Posts Tagged ‘research funding’

NIH awards $6.4 million to Case Western Reserve School of Medicine researchers

 :: Posted by American Biotechnologist on 12-08-2010

Case Western Reserve University School of Medicine faculty members are reaping the rewards of funding from the National Institutes of Health (NIH), in the form of grants and contracts. The funding totals more than $6.4 million for four different research endeavors.

Researchers Mark Chance, PhD, professor of physiology and biophysics, director of the Center for Proteomics and Bioinformatics, and interim chair of the Department of Genetics, and W. Henry Boom, MD, professor of medicine and director of the Tuberculosis Research Unit, are working to tackle the easily transmissible, and often deadly, Mycobacterium tuberculosis (MTB). They received a grant for more than $750,000 from the NIH, with the potential to receive up to $2.8 million over the next four years. The researchers are bringing together a multidisciplinary team of experts in proteomics, genetic epidemiology and cytokine biology to study a population within the spectrum of MTB exposure, infection, and disease in the United States, Uganda, and South Africa, in order to apply novel systems biology approaches to latent infection of the disease.

Recent studies suggest that proteomic approaches aimed at identifying protein-protein interaction networks result in the identification of functional sub-networks with a role in disease pathogenesis. The School of Medicine-led team will apply this approach to the analysis of latent MTB infection in humans and link proteomic results with parallel studies using human genetic and systemic chemo-/cytokine approaches to understanding the disease’s pathogenesis.

The Case Comprehensive Cancer Center was awarded a new $2.5 million grant from the National Cancer Institute (NCI) to evaluate the introduction and expression of the modified MGMT gene in hematopoietic stem cells in an effort to improve efficacy of chemotherapy for glioblastoma multiforme (GBM), the most common and most aggressive type of primary brain tumor in humans. The current treatment therapy is hampered by the dose-limiting bone marrow toxicity. This Phase I clinical trial will enable bone marrow to repair DNA alkylation, which is produced by concurrent radiation and temozolomide chemotherapy, by allowing patients to tolerate higher doses of chemotherapy.

This trial will build on the more than two decades of research by Stanton Gerson MD, principal investigator of the study, the Asa and Patricia Shiverick-Jane Shiverick (Tripp) Professor of Hematological Oncology, and director of the NCI-designated Case Comprehensive Cancer Center. He discovered that MGMT gene mutations may protect bone marrow from the drug’s toxicity, and in addition, introduction of these mutations can protect viral-transduced cell lines and primary hematopoietic progenitors from chemotherapy-associated toxicity. This trial will be the first-in-man study of in-vivo stem cells selection mediated by a drug resistance gene in patients with GBM. The trial is important not only for GBM patients, but it is also a means to demonstrate the effective development of a platform for selecting gene-modified stem cells that could be used for the correction of numerous monogenic disorders.

In another example of a team science approach, members of the Case Comprehensive Cancer Center have been tapped to join an important NCI multi-site prospective study of all grade II, II and IV glioma patients within the state. With a NIH-awarded contract of $715,000 with the potential for an extension leading to more than $2.5M, researchers will be part of The Cancer Genome Atlas (TCGA) Project, which is a national comprehensive and coordinated effort to accelerate understanding of the genetics of cancer using innovative genome analysis technologies. The overarching goal of TCGA is to improve the ability to diagnose, treat and prevent cancer. Under the direction of principal investigator Jill Barnholtz-Sloan, PhD, assistant professor of general medical sciences, newly diagnosed patients with gliomas will be prospectively accrued from her Ohio Brain Tumor Study (OBTS), a multi-site study within the State of Ohio that includes Case Western Reserve University and University Hospitals (UH) Case Medical Center (the lead site), the Cleveland Clinic Brain Tumor Center, the Department of Neurosurgery at the Ohio State University Medical Center, and the Department of Neurosurgery at the Mayfield Clinic/University of Cincinnati Medical Center.

Case Western Reserve faculty have worked closely with TCGA for many years; Dr. Barnholtz-Sloan and Andrew Sloan, MD, the Peter D. Cristal Chair in Neurosurgery at the School of Medicine and director of the Brain Tumor and Neuro-Oncology Center at UHCMC are active members of the TCGA Glioma Disease Expert Working groups. In this role, they are actively involved in decisions regarding the inclusion criteria for glioma patients and which scientific questions have been prioritized for analysis and publication. In addition, Neal Meropol, MD Chief, Division of Hematology and Oncology, Case Western Reserve University School of Medicine and UH Case Medical Center and Associate Director for Clinical Research, Case Comprehensive Cancer Center is a member of the TCGA Colorectal Cancer Disease Expert Working group.

