Recovery Act Limited Competition for NIH Grants: Research and Research Infrastructure “Grand Opportunities” (RC2)

http://grants.nih.gov/grants/guide/rfa-files/RFA-OD-09-004.html

The purpose of the Research and Research Infrastructure Grand Opportunities program is to support high impact ideas that lend themselves to short-term, non-renewable funding, and may lay the foundation for new fields of investigation. The program will support large-scale research projects that accelerate critical breakthroughs, early and applied research on cutting-edge technologies, and new approaches to improve the synergy and interactions among multi and interdisciplinary research teams.

This initiative is one of several being offered by NIAAA to help fulfill the goals of the American Recovery and Reinvestment Act (ARRA) to help stimulate the economy through support of biomedical and behavioral research. Additional information about the Recovery Act and related NIH opportunities is available through the Office of Extramural Research http://grants.nih.gov/recovery/.
 

Funding Priorities:

Overall, NIAAA expects to devote $10,000,000 to the Grand Opportunity program. In addition, NIAAA will give higher-priority to application requests that do not exceed $1,000,000 in total costs per year. Applicants interested in pursuing topics with higher requested costs, should contact Dr. Trish Powell prior to application submission to discuss the rationale for the costs and ascertain Institute interest.
 

Key Dates:

Release/Posted Date: March 20, 2009
Opening Date:  April 27, 2009 (Earliest date an application may be submitted to Grants.gov)
Letter of Intent Receipt Date(s): April 27, 2009.  Please send to Dr. Abe Bautista at bautista@mail.nih.gov
NOTE: On-time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization). 
Application Due Date(s):  May 27, 2009
AIDS Application Due Date(s): Not applicable
Peer Review Date (s): June/July 2009
Council Review Date(s): August 2009
Earliest Anticipated Start Date(s): September 30, 2009
Additional Information To Be Available Date (Activation Date): Not Applicable 
Expiration Date: May 28, 2009
 

Contact Information:

Program Contact:  Trish Powell, Ph.D., 301-443-5106, ppowell@mail.nih.gov
In addition, please see program contacts at the end of each topic description. 

Review contact: Abe Bautista, Ph.D., 3301-443-9737, bautista@mail.nih.gov
Grants Management Contact: Judy Fox, 301-443-4704, jfox@mail.nih.gov

Areas of Scientific Priority:

For this initiative, examples of scientific interest areas include, but are not limited to the following:
 
Biomarker Pre-Validation Reference Set

It is the goal of this new specimen reference collection to jumpstart the aims of the NIAAA Biomarkers Initiative (i.e., testing and implementation of biomarkers useful for the detection of alcohol exposure expressed in the time domain, and alcohol-associated organ pathology).  In the past, much of the biomarker discovery work was performed using convenience samples from cases and controls.  Since these samples were collected in a variety of ways, under varying conditions of alcohol exposure, comparisons have been difficult. Furthermore, cases and controls may not have been selected and matched using appropriate rigor to reduce bias. Finally, since there has not been a common resource with sufficient amounts of sample, comparison or integration of multiple markers has not been feasible. This resource will be accessible to any NIAAA investigator based upon a common, flexible and transparent set of criteria.

Program Contact:  Howard Moss, M.D., Associate Director for Clinical and Translational Research, 301.402.0944, mossh@mail.nih.gov 

Development of a Point-of-Care Alcohol Biomarker Technology

Several biochemical biomarkers have been developed for alcohol consumption and alcohol-associated organ damage.  These include the traditional biomarkers, like gamma glutamyl transferase, and newer biomarkers such as carbohydrate-deficient transferring (CDT) and several alcohol metabolites. Nonetheless, few biomarkers are currently being utilized by clinicians in the office or at the bedside. Many of the newer biomarkers, such as CDT and the alcohol metabolites, can only be measured in specialized laboratories, making it difficult for clinicians to conveniently use these biomarkers in their settings. The goal of this proposal is to jumpstart the development of point-of-care alcohol biomarker technologies that will translate extant research biomarkers into readily utilized clinical tools for the practitioner and the clinical researcher. 

