Building Partnerships with NCTR
The National Center for Toxicological Research (NCTR) conducts peer-reviewed
scientific research that improves public health by increasing access to
innovative technologies essential to advance medical research/health care and
improving product quality and safety. Solving today’s public health issues
requires innovative, multidisciplinary, integrative approaches. The NCTR, with
its internationally recognized research staff, unique facilities, and scientific
capabilities, provides the opportunity to conduct collaborative research that
addresses a wide variety of specific public health questions. NCTR is actively
seeking new opportunities for collaborative partnerships.
Opportunities for Leveraging Resources with NCTR
- Interagency Agreements (IAGs): Formal financial partnerships with
other government agencies
- Collaborative Research and Development Agreements (CRADAs): Formal
financial partnerships with nongovernmental organizations, nonprofit
organizations and private companies
- Informal Collaborations: Informal agreements to work
collaboratively on projects of mutual interest
- Visiting Scientists: Opportunities for scientists to conduct
research on the NCTR campus
Examples of current leveraging efforts at NCTR:
Interagency Agreements (IAGs)
National Institute for Environmental Health Sciences (NIEHS)
In 1992 the Food and Drug Administration (FDA) entered into an
Interagency Agreement (IAG) with the NIEHS. The design for this agreement
concentrated on FDA’s priority National Toxicology Program (NTP) nominations
of chemicals/agents and utilized the unique resources and facilities at the
National Center for Toxicological Research (NCTR). The research conducted
under the IAG provided FDA the ability to better assess the safety of a number
of FDA-regulated products.
The 1992 agreement provided support for five FDA priority chemical/agent
NTP nominations. The agreement has expanded to include collaborative research
on five commonly accepted endocrine disrupter compounds, which include three
multigeneration studies and two chronic cancer studies. Currently the IAG
includes the evaluation of AIDS therapeutic drugs, dietary supplements,
anesthetic agents, mycotoxins, such as fumonisin, and acrylamide, a chemical produced when some
food products, such as potatoes, are cooked at high temperatures. In 1998 NCTR
opened a FDA/NIEHS Phototoxicity Research and Testing Laboratory. The facility
is state-of-the-art, testing compounds applied to the skin in simulated solar
light.
All research under the NIEHS/NTP IAG is designed with input from FDA
regulatory scientists, NCTR and NIEHS scientists, experts from universities,
and often experts from the regulated industry. The IAG utilizes resources from
public funds and exceptional scientific expertise to provide the best possible
assessment of product safety resulting in accomplishment of the missions of
the FDA and NIH.
PI/Spokesperson: William Allaben, PhD., Associate Director of Scientific
Coordination, NCTR, Jefferson, Arkansas.
Environmental Protection Agency (EPA)
In addition to the IAG with NIEHS/NTP, NCTR has received support from other
governmental agencies. For example, the EPA has supported NCTR in conducting a
broad area of research on neurotoxicity risk assessment and risk assessment
associated with waterborne and foodborne pathogens. Currently, research is
being conducted for an infectivity model for Cryptosporidium, which can
potentially contaminate drinking water and the food supply.
PI/Spokesperson: William Slikker, PhD., Office of Research,
NCTR, Jefferson, Arkansas.
Federal Aviation Administration (FAA)
The FAA has entered into an IAG with scientists at the Center to develop
rapid sensor detection methods to screen for explosives in counterterrorism.
Additionally, the National Cancer Institute (NCI) is supporting a study at the
NCTR evaluating the role of dietary constituents (e.g., methionine, choline,
folate, alcohol) in the early phases of carcinogenesis (liver and possibly
mammary) and effects on global and site-specific DNA hypomethylation.
PI/Spokesperson: Dwight Miller, PhD., Division of Systems Toxicology,
NCTR, Jefferson, Arkansas.
Collaborative Research and Development Agreements (CRADAs)
University of Arkansas at Little Rock (UALR)
Under this partnership arrangement, scientists from NCTR’s Division of
Neurotoxicology and the UALR explore their initial observations that animals
exposed to cocaine during gestation fail to adapt to important changes in
their environment. The studies examine additional aspects of behavioral
adaptability by changing “the rules of the game” for a variety of behavioral
tasks.
PI/Spokesperson: Merle Paule, PhD., Division of Neurotoxicology, NCTR,
Jefferson, Arkansas.
