Harvard Epidemiologist Seeks Postdoc in Epigenetics
Dec 11, 2006 cancer, careers, imprinting, methylation
Dr. Karin Michels, an associate professor of Harvard Medical School and clinical epidemiologist of Brigham and Women’s Hospital, is seeking a postdoctoral research associate for her lab in Boston, MA.
- A postdoctoral position will be available at Brigham and Women’s Hospital, Harvard Medical School, to study gene imprinting and methylation starting in February or March 2007. The focus of our research is to identify environmental factors that predict loss of imprinting. A birth cohort is available to study epigenetic variation in newborns. We also examine imprinting pattern in human breast cancer. Candidates with strong background in molecular biology and epigenetics are encouraged to apply. Experience in human genome research and transcriptional gene regulation is particularly desirable.
- Her research ranges from early intrauterine nutrition of the fetus, breastfeeding and early life and adolescent diet to the role of adult diet on chronic disease risk, in particular, breast and other cancers. As diet is difficult to assess, Dr. Michels is studying the degree of measurement error associated with the different diet assessment methods. She is developing improved methods to analyze dietary data in epidemiologic studies. Dr. Michels is the Principal Investigator of a research grant from the National Institutes of Health to explore methods in nutritional epidemiology in the Nurses’ Health Study.
Dr. Michels is also exploring the role of intrauterine and early life exposures in chronic diseases in adult life. Numerous studies have indicated that events in vitro may affect the risk of chronic disease in the offspring later in life. Dr. Michels is using several databases around the world to study this challenging hypothesis in more detail.
Epigenetics May Hold Promise for Acute Lymphoblastic Leukemia
Nov 25, 2006 cancer, environmental alterations, imprinting, methylation, news links
A recent article in The New Zealand Herald reports on research investigating the cause of a common childhood cancer, acute lymphoblastic leukemia. Dr. Ian Morison, curator of the Imprinted Gene and Parent-of-origin Effects Database at Otago University, “is trying to pinpoint the exact period between conception and birth when leukaemic cells start to develop, and to better understand what genetic factors make that happen.” Dr. Morison is attempting to pin down why rates of leukemia have increased in recent years.
- “There seems to be something about modern life, but that doesn’t mean it’s cellphone towers - it could equally be the nutrition of the mum. It could be any one of a thousand factors we hadn’t thought of.”
Epigenetics is a promising new area of interest.
Traditionally, cancers were thought to be caused by gene mutations.
“A mutation can affect just a single letter of DNA and disrupt a very important gene that puts brakes on a cell, controlling the cell’s growth,” said Dr Morison. “It’s like if a cable breaks on the handbrake of a car.”
Otago’s Cancer Genetics Laboratory is looking at epigenetic changes, which modify cell function without mutation taking place.
New Research: Epigenetic Transgenerational Adult-Onset Disease
Nov 24, 2006 environmental alterations, imprinting, methylation, research articles
New research from the laboratory of Dr. Michael Skinner at Washington State University shows that the endocrine disruptor vinclozolin, a fungicide used in agricultural crops such as grapes grown for the wine industry, can induce adult-onset diseases in the offspring of an exposed pregnant female rat such as prostate disease, kidney disease, immune system abnormalities, and tumor development that remain highly prevalent in four generations of offspring.
The December issue of the journal Endocrinology contains two articles related to the studies in the lab of Dr. Skinner, including “Endocrine Disruptor Vinclozolin Induced Epigenetic Transgenerational Adult-Onset Disease” by Anway et. al and “Epigenetic Imprinting of the Male Germ-Line by Endocrine Disruptor Exposure During Gonadal Sex Determination” by Chang et. al. These research articles provide further insights into the phenomenon first described in the June 2005 issue of Science, “Epigenetic Transgenerational Actions of Endocrine Disruptors and Male Fertility.”
- The fetal basis of adult disease is poorly understood on a molecular level and cannot be solely attributed to genetic mutations or a single etiology. Embryonic exposure to environmental compounds has been shown to promote various disease states or lesions in the first generation (F1). The current study used the endocrine disruptor vinclozolin (antiandrogenic compound) in a transient embryonic exposure at the time of gonadal sex determination in rats. Adult animals from the F1 generation and all subsequent generations examined (F1–F4) developed a number of disease states or tissue abnormalities including prostate disease, kidney disease, immune system abnormalities, testis abnormalities, and tumor development (e.g. breast). In addition, a number of blood abnormalities developed including hypercholesterolemia. The incidence or prevalence of these transgenerational disease states was high and consistent across all generations (F1–F4) and, based on data from a previous study, appears to be due in part to epigenetic alterations in the male germ line. The observations demonstrate that an environmental compound, endocrine disruptor, can induce transgenerational disease states or abnormalities, and this suggests a potential epigenetic etiology and molecular basis of adult onset disease.
- Embryonic exposure to the endocrine disruptor vinclozolin at the time of gonadal sex determination was previously found to promote transgenerational disease states. The actions of vinclozolin appear to be due to epigenetic alterations in the male germline that are transmitted to subsequent generations. Analysis of the transgenerational epigenetic effects on the male germline (i.e. sperm) identified 25 candidate DNA sequences with altered methylation patterns in the vinclozolin generation sperm. These sequences were identified and mapped to specific genes and noncoding DNA regions. Bisulfite sequencing was used to confirm the altered methylation pattern of 15 of the candidate DNA sequences. Alterations in the epigenetic pattern (i.e. methylation) of these genes/DNA sequences were found in the F2 and F3 generation germline. Therefore, the reprogramming of the male germline involves the induction of new imprinted-like genes/DNA sequences that acquire an apparent permanent DNA methylation pattern that is passed at least through the paternal allele. The expression pattern of several of the genes during embryonic development were found to be altered in the vinclozolin F1 and F2 generation testis. A number of the imprinted-like genes/DNA sequences identified are associated with epigenetic linked diseases. In summary, an endocrine disruptor exposure during embryonic gonadal sex determination was found to promote an alteration in the epigenetic (i.e. induction of imprinted-like genes/DNA sequences) programming of the male germline, and this is associated with the development of transgenerational disease states.
- Disease etiology and development mechanisms could involve this epigenetic transgenerational phenomenon and be a factor in disease development that is not currently not understood. What aspects of disease are due to DNA sequence mutations versus epigenetics involving chemical modification of the DNA?
- Since this is an environmental effect that is multigenerational, it could explain why different sub-populations in different regions may develop different diseases.
- This new phenomena may provide alternate approaches for disease diagnosis and therapy.
- The influence of environmental toxicant exposures on disease development for offspring of exposed pregnant mothers needs to be further explored.
Breath Test Used to Detect DNA Methylation
Nov 14, 2006 cancer, methylation, news links
Researchers at the Wadsworth Center, the public health laboratory of the New York State Department of Health, have shown it is technically feasible to detect DNA methylation using a simple breath test. Dr. Weiguo Han and Dr. Simon D. Spivack have tested seven patients by having them breath into a handheld device for 10 minutes, which forms a condensed vapor, to which the methylation assay is applied. The methylated form of all six tumor suppressor genes could be detected using the simple breath test.
- The DNA is believed to be released when cells turn over, or are damaged, in the lungs and airways, he said. “Although it is not possible to say at this point the precise anatomic origin of the airway-derived DNA being tested, it may be that different patterns of gene methylation will themselves actually map the origin of this DNA to particular regions of the airway,” Spivack said.
The researchers hope that the test can be further developed into a non-invasive test for the early detection of lung cancer. Link
