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Principal Investigator: Maggie A Stanislawski
Organization: UNIVERSITY OF COLORADO DENVER
Fiscal Year: 2024
Award: $158,779
Funding agency: National Heart Lung and Blood Institute
PROJECT SUMMARY
The development of cardiovascular disease (CVD) is a complex process, with obesity being a major risk factor.
Weight loss among overweight/obese individuals is a key component of the primary prevention of CVD, but
there is marked variability across individuals in response to lifestyle weight loss interventions. It is critical to
improve our understanding of drivers of weight loss responsiveness as this may help identify causal factors in
obesity and may ultimately lead to new or more personalized prevention or treatment opportunities. This study
will examine how genetics, gut microbiota (GM), and metabolites contribute towards measures of
responsiveness during an ongoing 1-year lifestyle weight loss trial of the standard weight loss approach, daily
caloric restriction (DCR), versus a novel alternative, intermittent fasting (IMF). This understanding of the causal
relationships between omic profiles and weight loss/health improvements in an interventional setting will target
an investigation into GM and metabolites as mediators of the association between genetic obesity risk and
obesity-related phenotypes in larger epidemiological cohorts. Preliminary data from a participant subset in the
intervention that provides evidence of feasibility and informs the hypotheses for the following innovative aims:
Aim 1: Assess longitudinal changes in GM and metabolites, as well as the predominant drivers of these
changes, during a lifestyle weight loss intervention of DCR versus IMF. Aim 2: Evaluate associations of a
measure of genetic risk for obesity and GM/metabolites with responsiveness during a lifestyle weight loss
intervention. Aim 3: Investigate whether GM/metabolites mediate the association between a multiethnic
obesity polygenic risk score and measures of obesity in two epidemiological cohorts.
This Career Development Award will also provide the Candidate with the opportunity to gain important skills
and expertise. She has a clear plan to gain training related to: 1) processing shotgun metagenomic GM and
metabolomic data; 2) causal inference and other relevant methods for the analysis of multi-omics data; and 3)
multiethnic polygenic risk scores. The training plan involves coursework, conference attendance, and in-person
training with leading scholars, in conjunction with guidance from a mentorship team of renowned leaders in
their respective fields of genetic epidemiology (Dr. Leslie Lange; Primary Mentor), bioinformatics and the
human gut microbiome (Dr. Catherine Lozupone), biostatistics (Dr. Katerina Kechris), and clinical weight loss
interventions (Dr. Victoria Catenacci). This training plan combines the exceptional research environment at the
University of Colorado Anschutz Medical Campus with generous institutional support and ample resources, as
well as an outstanding network of advisors. This work will facilitate the candidate's successful transition to an
independent career in molecular epidemiology with the expertise to integrate complex types of omics data in
order to improve our understanding of disease pathophysiology and to inform innovative prevention and
intervention efforts for obesity and CVD.