SAS Institute
The SAS system, a primary statistics tool used by FDA, and ArrayTrack, DNA
microarray data management, mining, analysis and interpretation software
developed by the NCTR/FDA, are readily available both for FDA scientists and
reviewers. A CRADA with the SAS Institute will combine ArrayTrack with SAS
Scientific Discovery Systems (SDS) to provide the FDA scientist and reviewers
key capabilities for analyzing data from toxicogenomic/pharmacogenomic studies
for scientific research and regulation.
PI/Spokesperson: Weida Tong, PhD., Division of Systems Toxicology, NCTR,
Jefferson, Arkansas.
Pfizer
The effects of a variety of psychotropic agents on important cognitive
processes, such as short-term memory, learning, visual and position
discrimination, time perception and motivation, on the nonhuman primate will
be supported by a CRADA with Pfizer. These data will help further characterize
the influence of specific neurotransmitter manipulations on cognitive function
and identify specific cognitive domains most likely to be affected by other
drugs with similar mechanisms of action.
PI/Spokesperson: Merle Paule, PhD., Division of Neurotoxicology, NCTR,
Jefferson, Arkansas.
AstraZeneca
AstraZeneca is currently supporting a study to determine whether ketamine,
an NMDA receptor antagonist frequently used as an anesthetic in children, and
remacemide, an antiepileptic agent with both NMDA receptor antagonist and
sodium channel blocking properties, cause adverse effects similar to those
noted in previous studies. Researchers have confirmed that administration of
ketamine during the brain growth spurt results in widespread neuronal
apoptosis in the rat. Further evidence in a non-human primate model is in
progress.
PI/Spokesperson: Merle Paule, PhD., Division of Neurotoxicology, NCTR,
Jefferson, Arkansas.
Litmus
The NCTR Division of Chemistry developed small disks called Food Quality
Indicators (FQIs) as rapid chemical sensors to assess food for freshness.
These FQIs were evaluated by the Canadian Centre for Fisheries Innovation, St.
John’s, Newfoundland, Canada. This independent evaluation confirmed that the
FQI is rapid, sensitive, rugged, and simple enough that multiple analysts can
obtain results of equal and high quality. A CRADA has been developed with
Litmus to develop a commercial outlet for this FQI and also to support the
further development of FQI technologies.
PI/Spokesperson: Dwight Miller, PhD., Division of Systems Toxicology,
NCTR, Jefferson, Arkansas.
Sigma Tau Research, Inc.
NCTR’s Division of Neurotoxicology is collaborating with Sigma Tau
Research, Inc. to characterize the early genomic biomarkers of mitochondrial
dysfunction, a frequently observed effect of neurotoxicants. This research may
provide information on a standardized microarray system that will allow for
the screening of agents with the potential to predict brain injury.
PI/Spokesperson: Zbigniew Binienda, PhD., Division of Neurotoxicology,
NCTR, Jefferson, Arkansas.
RxGen
A CRADA between the NCTR Metabolomics research team and RxGen will develop
a method for predicting human hepatotoxicity through the identification of
characteristic high-resolution proton nuclear magnetic resonance (NMR)
spectroscopic profiles in biofluids and liver tissue.
PI/Spokesperson: Richard Beger, PhD., Division of Systems Toxicology,
NCTR, Jefferson, Arkansas.
University Interactions
NCTR scientists actively pursue collaborations with individuals and
departments of universities. Currently, many NCTR scientists hold adjunct
academic positions and research collaborations exist with more than 20
universities. Thus, the NCTR staff is collaborating with various university
staffs to solve problems of mutual interest to FDA and the respective
university. Academic collaborations include mutual use of specialized equipment,
sharing of research samples to maximize the gain of information from a project,
and the exchange of staff between the institutions for lectures, seminars, and
conduct of research.
University of Arkansas for Medical Sciences (UAMS)
Of particular importance are the close collaborations between NCTR and the
UAMS in Little Rock, AR. In addition to the adjunct positions held by NCTR
scientists at the UAMS, NCTR participates in the UAMS Interdisciplinary
Toxicology Program through which graduate students receive a PhD in
toxicology. Many of the graduate students perform research for their
dissertations in an NCTR laboratory under NCTR staff supervision.
Other collaborations with UAMS scientists include projects that:
- investigate the biological effects of ephedrine, ethanol, baby
diets, cardiovascular disease, and aging on health using the metabonomics
approach;
- investigate the influence of biotin on the developing embryo;
- identify the brain tumor diagnostic method to achieve tissue
characterization;
- assess DNA from breast epithelial cells for the presence of carcinogen
adducts,
- develop methodology and determine the critical biotransformation
pathways involved in adduct formation and assess possible differential
sensitivity in normal-risk women as opposed to women at high risk for breast
cancer;
- conduct the first LCM-based study on genetic changes of the
mitochondrial genome in prostate cancer and precursor lesions; and
- develop a microarray-based method for the detection of 150 genes
associated with 22 antibiotics, some of which are used to promote growth in
poultry and animal farming while others are used to treat infections in both
humans and animals.
