Core Faculty & Collaborator NIH Funding
Please click on a title to see the corresponding NIH RePORTER page.
Beckman
The Impact of Diabetes on Revascularization in BEST-CLI
R01 HL131977, NHLBI, 2016-2021
The BEST-CLI trial is a multi-center, randomized, comparative effectiveness trial comparing open surgical bypass therapy to endovascular therapy in CLI patients with a composite clinical endpoint denoted as Major Adverse Limb Event free survival (MALE-free survival). This proposal will extend the work of the BEST-CLI trial by studying the mechanisms of bypass vein graft and stent failure.This trial investigates the mechanisms by which diabetes affects surgical and endovascular revascularization procedures in the context of Peripheral Artery Disease.
Brittain
A Mobile Health Intervention in Pulmonary Arterial Hypertension
R34 HL136989, NHLBI, 2018-2020
This project utilizes a fully-automated mobile health (mHealth) intervention and looks at its feasibility in a population of people with pulmonary arterial hypertension (PAH). The hypothesis is that an mHealth intervention is feasible and will increase step counts in subjects with PAH. The goals of this proposal are to 1) assess the feasibility of an mHealth intervention in the PAH population and 2) identify aspects of the protocol that may need to be refined for a larger trial in this population.
PDE5 Inhibition for Obseity-related Cardiometabolic Dysfunction
R01 HL128983, NHLBI, 2018-2020
This intervention directly targets metabolic fitness in obesity to investigate increased cardiovascular risk in obesity and its relation to metabolic dysregulation. It proposes a randomized, placebo-controlled study to examine the cardiometabolic effects of phosphodiesterase type 5 (PDE5) inhibition in obese prediabetic individuals. Tadalifil, a PDE5 inhibitor, prevents the degradation of cGMP, a critical mediator of insulin resistance and energy homeostasis. Our endpoints were selected to provide highly relevant clinical outcomes and mechanistic insight into the cardiometabolic effects of cGMP action. Therapy that improves metabolic fitness independent of weight loss would represent an important advance in the effort to reduce cardiovascular risk in obesity.
Carr
Skeletal Muscle Adiposity in Black Men with High Type 2 Diabetes Risk
R01 DK097084, NIDDK, 2012-2017
Through a subcontract with the University of Pittsburgh, the Vanderbilt CT Reading Center will analyze 1600 CT scans from subjects in the Tobago study for coronary artery calcium, aortic artery calcium, abdominal adipose tissue volumes, abdominal muscle volumes and composition, pericardial adipose tissue, and liver attenuation.
Freiberg
Vanderbilt SCHolars in HIV and Heart, Lung, Blood, and Sleep ReSearch (V-SCHoLARS, K12)
K13 HL143956, NHLBI, 2018-2022
With effective contemporary antiretroviral therapy (ART), people living with HIV/AIDS are living longer, but experience a rising burden of heart, lung, blood, and sleep (HLBS) comorbidities. The Southeastern United States has the highest rates of incident HIV infection and heart and lung disease. As Vanderbilt’s geographic location sits at the intersection of HIV, heart, and lung disease, we propose an interdisciplinary faculty career development program to increase the number of well-prepared investigators with expertise in the risk factors for, and mechanisms underlying, HIV-related HLBS disease and the behavioral, environmental, and health disparity aspects of HLBS comorbidities.
Microbiome, Metabolites, and Alcohol in HIV to Reduce CVD (META HIV CVD)
P01 AA029542, NIAAA, 2021-2026
The overarching theme for this program project grant (PPG) is that alcohol associated gut dysbiosis and gut dysbiotic metabolites are cardiovascular disease (CVD) risk factors among people living with HIV infection (PLWH) who are heavy drinkers. The goals of this research are (1) to determine if a tailored probiotic (i.e., contains bacteria supporting butyrate synthesis) can mitigate alcohol associated gut dysbiosis and lower levels of microbial translocation, inflammation, and improve harmful dysbiotic metabolite profiles (e.g. trimethylamine N oxide, TMAO) and (2) to determine if these metabolites are associated with incident CVD and death among PLWH. We hypothesize that, among PLWH, a probiotic vs. placebo can mitigate alcohol associated gut dysbiosis and lower levels of microbial translocation, inflammation, and improve metabolite profiles (Project 1 RCT, n=250); and that harmful alterations of these metabolites will be associated with higher risk of incident CVD and death (Project 2 Cohort, n=2,900).