The Department of Bioethics was awarded a $2.5 million continuation grant from the National Human Genome Research Institute that will extend funding for its Center for Genetic Research Ethics and Law (CGREAL) for an additional four years. The School of Medicine’s CGREAL is a national NIH Center of Excellence in Ethical, Legal, and Social Issues (ELSI) Research, which includes more than 20 faculty members across multiple academic departments, clinical units, and institutions in Northeast Ohio. It is co-directed through the collaborative partnership of Patricia Marshall, PhD, professor of bioethics, and Richard Sharp, PhD, director of research in the Department of Bioethics at the Cleveland Clinic. The mission of the CGREAL is to conduct transdisciplinary studies of ethical and societal issues in human genetic research and the introduction of new genetic technologies into patient care and public health; additionally it seeks to prepare young scholars for successful careers in Ethical, Legal, Social Issues (ELSI) research.

In the CGREAL’s first five years, it explored a range of ethical, legal and policy issues in the design and conduct of genomic gene-discovery research. In the four years supported by this renewal grant, the center will follow the trajectory of genomics into its “translational” phase, where expanded research needs and higher clinical aspirations are creating new ethical, legal, and policy challenges.

Source: Case Western Reserve University press release

Industry Funded? Do Tell!

 :: Posted by American Biotechnologist on 08-03-2010

Drug Discovery News recently reported a proposed change to the National Institute of Health’s (NIH) policy on financial conflict of interest (FCOI) disclosure. Under the proposed regulation, academic institutions will assume responsibility for reporting to the NIH any FCOI above $5,000. Currently, individual scientists, (as opposed to institutions), are responsible for reporting FCOIs in excess of $10,000.

It is hoped that moving the disclosure obligation from the individual scientist to the institution will be accompanied by the implementation of a systematic review process and technological infrastructure only available at the institutional level.

Although the proposed changes will make the system more robust and transparent, it will also make it more difficult for multi-disciplinary teams comprised of both academic and industrial scientists to secure NIH Phase I funding. This may slow down the pace of “translational” research since most “bench-to-bedside” studies are comprised of teams from both academia and industry.

Over the last number of years we have seen a significant push towards funding “translational” academic research which may be more palpable to the general public than pure academic science. Government funding of granting agencies is partially based on the electorate’s perception of what’s important in the current environment. Since it is easier to convince Joe Public of the importance of translational research projects which hold the promise of directly and “immediately” impacting on their medical well-being, translational research grants have become more in vogue than pure academic research. However, translation research is expensive and requires contributions from both academia and industry.

What do you consider more important?

A) Implementing a more transparent and robust FCOI disclosure policy which may slow down the progress of translational research.

or

B) Maintaining a more relaxed policy that can keep up with the current growth rate in biomedical research but runs the risk allowing research projects to be influenced by industrial strategic interests.

Linking Diabetes and Cancer: Where’s the Evidence?

 :: Posted by American Biotechnologist on 06-21-2010

If you’ve been following the Diabetes news lately, you likely noticed that two stories have dominated the news over the last couple of days. The first is a widely published study that implicates the consumption of white rice (as opposed to brown rice) in increased incidents of diabetes and the second relates to emerging evidence linking diabetes and cancer. According to a recent report published by Giovannucci et al in CA (A Cancer Journal for Clinicians), despite there being a high degree of epidemiologic evidence linking cancer and diabetes the biological mechanism linking the two diseases is poorly understood.

