Posts Tagged ‘NIH’

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

Molecular Biologists in Space

 :: Posted by American Biotechnologist on 09-20-2010

In a statement released earlier this month, the National Institutes of Health (NIH) announced that it has awarded the first new grants under the Biomedical Research on the International Space Station (BioMed-ISS) initiative, a collaborative effort between NIH and NASA. Using a special microgravity environment that Earth-based laboratories cannot replicate, researchers will explore fundamental questions about important health issues, such as how bones and the immune system get weak.

The National Laboratory at the ISS provides a virtually gravity-free — or microgravity — environment where the cellular and molecular mechanisms that underlie human diseases can be explored.

NIH is hosting three rounds of competition for the BioMed-ISS initiative. The first round of grants for the ground-based phase — totaling an estimated $1,323,000 included an award to Millie Hughes-Fulford, from the Northern California Institute for Research and Education, San Francisco who is studying immune system suppression in space. A reduction in the immune response also occurs in the elderly, who, like astronauts, are at increased risk for infection. As a former astronaut, Hughes-Fulford aims to apply lessons learned from studies of immune cells in microgravity to a new model for investigating the loss of immune response in older women and men.

For more information on this exciting new initiative see the NIH website.

Here’s a video of Millie’s trip to space:

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.


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.

Does NIH Policy Complement Obama’s Executive Order Concerning Stem Cell Research?

 :: Posted by American Biotechnologist on 06-28-2010

Here’s my question:

Barack Obama issued an executive order for removing barriers to responsible scientific research involving human stem cells. How effective do you believe that the NIH’s 2009 Guidelines on Stem Cell Research are in removing these barriers?

Please see the poll at the end of this post to cast your vote.

Here’s some background:

Yesterday I vented my frustration with the recent decision by the NIH to deny approval for the use of 47 human embryonic stem cell lines in NIH funded research. More specifically, I was frustrated by the fact that the denial was linked to the use of exculpatory language (unacceptable legal language) in the consent form used by the RGI to obtain the embryonic stem cells rather than a more conventional medical ethics question.

What struck me as even more interesting is the story behind this whole fiasco. According to the NIH, on March 9, 2009, President Barack H. Obama issued Executive Order 13505: Removing Barriers to Responsible Scientific Research Involving Human Stem Cells. The order was meant to help establish policy and procedures under which the NIH will fund such research, and to ensure that NIH-funded research in this area is ethically responsible, scientifically worthy, and conducted in accordance with applicable law. Since the procedures for receiving NIH approval of human Embryonic Stem Cells may be complicated and lengthy the NIH established a stem cell registry which would avoid burdensome and repetitive assurances from multiple funding applicants.

Now for an explanation on NIH policy and my take on how RGI ended up in this precarious position. Most of what I’m about to tell you can be found in full in the NIH document National Institutes of Health Guidelines on Human Stem Cell Research. If you want to read the story from the primary source feel free to visit the website. If you want the “version in a nutshell” peppered with some of my commentary please read on.

The NIH policy is primarily concerned with the official definition of stem cells, ethical issues such as financial gain and informed consent, pre-existing stem cell populations, “extra” embryos leftover from Pre-Implantation Genetic Diagnosis (i.e. the source of RGI’s embryos) and monitoring and enforcement of the NIH stem cell policies.

The first challenge for the NIH was to define the scope of its policy vis-a-vis stem cell types. (For a great review on the various types of stem cells be sure to download Bio-Rad’s Stem Cell Basics for Life Science Researchers.) In the end, the NIH pretty much restricted its policy to the use of human embryonic stem cells proper, which encompass “cells that are derived from the inner cell mass of blastocyst stage human embryos, are capable of dividing without differentiating for a prolonged period in culture, and are known to develop into cells and tissues of the three primary germ layers.”

Financial gain really deals with 2 main issues. One issue concerns the fact that the stem cell recipient (i.e. the scientist) might derive profit from developing the hESCs without the knowledge of the hESC donor which might lead to exploitative practices. The other financial concern is that scientists may use their intellectual property rights to impose conditions that significantly restrict the use of these cells in biomedical research and therefore hold back scientific progress.

The big issue that really served as the backbone to the RGI story was that of informed consent and the specific language used to obtain such consent. I believe that the standard practice of informed consent is to uphold the right of any individual to not have their biological material used in a fashion that they don’t agree with and to ensure that individuals are not coerced into participating an a research study. These policies make sense and are widely accepted by the scientific community. The problem that arises in this specific case is that the use of stem cells in scientific research has been around for over decade and numerous regulatory bodies have differed in their approach to obtaining informed consent for the use of stem cells. As such, informed consent policies and procedures vary and may lead to confusion regarding the acceptable use of stem cells that pre-exsited the NIH policy in NIH-funded research. In dealing with this problem, the NIH has declared that “applicant institutions wishing to use hESCs derived from embryos donated (in the United States) prior to the effective date of the Guidelines may either comply with Section II (A) of the Guidelines or undergo review by a Working Group of the Advisory Committee to the Director (ACD).” The “patchwork of standards” referred to in the NIH document may very well have precipitated the poorly written informed consent form used by RGI thereby rendering 47 of their cell lines ineligible for NIH funded research. Furthermore, the policy also states that informed consent needs to be obtained during the time of donation and that there needs to be a degree of separation between the physician obtaining the embryo and the scientist. This further exacerbated RGI’s predicament and made it next to impossible for them to rectify the situation ipso facto.

When looking at the number of cell lines approved by the NIH, it is striking that only 75 cell lines from a handful of scientific researcher have been approved for the registry since its implementation in December 2009. Furthermore, 48 cell lines are currently pending approval 232 are in draft status, and 48 have been rejected. While it might seem like 232 stem cell lines are a significant number to have in the pipeline, it is telling to note that the huge majority of these applications were submitted by RGI followed in large part by Harvard University. Furthermore, 47 out of the 48 stem cell lines rejected by the NIH came from RGI.

If stem cell research has been around for a decade and several other regulatory bodies such as the International Society for Stem Cell Research (ISSCR) and the National Academy of Sciences (NAS) have long been involved in regulating their use, why is the NIH’s current list so short? Furthermore, why are there only a handful of institutions submitting applications for NIH approval? This seems a bit concerning to me especially considering that the NIH is the largest funding institution in the United States.

Well…now’s your chance to vote.

How effective are NIH Guidelines in implementing Obama’s order to remove barriers to stem cell research?

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