Wednesday, September 12, 2012

AACR Progress against Cancer report now available

The AACR is the American Association for Cancer Research - they have just published this comprehensive report on cancer - potential causes, including diet, environment and genetics - and how we are going in terms of treating patients and survivorship - it is free to down load so if you are interested, click here

Friday, September 7, 2012

Journal Impact Factors 2011

I have updated the list for the journals that we are likely to publish in.  Or at least would like to publish in....
You can get to it by clicking here

Thursday, September 6, 2012

Institute of Medicine: the U.S. wastes $750 billion on medical costs annually

Read this stunning report regarding medical dollar spending in the U.S. In short, the non-government, IOM has concluded the as much as 30 cents of every medical dollar spent is wasted due to "unneeded care, byzantine paperwork, fraud and other waste" - every year - to use an analogy -" If banking worked like health care, ATM transactions would take days" you can read all about the report here -

Activation of the Innate Anti-Viral Immune System in BPH - now published on-line!

Allison's paper has just been published on-line in Genes & Immunity, prior to being published in the print version - if you have access, you can down-load the paper here - step by step, we're going to figure out what is going on in these patients...

Monday, September 3, 2012

High serum folate levels in patients with prostate cancer

I posted on this subject last year when our paper was published in The Prostate - it has subsequently been one of the most popular posts on the blog - because of that, I have updated the post to include a link to the original paper as it is now available free of charge - because this research was funded by the National Institutes of Health (and therefore you, the tax payer), it must be made available to the public one year after publication - click here to read the updated post with the link to the pdf.

Friday, August 31, 2012

Lupus: (aka SLE) an Autoimmune disease induced by DNA demethylation

Since discovering that a friend had to quit her promising postgraduate degree at CMU because she had lupus, I have been interested in what could possibly cause such a debilitating downfall in such a young, healthy woman - as I read the scientific literature on the subject, it became clear that at the molecular level there is a methylation defect - that is there is demethylated DNA present in the patient --- we've seen demethylated DNA in several different disease states; Benign Prostatic Hyperplasia (our manuscript in press), cancer, and rheumatoid arthritis -- at a simplistic level, all these diseases have inflammation. Can demethylated DNA induce inflammation?  Does how the cell see that inflammation differ depending on the type of cell or tissue, and the epigenetic background of the patient?  I bet it does.  I could theorize forever but as action speaks louder than's a paper I found today which describes the development of a novel model for Lupus (as scientists we need realistic models to test potential mechanisms and treatments) - drug induced lupus can be induced by drugs that  are known to inhibit DNA methylation, for example procainamide.  This model extends those findings and will help to further our understanding of what treatments may, if any, be able to stop the disease from progressing. 

Methods Mol Biol. 2012;900:169-80.

Murine models of lupus induced by hypomethylated T cells (DNA hypomethylation and lupus…).

Richardson B, Sawalha AH, Ray D, Yung R.


University of Michigan and the Ann Arbor Veteran's Affairs Hospital, Ann Arbor, MI, USA,


CD4+ T cell DNA hypomethylation may contribute to the development of drug induced and idiopathic human lupus. Inhibiting DNA methylation in mature CD4+ T cells causes MHC-specific autoreactivity in vitro. The lupus-inducing drugs hydralazine and procainamide also inhibit T cell DNA methylation and induce autoreactivity, and T cells from patients with active lupus have hypomethylated DNA and a similarly autoreactive T cell subset. Further, T cells treated with DNA methylation inhibitors demethylate the same sequences that demethylate in T cells from patients with active lupus. The pathologic significance of the autoreactivity induced by inhibiting T cell DNA methylation has been tested by treating murine T cells in vitro with drugs which modify DNA methylation, then injecting the cells into syngeneic female mice. Mice receiving CD4+ T cells demethylated by a variety of agents including procainamide and hydralazine develop a lupus-like disease. Further, transgenic mice with an inducible T cell DNA methylation defect also develop lupus-like autoimmunity. This chapter describes the protocols for inducing autoreactivity in murine T cells in vitro and for inducing autoimmunity in vivo using an adoptive transfer approach or transgenic animal models.
[PubMed - in process]

Thursday, August 30, 2012

How to get your NIHRO1 grant renewed!

