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, The Ashkenazi Genome Consortium) 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. We identified mutations in genes in the MAP kinase pathway in abnormal testicular development and have investigated 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 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. We have also developed flow variant assays as a novel method for identifying germline risks of cancer

Syeda MM, Upadhyay K, Loke J, Pearlman A, Klugman S, Shao Y, Ostrer H. Prediction of breast cancer risk based on flow-variant analysis of circulating peripheral blood B cells. Genet Med. 2017 Sep;19(9):1071-1077. doi:10.1038/gim.2016.222. Epub 2017 Mar 16. PubMed PMID: 28301456.

diSibio G, Upadhyay K, Meyer P, Oddoux C, Ostrer H. Assessing risk for Mendelian disorders in a Bronx population. Mol Genet Genomic Med. 2017 Jul 6;5(5):516-523. doi: 10.1002/mgg3.307. eCollection 2017 Sep. PubMed PMID: 28944235; PubMed Central PMCID: PMC5606885.

Upadhyay K, Loke J, O V, Taragin B, Ostrer H. Biallelic mutations in FLNB cause a skeletal dysplasia with 46,XY gonadal dysgenesis by activating β-catenin. Clin Genet. 2018 Feb;93(2):412-416. doi: 10.1111/cge.13165. Epub 2017 Dec 26. PubMed PMID: 29095481.

Lee S, Kerns S, Ostrer H, Rosenstein B, Deasy JO, Oh JH. Machine Learning on a Genome-wide Association Study to Predict Late Genitourinary Toxicity After Prostate Radiation Therapy. Int J Radiat Oncol Biol Phys. 2018 May 1;101(1):128-135. doi: 10.1016/j.ijrobp.2018.01.054. Epub 2018 Jan 31. PubMed PMID: 29502932; PubMed Central PMCID: PMC5886789.

Lencz T, Yu J, Palmer C, Carmi S, Ben-Avraham D, Barzilai N, Bressman S, Darvasi A, Cho JH, Clark LN, Gümüş ZH, Joseph V, Klein R, Lipkin S, Offit K, Ostrer H, Ozelius LJ, Peter I, Atzmon G, Pe'er I. High-depth whole genome sequencing of an Ashkenazi Jewish reference panel: enhancing sensitivity, accuracy, and imputation. Hum Genet. 2018 Apr;137(4):343-355. doi:10.1007/s00439-018-1886-z. Epub 2018 Apr 28. PubMed PMID: 29705978.

Pearlman A, Upadhyay K, Cole K, Loke J, Sun K, Fineberg S, Freedland SJ, Shao Y, Ostrer H. Robust genomic copy number predictor of pan cancer metastasis. Genes Cancer. 2018 Jan;9(1-2):66-77. doi: 10.18632/genesandcancer.165. PubMed PMID: 29725504; PubMed Central PMCID: PMC5931251.

Kerns SL, Chuang KH, Hall W, Werner Z, Chen Y, Ostrer H, West C, Rosenstein B. Radiation biology and oncology in the genomic era. Br J Radiol. 2018 Nov;91(1091):20170949. doi: 10.1259/bjr.20170949. Epub 2018 Jun 14. Review. PubMed PMID: 29888979.

