2012 Grant Project Profiles
ABMRF/The Foundation for Alcohol Research has played a major role in shaping the early careers of the most prominent alcohol researchers across North America. Since our founding in 1982, we have maximized our impact as a relatively small foundation by centering the grant program on novel research proposals put forth by the most promising investigators. Recently funded research projects which are described below offer an exciting opportunity to view the future through the studies currently underway by Foundation grantees.
Behavioral and Social Advisory Council
Tara Chaplin, Ph.D., Yale University, "Responses during parent-child interactions and alcohol-use behaviors in adolescents."
Adolescence is a period of risk for alcohol use and problem use. One important factor in adolescents' problem alcohol use is their family environment. Several questionnaire-based studies have found that poor self-reported parenting is a risk factor for teens' alcohol use. However, laboratory studies have not been done to examine how adolescents respond to family conflict interactions and if adolescents' emotional and physiological responses to these interactions have implications for their alcohol use. If adolescents are overly aroused by family interactions about difficult topics, they may avoid such talks and consequently have a less close family relationship, which may lead to decreased monitoring, increased involvement with deviant peers, and increased alcohol use. The proposed laboratory study will observe parent-adolescent conflict interactions in 60 14-16 year olds and their parents. Parenting behaviors during the interaction, including parental warmth, structuring, criticism, and negative emotion will be coded. Before the interaction and at repeated time-points after the interaction, adolescents' and parents' emotional, physiological (HR, BP), and neuroendocrine (cortisol) arousal will be assessed. Adolescents will complete assessments of alcohol use/problem use at the time of the laboratory session and 9 months later. The hypothesis is that adolescents who show high levels of emotional and physiological arousal in response to the family conflict interaction will show greater alcohol use and alcohol problems currently and at the 9 month follow-up. In addition, adolescents who experience more negative parenting, including lower parental warmth and structure and higher criticism and negative emotion, will show greater alcohol use/problem use, particularly if they show high arousal to the conflict interaction. The proposed study will contribute to the field by identifying specific family interaction responses that are associated with risk for or resilience from alcohol use in adolescents. These responses could then be targeted in family-based alcohol abuse prevention programs.
Catherine Anne Cluver, MBChB, FCOG, Stellenbosch University, "Does in utero alcohol exposure have an effect on the early neurocognitive and behaviour profiles of children at 4 years of age?"
There is still much debate about the exact effect of alcohol exposure during pregnancy. The detrimental effects of heavy or binge drinking on the fetus have been well studied and described, but the effects of low to moderate exposure are less well known. Our hypothesis is that prenatal alcohol exposure negatively impacts neurocognitive development and physical growth at 4 years of age and that these effects are related to alcohol dose and timing of exposure. In our study 500 children from the Safe Passage Study will be enrolled. The Safe Passage Study by the PASS (Prenatal Alcohol SIDS and Stillbirth) Network is an international collaboration to investigate the role of prenatal alcohol exposure in the risk for sudden infant death syndrome, stillbirth and fetal alcohol spectrum disorders. Detailed prospective information is collected on alcohol exposure in pregnancy for this study. At 4 years of age we will collect routine anthropometrical information (which includes height, weight and head circumference), we will do an assessment for dysmorphology and we will perform the Kaufman Assessment Battery for children, the NEPSY-II neuropsychological instrument and the Preschool Child Behavior checklist (CBCL/1 ½ -5) by Achenbach. The relationship of these outcome measures will then be compared to alcohol exposure level (none; light/moderate; heavy/binge) and other maternal/fetal variables. The benefit of this study is a more detailed understanding of the effects of prenatal alcohol exposure on early childhood development and growth.
Blas Espinoza-Varas, Ph.D., University of Oklahoma Health Sciences Center, "Auditory-information conflict and alcohol-use disorder in the adolescent."
Research on the inhibition or activation of inappropriate behaviors prompted by conflicting verbal commands (i.e., auditory inhibitory control) is critically important in the prevention and treatment of alcohol-use disorders (AUD) in adolescents. In this age group, drinking alcohol is a behavioral self-control failure that occurs most often in settings in which the peer pressure is strong, and the psychosocial interaction is mainly through verbal communication; that is, through verbal commands that encourage or discourage the adolescent's choices and actions. Peer pressure, the main cause of adolescent AUD, exerts largely through verbal commands, and decisions to abstain or to drink alcohol depend heavily on auditory verbal information. Some teenagers can be "talked into" drinking alcohol with relative ease, but others desist under compelling verbal pressure, pointing to large individual differences in the ability to inhibit inappropriate behavior prompted by conflicting commands such as "have a drink" versus "just say no." In late adolescents, this project will assess AUD-risk effects on inhibitory control for conflicting information conveyed by verbal commands that are used habitually to control actions (e.g., "quit"). The voice tone and the speaking rate of these commands are critical task-relevant dimensions because they encode how strict or firm a command is. Thus, the experiments will assess classification of impeding (e.g., "quit") or instigating commands (e.g., "do it"), along the lenient/stern task-relevant dimension, and classification of speed up (e.g., "hurry") or slow down (e.g., "wait") commands along the slow/fast speaking-rate relevant dimension; in both cases, the conflicting task-irrelevant dimension is laterality or left/right ear presentation. This study is innovative because, in adolescents, there are no studies of AUD-risk effects on self-control for conflicting auditory information. The study could unveil basic mechanisms involved in the processing of conflicting auditory information, and help understand the transition from normal to disordered alcohol use.
Lucy Kilp-Napper, Ph.D., Loyola Marymount University, "A parent-based social norms alcohol intervention for first-year college students."
The transition from high school to college is often associated with substantial increases in alcohol use, making this a critical period for interventions targeting young adult populations. A growing body of research has demonstrated that parents can have a significant impact on their child’s alcohol-related attitudes and behavior, even after matriculation to college. Indeed, multi-component parent-based interventions (PBIs) appear to be a promising avenue for decreasing alcohol risk in college populations. The goal of the proposed study is to evaluate the effectiveness of a brief web-based PBI that focuses on one intervention component - social norms. The social norms approach suggests that perceptions of what important others do and think can influence an individual’s own behavior and attitude. The proposed intervention will utilize modified personalized normative feedback (PNF) to correct parents’ misperceptions about the prevalence of student alcohol use, how approving other parents are towards alcohol use, and the frequency of other parents’ alcohol-specific communication. Although PNF has demonstrated efficacy among students, this would be the first study to extend the approach to parents. Student-parent dyads will be recruited during the summer prior to matriculation to college, and randomized to either the PNF intervention or a control condition. Students’ alcohol-related behaviors and attitudes will be assessed prior to the intervention, and at one- and six-months following the beginning of the fall semester. It is hypothesized that PNF will encourage parental alcohol disapproval, and promote more in-depth and frequent alcohol-related communication. This, in turn, should lead students to hold less approving attitudes towards alcohol, to engage in less risky alcohol behaviors, and experience fewer negative consequences than control group peers. We will also examine potential mediators and moderators of intervention efficacy. If successful, this brief intervention would offer a cost-effective approach to implementing PBIs with parents located over wide geographical areas.
Sean D. Kristjansson, Ph.D., Washington University, "Alcohol misuse: Drinking motives, familial risk, and tobacco use."
This project seeks to shed light on the etiology of alcohol misuse. It is well known that risks for problem drinking and alcohol-use disorders (AUDs) are transmitted in families via shared genes and shared environments. However, less is known about the specific pathways through which familial risks travel to influence problem drinking outcomes. The Motivational Model of Alcohol Use provides a good framework for characterizing such pathways. It states that the final decision to drink or not drink depends on one's drinking motives. Drinking motives, or reasons for drinking, include consuming alcohol to attain a positive affective state (drinking for enhancement), and consuming alcohol to relieve negative affective state (drinking to cope). One purpose of this project is to examine how familial risk is transmitted via drinking motives to different types of alcohol misuse outcomes (e.g., binge drinking, frequently drinking to intoxication). Familial risk is defined in two ways: 1) having a parent with an AUD; and 2), as possessing specific genes known to be associated with AUDs. Further, it is also well known that drinking and smoking often co-occur, in part because alcohol and nicotine act on similar motivational mechanisms in the brain. A second purpose of this project is to examine how tobacco use might alter the transmission of familial risk to problem drinking. For example, are familial risk-drinking motive-alcohol misuse pathways different in smokers compared to non-smokers? If so, how and why are they different? Existing data from four complementary large-sample studies, which together include approximately 6000 individuals of different ages and races/ethnicities, will be combined into one large data set for analysis. Characterizing the interplay among familial risk, drinking motives and tobacco use to disentangle the etiology of alcohol misuse will provide information for developing more effective prevention and intervention strategies.
Robert Leeman, Ph.D., Yale University, "A brief, web-based alcohol reduction intervention for undergraduates: An initial study."