Considering that both of these diseases are highly prevalent among the world’s population one needs to ask why, if indeed there is a biological link between the two diseases, it has not been studied as of yet. Could it be that scientists are so focused on their particular field of interest that they are ignoring the “bigger scientific picture?” Or perhaps the grant-funding mechanism is biased towards individual diseases thereby influencing researchers to channel their efforts on one disease at a time. The fact that we commonly measure research funding by discipline seems to support this segregated approach. According to the NIH’s Estimates of Funding for Various Research, Condition, and Disease Categories (RCDC), Cancer is the third most funded disease category in the United States and is expected to receive over $6 Billion dollars in funding in 2011. This is compared to $2 billion for the study of cardiovascular disease and $1 billion for the study of diabetes. Scientists applying for grant funding must surely consider the availability of cash prior to beginning the grant writing process (imagine how hard it must be to receive funding for the study of Paget’s Disease which only receives $1 million per year in grant funding) and would be wise to pay homage to the source of their funding when considering the focus of their research publications. After all, if a scientist received funding from the American Diabetes Association, should we expect their research efforts to focus more on diabetes or cancer? If all of their publications detailed the molecular mechanisms of Alzheimer’s Disease how likely would it be for the ADA to renew the researcher’s grant funding? So the question remains: does this type of silo-ed approach to funding bias against valuable inter-disciplinary research?

Taking a less sinister approach, it is possible that the paucity of studies linking biological mechanisms in diabetes and cancer is due to the fact that the connection is not as obvious as it may seem. According to Giovannucci, Cancer and diabetes are diagnosed within the same individual more frequently than would be expected by chance. Nonetheless, both diseases are complex, with multiple subtypes and therefore it would be difficult to find a generic link between the two diseases. Moreover, as highlighted in Table 1 of the study, diabetes is associated with an increased risk of some cancers (liver, pancreas, endometrium, colon/rectum, breast, and bladder), a reduced risk of others (such as prostate cancer) and no association at all with other forms of cancer. Yet many questions still remain. Are the associations that have been observed direct or indirect? Does diabetes increase the risk of cancer or do they simply share common risk factors? These questions are compounded by the fact that there are multiple categorizations for both diseases (there are more than 50 subtypes of cancer alone) making it rather difficult to point to a link between what we broadly term as “cancer” and “diabetes.”

Despite coming out with a joint statement encouraging inter-disciplinary studies, The American Cancer Society and the American Diabetes Association discourage studies exploring links between diabetes and risk of all cancers combined. They explain this caveat using the example that because lung cancer does not appear to be meaningfully linked with diabetes, including this common cancer in studies will dilute observed associations, should they exist.

According to the joint statement the consensus seems to be that future studies should focus on uncovering potential biological links between the two diseases and that research should focus particularly on the following questions:

Is there a meaningful association between diabetes and cancer incidence or prognosis?
What risk factors are common to both cancer and diabetes?
What are possible biologic links between diabetes and cancer risk?
And do diabetes treatments influence cancer risk or cancer prognosis?

Whether the lack of information on biological links between diabetes and cancer has been due to a myopic view of diabetes and cancer researchers, a biased model of research funding or the difficulty in discerning connections between two very complex pathologies (I tend to subscribe to this last statement), it is clear that the statement of the American Cancer Society and the American Diabetes Association will help set the way for much needed inter-disciplinary research in the years to come.

Giovannucci, E., Harlan, D., Archer, M., Bergenstal, R., Gapstur, S., Habel, L., Pollak, M., Regensteiner, J., & Yee, D. (2010). Diabetes and Cancer: A Consensus Report CA: A Cancer Journal for Clinicians DOI: 10.3322/caac.20078

Do Pressures to Publish Increase Scientists’ Bias?

 :: Posted by American Biotechnologist on 04-26-2010

Several weeks ago in the blog post “Is the Institution of “Grant-Funded” Research Killing Scientific Integrity?” I wrote about the Scientific American article suggesting that scientific retraction can change public opinion. In that post, I suggested that perhaps the pressures to publish or perish are leading some of our colleagues down the unethical road of publishing false results.

This past week, a researcher at University of Edinburgh published her findings that scientific research is suffering due to pressure on scientists to publish only “publishable” (i.e. positive) results. Certainly negative findings are critical to advancing scientific knowledge but who wants to become engaged in an unsexy project. Worse yet, if the data isn’t publishable then you are definitely at risk of losing your grant funding.

Check out the press release from the Public Library of Science and let me know your thoughts. What can we do (or do we need to do anything) to overcome this bias?

A press release from PLoS ONE
April 22, 2010

The quality of scientific research may be suffering because academics are being increasingly pressured to produce ‘publishable’ results, a new study suggests. A large analysis of papers in all disciplines shows that researchers report more “positive” results for their experiments in US states where academics publish more frequently. The results are reported in the online, open-access journal PLoS ONE on April 21st, by Daniele Fanelli, of the University of Edinburgh.