Dadaev T, Saunders EJ, Newcombe PJ, Anokian E, Leongamornlert DA, Brook MN, Cieza-Borrella C, Mijuskovic M, Wakerell S, Olama AAA, Schumacher FR, Berndt SI, Benlloch S, Ahmed M, Goh C, Sheng X, Zhang Z, Muir K, Govindasami K, Lophatananon A, Stevens VL, Gapstur SM, Carter BD, Tangen CM, Goodman P, Thompson IM Jr, Batra J, Chambers S, Moya L, Clements J, Horvath L, Tilley W, Risbridger G, Gronberg H,
Aly M, Nordström T, Pharoah P, Pashayan N, Schleutker J, Tammela TLJ, Sipeky C, Auvinen A, Albanes D, Weinstein S, Wolk A, Hakansson N, West C, Dunning AM, Burnet N, Mucci L, Giovannucci E, Andriole G, Cussenot O, Cancel-Tassin G, Koutros S, Freeman LEB, Sorensen KD, Orntoft TF, Borre M, Maehle L, Grindedal EM, Neal DE, Donovan JL, Hamdy FC, Martin RM, Travis RC, Key TJ, Hamilton RJ, Fleshner NE, Finelli A, Ingles SA, Stern MC, Rosenstein B, Kerns S, Ostrer H, Lu YJ, Zhang HW, Feng N, Mao X, Guo X, Wang G, Sun Z, Giles GG, Southey MC, MacInnis RJ, FitzGerald LM, Kibel AS, Drake BF, Vega A, Gómez-Caamaño A, Fachal L, Szulkin R, Eklund M, Kogevinas M, Llorca J, Castaño-Vinyals G, Penney KL, Stampfer M, Park JY, Sellers TA, Lin HY, Stanford JL, Cybulski C, Wokolorczyk D, Lubinski J, Ostrander EA, Geybels MS, Nordestgaard BG, Nielsen SF, Weisher M, Bisbjerg R, Røder MA, Iversen P, Brenner H, Cuk K, Holleczek B, Maier C, Luedeke M, Schnoeller T, Kim J, Logothetis CJ, John EM, Teixeira MR, Paulo P, Cardoso M, Neuhausen SL, Steele L, Ding YC, De Ruyck K, De Meerleer G, Ost P, Razack A, Lim J, Teo SH, Lin DW, Newcomb LF, Lessel D, Gamulin M, Kulis T, Kaneva R, Usmani N, Slavov C, Mitev V, Parliament M, Singhal S, Claessens F, Joniau S, Van den Broeck T, Larkin S, Townsend PA, Aukim-Hastie C, Gago-Dominguez M, Castelao JE, Martinez ME, Roobol MJ, Jenster G, van Schaik RHN, Menegaux F, Truong T, Koudou YA, Xu J, Khaw KT, Cannon-Albright L, Pandha H, Michael A, Kierzek A, Thibodeau SN, McDonnell SK, Schaid DJ, Lindstrom S, Turman C, Ma J, Hunter DJ, Riboli E, Siddiq A, Canzian F, Kolonel LN, Le Marchand L, Hoover RN, Machiela MJ, Kraft P; PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium, Freedman M, Wiklund F, Chanock S, Henderson BE, Easton DF, Haiman CA, Eeles RA, Conti DV, Kote-Jarai Z. Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants. Nat Commun. 2018 Jun 11;9(1):2256. doi:10.1038/s41467-018-04109-8. PubMed PMID: 9892050; PubMed Central PMCID: PMC5995836.

Fofanov VY, Upadhyay K, Pearlman A, Loke J, O V, Shao Y, Freedland S, Ostrer H. Rapid Next-Generation Sequencing Method for Prediction of Prostate Cancer Risks. J Mol Diagn. 2019 Jan;21(1):49-57. doi: 10.1016/j.jmoldx.2018.07.007. Epub 2018 Dec 12. PubMed PMID: 30553750; PubMed Central PMCID: PMC6334266. Rutgers L, Ostrer H, Prowse T, Schroeder H. Diaspora, migration, and the sciences: a new integrated perspective. Eur J Hum Genet. 2018 Dec 19. doi:10.1038/s41431-018-0314-0. [Epub ahead of print] Review. PubMed PMID: 30568243.

Chamberlin A, Huether R, Machado AZ, Groden M, Liu HM, Upadhyay K, O V, Gomes NL, Lerario AM, Nishi MY, Costa EMF, Mendonca B, Domenice S, Velasco J, Loke J, Ostrer H. Mutations in MAP3K1 that cause 46,XY disorders of sex development disrupt distinct structural domains in the protein. Hum Mol Genet. 2019 Jan 4. doi: 10.1093/hmg/ddz002. [Epub ahead of print] PubMed PMID: 30608580.

Pearlman A, Rahman MT, Upadhyay K, Loke J, Ostrer H. Ectopic Otoconin 90 expression in triple negative breast cancer cell lines is associated with metastasis functions. PLoS One. 2019 Feb 14;14(2):e0211737. doi:10.1371/journal.pone.0211737. eCollection 2019. PubMed PMID: 0763339; PubMed Central PMCID: PMC6375562.

Kerns SL, Fachal L, Dorling L, Barnett GC, Baran A, Peterson DR, Hollenberg M, Hao K, Narzo AD, Ahsen ME, Pandey G, Bentzen SM, Janelsins M, Elliott RM, Pharoah PDP, Burnet NG, Dearnaley DP, Gulliford SL, Hall E, Sydes MR, Aguado-Barrera ME, Gómez-Caamaño A, Carballo AM, Peleteiro P, Lobato-Busto R, Stock R, Stone NN, Ostrer H, Usmani N, Singhal S, Tsuji H, Imai T, Saito S, Eeles R, DeRuyck K, Parliament M, Dunning AM, Vega A, Rosenstein BS, West CML. Radiogenomics Consortium Genome-Wide Association Study Meta-analysis of Late Toxicity after Prostate Cancer Radiotherapy. J Natl Cancer Inst. 2019 May 16. pii: djz075. doi: 10.1093/jnci/djz075. [Epub ahead of print] PubMed PMID: 1095341.