Yikes! It's that time again...our once 5 year grant has 2 and a half years to go, time to think about renewal!  What you say? But you're only half-way through - but think about it - the time from submission to actually getting the $ is 9 months!  And that's assuming you get it funded the first time -- and usually, that's not a safe assumption to make, for anyone [OK good on you people who get everything you put in funded, I'm happy for you!] - as we probably are not the only people in this situation, I thought I would post this link to a very helpful website -- the NIH NIAID has a newsletter covering exactly these topics, and let's face it, if anyone is going to provide good advice, it's likely to be the all about it here.

Thursday, August 16, 2012

Congratulations Jenn!

A big congrats to Jennifer Gregg in the lab, for placing second in the poster competition at the SBUR meeting in Baltimore over the weekend!  Jenn's poster was regarding the mechanism by which PSMA increases uptake of monoglutamated folates - i.e. folic acid and methotrexate -- Congrats once again Jenn!

Jennifer Gregg, and her winning poster August 2012

Wednesday, August 15, 2012

Activation of innate anti-viral immune response genes in symptomatic benign prostatic hyperplasia

A big CONGRATS to Allison Atwood-Madigan in the lab, the above paper has just been accepted for publication in Genes & Immunity (a Nature journal)!  Bring on the celebratory laser-tag!

Friday, August 10, 2012

Magical Beets?

We all know you should eat your veggies, and here's another reason -- according to this paper by Hobbs et al., beets (called beetroot down under), pretty much instantly lower blood pressure after they are ingested! My hubby was so excited that he bought a dehydrator to start making beet-chips, which aren't too bad - but these veggies look great in salads or with a sunday roast -- and, unlike some food studies, you don't have to eat 50 beets to get the effect - just one 100g beet should do it!  Try to beet that!

Blood pressure-lowering effects of beetroot juice and novel beetroot-enriched bread products in normotensive male subjects.

Hobbs DAKaffa NGeorge TWMethven LLovegrove JA.


Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, The University of Reading, Whiteknights, PO Box 226, Reading, Berks RG6 6AP, UK.


A number of vegetables have a high nitrate content which after ingestion can be reduced to nitrite by oral bacteria, and further to vasoprotective NO endogenously. In the present study, two separate randomly controlled, single-blind, cross-over, postprandial studies were performed in normotensive volunteers. Ambulatory blood pressure (BP) was measured over a 24 h period following consumption of either four doses of beetroot juice (BJ), 0, 100, 250 and 500 g (n 18), or three bread products, control bread (0 g beetroot), red beetroot- and white beetroot-enriched breads (n 14). Total urinary nitrate/nitrite (NOx) was measured at baseline, and at 2, 4 and 24 h post-ingestion. BJ consumption significantly, and in a near dose-dependent manner, lowered systolic BP (SBP, P < 0·01) and diastolic BP (DBP, P < 0·001) over a period of 24 h, compared with water control. Furthermore, bread products enriched with 100 g red or white beetroot lowered SBP and DBP over a period of 24 h (red beetroot-enriched bread, P < 0·05), with no statistical differences between the varieties. Total urinary NOx significantly increased following the consumption of 100 g (P < 0·01), 250 g (P < 0·001) and 500 g BJ (P < 0·001) and after red beetroot-enriched bread ingestion (P < 0·05), but did not reach significance for white beetroot-enriched bread compared with the no-beetroot condition. These studies demonstrated significant hypotensive effects of a low dose (100 g) of beetroot which was unaffected by processing or the presence of betacyanins. These data strengthen the evidence for cardioprotective BP-lowering effects of dietary nitrate-rich vegetables.

Tuesday, July 31, 2012

New study finds low levels of MLV GAG sequences in samples from CFS patients

Just spotted this today -- the authors appear to have carefully controlled for mouse contamination (using the mitochondrial DNA assay), and found that 2 of 12 CFS patient samples were positive for MLV-GAG region sequences...they were unable to find other genes related to MLVs...sound familiar?  Again, if all these patients that come up negative for mouse DNA come up positive for MLV GAG -- but not for env or other genes...maybe people are looking for the wrong genes...the title of the paper is somewhat misleading but perhaps necessary to get it published "Xenotropic and polytropic murine leukemia virus-related sequences are not detected in the majority of patients with chronic fatigue syndrome", it is by an Italian group --Paolucci et al. and you can find it here

Sunday, July 22, 2012

Congratulations Katy and Matt! The newest addition to the lab has (finally!) arrived!

