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James Wetmur

  • PROFESSOR EMERITUS Microbiology
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Education

  • Ph.D., California Institute of Technology
    Chemistry (biophysical)

  • B.S., Yale University
    Chemistry

Biography

    James G. Wetmur, Ph.D.
    Professor, Microbiology
    Professor, Genetics And Genomic Sciences

    E-mail: james.wetmur@mssm.edu
    Tel: (212) 241-7685

    Mailing Address
    One Gustave L. Levy Place, Box 1124, New York, NY 10029

    Video

    Watch a video featuring the Microbiology and Virology PhD Graduate School Program.

Research

A major focus of our research has dealt with biophysical chemistry of nucleic acid hybridization and branch migration as well as DNA-interacting proteins. In recent work related to single cell analyses, we have developed a single molecule-based molecular haplotyping system. The system begins with simultaneous PCR across two heterozygous polymorphic sites on single template molecules isolated by an oil-water emulsion. The method relies on linking PCR in the emulsion to connect the two PCR products, capping and allele-specific PCR readouts.

Human PON1 haplotypes were determined in a large cohort to demonstrate haplotype-phenotype association. PON1 is essential for the detoxification of organophosphates. As part of the birth cohort study in the Mount Sinai Children's Environmental Health Center, we have examined human variation in activation and detoxification of organophosphates. We have found that not only do neonates have four-fold lower levels of PON1 than adults, but that those levels vary more widely with common promoter polymorphisms in neonates than in adults. Thus certain neonates have up to 10-fold less protection than adults. Low maternal PON1 together with maternal exposure to a commonly used organophosphate had a significant effect on birth outcome in the cohort.

In additional current work related to individual genetic variation, we are developing high-throughput methods for measuring mRNA allelic imbalance in human dendritic cells challenged with viruses in the Technology Development Component (TDC) of the Center for Investigating Viral Immunity and Antagonism (CIVIA) and in the Program for Research in Immune Modeling and Experimentation (PRIME). These studies complement the transcriptome approaches in CIVIA and PRIME and enable the discovery of new human variation evident only in the context of viral challenge. In addition, we have developed new technology allowing measurement of transcription from single human dendritic cells and from individual chromosomes within these single cells. Such variation may be important in identification of susceptible individuals and in the development of vaccines.

Publications

Hartmann BM, Li W, Jia J, Patil S, Marjanovic N, Martínez-Romero C, Albrecht RA, Hayot F, García-Sastre A, Wetmur JG, Moran TM, Sealfon SC. Mouse dendritic cell (DC) influenza virus infectivity is much lower than that for human DCs and is hemagglutinin subtype dependent. Journal of virology 2013 Feb; 87(3).

Xu X, Gammon MD, Hernandez-Vargas H, Herceg Z, Wetmur JG, Teitelbaum SL, Bradshaw PT, Neugut AI, Santella RM, Chen J. DNA methylation in peripheral blood measured by LUMA is associated with breast cancer in a population-based study. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2012 Jun; 26(6).

Engel SM, Wetmur J, Chen J, Zhu C, Barr DB, Canfield RL, Wolff MS, Wolff MS. Prenatal exposure to organophosphates, paraoxonase 1, and cognitive development in childhood. Environmental health perspectives 2011 Aug; 119(8).

Hu J, Nudelman G, Shimoni Y, Kumar M, Ding Y, López C, Hayot F, Wetmur JG, Sealfon SC. Role of cell-to-cell variability in activating a positive feedback antiviral response in human dendritic cells. PloS one 2011; 6(2).

Hu J, Nistal-Villán E, Voho A, Ganee A, Kumar M, Ding Y, García-Sastre A, Wetmur JG. A common polymorphism in the caspase recruitment domain of RIG-I modifies the innate immune response of human dendritic cells. Journal of immunology (Baltimore, Md. : 1950) 2010 Jul; 185(1).

Zaslavsky E, Hershberg U, Seto J, Pham AM, Marquez S, Duke JL, Wetmur JG, Tenoever BR, Sealfon SC, Kleinstein SH. Antiviral response dictated by choreographed cascade of transcription factors. Journal of immunology (Baltimore, Md. : 1950) 2010 Mar; 184(6).

Nudelman G, Ge Y, Hu J, Kumar M, Seto J, Duke JL, Kleinstein SH, Hayot F, Sealfon SC, Wetmur JG. Coregulation mapping based on individual phenotypic variation in response to virus infection. Immunome research 2010; 6.