The condition of today’s scientists is commonly described by the expression “publish or perish”. Their careers are increasingly evaluated based on the sheer number of papers listed in their CVs, and by the number of citations received – a measure of scientific quality that is hotly debated. To secure jobs and funding, therefore, researchers must publish continuously. The problem is that papers are likely to be accepted by journals and to be cited depending on the results they report.

“Scientists face an increasing conflict of interest, torn between the need to be accurate and objective and the need to keep their careers alive” says Fanelli, “while many studies have shown the deleterious effects of financial conflicts of interests in biomedical research, no one has looked at this much broader conflict, which might affect all fields”.

Dr Fanelli analysed over 1300 papers that declared to have tested a hypothesis in all disciplines, from physics to sociology, the principal author of which was based in a U.S. state. Using data from the National Science Foundation, he then verified whether the papers’ conclusions were linked to the states’ productivity, measured by the number of papers published on average by each academic.

Findings show that papers whose authors were based in more “productive” states were more likely to support the tested hypothesis, independent of discipline and funding availability. This suggests that scientists working in more competitive and productive environments are more likely to make their results look “positive”. It remains to be established whether they do this by simply writing the papers differently or by tweaking and selecting their data.

“The outcome of an experiment depends on many factors, but the productivity of the US state of the researcher should not, in theory, be one of them,” explains Fanelli “we cannot exclude that researchers in the more productive states are smarter and better equipped, and thus more successful, but this is unlikely to fully explain the marked trend observed in this study”.

Positive results were less than half the total in Nevada, North Dakota and Mississippi. At the other extreme, states including Michigan, Ohio, District of Columbia and Nebraska had between 95% and 100% positive results, a rate that seems unrealistic even for the most outstanding institutions.

These conclusions could apply to all scientifically advanced countries. “Academic competition for funding and positions is increasing everywhere”, says Fanelli “Policies that rely too much on cold measures of productivity might be lowering the quality of science itself”.

Public Library of Science

Is the Institution of “Grant-Funded” Research Killing Scientific Integrity?

 :: Posted by American Biotechnologist on 03-04-2010

Katherine Harmon of Scientific American questions whether scientific retraction can change public opinion. In her blog post, Katherine writes that recent high-profile retractions such as the Wakefield paper linking Autism to vaccination or the retraction of a South Korean claim that a lab had cloned human embryonic stem cells has resulted in what is perhaps an unfair jading of public opinion against the validity of scientific research.

The big question that looms over our heads is why are scientists finding it (increasingly) tempting to publish false data or conduct scientific experiments using questionable research practices? Is it the enticement for fame and glory that fuels their unethical behavior? One foreign post doc recently told me that many of his colleagues were eager to find post doc positions in high-profile American labs with the expectation that they would finish their post-doctoral work with a Nature paper or two under their belts. Of course, it didn’t take them long to realize that precious few people have the merit of publishing a paper in such a high-impact journal especially so early in their career.

Or perhaps the structure of grant-funded research is to blame. The old adage of “publish or perish” is stronger than ever and with the latest in “omics” technology, the amount of data needed to publish is becoming staggering.

This whole debate reminds me of an experiment that I conducted while completing my masters. I was studying the transcriptional activity of a certain gene and I found a paper in a peer reviewed journal that had published PCR results on my gene of interest. Since I needed to conduct a similar PCR experiment, I ordered the same set of primers and followed the PCR protocol as per the published methods. Unfortunately, I was disappointed when the expression levels of the gene I had expected to be upregulated under the treatment conditions did not appear in my PCR results. Perplexed, I blasted the primers in genebank and I found that the primers were actually located in the gene’s intron! (In case you’ve forgotten your central dogma, the intron is the part of the gene that is excluded from the mRNA transcript). Needless to say, I was pretty upset. I didn’t even think about Blasting the primers prior to ordering them. Positive PCR results (using mRNA) had already been published in a peer reviewed journal using the same primers. I didn’t feel the need to repeat the due diligence that another scientist had already done. I felt duped.

All this is to say that one cannot overstress the importance of using solid scientific methodology. Skipping steps in today’s world is simply not an option. With the thousands of data points to be gleamed from both proteomic and genomic studies, how can you afford to rely on someone else’s “honesty” when conducting your own research. Moreover, it becomes even more critical to engage in proper sample handling and preparation techniques. Everything that you do needs to be documented properly and followed to the letter. Protect yourself and your research. Our world simply cannot afford another retraction.