It is my absolute pleasure to welcome Samuel Steven Sobek into the world...born last night, July 21 - 21.25 inches and 8lbs 3oz (hey, I think that means I win the weight/length bet...!) -- Mom and Dad are ecstatic - Samuel was born the day after Katy uploaded all but one file to submit her first paper from her PhD studies -- so effectively she has given birth twice in the space of 24 hours!

we look forward to meeting Samuel in person, and putting him to work at the bench :)

Friday, July 20, 2012

PSMA as a therapeutic target for most cancers: one step closer to the clinic

As I mentioned previously, there's several papers that I want to blog about right now but I have been too busy writing grants and papers.  But as another paper goes off today, I am going to write about this really awesome work that was published a couple of weeks ago by Sam Denmeade and John Isaacs, and their collaborators.  Sam and John are at Hopkins, and have been working on targeting PSMA for a very long time - Let me digress for a minute and give some of the background - PSMA is an abbreviation for Prostate-Specific Membrane Antigen, but the term is somewhat a misnomer as it is expressed in a variety of tissues. The protein and the gene encoding it were identified in the lab of Skip Heston in 1993 --  who was at that time leading a lab at Memorial Sloan-Kettering Cancer Center.  Skip was actually looking to use a bacterial glutamate carboxypeptidase to activate methotrexate triglutamate, a prodrug (meaning once the additional glutamates are removed, the drug will be active).  I like to think of this story as a classic example as to how including the correct controls in an experiment, and being open to the unexpected, might lead to a serendipitous finding - in this case (as the story was told to me), the control cells (no bacterial glutamate carboxypeptidase added), unexpectedly died after addition of the prodrug.  The cells were LNCaP, a prostate cancer cell line that, like most prostate cancer, expresses large amounts of PSMA. Together with John Pinto and apparently over a couple of beers, Skip figured out that PSMA was a glutamate carboxypeptidase itself, and in fact it is the previously sought-after folate hydrolase that removes glutamates from dietary folates so that they can be absorbed by the small intestine.  Dean Bacich - at the time a postdoc in Skip's lab at Sloan made several types of PSMA transgenic mice - mice don't normally express PSMA in the prostate so Dean engineered the mice so that they expressed moderate levels (equivalent to humans) in the prostate epithelial cells.  These mice got what is considered the precursor to prostate cancer, PIN, suggesting that PSMA expression can cause or promote cancer, and later he showed that if the mice lived as long as humans, it would have been cancer.  David Silver and Sam Chang, both fellows at Sloan were the lead authors on papers showing the expression of PSMA on tumor-associated vasculature.  This was really exciting because almost all tumors that we looked at expressed PSMA in the endothelial cells of the vasculature, and the one non malignant tumor we looked at, which from memory was a hemangioma, did not express it -- and so the idea of targeting PSMA in tumor-associated vasculature was born.  Although he officially retired on July 1, Skip is now at the Cleveland Clinic and still working on targeting PSMA (the word retirement is not exactly in his vocabulary...but anyone who knows him won't be surprised about that).  As Bob Silverman pointed out at Skip's "transition" party, there are currently 26 clinical trials registered that target PSMA either as a therapeutic or for imaging for prostate and kidney cancer.  So back to the current work -- the major leaders of this study, Sam and John, are two of the guys whom I most respect as scientists.  It seems to me that a lot of people are in this field for all the wrong reasons -- but these guys are genuinely driven to help people -- and are truly excited by science [I'm sorry but its almost impossible to stop John from talking about his and anybody else's research - not that that's a bad thing :) - we could use a lot more people like him around here!] -- their paper, published in Science Translational Medicine, is entitled "Engineering a Prostate-Specific Membrane Antigen Activated Tumor Endothelial Cell Prodrug for Cancer Therapy".  To summarize, they took a peptide that specifically binds to PSMA, and coupled it to the toxin thapsigargin (and called it G202). There are two major differences between this and other chemotherapeutic drugs; first, it targets the tumor vasculature, meaning the cells that supply the tumor with the nutrients it needs to grow.  Secondly, the cells don't need to be dividing to be effected - most chemotherapies target some aspect of dividing cells, which is also why any other rapidly dividing cells, for example gut cells, are also targeted, leading to side-effects for the patient.  They tested the drug in mice against a number of human cancers, and it caused regression while causing very little toxicity to the animals.  The drug is now entering a phase I clinical trial.  I highly recommend reading this paper - it may seem like a logical series of successful experiments, but it is really the culmination of nearly 20 years of work done by many dedicated scientists, whom I feel honored to be acquainted with.