Pozharny Y, Lambertini L, Ma Y, Ferrara L, Litton CG, Diplas A, Jacobs AR, Chen J, Stone JL, Wetmur J, Lee MJ. Genomic loss of imprinting in first-trimester human placenta. American journal of obstetrics and gynecology 2010 Apr; 202(4).

Hu J, Iyer-Biswas S, Sealfon SC, Wetmur J, Jayaprakash C, Hayot F, Wetmur JG, Wolff MS. Power-laws in interferon-B mRNA distribution in virus-infected dendritic cells. Biophysical journal 2009 Oct; 97(7).

Diplas AI, Hu J, Lee MJ, Ma YY, Lee YL, Lambertini L, Chen J, Wetmur JG. Demonstration of all-or-none loss of imprinting in mRNA expression in single cells. Nucleic acids research 2009 Nov; 37(21).

Lambertini L, Diplas AI, Lee MJ, Sperling R, Chen J, Wetmur J, Chen J, Wetmur JG. A sensitive functional assay reveals frequent loss of genomic imprinting in human placenta. Epigenetics : official journal of the DNA Methylation Society 2008 Sep; 3(5).

Engel SM, Berkowitz GS, Barr DB, Teitelbaum SL, Siskind J, Meisel SJ, Wetmur JG, Wolff MS, Sealfon SC. Prenatal organophosphate metabolite and organochlorine levels and performance on the Brazelton Neonatal Behavioral Assessment Scale in a multiethnic pregnancy cohort. American journal of epidemiology 2007 Jun; 165(12).

Wolff MS, Engel S, Berkowitz G, Teitelbaum S, Siskind J, Barr DB, Wetmur J. Prenatal pesticide and PCB exposures and birth outcomes. Pediatric research 2007 Feb; 61(2).

Hu J, Sealfon SC, Hayot F, Jayaprakash C, Kumar M, Pendleton AC, Ganee A, Fernandez-Sesma A, Moran TM, Wetmur JG. Chromosome-specific and noisy IFNB1 transcription in individual virus-infected human primary dendritic cells. Nucleic acids research 2007; 35(15).

Wolff MS, Engel SM, Berkowitz GS, Ye X, Silva MJ, Zhu C, Wetmur J, Calafat AM, García-Sastre A, Wetmur JG, Moran TM, Sealfon SC. Prenatal phenol and phthalate exposures and birth outcomes. Environmental health perspectives 2008 Aug; 116(8).

Berkowitz GS, Wetmur JG, Birman-Deych E, Obel J, Lapinski RH, Godbold JH, Holzman IR, Wolff MS. In utero pesticide exposure, maternal paraoxonase activity, and head circumference. Environ Health Perspect 2004 Mar; 112(3): 388-91.

Chen J, Kumar M, Chan W, Berkowitz G, Wetmur JG, Meisel SJ, Wetmur JG, Wolff MS, Sealfon SC, Kleinstein SH. Increased influence of genetic variation on PON1activity in neonates. Environ Health Perspect 2003 Aug; 111(11): 1403-9.

Chen J, Germer S, Higuchi R, Berkowitz G, Godbold J, Wetmur JG, Wetmur JG, Wolff MS, Sealfon SC, Wetmur JG. Kinetic polymerase chain reaction on pooled DNA: a high-throughput, high-efficiency alternative in genetic epidemiological studies. Cancer Epidemiol Biomarkers Prev 2002 Jan; 11(1): 131-6.

Putnam CD, Clancy SB, Tsuruta H, Gonzalez S, Wetmur J, Tainer JA, Holzman IR, Wolff MS, Stone JL, Wetmur J, Lee MJ. Structure and mechanism of the RuvB Holliday junction branch migration motor. J Mol Biol 2001 Aug 10; 311(2): 297-310.

Wetmur JG, Berkowitz G, Wetmur JG, Tainer JA, Holzman IR, Wolff MS. Nucleic Acid Hybridization. In: Rubin H, Wood DH, editors. DNA Based Computers III. American Mathematical Society; 1999.prettyprintp1-23.

Industry Relationships

Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.

Dr. Wetmur did not report having any of the following types of financial relationships with industry during 2012 and/or 2013: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.

Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.

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Address

Annenberg Building Floor 16 Room 16-98
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Address

Annenberg Building Floor 16 th floor Room 16-98
1468 Madison Avenue
New York, NY 10029

Tel: 212-247-7685
Fax: 212-534-1684