Arkansas Children's Hospital (ACH)
NCTR staff in the Division of Neurotoxicology has access to a Complex Brain
Function Laboratory at the Arkansas Children's Hospital (ACH). Results of
behavioral studies obtained in animals using the Operant Test Battery at NCTR
are verified in humans at ACH.
NCTR staff collaborates on a number of grants with area universities. These
include a NASA-funded UAMS (Department of Otolarynology) project designed to
provide information on the efficacy of several drugs used as anti-space motion
sickness therapies and their effects on cognitive function as assessed using
the NCTR Operant Test Battery. Grant funding via UAMS/UALR and NIH has
provided support for studies to examine the ability of the NCTR Operant Test
Battery to detect and monitor cognitive dysfunction in Alzheimer’s patients.
Central Arkansas Veterans Healthcare System (CAVHS)/ACH/UAMS the
University of Arkansas
Recent projects that include collaborations with area universities and
hospitals include those with Central Arkansas Veterans Healthcare System (CAVHS),
ACH, and the University of Arkansas. A project with UAMS and CAVHS will
identify the measurement of cancer-associated gene mutation in colon tumor and
non-tumor tissue. Collaborations with UAMS/UALR/ACH have begun on a project to
determine if children diagnosed with major depression perform differently than
children without such a diagnosis on tests of motivation, simple visual
discrimination, timing ability, memory, and learning. In addition, the
University of Arkansas and NCTR scientists will address the extent to which
the disruption of the monoaminergic system and oxidative stress are involved
in the progression of Parkinsonism or Parkinson-like symptoms.
Visiting Scientists
NCTR scientists collaborating with universities in the U.S. and abroad have
resulted in, at no cost to FDA, a number of visiting scientists who come to
NCTR to pursue research in areas developed by NCTR scientists. Thus far, NCTR
has hosted more than 36 visiting scientists from the U.S. and 15 foreign
countries. These visiting scientists not only contribute valuable scientific
expertise to NCTR research programs, but many return to their respective
institutions to continue research on problems of interest to FDA and NCTR.
Intra-Agency Agreements:
Consistent with its role within the FDA, NCTR actively participates in
collaborative research with the other FDA Centers. For some high priority
research projects, NCTR receives financial resources from the other Centers to
facilitate the timely conduct and completion of important studies. For example,
ketamine studies (supported in part by the Center for Drug Evaluation and
Research (CDER)) may provide pivotal information for assessing the potential
public health risk associated with ketamine’s use as an anesthetic agent in
children. The Center for Food Safety and Applied Nutrition’s (CFSAN’s)
collaboration on identifying the methods for the safety testing of pigments used
for tattooing could determine if tattoo inks have toxic or phototoxic potential.
Informal Collaborations:
NCTR scientists are active collaborators with investigators at numerous
national and international organizations in a wide variety of research projects.
Organizations with which NCTR scientists have collaborated include:
- University of Arkansas for Medical Sciences
- University of Arkansas at
Little Rock
- Arkansas Cancer Research Center
- Arkansas Children’s Hospital
- Central Arkansas Veterans Health Care Systems
- MD Anderson
- National Cancer Institute
- National Institutes of Health
- U.S. Department of Agriculture
- New York Department of Health
- Environmental Protection Agency
- Environ
- National Institute of Standard Technology (NIST)
- Litron Laboratories
- Health Canada
- National Institute of Health Sciences, Tokyo, Japan
- University of Mississippi
- Harvard University
- University of Montreal
- Massachusetts Institute of Technology
- North Carolina State University
- State University of New York – Stony Brook
- Wake Forest
- Washington School of Medicine
- ARS Biosciences Research Laboratory in Fargo, ND
- Institute of Statistical Science in Taiwan
- Lovelace Inhalation Toxicology Research Institute
- NASA Johnson Space Center
Guiding principles for conducting leveraging activities with the
FDA can be found on the FDA website at
http://www.fda.gov/oc/leveraging/principles.htm.
Contact information:
Bill Slikker., 870-543-7517,
william.slikker@fda.hhs.gov
Other places to look in FDA: http://www.fda.gov/oc/leveraging/default.htm
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