Tuesday, July 17, 2012

Another great link for scientists...

Nature now has a new website to help you find antibodies against your target of interest... complete with an easy-to-use system that let's you compare demonstrated usefulness of the we all know, just because the company says it works, doesn't actually mean that it does that can get to the new site, called Antibodypedia, by clicking here

Another great site, and my personal favorite, is this one, protein atlas -- it comes with actual pictures of antibodies used in immunohistochemistry of particular tissues, including normal samples and cancer. You can get there by clicking here

Tuesday, July 10, 2012

Next gen sequencing reveals that Pre-XMRV-2 is part of an evolutionarily young clade and more issues with PCR amplification of MLV-related sequences

There are a load of papers I'd love to blog about right now, but have been too busy writing grants to get them up -- this one however caught my eye today -- I think we have a lot of very interesting data yet to be revealed by next-gen sequencing - this paper, in Virus Research, compares pre-XMRV-2 sequences found in both wild-mice and inbred mouse populations.  It also seems that despite the fact that the virus appears to be a polytropic non-ecotropic virus [thus can infect other wild mice], not all wild mice in the same geo area carry the virus (in this case, Germany), and phylogenetic analysis implies that the clade is evolutionarily young and wide-spread amongst M.m. domesticus.  Also interesting is that the authors, Mayer et al., demonstrate the issues involved with PCR amplifying the gag region from these mice - and the utility of high throughput deep sequencing.  If you have access to Virus Research, you can read all about it - click here for the abstract -

Wednesday, June 13, 2012

Cool Fast Fact!

The gut microbiome, that is the microorganisms, "bugs" in the human gut, contribute 36% of the small molecules found in our blood stream.  That's food for thought!  To read more, pick up Leroy Hood's editorial in this week's Science magazine --

Wednesday, May 30, 2012

Yet another reason to drink coffee!

Anyone that knows me knows that I have been called a bit of a coffee snob, as I like to roast my own beans at I don't really need another reason to drink coffee - however I thought that I would mention the findings of this just-published study in New England Journal of Medicine, ominously titled "Association of Coffee Drinking with Total and Cause-Specific Mortality".  I held my breath as I read that the study, carried out by the Epidemiology group at the National Institutes of Health, followed the health outcomes of nearly 230,000 men and 170,000 women aged 50-71 years of age.  Those are some big numbers - over the period of the study, some 13 years, nearly 50,000 participants passed away.  After adjusting for age, coffee drinkers were more likely to die! **stifle inward scream**.  However, it turns out however, that coffee drinkers actually also include many more smokers than non-coffee drinkers - so after separating out the smokers, coffee drinkers actually have a significantly reduced risk of dying from heart disease, respiratory disease, stroke, injuries and accidents, diabetes, and infections, but not for deaths due to cancer.  I know you want to know *how* much coffee had an effect - interestingly it was different for men and women - for men, the effect was evident at less than a cup a day, and maxed at 1 cup thru more than 6.  For women, 2-3 cups produced an average 13% reduction in mortality, with protection maxing out at more than 6 cups per day (average 15% reduction).  Apparently, it didn't matter if you drank mostly caffeinated, or decaf either -- but what I wonder is if there was also any relationship with use of sweetener (sugar or artificial) in the coffee.  Anyhow, studies like this do still have limitations - people with existing cancer, heart disease or who had had a stroke at baseline were excluded, and coffee intake was reported once, at baseline.  Nevertheless, I'm liking this data - if you have access to NEJM, you can read the paper, by Neal Freedman et al.  here --