1/2 Alcohol Associated Comorbidities and Microbiome Evaluation in HIV
U01 AA26222, NHLBI, 2017-2022
We hypothesize that alcohol-associated dysbiosis will: (1) be greater in HIV+ very heavy drinkers (AUDIT score≥20) vs. heavy drinkers (AUDIT<20); (2) increase biomarker levels of intestinal permeability (e.g., intestinal fatty acid binding protein (IFABP), MT (e.g., endotoxin), inflammation (interleukin 6) and TMAO; and (3) increase serum biomarkers for and alter echocardiographic (Echo) measures of cardiac function (N-terminal pro Brain Naturetic Peptide, NT pro-BNP, and left ventricular ejection fraction, LVEF, respectively). To test these hypotheses, we will enroll 200 HIV+ participants from St. PETER HIV, a funded RCT using pharmacotherapy to reduce alcohol use, smoking, inflammation, and CVD risk.
Protein Biomarkers for CVD Prediction in HIV-Infected and Uninfected Veterans
R01 HL129856, NHLBI, 2016-2020
Using the VACS biomarker cohort, the goals of this project are to: 1) discover a broad range of protein biomarkers predictive of CVD and mortality events; 2) identify a small multi-protein panel of biomarkers among HIV+ individuals to predict cardiovascular outcomes and mortality events; and 3) determine whether an optimal combination of proteins in a panel derived in Aim 2 can improve on the prognostic performance of existing models based on traditional risk factors.
URBAN ARCH 4/5 Russia Cohort-Targeting HIV-Comorbidities with Pharmacotherapy to Reduce Alcohol and Tobacco Use in HIV-Infected Russians
U01 AA020780, NIAAA, 2016-2021
The Russia ARCH Cohort and the Studying Partial agonists for Ethanol and Tobacco Elimination in Russians with HIV (St PETER HIV) trial will draw from an established cohort of HIV-infected smokers and heavy drinkers to compare the effects of two nicotinic receptor partial agonists, varenicline and cytisine, on alcohol consumption, alcohol craving, smoking, inflammation, CHD risk and mortality risk.
Innate and adaptive immunity in HIV-associated impaired glucose tolerance and diabetes
R56 DK108352, NIDDK, 2015-2017
This project will study alterations in innate adaptive immune function in persons with HIV infection. We hypothesize that persistent monocyte activation and a confluence of T-cell changes are central to the development of HIV-associated diabetes.
Immune function and the risk of CVD among HIV infected and uninfected Veterans
R01 HL125032, NHLBI, 2014-2018
This study will leverage the Veterans Aging Cohort Study (VACS) biomarker cohort, a longitudinal, prospective observational cohort of 1525 HIV+ and 853 HIV- Veterans. We propose to measure immune cell types and subsets from existing cryopreserved cells collected in 2005-2006 and to adjudicate CVD events including acute myocardial infarction, coronary heart disease, ischemic stroke, heart failure, peripheral vascular disease, and CVD death) from 2005-2018.
HIV, depression, and cardiovascular risk
R01 HL126557, NHLBI, 2014-2018
This study will leverage the Veterans Aging Cohort Study (VACS) biomarker cohort to examine the association between HIV, Depression, Depression treatment, and biomarkers of innate and adaptive immunity. This study will also conduct a single site RCT to examine whether depression interventions reduce biomarkers of inflammation and improve measures of subclinical atherosclerosis.
Cardiac pathology and risk factors for sudden cardiac death in patients with HIV
R01 HL126555, NHLBI, 2014-2018
This study will leverage the Veterans Aging Cohort Study (VACS) virtual cohort to examine the association between HIV and sudden cardiac death and to assist with the construction of a sudden cardiac death tool for risk prediction.
Zinc for HIV disease among alcohol users-an RCT in the Russia ARCH cohort
U01 AA021989, NIAAA, 2012-2017
This double-blinded randomized controlled trial will assess the efficacy of zinc supplementation vs. placebo among 250 HIV-infected Russians, who are ART-naïve at enrollment and have a recent history of heavy drinking to determine if zinc supplementation reduces alcohol associated microbial translocation and inflammation and is associated with reduced CHD and total mortality risk.