Terms: <21+ years old><Active Follow-up><Address><Adult><Adult Human><Approaches to prevention><Area><Assay><BMI><BMI percentile><BMI z-score><Bio-Informatics><Bioassay><Bioinformatics><Biological Assay><Biometrics><Biometry><Biostatistics><Blood Sample><Blood Serum><Blood specimen><Body Weight decreased><Body mass index><CVD prevention><Caloric Restriction><Cardiovascular Diseases><Career Development Awards><Career Development Awards and Programs><Career Development Programs K-Series><Cause of Death><Cell Communication and Signaling><Cell Signaling><Clinical><Colorado><Complex><Coronary Artery Risk Development in Young Adults><Coronary Artery Risk Development in Young Adults Study><Data><Development><Diet><Dietary intake><Disease><Disorder><Dysfunction><Environment><Epidemiology><Ethnic Origin><Ethnicity><Foundations><Functional Metagenomics><Functional disorder><GI microbiome><GI microbiota><Gastrointestinal microbiota><Gene variant><General Taxonomy><Genetic><Genetic Risk><Goals><H+ element><HCHS/SOL Study><HCHS/SOL cohort><Health><Hispanic Community Health Study/Study of Latinos><Human><Hydrogen Ions><Individual><Institution><Intermittent fasting><Intervention><Intervention Strategies><Intervention Studies><Intervention Trial><Interventional trial><Intracellular Communication and Signaling><Investigation><Investigators><K-Awards><K-Series Research Career Programs><Life Style><Lifestyle><Measures><Mediating><Mediation><Mediator><Medical><Mentors><Mentorship><Metabolic dysfunction><Metabolic syndrome><Metagenomics><Methods><Modern Man><Molecular Epidemiology><Multiomic Data><Negotiating><Negotiation><Obesity><Observation research><Observation study><Observational Study><Observational epidemiology><Observational research><Outcome><Over weight><Overweight><Participant><Pathway interactions><Personalized medical approach><Persons><Phenotype><Physical activity><Physiopathology><Play><Population><Prevention><Prevention approach><Primary Prevention><Process><Protons><Quetelet index><R-Series Research Projects><R01 Mechanism><R01 Program><Randomized><Research><Research Career Program><Research Grants><Research Personnel><Research Project Grants><Research Projects><Research Resources><Researchers><Resources><Risk Factors><Risk Reduction><Role><Serum><Shotguns><Signal Pathway><Signal Transduction><Signal Transduction Systems><Signaling><Taxonomy><Training><Universities><Weight Loss><Weight Reduction><Work><active followup><adiposity><adulthood><allele variant><allelic variant><biological signal transduction><body weight loss><caloric restricted><calorically restricted><calorie restricted><calorie restriction><cardiac disease prevention><cardiometabolic><cardiometabolism><cardiovascular disease prevention><cardiovascular disease risk><cardiovascular disorder><cardiovascular disorder prevention><cardiovascular disorder risk><career><cohort><conference><convention><corpulence><developmental><diaries><dietary><diets><differences due to race><differences in race><differs by race><differs in race><digestive tract microbiome><enteric microbial community><enteric microbiome><enteric microbiota><epidemiologic><epidemiological><ethnic diversity><ethnically diverse><fecal sample><follow up><follow-up><followed up><followup><gastrointestinal microbial flora><gastrointestinal microbiome><genetic epidemiologic study><genetic epidemiology><genetic variant><genomic variant><group intervention><gut commensal><gut community><gut flora><gut microbe community><gut microbial community><gut microbial composition><gut microbial consortia><gut microbiome><gut microbiota><gut microbiotic><gut microflora><gut-associated microbiome><high risk><improved><individualized approach><individualized prevention><innovate><innovation><innovative><insight><intervention arm><intervention research><interventional research><interventional strategy><interventional study><interventions research><intestinal biome><intestinal flora><intestinal microbiome><intestinal microbiota><intestinal microflora><intestinal tract microflora><life style intervention><lifestyle intervention><metabolism measurement><metabolomics><metabonomics><multi-ethnic><multiethnic><multiple omic data><new approaches><novel><novel approaches><novel strategies><novel strategy><obese individuals><obese people><obese person><obese population><obese subjects><obesity genetics><obesity intervention><obesity prevention><obesity risk><obesity therapy><obesity treatment><pathophysiology><pathway><personalization of treatment><personalized approach><personalized medicine><personalized prevention><personalized therapy><personalized treatment><polygenic risk score><precision approach><precision prevention><predict responsiveness><predicting response><prevent obesity><race based differences><race differences><race related differences><racial difference><racially different><randomisation><randomization><randomly assigned><reduce risk><reduce risks><reduce that risk><reduce the risk><reduce these risks><reduces risk><reduces the risk><reducing risk><reducing the risk><response><risk for obesity><risk of obesity><risk-reducing><shot gun><skills><social role><stool sample><stool specimen><success><summit><symposia><symposium><tailored approach><treatment arm><waist circumference><weight loss intervention><weight loss therapy><weight loss treatment><wt-loss>