Tuesday, May 22, 2012

Novel MLV-GAG sequences detected in blood samples of ME/CFS patients

From the Hanson lab, this paper published today in PLoS ONE describes a study carried out with meticulous attention to detail and proper use of controls while analyzing ME/CFS patient samples for murine-leukemia related viruses.  Although novel MLV-like GAG sequences were isolated and sequenced from the patient samples (as opposed to controls collected from the same sites) Lee et al. concludes that it is not possible to determine the origin of these sequences, although the samples were not contaminated with mouse DNA at a detectable level.  First, bravo! to the Hanson group for being able to get anything published that might go against the current dogma regarding MLV-like viruses in human samples published -- I guarantee you that there are people with similar data whom don't want to torture themselves by attempting to publish.  The fact is, that it seems somehow MLV-like nucleic acids somehow end up in patient samples quite a bit, albeit at exceedingly low levels.  Theoretically, even if there was an MLV-type infection in a human, it would be rapidly eliminated (unless of course we don't know everything about the immune system yet).  I wonder if it is possible that such viruses could hide somewhere in the body, not replicating much - perhaps killing host cells occasionally resulting in a release of (potentially degraded) viral nucleic acid that is ultimately detected in the blood stream.  I haven't analyzed these sequences yet compared to those we have detected in tissue samples from BPH patients, but seeing as our sequences were recently published on the USPTO website, someone else will probably try that.  The link to the Hanson paper is here --

Thursday, May 17, 2012

How YOU can help biomedical research in the U.S.!

OK so for those fellow scientists out there that might read this blog, this is depressing - but we need to think about it is more than likely that due to a failure of congress to agree on the budget, sequestration will kick in in January 2013.  That means if you are lucky enough to have NIH funding, then you will likely suffer a cut of 7.3% of your yearly budget (as prices for everything we use in the lab increase) -- in addition, that will be on top of the already 17% cut from your budget (or more or less, depending on which part of NIH funds you) -- so how do you do the same for less and less each year?  In my lab, we already started making most of our own kits, which takes extra time and has its own risks -- potentially diminishing productivity - but can save a lot of money --  we were able to cut about 20% of overall consumable costs this way, but now we are  at the bare bones level - so if this cut comes in, the logical choice is to cut salaries - and that means jobs.  We are not unique, this is going to affect everyone who is NIH funded, or funded by any other part of government.  Furthermore, Dr. Collins, who is the NIH Director, testified to congress that if the "Budget Control Act" is implemented, then thousands of less grants will be able to be funded.  That's more jobs gone.  But this isn't just about jobs either, its about moving forward with research on cancer treatment and prevention- and every other disease - it's about making sure there is a reason for young people who are interested in science feel that there is a future career in scientific research - What can you do if you care about NIH funded research?  Click on the link below, it will lead you to the American Association for Cancer Research website and from there you can contact your members in congress to let them know, they need to do whatever it takes to prevent forced sequestration - and pass a fair budget now!  Contact Congress now!

Tuesday, May 15, 2012

Supplements and Cancer Prevention: A Cautionary Tale

Can there possibly be too much of a good thing?  Supplements such as folic acid can be vital if your diet is deficient in folate (as most people's diets were prior to the mandated fortification of the US), especially if you are planning to have a child...and in the case of folate deficiency, it is clear that DNA is likely to become damaged, potentially causing tumors- but if it is so important to have enough, can having too much also be a problem?  Read all about it at JNCI -

Thursday, May 10, 2012

NAR list of useful databases 2012

everything from the genome to the metabolome...if you can think it, there is probably a database for it - the journal Nucleic Acids Research has kindly put together a list of these sites -- access it here --

Monday, May 7, 2012

DNA methylation serves as a molecular memory for gene silencing

In this recent manuscript from JP Issa's group, DNA methylation of a CMV promoter driving GFP was examined - histone deacetylase inhibitors were able to reactivate the promoter, leading to GFP expression; however the promoter remained methylated.  The inhibitors were effective for approximately two weeks, after which time the promoter became silent once again.  Treatment with inhibitors of DNA methylation however, were able to induce permanent activation of the gene.  These findings suggest that if this scenario is relevant to other promoters, it will be necessary to target DNA methylation when designing novel treatments as HDAC inhibitors are only able to temporarily "reset" chromatin.  click here to read it for yourself.

Wednesday, May 2, 2012

Pittsburgh Chromatin Club Minisymposium

May 4, 2012
1:00-5:00 PM

West Wing Auditorium, Shadyside Hospital, 5230 Centre Ave (NOTE LOCATION)

Session 1

1:00     Dr. Tony Schwacha, Department of Biological Sciences, University of Pittsburgh
            “The Mcm2-7 helicase couples DNA replication to checkpoint control and sister chromatid cohesion”

1:30     Shweta Nayak, Oesterreich Lab, Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Magee Womens Research Institute
            “Epigenetic regulation of histone variants—role in endocrine resistant breast cancer?”

