Sam-Judith-Singer

Judith Singer-Sam, Ph.D.

  • Professor Emeritus, Diabetes & Metabolism Research Institute

Judith Singer-Sam, Ph.D.

Research Focus :
  • Epigenetics
  • Mono-allelic Expression
  • Central Nervous System
Other Languages Spoken
  • French
  • 2012-present, Professor Emeritus, Department of Diabetes and Metabolic Diseases
  • 2008 - 2012, Professor and Director, Division of Biology, Beckman Research Institute of City of Hope, Duarte, CA
  • 2009 - 2012, Associate Chair, Department of Cancer Biology, Beckman Research Institute of City of Hope, Duarte, CA
  • 2006 - 2009, Professor, Department of Biology, Beckman Research Institute of City of Hope, Duarte, CA
  • 2001 - 2009, Associate Chair, Department of Biology, Beckman Research Institute of City of Hope, Duarte, CA
  • 2003 - 2006, Professor, Department of Biology, Beckman Research Institute of City of Hope, Duarte, CA
  • 1999, Associate Professor, Beckman Research Institute of City of Hope, Duarte, CA 1985 - 1993, Associate Research Scientist, Beckman Research Institute of City of Hope, Duarte, CA
  • 1981, Visiting Scientist, Pasteur Institute, Paris
  • 1979 - 1985, Assistant Research Scientist, City of Hope, Duarte, CA 1976 - 1979, Research Associate, City of Hope, Duarte, CA 1972 - 1975, Postdoctoral Fellow, City of Hope, Duarte, CA
  • Diabetes & Metabolism Research Institute

Degrees

  • 1967, City College of New York, B.S., Biology
  • 1973, University of California, Santa Barbara, Ph.D., Biology (Microbial Genetics & Biochemistry)
Monoallelic Expression in the Central Nervous System
 
Although most genes in a cell are expressed from both the maternal and paternal chromosome, there are exceptions. For example, in women, most X-linked genes are expressed from only one of the two X chromosomes, a phenomenon called X inactivation. In addition, there is a class of autosomal genes, termed imprinted genes, for which parental origin determines which allele is expressed. Finally, there are autosomal genes that appear at first glance to be bi-allelically expressed but actually show random monoallelic expression (sometimes termed allelic exclusion) at the single-cell level. These exceptions, examples of epigenetics, have proven to be of great interest for researchers because they shed light on gene regulation, chromatin structure, development, and the pattern of inheritance of certain genetic disorders.
 
My research program is focused on the potential role of allele-specific expression in development and function of the central nervous system (CNS). What is the evidence that genes likely to play a role in CNS function show such expression? Olfactory receptors, which are expressed in specialized cells of the CNS, show allelic exclusion, as does p120 catenin, which is involved in synapse formation. Intriguing recent work has shown that a number of factors involved in the immune response, including the genes for interleukin-2 and interleukin-4, also show allelic exclusion. Some of these genes are expressed in the CNS, leading us and others to explore the possibility that other genes in the CNS, including ones that are inflammation-sensitive, may show a similar pattern of expression. 
 
Our current work is focused on several questions:
  1. Can we identify genes showing monoallelic expression that may be implicated in certain genetic disorders of the CNS?
  2. Are there specific regulatory DNA sequences associated with the potential for monoallelic expression?
  3. Can we “repair” the effects of mutations in such genes by activating the silent allele?
 
For a growing number of genes, only one of the two chromosomal copies (or alleles) is expressed, a phenomenon termed monoallelic expression. In some cases, there is random selection of the expressed allele; in others parental origin determines which allele is expressed, which is termed imprinting. Disorders with a genetic component in which either random monoallelic expression or imprinting may play a role include schizophrenia, multiple sclerosis, and diabetes.
 
Our goal is to understand the mechanism and extent of imprinting and monoallelic expression, and their possible relevance to inherited disorders, particularly those of the central nervous system. Towards this goal, we developed a high-throughput assay for monoallelic expression, using clonal lines of genetically hybrid neural stem cells derived by crossing two inbred strains of mice.   This assay allowed us to identify over 100 genes that show monoallelic expression in these cells.  We have recently expanded the assay to analyze clonal astrocytic populations as well as single hippocampal neurons, and are currently doing experiments to probe the mechanism that leads to monoallelic expression in these cells.
Li, M., Valo, Z., Wang, J., Gao, H., Bowers, C.W., Singer-Sam, J. (2012). Transcriptome-wide survey of     mouse CNS-derived cells reveals monoallelic expression within novel gene families.  PLoS ONE  7,     e31751.

Wang, J., Valo, Z., Bowers, C., Smith, D., Liu, Z, Singer-Sam, J. (2010). Dual DNA methylation patterns in     the CNS reveal developmentally poised chromatin and monoallelic expression of critical genes.  PLoS     ONE  5, e13843.

Singer-Sam, J. (2010).  Monoallelic expression. Nature Education 3, 1.

Wang, J., Valo, Z., Smith, D., and Singer-Sam, J. (2007). Monoallelic expression of multiple genes in the CNS. PLoS ONE 2, e1293.

Bowers, C.H. and Singer-Sam, J. (2007).  Unique retrotransposon LINE-1 distribution at the Prader-    Willi/Angelman syndrome locus. J. Mol. Evol. 65, 475-484.

Buettner, V. L., Walker, A. L., and Singer-Sam, J. (2005). Novel paternally expressed intergenic transcripts  at the mouse Prader-Willi/Angelman Syndrome locus. Mammalian Genome 16, 219-227.

Buettner, V. L., Longmate, J. A., Barish, M. E., Mann, J. R., and Singer-Sam, J. (2004). Analysis of imprinting in mice with uniparental duplication of proximal chromosomes 7 and 15 by use of a custom oligonucleotide microarray. Mammalian Genome 15, 199-209.

Shively, L., Chang, L., LeBon, J. M., Liu, Q., Riggs, A. D., and Singer-Sam, J. (2003). A real time PCR assay for quantitative mismatch detection. BioTechniques 34, 498-504.
 
Ring, R. H., Valo, Z., Gao, C., Barish, M. E., and Singer-Sam, J. (2003). The Cdkn1a gene (p21WAf1/Cip1) is an inflammatory response gene in the mouse central nervous system. Neurosci. Lett. 350, 73-76.
 
Singer-Sam, J., and Gao, C. (2001). Quantitative RT-PCR-based analysis of allele-specific gene expression. In Methods in Molecular Biology, A. Ward, ed. (Totowa, NJ, Humana Press), pp. 145-152.
 
Mann, J. R., Szabo, P. E., Reed, M. R., and Singer-Sam, J. (2000). Methylated DNA sequences in genomic imprinting. In Critical Reviews in Eukaryotic Gene Expression, G. S. Stein, J. L. Stein, and J. B. Lian, eds. (New York, Begell House, Inc.), pp. 241-257.
 
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