Program Contact:  Howard Moss, M.D., Associate Director for Clinical and Translational Research, 301.402.0944, mossh@mail.nih.gov 

Alcohol-Induced Metabolic and Hepatic Injury (AIMHI)

 
Alcohol consumption results in fatty liver disease (AFLD), which, under chronic conditions, progresses in about 35% of patients to steatohepatitis, and in 15% to cirrhosis.  Obesity and Hepatitis C viral infection are risk factors for further liver damage due to alcohol consumption.  Obesity alone affects about 25-30% of the population and is commonly associated with Metabolic Syndrome, one manifestation of which is non-alcoholic fatty liver disease (NAFLD). In some patients with AFLD or NAFLD, there is progressive fibrosis, and without biopsy there is no way to determine the degree of fibrosis in these patients.  Pathways important in the development of fibrosis could be common in obesity, hepatitis C infection, alcohol consumption, or any combination thereof.  Early identification of such patients would enable clinicians to evaluate and treat them early, avoiding advanced fibrosis and cirrhosis.  In addition, metabolic derangements in obesity and after chronic alcohol consumption will influence disease outcome, including diabetes, hypertension, and vascular disorders.  The purpose of this line of inquiry is to develop a strong clinical-translational research that focuses on:

(1)       Determination of gene expression signatures associated with early liver fibrosis in patients with AFLD and/or NAFLD, with or without hepatitis C infection.

(2)       Collection of samples for future identification of candidate genes associated with liver fibrosis due to alcohol, obesity, or hepatitis C.

Contact:  Samir Zakhari, Ph.D., Director, Division of Metabolism and Health Effects, 301-443-0799, szakhari@mail.nih.gov

Molecular Markers of Alcohol Exposure and Alcohol-induced Tissue Injury

A variety of biomarkers of alcohol exposure and alcohol-associated tissue injury are needed.  Biomarkers of prenatal exposure could augment patient histories which are often unreliable to better guide clinical decisions and identify in utero-exposed fetuses at risk of FASD.  For a different population, biomarkers of alcohol-associated tissue injury would be valuable for early diagnosis, monitoring disease progression and the effectiveness of treatment, and understanding disease mechanisms.  However, the pursuit of biomarkers is complicated by the variety of alcohol consumption patterns that exist (e.g., acute, chronic, binge) and the multiplicity of specimens that could be analyzed, ranging from those more practical in a clinic setting (e.g., blood, sputum, hair) to those less easily obtained that might be most informative for tissue or fetal injury (e.g., liver biopsy, placenta).  While a number of metabolites of alcohol have been shown to be promising biomarkers of exposure, a broader panel of molecular measures will almost certainly be required to establish robust molecular "signatures" of alcohol exposure history and alcohol-induced tissue injury.

This significant challenge may be best met by a group of investigators capable of:

(1)  developing a well-conceived animal model of alcohol exposure and/or tissue injury, and collecting various appropriate biological specimens from the model;

(2)  performing parallel analyses of these shared specimens using multiple, distinct high-throughput discovery approaches (e.g., epigenomics, transcriptomics, proteomics, metabolomics); and applying rigorous statistical approaches to define molecular signatures that are either informative in terms of alcohol exposure history or predictive of alcohol-induced tissue injury.

Contact:  Samir Zakhari, Ph.D., Director, Division of Metabolism and Health Effects, 301-443-0799, szakhari@mail.nih.gov

The Role of Mitochondria and Endoplasmic Reticulum in Alcohol-Induced Tissue Injury

Excessive alcohol consumption can damage many organs including the liver, heart, pancreas, brain, and lung.  However, the mechanisms for these injuries are currently not fully understood.  Mitochondria and ER play an important role in cellular function and are significantly involved in alcohol-induced tissue injury.  Thus, studies of alcohol’s effects on the structure and function of mitochondria or ER are critical to better understand the mechanisms of alcohol-induced injuries and to develop new strategies for their diagnosis and treatment.  The purpose of this FOA is to investigate how variations of proteins in the mitochondria or ER, or in the control of their expression or function, including cellular signaling pathways, contribute to an individual’s response to acute or chronic alcohol intake and alcohol-induced tissue injury.

Contact:  Samir Zakhari, Ph.D., Director, Division of Metabolism and Health Effects, 301-443-0799, szakhari@mail.nih.gov

Impaired Retinoic Acid Metabolism and Signaling in Alcohol- Related Organ Pathologies

A large body of evidence indicates that retinoic acid (RA) is involved in the regulation of cell proliferation, differentiation and apoptosis.  Since alcohol interferes with RA biosynthesis and metabolism, it can significantly change RA availability and thus modulate the cellular functions and outcome of organ repair and regeneration.  However, the mechanisms underlying the role of RA in alcohol-induced tissue injury is still not well-understood.  The purpose of this FOA is to solicit grant applications that aim to understand how the impaired metabolic and signaling pathways involving RA contribute to alcohol-induced tissue injury.  Areas that are ripe for investigation include embryonic stem cells and fetal alcohol spectrum disorders, adult stem cells, carcinogenesis, and alcohol-induced activation of hepatic stellate cells.

Contact:  Samir Zakhari, Ph.D., Director, Division of Metabolism and Health Effects, 301-443-0799, szakhari@mail.nih.gov

Alcohol, Decision-Making and Adolescent Brain Development

Alcohol remains the most commonly abused substance among adolescents.  However, little is known about the cognitive, emotional, and social factors that may contribute to high rates of adolescent drinking and to other behavioral problems during the adolescent period.  During adolescence, developing brain systems underlying cognitive, emotional, and social behaviors develop at different rates.  This asynchronous maturation of intellectual and emotional skills and their underlying neural substrates may help explain age differences in judgment, decision-making, sensation seeking, and risk taking which make adolescents vulnerable to developing alcohol abuse and dependence.  The focus of this initiative is to stimulate research on decision-making processes in adolescents as they relate to drinking behavior and related behavioral problems, and on the role of neural circuitry development in adolescent decision-making, emotional regulation, and alcohol abuse and dependence.

Contact:  Ellen Witt, Ph.D., Deputy Director, Division of Neuroscience and Behavior, 301-443-6545, ewitt@mail.nih.gov 

Mechanisms of Alcohol and Nicotine Co-Dependence

Alcohol and nicotine are the most commonly misused non-therapeutic drugs in the United States. Nearly 50 million Americans smoke cigarettes; almost 20 million Americans are alcohol dependent or regularly drink alcohol in harmful quantities. People who drink alcohol are 3 times more likely than the general population to smoke, and tobacco dependent individuals are 4 times more likely than the general population to be alcohol dependent. Because of the limited understanding of the underlying causes of co-occurring alcohol and nicotine dependence, effective treatment strategies for treating patients presenting with both are lacking. Therefore, this FOA will promote 2-year exploratory research leading to outputs that will enhance our understanding of neurobiological and behavioral mechanisms of dependence and how alcohol and nicotine use interact through these mechanisms in ways leading to dependence. Such an understanding is essential to guide the development of better prevention and treatment strategies for alcohol and nicotine co-abuse.

Contact:  Ivana Grakalic, Ph.D., Division of Neuroscience and Behavior, 301-443-7600, igrakalic@mail.nih.gov

Health Care and Alcohol Screening Survey

Based on the National Epidemiologic Survey of Alcohol Related Conditions, 3.81% of the U.S. population 16 and older in the past year met alcohol dependence criteria and 4.65% alcohol abuse criteria.  A total of 17 million U.S. adults met either alcohol dependence or abuse criteria and are in need of alcohol treatment.

Twenty eight percent of the U.S. population or approximately 58 million exceed NIAAA recommended guidelines for weekly or daily drinking, more than 4 drinks per day or 14 drinks per week for men and 3 drinks per day or 7 drinks per week for women.

It has been documented that only 16% of people who met alcohol dependence or abuse criteria in the past year received alcoholism treatment in the past year.

NIAAA has recently reissued its Clinician’s Guide to facilitate screening and brief intervention for alcohol problems.  Meta-analytic research reviews indicate that screening and brief intervention by primary care providers is a highly effective and cost-effective prevention practice comparable in benefit to screening for hypertension, colorectal cancer, or low vision for persons over age 65 (Solberg et a. 2008).

Unknown is what proportion of the U.S. adult population understands the definition of a standard drink and NIAAA's recommended daily and weekly standard drink limits.  Also unknown is what proportion of the U.S. adult population: 1) saw a health care provider in the past year and the types of providers seen; 2) was asked during those health care visits about how much they drink; 3) wanted to be asked about their drinking; 4) was given advice about what constitutes safe drinking limits;  5) understands safe drinking limits and what constitutes binge drinking; and 6) if they exceeded safe drinking limits or met alcohol abuse or dependence criteria, were advised to reduce or stop drinking alcohol or seek treatment and were offered medication to help control their drinking.

Baseline information regarding these questions is needed for the population as a whole, for persons of different ages and genders, racial/ethnic groups, occupational status, including college students and persons in the military, as well as for certain sub-populations, for example persons in the criminal justice system, pregnant women, persons of various sexual orientations and persons with and without health care coverage.

An NIAAA priority within this FOA is the conduct and analysis of an initial and repeatable national probability survey to address these issues.  This would establish a baseline to measure the impact of initiatives going forward to increase the proportion of the U.S. population who are annually screened by health care providers about their drinking and provided appropriate advice. 

To the extent possible, the survey should include probability samples within each state so that the NIAAA Alcohol Policy Information System can be used to assess whether state government reimbursement policies as well as NIAAA’s Clinician's Guide and Rethinking Drinking program, or other initiatives can increase the proportion of the U.S. population that receives appropriate alcohol screening, counseling, and referral.

Contact:  Ralph Hingson, Sc.D., Director, Division of Epidemiology and Prevention Research, 301-443-1274, rhingson@mail.nih.gov.

Expanding and Personalizing Treatment Options for Alcohol Disorders

Expanding and Personalizing Treatment Options for Alcohol Disorders:  In spite of advances in the scientific understanding and treatment of alcohol use disorders, there is no indication of a reduction in their incidence and prevalence; and community-level treatment outcomes have not appreciably improved. Moreover, most people who develop alcohol dependence never receive any professional treatment, and those who do primarily represent the most severely and chronically affected. The focus of this FOA is to stimulate transformative research aimed at risk reduction, early identification and diagnosis, and personalized treatment resulting in improved outcomes, and thereby reduce the prevalence and overall disease burden attributable to harmful alcohol use including alcohol use disorders.  The organizing principle underlying this initiative is that heavy drinking and alcohol use disorders vary in severity and type across a broad continuum, and thus, identification, diagnosis and treatment need to be carefully tailored in terms of timing, type, location, intensity and length of interventions recommended. NIAAA is seeking applications for transformative work that cuts across boundaries/fields, which can be done within the prescribed timeframe. Applications could focus on one, or two or more, components of the continuum of care.

• Specific types of research needed to achieve the goals of this project include (but are not restricted to):
• Demonstration of predictive validity of subtypes of alcohol dependence in terms of treatment response and outcome
• Identification of pharmacogenomic markers of response to specific pharmacological agents
• Development and testing of innovative methods of providing services to large numbers of people, especially those with milder illness and/or at an earlier stage of illness
• Investigation of the role of pharmacological agents for risk reduction among (non-dependent) at-risk drinkers
• Use of new technologies for delivering treatment services, including internet, smartphones, text messaging, telephone care, tele-medicine with video capacity, and others
• Determination of the cost-effectiveness of large-scale risk reduction and early identification and treatment strategies

Contact:  Mark Willenbring, M.D., Director, Division of Treatment and Recovery Research, 301-443-1208, mlw@niaaa.nih.gov