College drinking is a public health concern. Computer-based interventions have grown in popularity and web-based interventions that are self-contained with no direct contact between participant and researcher offer even more convenience. Most brief interventions require 45-60 minutes to complete. While this is a short time period, an even briefer, web-based intervention that is comprehensive and freely available has the potential to facilitate drinking reductions in more students.Tertiary Health Research Intervention Via Email (THRIVE), developed by Kypri and colleagues, is unique because it contains intervention components that are supported by research evidence and is very brief. Research findings from the Australian version of THRIVE have been very promising and THRIVE requires an average of only 9 minutes to complete. THRIVE’s free availability could save an institution thousands of dollars compared to a commercial intervention. We propose to test a form of THRIVE for U.S. students (US-THRIVE). We will also conduct tests of alternate versions of THRIVE providing focused sets of protective behavioral strategies to limit alcohol use and to drink more safely. A total of 248 heavy-drinking undergraduates will be randomly assigned to 1 of 4 conditions: 1) a US-THRIVE replication that includes a full list of protective behavioral strategies; 2) a US-THRIVE version providing focused strategies directly related to drinking behavior itself (for instance, making sure to allow enough time to pass between drinks); 3) US-THRIVE including focused strategies indirectly related to drinking itself (for instance, securing a designated driver); and 4) a brochure and assessment control. Primary outcomes will be the number of days students report having alcohol; overall number of drinks per week and reports of protective behavioral strategy use at 1-month follow-up. Secondary goals will be to relate strategy set condition to these drinking outcomes and test hypotheses over time including multiple follow-ups.
Elena Stepanova, Ph.D., Florida Gulf Coast University, "Effects of exposure to alcohol-related cues on prejudice, stereotyping and discrimination."
This research will investigate the extent to which the mere presence of alcohol-related stimuli in the environment affects the expression of bias and discrimination against racial minorities. Previous research has shown that drinking alcohol increases the expression of bias, but the possibility that merely seeing alcohol-related cues (such as advertisements for alcohol) could affect racial bias has wide-ranging implications for public health and policy. Three major goals of this work are to determine: (1) whether brief exposure to alcohol-related cues affects attitudes, stereotypes, and discrimination towards Blacks; (2) the underlying mechanisms of these effects, that is, how brief exposure to alcohol-related cues affects racial biases (for example, by increasing automatic activation of racial attitudes; by decreasing inhibition of race-based responses; by activation of general negative evaluations); and (3) factors moderating these effects, such as motivation to control prejudice, explicit racial attitudes and the strength of pre-existing alcohol-related expectancies. In a series of five experiments, participants will be primed with alcohol-related cues or neutral cues, and their affective, cognitive and behavioral responses related to racial biases will be measured. The most important implication of this research is that consumption, or even purported consumption of alcohol might not be necessary for alcohol to increase expression of racial biases. This work would suggest that people could be more likely to act upon their prejudices simply for having entered a bar, watched an alcohol advertisement, or passed a billboard on the freeway. Such findings will have important implications for social engineering campaigns designed to limit the likelihood of alcohol-related harm, going beyond considerations of limiting consumption. Identifying the mechanism by which these effects occur will help design intervention techniques for reduction of bias.
Medical Advisory Council
M. Scott Bowers, Ph.D., Virginia Commonwealth University, “Role of rat nucleus accumbens astrocytes in alcoholism.”
The mammalian brain is predominantly composed of non-neuronal cells; the astrocytes. Abnormal astrocyte shape and abundance are frequently observed in postmortem brains from alcoholics. Traditionally, astrocytic responses were solely thought to reflect injury or toxic insult. A growing literature is now revealing that astrocytes actively shape neuronal communication. Importantly, rat strains with a smaller cortical astrocyte population exhibit increased alcohol consumption and preference. Further, poisoning astrocytes or interfering with astrocyte-to-astrocyte communication in the cortex also increased alcohol consumption and preference. My data revealed a decreased astrocyte population (fewer, smaller cells) in another brain region (the nucleus accumbens core, which is critical for cocaine, heroin, and alcohol craving and relapse). Significantly, this reduced astrocyte population appears to depend upon the repeated choice to consume cocaine or alcohol. Specifically, following repeated injection of a rat with cocaine or alcohol, astrocytes proliferate and grow, but if the rat repeatedly chooses to consume either of these drugs, the astrocyte population decreases. Thus, these data suggest that astrocyte stimulation may reduce the drive to consume alcohol. In partial support of this hypothesis, I have recently poisoned rat nucleus accumbens astrocytes and observed a significantly increased motivation to consume alcohol. Thus, I sought ABMRF support to characterize the biochemical and structural changes of rat nucleus accumbens astrocytes following repeated alcohol consumption. Further, I proposed to optically stimulate the astrocytes while the motivation to consume alcohol is measured. This AMBRF supported research will elucidate if astrocytes contribute to the etiology of alcoholism and will facilitate future funding for astrocyte transplantation that are derived from human embryonic stem cell lines. This should reduce the motivation to consume alcohol. To this end, I have already secured a highly interested and local expert in human embryonic stem cell line-derived astrocyte transplantations into the rat brain.
