Tuesday, September 27, 2011

Epigenetic CpG Demethylation of the Promoter and Reactivation of the Expression of Neurog1 by Curcumin in Prostate LNCaP Cells

In an interesting manuscript from the Kong lab at Rutgers, MeCP2 was excluded from binding the Neurog1 promoter in LNCaP cells treated with curcumin...this would present a novel mechanism for curcumin action and leaves open the question of how specific gene promoters are targeted for de-methylation.  You can read the paper here

Friday, September 23, 2011

Friday's fun fact...

$47 trillion — Amount that five common, chronic noncommunicable diseases—heart disease, chronic respiratory disease, cancer, diabetes, and mental health issues—will cost the world by 2030, according to a study released 19 September by the World Economic Forum.- from Science Magazine, Sept. 23 2011

Nature Reviews Cancer: Biology and translation of the epigenome

A decade of exploring the cancer epigenome — biological and translational implications
Stephen B. Baylin & Peter A. Jones
p726 | doi:10.1038/nrc3130
Epigenetic alterations are leading candidates for the development of specific markers for cancer detection, diagnosis and prognosis, as well as new targets for cancer therapy. Which of the discoveries in the past 10 years are ready for advancement?

Epigenetics recognized as an important area of the National Urology Research Agenda

For those of us interested in urology research and epigenetics, this is good news:  The American Urology Association has brought together a team of experts encompassing urologists, researchers, the NIH and the Department of Defense Prostate Cancer Research Program to formulate the National Urology Research Agenda.  This document summarizes the current thinking and status of the field of urology research, and identifies the challenges that lay ahead; especially with our aging population.  If you are planning grant applications in this area, this might be a good document to read -- I personally was glad to see the inclusion of epigenetic studies on BPH - benign prostatic hyperplasia -- very little is known about the molecular pathogenesis of BPH -- but I can guarantee that there are indeed epigenetic changes in affected tissues.  If you think that you have a fundable project relating to these areas, you might want to try for some seed funding from the AUA - The application cycle for the 2011 AUA Foundation Urology Research Success Award will open in October. The awards will provide up to $10,000 in funds to be used by the applicant to initiate critical experiments while they await approved funding or to strengthen resubmission of an application that was scored but not funded.Check the AUA's website for more details in October.

Thursday, September 22, 2011

Wednesday, September 21, 2011

Some surprising insights on motivating people to be innovative....

One of the complaints that I hear from fellow faculty most often is that we weren't actually trained for the job!  What?  But let's think about grad school -- we learn how to do research, write papers, and maybe how to write grant applications...but when do we learn management skills?  As research lab directors, it isn't just ordinary management skills we need to learn - we need to know how to comply with complex regulations, how to write numerous types of regulatory documents (e.g. IACUC protocols, IRB protocols) - how to manage a budget or multiple budgets and projects, and how to manage people.  When it comes to managing people, it would have been nice to get some training at some point on what to do, and especially on what NOT to do....and I personally would have preferred it to not be "on the job" training...therefore one of the things I'm going to try to post here every so often are the handy links that I find that might help in preparing people for future careers as lab hopefully I can help other people to skip that part of the learning curve!  This short (10 minute) video is entertaining, and useful to a variety of disciplines - but especially ones that require motivation and innovation -- one of the hardest things in science (especially in these times of tight funding) is keeping people motivated...and let's face likely are you to get outstanding innovative research going on if you can't motivate your innovators?  Does money buy innovation? For the surprising answers (which are backed by top notch research), check out the video at

Tuesday, September 20, 2011

Depletion of B vitamins, including folate, activates the Wnt pathway

The Mason Lab at Tufts has just published a study examining the effect of mild B vitamin depletion in two models of colorectal cancer:  they fed mice a diet limiting in folate, B2, B6 and B12 - the diet induced a 4-fold increase in Wnt signalling, and a 50% increase in tumors and aberrant crypt foci compared to mice fed a diet with the basal requirements of these vitamins.  The Wnt pathway is known to be important in not only colorectal cancer, but also in prostate cancer progression as well - it remains to be seen if mild folate depletion can also affect Wnt signalling in prostate tissues and we are currently examining this in our lab.  Meanwhile, we have another example of how low folate can be implicated in carcinogenesis - read all about it at in FASEB journal

Monday, September 19, 2011

Transgenerational Epigenetic Inheritance: yes you can inherit your mother's methylation patterns...

In a report in Science Express, the Ecker lab describes a study utilizing Arabidopsis, following 30 generations of spontaneously generated DNA methylation marks - these "marks" were meiotically stable generating "epialleles".  As epialleles can significantly affect transcription, including the use of alternative promoters, they can have a major effect on phenotype.  But how often does a new epiallele get generated?  According to their study, epialleles are generated more frequently than genetic mutations; given that they are both meiotically and mitotically stable, understanding how these alleles are generated [and maintained] is important - if you have access to Science, click here

Fish oil can block chemo!

This is not directly related to our current interests, nevertheless I thought I'd mention it here because it is relevant to studies of nutrition and cancer -- basically Emile Voest used a proteomics study to identify two pretty much previously minor fatty acids - that were induced in cancer-protecting mesenchymal stem cells in response to cisplatin treatment -- these same fatty acids are found in "fish oil" capsules that many people take in order to prevent cancer, making this study very interesting -- and basically suggesting that certain nutrients are good in preventing cancer, maybe not so good during chemotherapy or after a cancer diagnosis -- the study was published in Cancer Cell - click here to read it if you have access

Wednesday, September 14, 2011

Large-intergenic-non-coding RNAs (linc-RNAs): not all HOTAIR!

In a recent epub from Nature, Eric Lander's group present data implicating these long non coding RNAs as major drivers of pluripotency and differentiation, at least in ES cells - through a huge series of linc-RNA knockdowns, the authors were able to demonstrate that many of these RNAs associate with proteins known to regulate chromatin structure, and thus alter or maintain gene expression - they suggest a similar mode of action to the well-studied non-coding RNAs HOTAIR and XIST, in that the lincRNAs may function in trans by coupling chromatin remodelling proteins - producing a global effect on transcription that is specific for the cell type.  Although this study was restricted to ES cells, it is likely that the same kind of process is utilized in the global alterations of gene expression seen in cancer, and if that is the case, learning how we can modulate lincRNAs might be another way we can target tumor cells and "reset" their programming.  You can read about it in Nature, just click here

Thursday, September 8, 2011

hydroxymethylcytosine - lost in prostate cancer ! And it is potentially a novel marker of the cancer field-defect!

Srinivasan Yegnasubramanian and his buddies from Hopkins have analyzed prostate, colon and breast tumors using an antibody against 5-hydroxymethylcytosine and immunostaining -- they demonstrate quite nicely that that global 5-hydroxymethylcytosine levels track with differentiation of cells; for example, normal prostate and other adult tissues express quite high levels of our favorite new base, but it is dramatically lost in "dedifferentiated" tissues, such as prostate cancer -- and YES, I know you were going to ask if it was part of the field-defect, these results suggest yes! (if you look hard enough!) you can read all about it online for free!

Oncotarget. 2011 Sep 2. [Epub ahead of print]

Global 5-hydroxymethylcytosine content is significantly reduced in tissue stem/progenitor cell compartments and in human cancers.

Haffner MC, Chaux A, Meeker AK, Esopi DM, Gerber J, Pellakuru LG, Toubaji A, Argani P, Iacobuzio-Donahue C, Nelson WG, Netto GJ, De Marzo AM, Yegnasubramanian S.

Friday, September 2, 2011

Single nucleotide polymorphisms that "attract" methylation -- a novel mechanism for inherited cancer susceptibility?

check out this paper in Cancer Cell, by Robyn Ward's group from down under --see it here

Dominantly Inherited Constitutional Epigenetic Silencing of MLH1 in a Cancer-Affected Family Is Linked to a Single Nucleotide Variant within the 5'UTR.

Hitchins MP, Rapkins RW, Kwok CT, Srivastava S, Wong JJ, Khachigian LM, Polly P, Goldblatt J, Ward RL.


Adult Cancer Program, Lowy Cancer Research Centre, Prince of Wales Clinical School, Faculty of Medicine at the University of New South Wales, NSW 2052, Australia.

NCBI NIH Epigenome Broswser Tools

NCBI NIH Epigenome Broswser Tools -- use these to get your epigenome on!

Thursday, September 1, 2011

new paper from Moshe Szyf...MBD2 and demethylation

Definition of the Landscape of Promoter DNA Hypomethylation in Liver Cancer.

Stefanska B, Huang J, Bhattacharyya B, Suderman M, Hallett M, Han ZG, Szyf M.

Szyf's group has characterized promoter methylation in liver cancer, and found that many genes are demethylated, and some are demethylated and induced, likely contributing to cancer progression. you can read about it for yourself in Cancer Research - click to get it in pubmed

new link for Dejavu website...

apparently I put in a broken link the other day, here it is again, used for checking the plagiarism database: