A National Cancer Institute-designated Comprehensive Cancer Center

Make an appointment: 800-826-HOPE

Singer-Sam, Judith, Ph.D. Laboratory

Laboratory of Judith Singer-Sam, Ph.D.
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 are studying a mouse locus corresponding to a human inherited mental retardation disorder known to involve imprinted genes, the Prader-Willi/Angelman Syndrome. We are also developing an assay that would make use of state-of-the-art microarray technology to probe for imprinting and monoallelic expression in the entire genome.
 

Research

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, and the possibility arises that other inflammation-sensitive genes in the CNS may show a similar pattern of expression.  Using gene expression profiling, we discovered that, Cdkn1a, coding for the cell cycle regulator p21Waf1/Cip1, is inflammation-sensitive in the CNS as well as other tissues.  While this gene is bi-allelically expressed, we expect to find additional immune response genes that do undergo monoallelic expression.
 
We have also developed an imprinting screen using expression microarrays. As a model system, we analyzed mice with imprinting defects in proximal chromosome 7; part of this region is analogous to human chromosome 15q11-q13, a locus associated with a number of behavioral and cognitive disorders including the well-studied Prader-Willi/Angelman Syndrome (PW/AS). Our analysis revealed the presence of two novel paternally expressed intergenic transcripts at the mouse PW/AS locus, in a region highly enriched in LINE-1 elements; the function of these transcripts is still unknown.  In separate work, we discovered, in collaboration with Dr. Chauncey Bowers (Department of Neurosciences) that the dense LINE-1 elements in this region are organized in a uniquely asymmetric way, perhaps related to imprinting at the locus.
 
Our current work involves the identification and characterization of genes that are subject to random monoallelic expression in the CNS. We have developed a microarray-based assay for genes that are both silenced and active at the same locus as evidenced by a dual DNA methylation pattern.  We further analyze candidate genes using SNP differences in cDNA of clonal neural stem cell lines derived from F1 hybrids of two different strains of mice. We have found a number of “hits” and are currently characterizing those that appear potentially most relevant to disorders of the CNS.
 
Our Scientists

Our research laboratories are led by the best and brightest minds in scientific research.
 

Beckman Research Institute of City of Hope is internationally  recognized for its innovative biomedical research.
City of Hope is one of only 41 Comprehensive Cancer Centers in the country, the highest designation awarded by the National Cancer Institute to institutions that lead the way in cancer research, treatment, prevention and professional education.
Learn more about City of Hope's institutional distinctions, breakthrough innovations and collaborations.
Develop new therapies, diagnostics and preventions in the fight against cancer and other life-threatening diseases.
 
Support Our Research
By giving to City of Hope, you support breakthrough discoveries in laboratory research that translate into lifesaving treatments for patients with cancer and other serious diseases.
 
 
 
 
NEWS & UPDATES
  • Cancer cells may be known for their uncontrollable growth and spread, but they also differ from normal tissue in another manner: how they produce energy. In healthy cells, energy is derived primarily from aerobic respiration, an oxygen-requiring process that extracts the maximum possible energy from glucose, or...
  • Clinical trials are expensive and complex, but they’re essential for bringing new therapies to patients. Edward Newman, Ph.D., associate professor of molecular pharmacology, just boosted City of Hope’s ability to conduct those studies with a five-year, $4.2 million grant from the National Cancer Institute...
  • Meet City of Hope’s new chair of the Department of Surgery – esteemed pancreatic and hepatobiliary surgeon, researcher and author Yuman Fong, M.D. As one of today’s most respected and recognizable physicians in the treatment of cancers of the liver, bile duct, gallbladder and pancreas, Fong has pioneered and en...
  • For most of her life, Southern California teenager Kayla Saikaly described herself as healthy, even very healthy. She played basketball. She never missed school with as much as a fever. Her worst childhood illness was nothing more than a cold. Then, when she was 13, her nose started bleeding after a basketball ...
  • Neuroblastoma is one of the deadliest childhood cancers, accounting for 15 percent of pediatric cancer deaths. For patients with high-risk neuroblastomas, the five-year survival rate is 40 to 50 percent even with the most rigorous treatments available today. But those odds may improve soon, thanks to a new comp...
  • For breast cancer survivors, a common worry is a recurrence of their cancer. Currently, these patients are screened with regular mammograms, but there’s no way to tell who is more likely to have a recurrence and who is fully cleared of her cancer. A new blood test – reported in Cancer Research, a journal of the...
  • Metastasis — the spreading of cancer cells from a primary tumor site to other parts of the body — generally leads to poorer outcomes for patients, so oncologists and researchers are constantly seeking new ways to detect and thwart this malicious process. Now City of Hope researchers may have identified a substa...
  • Deodorant, plastic bottles, grilled foods, artificial sweeteners, soy products … Do any of these products really cause cancer? With so many cancer myths and urban legends out there, why not ask the experts? They can debunk cancer myths while sharing cancer facts that matter, such as risk factors, preventi...
  • Cancer risk varies by ethnicity, as does the risk of cancer-related death. But the size of those differences can be surprising, highlighting the health disparities that exist among various ethnic groups in the United States. Both cancer incidence and death rates for men are highest among African-Americans, acco...
  • George Winston, known worldwide for his impressionistic, genre-defying music, considers music to be his first language, and admits he often stumbles over words – especially when he attempts languages other than English. There’s one German phrase he’s determined to perfect, however: danke schön. Winston thinks h...
  • Few decisions are more important than those involving health care, and few decisions can have such lasting impact, not only on oneself but on relatives and loved ones. Those choices, especially, should be made in advance – carefully, deliberately, free of pain and stress, and with much weighing of values and pr...
  • Using a card game to make decisions about health care, especially as those decisions relate to the end of life, would seem to be a poor idea. It isn’t. The GoWish Game makes those overwhelming, but all-important decisions not just easy, but natural. On each card of the 36-card deck is listed what seriously ill,...
  • Young adults and adolescents with cancer face unique challenges both during their treatment and afterward. Not only are therapies for children and older adults not always appropriate for them, they also must come to terms with the disease and treatment’s impact on their relationships, finances, school or ...
  • Breast cancer is the most common cancer, other than skin cancer, among women in the United States. It’s also the second-leading cause of cancer death, behind lung cancer. In the past several years, various task force recommendations and studies have questioned the benefits of broad screening guidelines fo...
  • Paternal age and the health effects it has on potential offspring have been the focus of many studies, but few have examined the effect parental age has on the risk of adult-onset hormone-related cancers (breast cancer, ovarian cancer and endometrial cancer). A team of City of Hope researchers, lead by Yani Lu,...