John C. Burnett, M.D.
Mayo Graduate School of Medicine, College of Medicine, Mayo Clinic
Dr Burnett is the Marriott Family Cardiovascular Research Professor and director of the Cardiorenal Research Laboratory. His research is focused on the heart as an endocrine organ with a special emphasis on integration of the heart and kidney in cardiorenal homeostasis. A special focus is on the cardiac natriuretic peptide system in cardiorenal regulation as it relates to the pathobiology, novel diagnostics, and innovative therapeutics of heart failure, hypertension, and acute myocardial infarction. With a long history of funding by the National Institutes of Health, his research group has demonstrated in cell systems, animal models, and humans that these peptides of cardiovascular origin may preserve cardiorenal structure and function via the second messenger cGMP in cardiovascular disease.
John C. Burnett talks with DXY.cn about his cardiovascular research stories on at the Third China Heart Failure Symposium in July 2011, at Dalian, China.
2011年7月，在大连举行的第三届中国心力衰竭论坛上， John C. Burnett教授向丁香园介绍了他作为梅奥诊所心肾实验室主任在心血管方面的研究历程，以前此次中国之行旨在寻求心衰药物研发的战略合作伙伴。
Burnett教授是马里奥特家族心血管研究方向的教授，梅奥诊所心肾实验室主任。主要致力于研究心脏作为内分泌器官的作用，并特别强调心脏和肾脏心肾动态平衡的整合。此外，Burnett教授也关注于心肾调控中的心脏利尿钠肽系统，进行心衰竭、高血压及急性心肌梗死的病理生物学研究、探寻新诊断学及新疗法。Burnett教授的团队获得美国国立卫生研究院资助已久，其团队证实了在细胞系统、动物模型及人类中，心血管肽类经过第二信使cGMP的介导，可以保留心血管疾病患者心肾结构及功能。
DXY: You have been investigating humoral peptides and heart failure since 1980s, with the first publication in Science and many other ones highly cited articles. In your opinion, what is the attractiveness of these peptides?
John C. Burnett: I think the reason is that these peptides have tremendous therapeutic potentials to be developed as drugs, not only for heart failure, but for hypertension, kidney diseases and other diseases.
DXY: You are leading a team of investigators focusing on the peptide research, which is very successful with many high-impact publications. How did you get involved in this?
John C. Burnett:When I got started as Assistant Professor, I have had a mentor, who told me that the relationship between the heart and kidney were very important and no one's interested in it. So I thought that was a very interesting area and while I was training, the first peptide in the heart, atrial natriuretic peptide was discovered. And it is said that it acts on the kidney, so I said to myself that this will be a very important area and decided to study that, but I also decided that to make progress, you need to stick with it, and you have to focus. You can't be thinking about other things. So if you want to go deep, you really have to become an expert in the area.
DXY: At this meeting I also talked to your college Dr Horng H. Chen. I asked him about the challenges he meets in his research. What is it in your opinion?
John C. Burnett:The challenge ultimately would be how to deliver the peptides as therapeutic agents. Right now, peptides are IV drugs, but in order to use them as chronic therapies, we have to figure our new technology to give them orally. An exciting avenue is to put them into Nano technology drug delivery systems, and we are doing these. So we can inject them under the skin, one injection lasts for 1 to 4 weeks. It's an exciting challenge that we think we can win and be successful.
DXY:What is this trip to China for? Is it just for this meeting or anything more?
John C. Burnett:Actually one of my goals here in China is to find collaborators. We think China is a country with great technology so I would like to create collaboration here. I would like to find collaborators of those three areas:
1) In basic science. I would like to put our heads together to understand how these peptides work individually in the heart and kidney cells.
2) In the development of new drugs. Maybe we can turn some of our peptides that we are designing now, jointly develop them, become partners to develop new drugs.
3) In diagnostics. Could we look at different populations in China and understand better how peptides perform in diagnostics in this population, because of your immense population, maybe we could help to diagnose early heart failure with our drugs. So I think those three areas, basic research, new drug discovery and development, and diagnostics, we want to find partners.
DXY: Are you already in cooperation with any investigators, laboratories, or hospitals in China?
John C. Burnett:No, not yet. I'm going to Beijing tomorrow (July 30th) and meet with some people and also meet with someone this afternoon from the affiliated academic medical school here in Dalian and want to start collaboration. We are on a mission here.
DXY: You do great in translating basic science research into clinical applications, which is very difficult for clinicians in China, who are too busy with patient care. However, basic scientists with no clinical experience may not understand the real problem very well. So how can you manage to do both so well?
