Luke Davis, JR
|Title||Assistant Adjunct Professor|
|School||UCSF School of Medicine|
|Address||1001 Potrero Ave, SFGH 5|
San Francisco CA 94143
My current research program comprises basic-translational, clinical, and implementation research on tuberculosis diagnosis in both high-burden/low-income (Uganda) and low-burden/high-income (San Francisco) settings. I am interested in how diagnostic tests, including tests for monitoring and prediction of treatment outcomes, perform in different clinical and epidemiologic settings, and how they can be integrated into TB evaluation strategies that improve patient and public health outcomes. I am currently involved in the following studies:
Biomarker Research within the Mulago Inpatient Noninvasive Diagnosis (MIND) of Pneumonia Study.The MIND Study, a longitudinal cohort study of patients hospitalized with pneumonia at Mulago Hospital, Kampala, Uganda, provides a robust platform for research on diagnosis and pathogenesis of acute opportunistic respiratory diseases. With input from an integrated group of U.S. and Ugandan researchers, I have focused on evaluating a diverse set of diagnostic and treatment response markers in TB and other HIV-related pulmonary infections. My two principal current studies are described below:
Our studies of human exosomes, in collaboration with colleagues at Colorado State University and the University of Notre Dame, constitute a novel biomarker discovery and validation effort. Our central hypothesis is that exosomes, small, circulating, host-derived vesicles, concentrate and sequester mycobacterial products in serum and other body fluids, and may therefore provide an ideal source of diagnostic biomarkers. We are currently pursuing a proteomic discovery strategy with the hope that if we are successful, exosomes could provide a simple and rapid test for TB for use in primary-care and community settings.
Our gene expression work is being pursued in cooperation with colleagues at the University of Colorado-Denver and Stanford University. Using preserved host and pathogen RNA from blood, sputum, and/or BAL isolated from our patients in Uganda, we are looking at associations between clinical factors, treatment adherence, and the change in expression patterns to develop better biomarkers of treatment response. In the process, we are making exciting discoveries about how M. tuberculosis adapts to HIV and how antibiotic tolerance and persistence emerge during TB treatment, insights which will improve our ability to understand and predict TB relapse. The latter observations in human are the basis of a current U19 proposal for a 7-project TB Research Unit designed to characterize fully the nature of Mtb persistence in single-cell, culture, and animal models, as well as in human patients, in order to develop novel surrogate markers and therapeutic targets.
Implementation Research within the Uganda Tuberculosis Surveillance Project (UTBSP). Beginning in several rural primary health clinics in Uganda, and now moving to urban sites in Kampala, UTBSP focuses on the use of real-time evaluation and monitoring systems to identify barriers to high-quality TB evaluation. When the current expansion is complete, we will have data on nearly 10,000 annual evaluations of adults and children with unexplained cough each year. Using mixed-methods approaches, we are curently focused on developing theory-grounded interventions to improve outcomes important to patients and TB programs. Mobile-phone applications for tracking and communicating with patients are central to exceuting these interventions, and we have recently been funded by the Nina Ireland Lung Disease Program and NIAID to develop and evaluate a home-based, mobile-phone facilitated TB contact investigation intervention in a household-randomized, controlled trial.
Implementation Research on Automated Nucleic Acid Amplification Testing for TB at San Francisco General Hospital. We have recently completed four studies examining the clinical and public health impact and cost-effectiveness of a novel automated nucleic acid amplification test (GeneXpert MTB/RIF, first developed for high-burden countries) for rapid TB evaluation in inpatient and outpatient settings in San Francisco. These studies have employed novel methods for describing the impact of novel TB diagnostics, and will help inform clinical practice and public health policy regarding use of the new assay in the U.S. This project is a great example of how a global health research agenda can complement a domestic research agenda, and lead to major benefits for vulnearable and underserved populations in the U.S.
This combination of basic-translational, clinical, and implementation research has fostered my transition to independence and given me a broad expertise in diagnostics spanning the spectrum of biomarker discovery, diagnostic test development, evaluation, implementation, and dissemination. In the process, I am also interesting in facilitating a greater understanding of TB pathophysiology through collaborations with basic investigators to provide well-selected and well-characterized clinical specimens and insights from clinical care, epidemiology, and public health. Importantly, our Uganda projects are also helping build local capacity in research and patient care in Uganda. While for many years, we have done this kind of work without additional resources, we know have the ability to do more through support from a Fogarty International Center AIDS International Research Training Program that I am leading with Professor Art Reingold from UC Berkeley, and through Walimu, an NGO which U.S. and Ugandan colleagues and I established to improve care of patients with severe illness in low-income countries.
Implementation Science, Socioeconomically marginalized groups, Global populations, Clinic, Hospital, International (public health), Audit and feedback, Team science, TB, HIV/AIDS, Pneumonia, Mentoring junior faculty or trainees, Interdisciplinary research collaboration, Brief implementation science training courses, Works-in-progress seminars
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