S, Upadhyay K, Ben-Avraham D, Mukherjee S, Bowen BM, Thomas T, Vijai J, Cruts M, Froyen G, Lambrechts D, Plaisance S, Van Broeckhoven C, Van Damme P, Van Marck H, Barzilai N, Darvasi A, Offit K, Bressman S, Ozelius LJ, Peter I, Cho JH, Ostrer H, Atzmon G, Clark LN, Lencz T, Pe'er I. Sequencing an Ashkenazi reference panel supports population-targeted personal genomics and illuminates Jewish and European origins. Nat Commun. 2014 Sep 9;5:4835. doi: 10.1038/ncomms5835.
Rosenstein BS, West CM, Bentzen SM, Alsner J, Andreassen CN, Azria D, Barnett GC, Baumann M, Burnet N, Chang-Claude J, Chuang EY, Coles CE, Dekker A, De Ruyck K, De Ruysscher D, Drumea K, Dunning AM, Easton D, Eeles R, Fachal L, Gutiérrez-Enríquez S, Haustermans K, Henríquez-Hernández LA, Imai T, Jones GD, Kerns SL, Liao Z, Onel K, Ostrer H, Parliament M, Pharoah PD, Rebbeck TR, Talbot CJ, Thierens H, Vega A, Witte JS, Wong P, Zenhausern F; Radiogenomics Consortium. Radiogenomics: radiobiology enters the era of big data and team science. Int J Radiat Oncol Biol Phys. 2014 Jul 15;89(4):709-13. doi:10.1016/j.ijrobp.2014.03.009. PubMed PMID: 24969789.
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