John C. Burnett:You have to be careful and work long hours. I get up early and go to bed late. It's a long day and I like what I do. I think the secret is if you like what you do, you will be successful. But I do think we are in an age where you do have to probably put more time on one part. So we are called the “US physician scientists” or “doctor scientists”. For me, I put most of my time on the research side and a small amount on the clinical side. But I think it changes all the time and we are able to strike the balance in a number of leading hospitals/universities/organization. But you are absolutely right. Some people think we are endangered species because there's so little time to do both. However, it is critical to understand both clinical and basic science 'language' to understand the real problem. We are the 'translators' and we can interpret the results from basic research to clinical application.
DXY: I saw that Mayo Clinic has a very special health care system. It has a central hospital in Rochester, Minnesota and has branch hospitals in the communities. What is the strength of this system?
John C. Burnett:I think the strength is it increases the quality of care, because that means that the expertise of the main center in Rochester can be available way out in all the communities and the physicians and the nurses have chance for educations, they know the latest therapy. And Mayo technology, online health data, and diagnostic machines are all in those communities. I think it helps everyone. If they have a problem in the community hospitals, doctors can talk by internet, by Skype to headquarters to see the patient. If it's a difficult problem, the patient will be immediately transferred to the center.
DXY: Is it far between different places?
John C. Burnett:It will be anywhere between half an hour to three hours, different places, close and far, between 20 miles and 150 miles.
DXY: In China, the medical resources are unevenly located, which congregates in big cities, both high educated doctors and robust technologies. How can China learn from Mayo?
John C. Burnett:It would be very appropriate to say that Beijing decide to put small clinics throughout China that are linked by internet, Skype. There also needs to be a design to identify difficult cases that could be referred quickly to the major centers. Then the big city like Beijing could do education lectures, so doctors from the small places could visit Beijing, let's say, for 2 to 4 days. In this way, the quality of healthcare throughout the country could be raised and it's cost effective too. It would be good to try that.
Selected publications
1. Macheret F, Boerrigter G, McKie P, Costello-Boerrigter L, Lahr B, Heublein D, Sandberg S, Ikeda Y, Cataliotti A, Bailey K, Rodeheffer R, Burnett JC Jr. Pro-B-type natriuretic peptide(1-108) circulates in the general community: plasma determinants and detection of left ventricular dysfunction. <http://www.ncbi.nlm.nih.gov/pubmed/21414536> J Am CollCardiol 2011;57:1386-95.
2. Cataliotti A, Tonne JM, Bellavia D, Martin FL, Oehler EA, Harders GE, Campbell JM, Peng KW, Russell SJ, Malatino LS, Burnett JCJr, Ikeda Y. Long-term cardiac pro-B-type natriuretic peptide gene delivery prevents the development of hypertensive heart disease in spontaneously hypertensive rats. <http://www.ncbi.nlm.nih.gov/pubmed/21403100> Circulation 2011;123:1297-305. Epub 2011 Mar 14.
3. Cataliotti A, Schirger JA, Martin FL, Chen HH, McKie PM, Boerrigter G, Costello-Boerrigter LC, Harty G, Heublein DM, Sandberg SM, James KD, Miller MA, Malkar NB, Polowy K, Burnett JC Jr. Oral human BNP activates cGMP and decreases mean arterial pressure. Circulation 2005;112:836-840.
4. Hawkridge AM, Heublein D, Bergen HR, Cataliotti A, Burnett JC Jr, Muddimun DC. Quantitative mass spectral evidence for the absence of circulating brain natriuretic peptide (BNP-32) in severe human heart failure. Proc Natl Acad Sci U S A 2005;102:17442-17447.
5. Costello-Boerrigter LC, Boerrigter G, Redfield MM, Rodeheffer RJ, Urban LH, Mahoney DW, Jacobsen SJ, Heublein DM, Burnett JC Jr. Amino-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide in the general community: determinants and detection of left
6. ventricular dysfunction. J Am Coll Cardiol 2006;217;47:345-353.
7. McKie PM, Rodeheffer RJ, Cataliotti A, Martin FL, Urban LH, Mahoney DW, Jacobsen SJ, Redfield MM, Burnett JC Jr. Aminoterminal pro-B-type natriuretic peptide and BNP: biomarkers for mortality in a large community-based cohort free of heart failure. Hypertension 2006;47:874-880.
8. Boerrigter G, Costello-Boerrigter LC, Cataliotti A, Lapp H, Stasch JP, Burnett JC Jr. Targeting heme-oxidized soluble guanylate cyclase in experimental heart failure. Hypertension 2007;49:1128-1133.