St. Peter HIV-Alcohol, Protein Biomarkers and cardiovascular disease risk
R01 AA025859, NIAAA, 2017-2020
We hypothesize that among HIV+ heavy drinkers, alcohol use is associated with higher levels of TMAO, and that higher TMAO levels are associated with subclinical measures and biomarkers of HF. We will test these hypotheses in ST. PETER HIV – CVD, an observational study that will be built on and complement St. PETER HIV, a randomized clinical trial (U01AA020780; begins enrollment Winter 2017).
Hulgan
Iron and Mitochondrial Genomics in Neuro-inflammation and HAND: A CHARTER Study
R01 MH095621, NIMH, 2011-2016
This project is a collaboration with the CHARTER study group to characterize iron-related and mitochondrial genomic regulation of HAND and neuroinflammatory biomarker levels in CSF from HIV-infected subjects.
Mitochondrial DNA Haplogroups and Diabetes-related Outcomes in MACS
R21 DK101342, NIDDK, 2015-2016
This project is a collaboration with the Multicenter AIDS Cohort Study (MACS) and Johns Hopkins University to examine associations between mtDNA haplogroups and diabetes-related outcomes (insulin resistance, incident diabetes, and serum adiponectin) among HIV-infected and uninfected MACS participants.
Vanderbilt HIV Clinical Trials Unit
UM1 AI069439, NIAID, 2013-2020
The Vanderbilt HIV Clinical Trials Unit (CTU) consists of an Administrative Component (AC), supporting the HIV Vaccine Clinical Research Site (Vaccine CRS) and the HIV Therapeutics Clinical Research Site (Therapeutics CRS).
Tennessee Center for AIDS Research (TN-CFAR)
P30 AI110527, NIAID, 2015-2020
The mission of the TN-CFAR is to leverage complementary strengths of partner institutions Vanderbilt University, Meharry Medical College, and the Tennessee Dept. of Health, to coordinate institutional and community resources and focus efforts on high-priority targets that will most effectively reduce the burden of HIV/AIDS, and generalize these benefits nationally and globally.
Koethe
The Role of Adipose-Resident T-Cells in HIV-Associated Glucose Intolerance
R01 DK112262, NIDDK, 2017-2022
HIV-infected (HIV+) persons can survive decades on antiretroviral therapy, but this success is accompanied by a disproportionate burden of metabolic disease, including type 2 diabetes, in the HIV population. This study will: 1.) clarify the role of chronic, HIV-related T cell activation in the development of glucose intolerance, 2.) assess whether the cytokine signaling profiles of adipose-resident activated, memory, and other T cell types differ from what is already known about circulating T cells, 3.) clarify the metabolic consequences of adipose tissue as a reservoir for latently HIV-infected CD4+ T cells, 4.) identify potential immunologic therapeutics targets for metabolic disease and HIV cure research, and 5.) assess whether adipose-resident CD8+ T cell oligoclonal expansion accompanies adipocyte dysfunction and glucose intolerance, and should be explored further to identify epitopes potentially contributing to HIV-associated metabolic disease.
The Role of Obesity and Adipocytes in Immune Activation on Antiretroviral Therapy
K23 AI100700, NIAID, 2012-2017
The focus of this research is the role of adipocytes in promoting innate and cellular immune activation in among HIV-infected persons on long-term antiretroviral therapy.
Innate and Adaptive Immunity in HIV-associated Impaired Glucose Tolerance and Diabetes
R56 DK108352, NIDDK, 2015-2017
This project investigates the relationship between circulating T cell and monocyte subsets and incident diabetes among HIV-infected veterans and non-HIV infected controls in the Veterans Aging Cohort Study (VACS) biospecimen cohort.
Role on the project: Principal Investigator
Tindle
URBAN ARCH 4/5 Russia Cohort-Targeting HIV-Comorbidities with Pharmacotherapy to Reduce Alcohol and Tobacco Use in HIV-Infected Russians
U01 AA020780, NIAAA, 2016-2021
The Russia ARCH Cohort and the Studying Partial agonists for Ethanol and Tobacco Elimination in Russians with HIV (St PETER HIV) trial will draw from an established cohort of HIV-infected smokers and heavy drinkers to compare the effects of two nicotinic receptor partial agonists, varenicline and cytisine, on alcohol consumption, alcohol craving, smoking, inflammation, CHD risk and mortality risk.