Cedrick D. Dotson, Ph.D., University of Florida College of Medicine, “Hormonal signaling by GLP-1 glucagon and leptin modulates the taste of alcohol.”
Prenatal exposure to alcohol and stimulants may negatively affect the developing brain with long term effects on development and behaviour. As drugs of abuse become more readily available and affordable, the problem of polysubstance abuse has become increasingly significant. South Africa has a high prevalence of alcohol abuse and associated fetal alcohol spectrum disorders. Researchers have largely relied on animal models in the past to study the effects of drugs of abuse on brain development. However advances in neuroimaging methods over the last decade have allowed researchers to study structural, metabolic, and functional abnormalities resulting from prenatal exposure to drugs of abuse in infants. Both basic and clinical research have begun to implicate a number of neurotransmitter and neuroendocrine systems as underlying the association between maternal alcohol, methamphetamine and polysubstance abuse and subsequent negative behavioural outcomes in offspring. In particular, the glutamatergic system, the most widespread excitatory neurotransmitter system in the brain, appears to be disrupted in offspring of rodent mothers exposed to stress. There has been relatively little work, however, on the glutamatergic system during early life in humans. Magnetic resonance spectroscopy (MRS) allows an assessment of both neuronal integrity, and of particular neurotransmitter concentrations (such as glutamate/glutamine). This study aims to assess the effects of maternal alcohol and methamphetamine use on infant neuronal integrity and glutamatergic function, as assessed by magnetic resonance spectroscopy and correlate with early neurobehavioural measures. This research aims to advance understanding of the relevant mechanisms resulting in the neurological effects of alcohol and stimulant exposure, as this may ultimately drive therapeutic approaches.
Christian Hendershot, Ph.D., University of Toronto, "A prospective study of alcohol sensitivity phenotypes in late adolescence."
Physiological, subjective and behavioral responses to alcohol intoxication can differ significantly across individuals. Individual differences in alcohol sensitivity have been linked to genetic liability for alcohol dependence (e.g., a family history of the disorder) and to future levels of alcohol use. Human laboratory studies of alcohol sensitivity have been conducted primarily with adult participants and have typically used oral alcohol administration methods, which are associated with high variability in blood alcohol concentration profiles due to large individual differences in ethanol absorption and metabolism. This study will evaluate aspects of alcohol sensitivity and self-administration in late adolescence using highly controlled intravenous alcohol administration paradigms. Heavy drinkers with a multigenerational family history of alcohol dependence will be recruited and compared to a control sample matched on demographic factors and drinking history. Participants will be recruited starting at age 19. An initial laboratory session will be conducted to characterize physiological and subjective responses to alcohol, as well as to evaluate a neurocognitive index of alcohol sensitivity. A subsequent laboratory session will assess alcohol self-administration under controlled conditions. Laboratory outcomes will be examined in relation to drinking behavior during ages 19-21, a developmental period associated with a high incidence of alcohol dependence onset.
Nirelia Idrus, Ph.D., San Diego State University, "Fetal alcohol effects and vitamin D."
Despite preventative measures, some women continue to drink alcohol while pregnant. The range of effects that result from developmental alcohol exposure include cell loss, hyperactivity and problems with learning and memory, and is referred to as fetal alcohol spectrum disorders (FASD). One percent of the U.S. population is thought to be affected, with 40,000 new FASD cases estimated each year; the estimated lifetime cost of one child with FASD being $1-2 million. It is therefore important that we identify effective interventions that can reduce the severity of FASD. One potential intervention is vitamin D. Alcohol exposure can decrease vitamin D levels in both humans and animals, including pregnant females, indicating that alcohol-induced vitamin D deficiencies may contribute to FASD. Vitamin D deficiency also disrupts development in a manner remarkably similar to those seen with developmental alcohol exposure. However, even in the absence of a deficiency, vitamin D has neuroprotective properties and can promote brain development. I will be examining whether vitamin D can mitigate alcohol-related neuropathology and behavioral alterations using a rat model of FASD. Vitamin D will be given prior to, during, and after 3rd trimester equivalent alcohol exposure and then subjects will be run through a battery of tasks that test behavioral functioning. Cell numbers in key brain regions will be estimated to determine whether vitamin D is neuroprotective. Preliminary results indicate that vitamin D reduces hyperactivity, motor and cognitive deficits associated with developmental alcohol exposure. These data will provide important information on a potential treatment for FASD.