2:00     Dr. J. Richard Chaillet, Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Magee Womens Research Institute
            “DNA demethylation in plants and animals”

2:30     Refreshment break

Session 2

3:00     Dr. Yoel Sadovsky, Department of OBGYN and Reproductive Sciences, Magee Womens Research Institute
            “Unprecedented functions of placental microRNAs”

3:30     Dr. Joe Martens, Department of Biological Sciences, University of Pittsburgh
            “Identification of a new set of molecular tools to study transcription-dependent chromatin dynamics”

4:00     Dr. Vasily Studitsky, Professor, Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, Rutgers University
            “Mechanisms and regulation of transcription in chromatin”

After the final talk we will adjourn to the Church Brew Works, 3525 Liberty Avenue in Bloomfield, for further discussions.

Please email to be included on the PCC email list.

Funding generously provided by Abcam and the University of Pittsburgh

Monday, April 30, 2012

Activation of silenced tumor suppressor genes in prostate cancer cells by a novel energy restriction-mimetic agent.

In this manuscript published in The Prostate, Ching-Shih Chen's group from Ohio State show that energy restriction (either by novel mimetics or 2-deoxyglucose), led to down-regulation of DNMT1  and 3A (DNA methyltransferases 1 and 3A) and subsequent reactivation of previously hypermethylated tumor suppressor genes - caloric restriction has been shown to suppress cancer in animal models, but these findings provide a novel mechanism for the effect -- read it for yourself at

Friday, April 27, 2012

Just what we've been waiting for: Quantitative Sequencing of 5-Methyl-cytosine and 5-Hydroxymethylcytosine at Single-Base Resolution

In this paper published yesterday in Science Express by Wolf Reik and Shankar Balasubramanian and friends, a novel method to quantitate hydroxymethylcytosine is described -- as anyone who has tried to quantitate this "new" base knows, it is not so easy -- but this technique takes advantage of the specific oxidation of 5hmC to 5fC, using a readily available chemical, potassium perruthenate. This is followed by bisulfite conversion, which differentially converts 5hmC, leaving 5mC unconverted (typically both 5hmC and 5mC are protected during bisulfite conversion).  The sequence resulting from this oxBS is compared to a regularBS (bisulfite conversion),  allowing quantification of 5hmC content.  Why do we care?  Well it has already been shown that 5hmC regulates cell lineage determination in mouse stem cells -- we work on cancer, but it doesn't take a rocket scientist to figure out that there are similarities between cancer cells and stem cells -- now we have an "easy" tool to look at this within particular genes -- Note to my Lab: I have just ordered potassium perruthenate....please read this paper!  Here's the link to the manuscript -- you may need to have access to Science magazine --click here--

Thursday, April 26, 2012

Inhibition of HIV-1 and dengue virus replication with a common dog medicine!

In this paper from down-under, the novel finding that Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import, and able to inhibit replication of HIV-1 and dengue virus -- ivermectin -- yep, that is the stuff that we give our dogs every month to prevent heartworm...although all the experiments here are in vitro and at high drug concentrations, these findings are interesting because they could provide the basis for future drug design as well drug target(s) --  the manuscript is open access - read all about it here -- by Wagstaff et al.

Wednesday, April 25, 2012

Similarities between long interspersed element-1 (LINE-1) reverse transcriptase and telomerase

It has long been known that tumor DNA is hypomethylated compared to DNA from normal tissue - one measure often used as a surrogate for global DNA methylation is that of LINE-1 retrotransposons, so-called "junk DNA" that makes up approximately 20% of the human genome -- there are about 500,000 of these elements in our genome - and 80-100 of these are capable of becoming activated -- an event that can cause major disruption to the nucleus -- the cell prevents this from occurring by heavily methylating these elements to suppress transcription -- but why do they become activated in cancer?  and as this paper suggests, is it possible that they can act to repair damaged telomeres?  And, if so, does that mean that we should be inhibiting LINE-1 rt as a cancer therapy?  How could we prevent LINE-1 activation in the first place...PNAS has a free on-line series of papers on retrotransposons and telomerase, just click here--



Wednesday, April 18, 2012

another awesome on-line resource for cancer researchers...