Developing Personalized Smoking Treatment in the Southern Community Cohort Study
U54 CA163072, NCI, 2016-2017
Our overarching aim is to leverage the Southern Community Cohort Study (SCCS) and the Outreach Core Community Advisory Board (CAB) to guide the development of two personalized care (PC) interventions for smoking cessation: PC-Respiragene and PC-NMR. Aim 1 will survey SCCS smokers residing in Tennessee and Mississippi to assess attitudes and beliefs on smoking-related health risk perceptions, personalized smoking treatment, and willingness to join a smoking cessation trial of PC (n=1647). Aim 2 will leverage CAB input to develop PC-Respiragene and PC-NMR for use among diverse, low SES community smokers in the SCCS. Aim 3 will conduct a 3-arm RCT (N=75) SCCS smokers to pilot PC-Respiragene and PC-NMR interventions for feasibility and determine preliminary estimates of biochemically-validated smoking cessation and lung cancer screening at 6 months vs. guideline based care (GBC). Completion of these aims will lay groundwork for a large RCT of personalized smoking cessation in the SCCS.
Cessation in Non-Daily Smokers: A RCT of NRT with Ecological Momentary Assessment
R01 DA034629, NIDA, 2014 - 2018
This study is a randomized clinical trial of oral nicotine replacement therapy for people who do not smoke every day. So-called non-daily smokers are increasingly prevalent (up to 25-35% of adult smokers) yet medication therapy has not been studied in this population. This study will combine the RCT design with ecological momentary assessment to study the process of quitting and relapse among non-daily smokers.
Connect to Quit: Coordinated Care for Smoking Cessation among Low Income Veterans
R01 CA141596, NCI, 2010-2016
The goal of this cluster randomized controlled trial is to examine the effectiveness and cost- effectiveness of a chronic care model-based intervention designed to reduce smoking in low income adults within a regional United States Veterans Administration health care system. We will also examine adherence to the smoking cessation program, including willingness to participate and use FDA-approved medication for cessation attempt post-relapse.
Comparative Effectiveness of Post-Discharge Strategies for Hospitalized Smokers
R01 HL111821, NHLBI, 2012-2017
This multi-site RCT tests the efficacy of usual care vs. enhanced care for long term smoking cessation in 1350 hospitalized smokers in Massachusetts and Pennsylvania.
Role: site Principal Investigator
Functional Assessment Screening Tablets-Patient Reported Measures
R18 HS018932, AHRQ, 2012-2016
This project evaluates a new tool, based our current “Functional Assessment Screening Tablets (FAST)”, that provides patients with self-management support through immediate, personalized, guideline-based feedback about their health behaviors and HRQoL based on their own patient reported information and encourage them to take a more active role in their health. Completion of this project, FAST-PRI, will provide important information on the effectiveness of using HIT patient feedback to inform and activate patients and promote health behavior change.
MMC, VICC & TSU: Partners in Eliminating Cancer Disparities
U54 CA163072, AHRQ, 2011-2016
The overall objectives are: (1) to increase and stabilize the competitive cancer research capability of MMC and TSU; (2) to create stable, long-term collaborative relationships between MMC, TSU and the VICC in cancer research, research training, career development and cancer outreach; and (3) to improve the effectiveness of VICC research, training, career development, cancer education and cancer outreach activities specifically designed to benefit minority populations in the region served by VICC.
Evaluating New Nicotine Standards for Cigarettes
U54 DA031659, NIDA, 2011-2016
This center will focus on the new “regulatory science” mandated by the Family Smoking and Prevention Tobacco Control Act, the 2009 federal law which gives the FDA the power to regular the tobacco industry. Several core studies will provide data for FDA efforts to understand how reducing nicotine content of cigarettes may favorably impact public health.
Aspirin in reducing events in the elderly: The ASPREE Study
U01 AG029824, NIA, 2009-2016
This project is a randomized double-blind placebo-controlled trial of aspirin in primary prevention. Its purpose is to determine whether low dose aspirin will extend the duration of disability-free life in an aging population.
Wells
The Vanderbilt Institute for Clinical and Translational Research (VICTR) Non-Germline Variation in Dilated Cardiomyopathy
UL1 TR000445, NCATS, 2014-2015
Awarded by the Vanderbilt Institute for Clinical and Translational Research (VICTR) to study non-germline variation in dilated cardiomyopathy.