Inna Kruman, Ph.D., Texas Tech University Health Sciences Center, "Alcohol-induced neurotoxicity and one-carbon metabolism."
Nearly 100 million people worldwide have alcohol-use disorders, yet the fundamental mechanisms underlying alcohol-mediated brain damage remain poorly understood. Increased homocysteine levels is common in most alcoholics and at the same time, is a risk factor for various neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Homocysteine is part of normal metabolism involved in vital cellular functions and its increase is associated with impairment of normal metabolism and disturbance of cellular functions, including biosynthesis of DNA precursors, essential for DNA repair. Defects in DNA repair lead to the accumulation of DNA damage, genome instability and cell death. A mild deficiency in methylenetetrahydrofolate reductase (MTHFR) induced by inherited polymorphisms of corresponding gene, involved in homocysteine metabolism is common in human population (10-15% in Caucasians). The mild MTHFR deficiency may be influenced by ethanol exposure, creating an additional risk factor for ethanol-induced neurotoxicity. Using a mouse model of MTHFR deficiency, this proposal explores how the impairment of homocysteine metabolism contributes to alcohol-induced neurotoxicity. We, therefore, will determine the impact of MTHFR deficiency on alcohol-induced brain damage. The proposed studies offer a new concept for understanding the mechanisms of alcohol-related pathological changes in the brain based on the key role of genome instability conveyed by the impairment of homocysteine metabolism. These studies will help to develop new therapies for preventing its adverse effects.
Zhiyong Lin, Ph.D., Case Western Reserve University, "KLF15 as a circadian regulator of alcohol metabolism in the liver."
Given the deleterious effects that alcohol abuse and alcoholism exert on individuals and our society, it is important to gain a better understanding of factors mediating physiological responses to alcohol. Our studies aim to address the regulation of alcohol metabolism by a genetic factor Kruppel-like factor 15 (KLF15). Across species, physiological processes are regulated by a circadian rhythm; a natural physiological and behavioral pattern that is timed to a near 24-hour period. It has been well documented that both acute and chronic alcohol consumption have detrimental effects on chronobiological processes in humans and other animals. Further, a number of studies indicate that some of alcohol's negative health consequences may be related to a disruption of normal physiological timing. Conversely, circadian rhythm disruption may also impact on alcohol mediated behavior and tissue damage. Despite considerable effort, the molecular connection between alcohol metabolism and circadian biology remain poorly understood. Preliminary studies from our lab have identified KLF15 as a circadian factor that is an important mediator of alcohol metabolism. We found that Kruppel-like factor 15 expression, like that of two critical enzymes involved in alcohol metabolism termed mitochondrial aldehyde dehydrogenase 2 and tryptophan 2,3 dioxygenase, exhibit circadian rhythmicity. Moreover, the circadian rhythm of these two enzymes is abolished in KLF15 knockout mice and these animals develop liver damage in response to alcohol feeding. In this application, we hope to accomplish two goals. First, we hope to determine how alcohol reduces KLF15 expression. Second, we will determine how altering KLF15 levels in the liver affects the animals ability to tolerate alcohol exposure. The results may provide the foundation for novel chronotherapeutic approaches to ameliorate the detrimental effects of chronic alcohol use.
Derick Lindquist, Ph.D., Ohio State University, "An investigation into the neurodevelopmental consequences of neonatal alcohol exposure on forebrain NMDA receptor composition and function in classically conditioned adult rats."
Alcohol consumption by pregnant women can result in a spectrum of mental and physical deficits in offspring, collectively termed fetal alcohol spectrum disorders (FASD). In our third-trimester equivalent animal model of fetal alcohol syndrome (FAS), neonatal rats are exposed to ethanol across postnatal days (PD) 4-9. As adults, the FAS rats display selective deficits in trace fear conditioning, a form of Pavlovian conditioning in which the tone conditioned stimulus (CS) and footshock unconditioned stimulus (US) are separated by a stimulus-free interval of time. The medial prefrontal cortex (mPFC) and the dorsal and ventral hippocampus (DH and VH) are required for its successful acquisition and expression (Gilmartin and Helmstetter, 2010). Learning the CS-US association requires CS-generated neuronal firing be maintained, following tone offset, via N-methyl-D-aspartate receptor (NMDAR)-gated synaptic excitation in mPFC and/or hippocampal neurons. Composition of forebrain NMDARs, comprised of NR1 and the NR2A or NR2B subunits, changes over development. Early in life, NR2B receptors are dominant, whereas NR2A receptors—which produce less robust learning-dependent synaptic plasticity—are expressed at higher rates with increasing age. Perinatal ethanol exposure is reported to increase NR2A subunit expression in the cortex and hippocampus (Samudio-Ruiz et al., 2010), which is predicted to impede the reverberating neural dynamics required for sustained firing following termination of the CS. In turn, at the time of US presentation, impaired NMDAR function is proposed to result in altered expression of downstream signaling cascades, within the mPFC, DH, or VH, responsible for the induction and/or consolidation of CS-US associative synaptic plasticity. Preliminary data suggests pharmacological enhancement of NMDAR function, prior to trace FC, may improve the acquisition and expression of trace fear conditioning in FAS rats. This research, focused on forebrain function in adult animals of both sexes, is expected to help delineate the long-term neurodevelopmental consequences of neonatal ethanol exposure.
Mei Qiang, M.D., Ph.D., The University of Texas Health Sciences Center at San Antonio, “MeCP2 mediates epigenetic regulation of ethanol withdrawal-related adaptation of NR2B gene."
Prolonged alcohol consumption is known to induce long-lasting neuroadaptations in the brain that are considered to be causal processes for development of alcohol addiction. One of these neuroadaptations observed is the compensatory up-regulation of NMDA receptor following withdrawal from chronic alcohol consumption. It is important to understand how alcohol induces up-regulation of NMDA receptor in order to develop safe and efficacious therapies. In this study, I will combine in vitro chronic intermittent ethanol treatment (CIE) in neuronal culture and in vivo chronic ethanol exposure animals to identify a novel mechanism called epigenetic regulation, which regulates gene transcription. Epigenetic modifications are hypothesized to mediate alcohol effect on inducing long-lasting up-regulation of NMDA receptor’s subunit, R2B (NR2B). Using cortical neuronal cultures, we previously found that CIE treatment and its removal induced a significant decrease in DNA methylation and methylated CpG binding protein 2 (MeCP2) binging to the chromatin in the NR2B promoter. To verify that these changes cause NR2B up-regulation and thus result in alcohol withdrawal-associated behaviors, we will knockdown MeCP2 using lentiviral delivery system. Epigenetic modifications in the brain will be examined and its role in control alcohol consumption will be assessed. MeCP2 is an important component of the co-repressor complex and binds only to methylated CpG dinucleotides. This protein may be a critical repressor molecule to regulating NR2B gene expression in the neurons and perhaps, inducing demethylation. Results generated from this proposal will greatly expand our knowledge of the mechanisms that contribute to the development and maintenance of alcohol-drinking behaviors. These studies will therefore help to develop new therapies for preventing alcohol withdrawal-related problems.
Sanjoy Roychowdhury, Ph.D., Cleveland Clinic, "RIP3-mediated necroptosis and ethanol-induced liver injury."
Excessive alcohol consumption leads to liver damage. There is no straightforward treatment available to date. Liver transplantation is the only possible option for the patient suffering from alcohol-induced liver damage. The project will help us to better understand the cause of alcoholic liver damage, as well as identify new therapeutic targets for prevention of alcoholic liver damage.
Bernd Schnabl, M.D., University of California, San Diego, "Analysis of the enteric microbiome associated with alcoholic liver disease."
Alcoholic liver disease affects several million people in the United States, and alcohol abuse is the most important cause of liver cirrhosis in industrialized countries. Gut-derived bacterial products are necessary for progression of alcoholic liver disease, but the exact mechanisms of intestinal bacterial overgrowth and translocation are poorly understood. Understanding the mechanisms by which alcohol results in intestinal bacterial overgrowth and promotes bacterial translocation by increasing intestinal permeability would greatly enhance our ability to design preventive and therapeutic interventions for patients with chronic alcohol abuse. We therefore will investigate the contribution of microbial and host factors to alcohol-induced liver disease.
Please refer to the links below for grants project profiles from previous years: