The Division of Cardiology at ZSFG is home for an active clinical pharmacology research program led by Dr. Neal Benowitz, who is also an attending physician in our cardiology clinic. This research group consists of 4 UCSF faculty whose studies are focused broadly on clinical investigation of the pharmacology and cardiovascular toxicities of tobacco, electronic cigarettes, and cannabis products.
The analytical chemistry laboratory is recognized as a national resource for biomarkers of tobacco exposure due to 10 staff members with training and expertise in demanding mass spectrometry and gas chromatography techniques that are required for accurate and reproducible measurements. Investigators at ZSFG are world leaders in research on nicotine and public health policies related to its regulation. They have published over 700 research papers in these areas. The Clinical Pharmacology Program is supported by 12 NIH and California Tobacco-Related Disease Research Program grants.
Published research papers
Center of Excellence in Vascular Research. The Division of Cardiology at ZSFG leads several highly successful research and discovery programs. Much of this work is funded through competitive peer-reviewed grants, primarily from the National Institutes of Health. The Center of Excellence in Vascular Research located on the ZSFG campus provides state-of-the-art assessments of human vascular function through non-invasive imaging including flow-mediated vasodilation of the brachial artery, carotid artery intima-media thickness, arterial stiffness, endothelial peripheral arterial tone (EndoPAT), and echocardiograms. 4 vascular technologists, 4 echocardiographers, and 2 coordinators have supported human vascular studies for more than 25 UCSF investigators and 14 fellows since 2008. The mission of this Center is to bring knowledge derived from basic science to clinical application, from cardiovascular disease mechanism to new therapy.
Large-Scale Proteomics. Research in the Division of Cardiology includes large-scale proteomics under the direction of Peter Ganz, MD. Using modified aptamers as capture reagents, 5000 unique plasma proteins can be measured simultaneously in 150 microliters of plasma. Proteomic information derived is valuable for:
- discovery of new biomarkers of diseases
- construction of risk models for diseases
- prediction of the clinical efficacy and adverse effects of drugs
- improved understanding of disease biology
High-impact recent publications are JAMA 2016;315:2532-2541 and Circulation 2018;137:999-1010. Current proteomics of observational cohorts involve 100,000 blood samples that generate a total of 500 million individual protein data points. These include Heart and Soul, HUNT, MESA, ARIC, REGARDS, CRIC, and VACS with cardiovascular and non-cardiovascular diseases of interest. UCSF investigators on the research team are Mark Segal (UCSF Bioinformatics), Priscilla Hsue (ZSFG Cardiology), Joseph Yang (VAMC Cardiology), and Ruth Dubin (VAMC Nephrology) in addition to collaborators at other U.S. and international academic centers. The industry collaborator is SomaLogic in Boulder, Colorado. Dr. Ganz’s research identifies proteomics as a powerful approach for precision medicine and is funded by NIH grants from the NHLBI, NIDDK, and NIA.
Cardiovascular Disease and HIV. Research in the Division of Cardiology is also focused on relationships between inflammation, immune function, and cardiovascular risk under the direction of Priscilla Hsue, MD. Clinical and translational studies on the pathogenesis, manifestations, and treatment of inflammation and cardiovascular risk in HIV-infected and uninfected individuals employ novel imaging to assess atherosclerosis burden, state-of-the-art measurements of vascular function, and large-scale proteomics. There are also single-center and multicenter clinical trials using biologic interventions in the setting of HIV, atherosclerosis, and rheumatoid arthritis. Recent investigations target the effect of PCSK9 inhibition on cardiovascular risk in treated HIV infection. Dr. Hsue’s research establishes HIV infection as a model of chronic inflammation with mechanistic and therapeutic implications for other types of cardiovascular disease. Project support is provided by highly-competitive peer-reviewed NIH grants from the NHLBI. She is also a principal investigator for the UCSF Career Development Program in Cardiopulmonary, Hematologic, and Immunologic Comorbidities of HIV (CHIC) which supports mentoring of talented researchers at all levels of training, from medical students to junior faculty.
Cardiovascular Disease and Chemical Biology. John Chorba, MD is a physician scientist who uses chemical tools to probe the biological mechanisms of cardiovascular disease with the ultimate goal of developing novel therapeutics. His research program is centered on genetic causes of hyperlipidemia and targets that prevent atherosclerosis. Recent translational studies of proprotein convertase subtilisin-kexin type 9 (PCSK9), a protein that causes elevated cholesterol levels, elucidate roles for its active site and cell trafficking in vascular dysfunction. Dr. Chorba is funded by NIH grants from the NHLBI.