this website compiles data resulting from the treatment of cancer cell lines with common chemotherapeutics, giving insight as to what genes might be good as targets for various cancers -- apparently the data is already changing the way we look at treating diseases such as Ewing's sarcoma -- again this is data that is available for everyone, the experiments are already done - that's my kind of data... you can get to the home page of the site here -- Genomics of Drug Sensitivity in Cancer

Wednesday, April 11, 2012

WOW! Exciting new findings reverse Alzheimer's disease in mice!

this is not usually my topic, but if the findings discussed in this recent Science paper are able to be replicated in humans, the impact will be huge!  An old drug, Bexarotene, was able to not only "dissolve" the Beta-amyloid deposits in a mouse model of Alzheimer's by 50% in a few days, but reversed cognitive defects as well -- sounds almost too good to be true!  Hopefully this drug will work the same way in humans, but just like cancer, mouse models don't always react to drugs in the same ways as humans...if you want to read about it, check out the journal article here --

Monday, April 2, 2012

NCI releases omnibus R03 and R21 (small and developmental) research grant opportunities!

As far as I recall, we've always needed an RFA or a PA for these type of grants from the NCI - so this is good news! Click here for the specifics...R21 and R03

Free data! the cancer cell line encyclopedia...

We just love free data portals!  Someone else has already done the technical stuff, and you just need to figure out what it means - and that's usually the most fun part of science...anyhow, thanks to the Broad Institute, and funded by Novartis, there are currently mutation data for 1651 genes across 909 cell lines (and growing) available free of charge...they do ask that you register, however it is free for research and instantaneous -- just click here!

The hard money - soft money it time for a change?

Today my grad student Katy asked me what "soft money" meant -- I found this article that really describes not only what soft money (money from grants) is, but how most faculty in the health sciences rely on it and how it has affected administrative decisions at universities...the article is mostly discussing Emory University, but the ideas apply across the board...the article is by Donald G Stein, and you can read about it by clicking here...

Friday, March 23, 2012

The DOD Prostate Cancer Research Program releases due dates!

This is what we have been waiting for! There are a couple of new mechanisms, and most of the old ones - read all about it  by clicking here!

Thursday, March 22, 2012

how you can help NIH research!

Just sign the petition at -- here's an email I received discussing why -- I can tell you from my own experience faculty are dropping out of research / retiring faster than most people are realizing -- we are losing amazingly talented and experienced people! All because NIH funding has been dropping since 2003!  Please read below, then take the link to sign the petition if you support a "cost of living" increase for the National Institutes of Health this year -- here's the promised email...

I was on a recent conference call with Administration officials, during which research funding was discussed. It seemed to me that these officials did not fully understand the central importance of NIH funding to our national research enterprise, to our local economies, to the retention and careers of our most talented and well-educated people, to the survival of our medical educational system, to our rapidly fading worldwide dominance in biomedical research, to job creation and preservation, to national economic viability, and to our national academic infrastructure. In response to a question from a participant, they staunchly defended the proposed flat $30.7 billion FY 2013 NIH budget as being perfectly adequate, remarking that “The NIH receives more funding than any other research entity; it will continue to be strong; it will do just fine.”

Unfortunately, this is not the case. The proposed flat NIH budget will severely exacerbate a catastrophic crisis that has been ongoing since 2003, when growth in NIH funding fell (and has continued to fall every subsequent year) behind the rate of inflation. As a consequence of this deeply flawed public policy, promising careers have been cut short, amazing research projects have been aborted, hundreds of laboratories nationwide have shrunk or been shut down, established and accomplished senior researchers have been forced to abandon their programs, young scientists have departed from research of even left the country (even after many years of productive training), thousands of ancillary jobs have been lost, our worldwide medical research dominance has been eroded (ceded to China, India, and other nations), and a large support network of laboratory supply and biotechnology companies has been drastically attenuated.

We successfully rescued the auto industry because we understood the ramifications of letting it fail. Our biomedical research infrastructure is just as far-reaching and vitally important to our nation’s economy as is the auto industry. I hope that our Administration understands this. For this reason, we started a petition at the “We The People” website on February 17, 2012.

However, our original petition to increase NIH funding expired on 3/18/12 (Sunday) at around 2 PM, with all supporters of this petition believing that there were still 10 more hours left. At the time it expired and disappeared from the We The People website, our petition was garnering approximately 4 signatures per minute, with only 446 of the 25,000 signatures remaining. I estimate that it would have taken less than two hours to meet the ‘threshold’ per the stated rules. Many people helped with this effort, especially towards the end. This outcome is indeed quite unfortunate and also seems unfair, particularly since some browsers weren't allowing people to sign, and the link to Help is still under construction.

We are still committed to pursue this cause, because it is simply too important to give up on. The future of biomedical research is in trouble, and this action may help at a critical time. Here is the link to our petition:

Stephen J. Meltzer, M.D.
The Harry & Betty Myerberg/Thomas R. Hendrix Professor Departments of Medicine (GI Division) and Oncology The Johns Hopkins University School of Medicine & Sidney Kimmel Cancer Center
1503 E. Jefferson Street, Room 112
Baltimore, MD 21287

Thursday, March 1, 2012

Low folate protective against colon cancer?

Ed Giovannucci and his team have long touted the protective effects of dietary folate for colon cancer -- however in this epub, he presents three nested case-controlled studies that suggests exactly the opposite -- the findings suggest that folate intake doesn't directly determine plasma folate levels (meaning all those dietary questionnaire studies that were apparently validated for folate might be called into question...) -- and that in this "prospective" study, low folate was actually protective against colon cancer.  I'm thinking that this study just opened up a whole load of new questions (but ones that I already had anyway, so I'm glad to see it!) - you can read about it here --

Plasma folate, methylenetetrahydrofolate reductase (MTHFR), and colorectal cancer risk in three large nested case-control studies.

Wednesday, February 22, 2012

Evidence for an XMRV-like sequence in prostate cancer?

Just saw this one today, published in the British Journal of Cancer, a respectable journal-- despite the title of the paper, "No evidence for the involvement of XMRV or MCV in the pathogenesis of breast cancer.", the paper goes on to describe single-round PCR amplification of an XMRV type sequence in two cases of prostate cancer (out of 12).  They had optimized the reaction so as to detect 700 copies of purified plasmid DNA -- one sample did not elicit sufficient product to clone, but the other did, and upon sequencing it was the same as the VP62 sequence with two exceptions - indicating it is not likely to be contamination from the plasmid the investigators used as a control.  One caveat, the group does not appear to have tested the tissues for mouse DNA -- and they acknowledge this by admitting that the sequence could be from exogenous DNA.  If you have access to the journal, you can read the paper here.

Saturday, February 18, 2012

NIH funding for FY13

no, no - congress has by no means finalized next year's budget for the NIH, FY13 doesn't start until October, so my guess is it will be at least that long before a budget is passed...nevertheless, President Obama had put forth his budget, and funding for the NIH (and DOD research) is at best, likely to be flat.  Apparently the NIH still wants to increase the number of new grants to be funded by 8%, so they will cut funds from currently active grants to help with this (1% below FY12).  Furthermore, for those fortunate individuals  who bring in more than 1.5 million total costs per year, there will be close scrutiny to see if they deserve more funding at the expense of lesser- or not-funded scientists.  In addition, there is talk of instituting a minimum 20% effort for principle investigators.  That would limit people to 5 RO1 type grants, and I can't say that I think that is a bad idea.  What I do wish is that scientists who are getting toward the end of their careers would get some kind of special award status to cover their salary, so as they are a) less stressed and b) therefore able to transfer their experience to their junior counterparts. I found a great blog that discusses the funding situation, you can get to it by clicking here.

Tuesday, February 14, 2012

Our research high-lighted by the National Cancer Institute!

it's always good to know someone is reading our's Jeff's work on serum folate and it's association with cancer cell proliferation being high-lighted in the Nutritional Sciences Research Group news letter - you can read all about it at:

Friday, January 20, 2012

Cooperative Dual-Activity Targeted Nanomedicine for Specific and Effective Prostate Cancer Therapy

Supra-magnetic nanoparticles combined with anti-PSMA antibodies and carrying paclitaxel result in a 20-fold increase in drug concentration at the target site - if this can be replicated in human subjects it would be a huge move forward for patients with prostate cancer - and perhaps even other cancers given that PSMA is expressed in most tumor neovasculature -- higher drug concentrations at the target tissue mean less side effects on non-target tissues -- read all about it here