Jay A. Tischfield, Ph.D.
Life Sciences Building,Room 136
145 Bevier Road, Piscataway
Fax: (732) 445-1147
Our primary research interests include studies of both somatically heritable and transient genetic changes in somatic cells that predispose to disease in humans. In addition, we are engaged in several large projects whose ultimate goal is the identification of genes that have major contributions to complex oligogenic disorders.
Loss of heterozygosity (LOH) for tumor suppressor genes in somatic cells frequently results in a recessive cellular phenotype that leads to cancer. We have studied the frequency and mechanisms of LOH in human heterozygotes and produced a heterozygous mouse model for investigation of LOH in different genetic backgrounds and after exposure to environmental agents. We have discovered that the major mechanisms for LOH in normal cells are mitotic recombination, followed by point mutation. Thus, we are investigating genes (e.g., Tp53, Mlh1, Msh2) and environmental agents that may affect these processes. The mouse is an excellent model for this research due to the availability of many "knockouts" for genes that might affect LOH and our ability to deliver environmental agents, such as chemicals and radiation, in a precise manner.
Our group has also produced a knockout mouse model for APRT deficiency, which produces a human genetic disease (dihydroxyadenine urolithiasis) characterized by severe kidney stones and, in rare cases, chronic renal failure. We are comparing gene expression in mice with and without kidney stones in order to identify genes that are involved in early and late pathological changes. Thus far, the expression of several known and novel genes has been shown to increase or decrease with stone disease. We are investigating the expression of these genes in specific kidney cell types and correlating it with pathologic changes. Such studies may produce new targets for early pharmacologic intervention in the progression of kidney stone disease.
We are collaborating in several large, multidisciplinary projects whose goal is the identification and characterization of genes that make major contributions to complex human diseases such as alcoholism, opiate addiction, autism, schizophrenia and bipolar disorder. We are collecting blood and producing cell lines and DNA from large numbers of individuals in families with a high incidence of a specific disorder in an effort to find such genes.
Derringer J, Krueger RF, Manz N, Porjesz B, Almasy L, Bookman E, Edenberg HJ, Kramer JR, Tischfield JA, Bierut LJ. (2011) Nonreplication of an association of SGIP1 SNPs with alcohol dependence and resting theta EEG power. Psychiatr Genet. Feb 10. [Epub ahead of print]
Saccone SF, Quan J, Mehta G, Bolze R, Thomas P, Deelman E, Tischfield JA, Rice JP.New tools and methods for direct programmatic access to the dbSNP relational database. (2011) Nucleic Acids Res. 39(Database issue):D901-907.
Saccone SF, Bolze R, Thomas P, Quan J, Mehta G, Deelman E, Tischfield JA, Rice JP. (2010) SPOT: a web-based tool for using biological databases to prioritize SNPs after a genome-wide association study. Nucleic Acids Res. 38:W201-209.
Kalsi G, Kuo PH, Aliev F, Alexander J, McMichael O, Patterson DG, Walsh D, Zhao Z, Schuckit M, Nurnberger J Jr, Edenberg H, Kramer J, Hesselbrock V, Tischfield, J, Vladimirov V, Prescott CA, Dick DM, Kendler KS, Riley BP. A systematic gene-based screen of chr4q22-q32 identifies association of a novel susceptibility gene, DKK2, with the quantitative trait of alcohol dependence symptom counts. Hum Mol Genet. 19(12):2497-2506, 2010.
Saccone SF, Bolze R, Thomas P, Quan J, Mehta G, Deelman E, Tischfield JA, Rice JP. SPOT: a web-based tool for using biological databases to prioritize SNPs after a genome-wide association study. Nucleic Acids Res. 38 Suppl:W201-209, 2010.
Bauer L, Dick D, Bierut L, Bucholz K, Edenberg H, Kuperman S, Kramer J, Nurnberger J, O'Connor S, Rice J, Rohrbaugh J, Schuckit M, Tischfield J, Porjesz B, Hesselbrock V. Obesity, smoking and frontal brain dysfunction. Am J Addict. 19(5):391-400, 2010.
Serrano L, Liang L, Chang Y, Deng L, Maulion C, Nguyen SC, Tischfield JA. Homologous Recombination conserves DNA sequence integrity throughout the cell cycle in embryonic stem cells. Stem Cells Dev. 20(2):363-374, 2011.
Willemsen G, de Geus EJ, Bartels M, van Beijsterveldt CE, Brooks AI, Estourgie-van Burk GF, Fugman DA, Hoekstra C, Hottenga JJ, Kluft K, Meijer P, Montgomery GW, Rizzu P, Sondervan D, Smit AB, Spijker S, Suchiman HE, Tischfield JA, Lehner T, Slagboom PE, Boomsma DI. TheNetherlandstwin register biobank: a resource for genetic epidemiological studies. Twin Res Hum Genet. 13(3):231-245, 2010.
Dick DM, Meyers J, Aliev F, Nurnberger J Jr, Kramer J, Kuperman S, Porjesz B, Tischfield J, Edenberg HJ, Foroud T, Schuckit M, Goate A, Hesselbrock V, Bierut L. Evidence for genes on chromosome 2 contributing to alcohol dependence with conduct disorder and suicide attempts. Am J Med Genet B Neuropsychiatr Genet. 153B(6):1179-1188, 2010.
Tichy ED, Pillai R, Deng L, Liang L, Tischfield JA, Schwemberger S, Babcock GF, Stambrook PJ. Mouse embryonic stem cells but not somatic cells predominantly use homologous recombination to repair double strand DNA breaks. Stem Cells Dev. 19(11):1699-1711, 2010.
Ercan-Sencicek AG, Stillman AA, Ghosh AK, Bilguvar K, O'Roak BJ, Mason CE, Abbott T, Gupta A, King RA, Pauls DL, Tischfield JA, Heiman GA, Singer HS, Gilbert DL, Hoekstra PJ, Morgan TM, Loring E, Yasuno K, Fernandez T, Sanders S, Louvi A, Cho JH, Mane S, Colangelo CM, Biederer T, Lifton RP, Gunel M, State MW. L-histidine decarboxylase and Tourette's syndrome. N Engl J Med. 362(20):1901-1908, 2010.
Lin P, Hartz SM, Zhang Z, Saccone SF, Wang J, Tischfield JA, Edenberg HJ, Kramer JR, M Goate A, Bierut LJ, Rice JP; COGA Collaborators COGEND Collaborators, GENEVA. A new statistic to evaluate imputation reliability. PLoS One. 5(3):e9697, 2010.
Tereshchenko IV, Chen Y, McDaniel LD, Schultz RA, Tischfield JA, Shao C. Small scale genetic alterations contribute to increased mutability at the X-linked Hprt locus in vivo in Blm hypomorphic mice. DNA Repair (Amst). 9(5):551-557, 2010.
Bierut LJ, Agrawal A, Bucholz KK, Doheny KF, Laurie C, Pugh E, Fisher S, Fox L, Howells W, Bertelsen S, Hinrichs AL, Almasy L, Breslau N, Culverhouse RC, Dick DM, Edenberg HJ, Foroud T, Grucza RA, Hatsukami D, Hesselbrock V, Johnson EO, Kramer J, Krueger RF, Kuperman S, Lynskey M, Mann K, Neuman RJ, Nöthen MM, Nurnberger JI Jr, Porjesz B, Ridinger M, Saccone NL, Saccone SF, Schuckit MA, Tischfield JA, Wang JC, Rietschel M, Goate AM, Rice JP; Gene, Environment Association Studies Consortium. A genome-wide association study of alcohol dependence. Proc Natl Acad Sci U S A. 107(11):5082-5087, 2010.