John C. Burnett Jr., M.D., studies the endocrine role of the heart in cardiorenal homeostasis with a focus on the natriuretic peptides in heart failure, hypertension and myocardial infarction. The long-term goal is the engineering and clinical development of novel designer natriuretic peptides for the treatment of human cardiorenal disease, including the development of innovative natriuretic peptide-based diagnostics.
With continuous funding from the National Institutes of Health, Dr. Burnett and his team have developed three novel designer peptides currently in clinical trials targeting heart failure and resistant hypertension. From this work, seven patents have been awarded and three new biotechnology companies founded.
- New drugs for heart failure, hypertension and myocardial infarction. Dr. Burnett's laboratory has advanced the field of novel drug discovery and development by taking advantage of guanylyl cyclase receptors possessing pleotropic cardiorenal and metabolic protective properties. Designer natriuretic peptides mediate actions thus enhancing renal function, suppressing the renin-angiotensin-aldosterone system (RAAS), suppressing sympathetic activity, reducing blood pressure, promoting lipolysis, and inhibiting myocyte hypertrophy and fibroblast proliferation.
Based upon the engineering of these novel drugs, Dr. Burnett's team individualizes their drugs based upon rational drug design so as to optimize specific properties for their disease targets, which may include inhibition of myocardial remodeling, promotion of renal enhancement, reduction in blood pressure and antagonism of the RAAS. Innovative and complementary platforms for chronic delivery of these novel peptides include subcutaneous delivery, gene delivery and oral delivery.
Biotechnology companies built around these designer natriuretic peptides include Nile Therapeutics in San Mateo, Calif.; Anexon in Boston; and Zumbro Discovery in Rochester, Minn.
- Innovative diagnostics for cardiorenal and metabolic disease. In 1986, Dr. Burnett and his team reported in the journal Science the elevation of the cardiac hormone ANP in human heart failure employing a newly developed radioimmunoassay. This landmark study led to the development of natriuretic peptides, especially BNP, as powerful biomarkers for the diagnosis of heart failure and risk stratification in cardiovascular disease. The laboratory continues to develop novel blood and urine biomarkers for cardiorenal disease as well as develop genetic tests based upon the natriuretic peptides.
Significance to patient care
Dr. Burnett's research is of high clinical impact. Specifically, his research addresses the huge unmet need for new drugs and biomarkers for cardiorenal disease. Progress in these areas may truly lead to reducing the burden of human disease.
- Marriott Family Cardiovascular Research Professor, Mayo Clinic, 2007-present
- Distinguished Investigator, Mayo Clinic, 2006
- Director for Research, Mayo Clinic, 1999-2004
- Member, American Society for Clinical Investigation, 1990-present
- Member, Association of American Physicians, 1994-present