Return from Honeymoon Vacation

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I have just returned from my honeymoon to Negril, Jamaica and wanted to let the readers know that the site will now be updated more regularly with the wedding complete.

Of course, according to some researchers, my marriage may have signaled the beginning of the end of my productivity in science. Link

Epigenetics a High Priority in New NIEHS 5-Year Plan

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This month, the U.S. National Institute of Environmental Health Sciences (NIEHS), which provides funding for a number of researchers investigating epigenetic alterations, published its 2006-2011 NIEHS Strategic Plan, entitled “New Frontiers in Environmental Sciences and Human Health.” The effort to create the strategic plan was spearheaded by NIEHS director David Schwartz, and was aided in its development by an online survey to the public (~400 respondents) and a strategic planning forum in October 2005 that allowed approximately 90 “invited fundamental and applied scientists and public interest group members” to engage in breakout group discussions on six core topics related to future NIEHS priorities.

Those involved in the strategic planning process recognized three key challenges facing the environmental health sciences field:

    1. What diseases and what exposures will be the focus of the NIEHS research portfolio? “In general, the NIEHS will set research priorities to focus on diseases for which there is a strong indication of an environmental component and for which there is high or increasing prevalence in the U.S. population. In addition, the NIEHS will focus on exposures that carry the highest risk to the largest population or hold the most promising hope of clarifying an important disease process.”
    2. Given the explosion in new science that has occurred in the last decade, how will we focus our research efforts on the most appropriate science for a given disease and the related environmental exposures? “The NIEHS will take a leadership role in improving human health by using environmental exposures to understand human biology and human disease. This vision is a complex one, requiring a change in approach to basic research, moving from our traditional science base of single investigators with a clear hypothesis to integrated research teams addressing the complex hypotheses associated with the interplay of environmental factors with many other factors (e.g., genetics, lifestyle, age, sex) on disease incidence and prognosis.”
    3. How will we develop the scientific knowledge that empowers people to improve their environmental choices, allows society to make appropriate public health decisions, and results in our living healthier lives? “The ways in which environmental agents increase disease risks for an individual are still poorly understood. As the NIEHS moves forward, we are committed to supporting the basic research that drives the scientific basis for health decisions, as well as the applied research that fills gaps in our understanding of environmental health risks.”
In addition, the strategic plan outlined seven key goals of the institute over the next five years:
    1. Expand the role of clinical research in environmental health sciences. One important area with high priority will be epigenetics, where environmental influences might have a particularly strong impact.
    2. Use environmental toxicants to understand basic mechanisms in human biology.
    3. Build integrated environmental health research programs to address the cross- cutting problems in human biology and human disease.
    4. Improve and expand community-linked research.
    5. Develop sensitive markers of environmental exposure, early (preclinical) biological response, and genetic susceptibility.
    6. Recruit and train the next generation of environmental health scientists.
    7. Foster the development of partnerships between the NIEHS and other NIH institutes, national and international research agencies, academia, industry, and community organizations to improve human health.
As part of the second goal, the strategic plan highlighted the crucial role that epigenetics could play in using toxicants to understand mechanisms in human biology.
    A dynamic interplay exists between the input received from the extra- cellular environment and the expression of genes within a cell. Integration of the key cellular signals to produce very specific genomic responses is essential to proper cellular function and disease avoidance. Environmental signals can alter the functioning of genes in many ways, both directly and indirectly. Epigenetics refers to a group of mechanisms that regulate patterns of inheritance and gene expression without changing DNA sequences and that are potentially crucial in the interface between genes, environment, and disease. These mechanisms include, but are not limited to, DNA methylation, imprinting, and histone acetylation and post-translational modifications. The overall impact of environmental changes on these mechanisms remains poorly understood, yet the consequences of modifying them can result in an increased risk of developing cancer, immunologic diseases, and other complex diseases.

Epigenetics in Nature

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Nature has posted an interesting article entitled “Epigenetics: Unfinished Symphony” [subscription required]. Beginning with a look at how epigenetics has been explored in identical twin studies, the article also takes a current look at the International Human Epigenome Project and its efforts to gain funding, better organization, and credibility as a worthwhile effort.

    Given…technological challenges, it is only natural to question whether the research community is ready for such an enormous undertaking. Drawing on the experience of the early days of planning for the HGP, researchers working on epi–genetics are unanimous in thinking they can do it.

Epigenetics is drawing a tremendous amount of interest because it has the potential to lead to new insights into the genetic basis of disease, as well as the genetics of cancer. As a result, new technologies are emerging that will make the Human Epigenome Project a feasible initiative for researchers around the world to tackle. Link

Hypomethylating Drug Approved by FDA for Treatment of MDS

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The U.S. Food and Drug Administration has approved Dacogen for Injection, a drug developed by MGI Pharma, Inc. and SuperGen, Inc. for the treatment of myelodysplastic syndromes (MDS).

    Results from a phase 3 clinical trial demonstrated an overall response rate of 21% in Dacogen-treated patients considered evaluable for response, defined as those patients with pathologically confirmed MDS at baseline who received at least 2 cycles of treatment, compared to 0% in the supportive care arm. All patients who responded to Dacogen treatment became or remained transfusion independent during the time of the response.

Dacogen for Injection works by inhibition of the enzyme DNA methyltransferase, which in turn affects the methylation of DNA that affects genes involved in cellular differentation and proliferation.

    Dacogen-induced hypomethylation in neoplastic cells may restore normal function to genes that are critical for the control of cellular differentiation and proliferation. In rapidly dividing cells, the cytotoxicity of Dacogen may also be attributed to the formation of covalent adducts between DNA methyltransferase and decitabine incorporated into DNA.

The drug will be commercially available by the end of June. Link