Research Interests: Pharmacogenomics, Cardiovascular drugs, Health disparities Summary: Cardiovascular disease is the most common cause of morbidity and mortality in the United States, affecting almost 100 million adults and costing over $300 billion. Death from cardiovascular disease had been steadily declining since the 1970s due in part to remarkable advances in pharmacotherapy, but more recently has started to worsen. Although the reasons for this reversing trend are likely multifactorial, it is evident that better optimization of therapy may help to improve this recent worsening. In particular, there exists considerable interindividual variability in response to cardiovascular drugs. We hypothesize that the discovery and clinical validity of molecular biomarkers for cardiovascular disease drug response will allow clinicians more precise select cardiovascular pharmacotherapy regimens, thereby improving population-wide cardiovascular health outcomes. The overall research goal of my group is to improve pharmacological regimens for the prevention and treatment of cardiovascular disease through precision medicine. To accomplish this objective, we combine computational approaches in pharmacogenomics, pharmacometrics, and pharmacoepidemiology using electronic health record-linked biobanks. In addition, only ~14% of participants from all genome wide association studies are of non-European descent, despite accounting for ~86% of the global population. This underrepresentation has the strong potential to exacerbate health disparities. Thus, another goal of our group is to ensure that study populations of genomics research studies are inclusive so that advances can benefit all. In accord with our overall research objectives and the approaches that we employ, we are currently investigating genetic determinants of efficacy and safety for hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor therapy in diverse populations.
Publications
Cytochrome P450 2D6 *17 and *29 Allele Activity for Risperidone Metabolism: Advancing Precision Medicine Health Equity.
Progress in Pharmacogenomics Implementation in the United States: Barrier Erosion and Remaining Challenges.
Uncertainty in the estimated effects of statin initiation on risk of dementia: using a multiverse analysis to assess sources of variability.
Response to "Comment on 'Independent associations of high-density lipoprotein cholesterol and triglyceride levels with Alzheimer's disease and related dementias' ".
Empowering Early-Career Scientists: Opportunities Through ASCPT Programs, Networks, and Communities.
MIR192 Upregulates GLP-1 Receptor and Improves Statin-Induced Impairment of Insulin Secretion.
SLCO1B1 Functional Variants, Bilirubin, Statin-Induced Myotoxicity, and Recent Sub-Saharan African Ancestry: A Precision Medicine Health Equity Study.
Sociodemographic modifiers of effects of statin initiation on dementia incidence: An emulated trial design in a large health care member population with 10+ years of follow-up.
Independent associations of high-density lipoprotein cholesterol and triglyceride levels with Alzheimer's disease and related dementias.
Design and implementation of an action plan for justice, equity, diversity, and inclusion within the Clinical Genome Resource.
Characterizing the genetic architecture of drug response using gene-context interaction methods.
X chromosome dosage drives statin-induced dysglycemia and mitochondrial dysfunction.
Preferences and Perspectives of Black Male Barbershop Patrons on Receiving Health Care in Nontraditional Settings.
SLCO1B1 functional variants and statin-induced myopathy in people with recent genealogical ancestors from Africa: a population-based real-world study.
Metformin Cessation and Dementia Incidence.
An Introductory Tutorial on Cardiovascular Pharmacogenetics for Healthcare Providers.
Gene expression in African Americans, Puerto Ricans and Mexican Americans reveals ancestry-specific patterns of genetic architecture.
Development and application of an algorithm for statin-induced myopathy based on electronic health record-derived structured elements.
Advancing CYP2D6 Pharmacogenetics through a Pharmacoequity Lens.
Diversity in Clinical Pharmacology: A Call to Action.
A large genome-wide association study of QT interval length utilizing electronic health records.
Polygenic Risk Score and Statin Relative Risk Reduction for Primary Prevention of Myocardial Infarction in a Real-World Population.
Modest effect of statins on fasting glucose in a longitudinal electronic health record based cohort.
Perceptions of Older Men Using a Mobile Health App to Monitor Lower Urinary Tract Symptoms and Tamsulosin Side Effects: Mixed Methods Study.
Tracking Lower Urinary Tract Symptoms and Tamsulosin Side Effects Among Older Men Using a Mobile App (PERSONAL): Feasibility and Usability Study.
QT Interval Dynamics and Cardiovascular Outcomes: A Cohort Study in an Integrated Health Care Delivery System.
Torsade de pointes: A nested case-control study in an integrated healthcare delivery system.
Advancing Precision Medicine Through the New Pharmacogenomics Global Research Network.
Effect of SLCO1B1 T521C on Statin-Related Myotoxicity With Use of Lovastatin and Atorvastatin.
Leveraging innovative technology to generate drug response phenotypes for the advancement of biomarker-driven precision dosing.
Embracing Genetic Diversity to Improve Black Health.
PERSONAL: Feasibility Study Protocol for Placebo-Controlled, Randomized n-of-1 Trials of Tamsulosin for Lower Urinary Tract Symptoms.
The impact of adjusting for baseline in pharmacogenomic genome-wide association studies of quantitative change.
Assessing the clinical impact of CYP2C9 pharmacogenetic variation on phenytoin prescribing practice and patient response in an integrated health system.
Characterization of Statin Low-Density Lipoprotein Cholesterol Dose-Response Using Electronic Health Records in a Large Population-Based Cohort.
Association between the EPHX2 p.Lys55Arg polymorphism and prognosis following an acute coronary syndrome.
Projected impact of a multigene pharmacogenetic test to optimize medication prescribing in cardiovascular patients.
Validation of Electronic Health Records for the Assessment of Statin Dosing In Research.
Blood pressure-associated polymorphism controls ARHGAP42 expression via serum response factor DNA binding.
Cytochrome P450-derived epoxyeicosatrienoic acids and coronary artery disease in humans: a targeted metabolomics study.
Pharmacogenomics in heart failure: where are we now and how can we reach clinical application?
Epoxyeicosatrienoic acids and cardioprotection: the road to translation.
Acute decompensated heart failure: evolving literature and implications for future practice.
Dual modulation of cyclooxygenase and CYP epoxygenase metabolism and acute vascular inflammation in mice.
Enalapril reverses high-fat diet-induced alterations in cytochrome P450-mediated eicosanoid metabolism.
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