Alan Daugherty, Ph.D., D.Sc.

Bio / Education: 
  • Sunderland Polytechnic, UK, B.Sc. (Hons), 1978, Pharmacology
  • University of Bath, UK, Ph.D., 1982, Pharmacology
  • University of Bath, UK, Fellow, 1981-1982, Cardiol. Physiol.
  • Washington University, St. Louis, MO, Fellow, 1982-1985, Atherosclerosis
  • University of Bath, UK, D.Sc., 2002, Pharmacology
Research Description: 

The Daugherty Lab is primarily focused on molecular mechanisms of human vascular diseases. Initially, the research was dedicated to modifications of lipoproteins and their roles in influencing the immune responses of atherosclerosis. Since arriving at the University of Kentucky in 1997, the lab has been focused on the role of the renin angiotensin system in atherosclerosis and aortic aneurysms. This work has been in close collaboration with the lab of Dr. Lisa Cassis. The group’s pioneer observation was that angiotensin II (AngII) infusion markedly promoted atherosclerosis and aortic aneurysms in hypercholesterolemic mice. We have subsequently published a series of articles in which we have routinely demonstrated profound effects and the related mechanisms of the renin angiotensin system on atherosclerosis and aortic aneurysms. The components of the renin angiotensin system we are interested in are the substrate, angiotensinogen, two critical enzymes (renin and angiotensin-converting enzyme), and one receptor (AngII type 1 receptor in humans and type 1a receptor in mice). To explore the molecular mechanisms by which AngII contributes to these vascular diseases, we focus on several inflammatory markers and lipoprotein metabolic regulators. During our research, we have developed many reagents including conditional cell specific deficient mice, vectors using adeno-associated virus and a pharmacological approach in antisense oligonucleotides. Some of our studies using mouse models have shown translational significance. Our study published in Journal of Clinical Investigation (2008; 118: 984-993) has led to the initiation of a clinical trial to determine the effects of renin inhibition (aliskiren) on preventing the progression of coronary atherosclerosis in humans measured by intravascular ultrasound (AQUARIUS). One of our ongoing stuies has demonstrated that inhibition of angiotensinogen not only prevents high blood pressure and atherosclerosis, but also ablates obesity. Based on these findings, a human antisense oligonucleotides targeting angiotensinogen has been developed and is awaiting approval for clinical trials.

Grants: 

NIH - Mechanisms of Thoracic Aortic Aneurysms
Role: PI

NIH - Sex Differences in Angiotensis-Induced Vascular Disease
Role: Co-Investigator

NIH - Angiotensin: a Link Between Obesity and Hypertension.
Role: Co-Investigator

NIH/NCRR - Center of Research in Obesity and Cardiovascular Disease
Role: Mentor

Selected Publications: 

Dr. Daugherty has over 260 publications with over 13,600 citations.  To see the complete list of publications, follow the links below.

 

Google Scholar Link

ResearchGate Link

 

PubMed Publications: 

  • Daugherty, A.;Chen, Z.;Sawada, H.;Rateri, D.L.;Sheppard, M.B. "Transforming Growth Factor-β in Thoracic Aortic Aneurysms: Good, Bad, or Irrelevant?" Journal of the American Heart Association 6, 1 (2017): [PubMed Link] | [ Full text ]
  • Alsiraj, Y.;Thatcher, S.E.;Charnigo, R.;Chen, K.;Blalock, E.;Daugherty, A.;Cassis, L.A. "Female Mice With an XY Sex Chromosome Complement Develop Severe Angiotensin II-Induced Abdominal Aortic Aneurysms." Circulation 135, 4 (2017): 379-391. [PubMed Link] | [ Full text ]
  • Daugherty, A. "Recipients of the 2017 Early Career Investigator Awards." Arteriosclerosis, thrombosis, and vascular biology (2017): [PubMed Link] | [ Full text ]
  • Lu, H.;Howatt, D.A.;Balakrishnan, A.;Graham, M.J.;Mullick, A.E.;Daugherty, A. "Hypercholesterolemia Induced by a PCSK9 Gain-of-Function Mutation Augments Angiotensin II-Induced Abdominal Aortic Aneurysms in C57BL/6 Mice-Brief Report." Arteriosclerosis, thrombosis, and vascular biology 36, 9 (2016): 1753-7. [PubMed Link] | [ Full text ]
  • Lu, H.;Sheppard, M.;Daugherty, A. "Calcification in atherosclerotic lesions." Current opinion in lipidology 27, 5 (2016): 543-4. [PubMed Link] | [ Full text ]
  • Liu, C.L.;Wemmelund, H.;Wang, Y.;Liao, M.;Lindholt, J.S.;Johnsen, S.P.;Vestergaard, H.;Fernandes, C.;Sukhova, G.K.;Cheng, X.;Zhang, J.Y.;Yang, C.;Huang, X.;Daugherty, A.;Levy, B.D.;Libby, P.;Shi, G.P. "Asthma Associates With Human Abdominal Aortic Aneurysm and Rupture." Arteriosclerosis, thrombosis, and vascular biology 36, 3 (2016): 570-8. [PubMed Link] | [ Full text ]
  • Sheppard, M.;Rateri, D.L.;Daugherty, A. "miRs, miRs in the Wall, Who Is the Most Causative of Them All?" Journal of the American College of Cardiology 67, 25 (2016): 2978-80. [PubMed Link] | [ Full text ]
  • Chen, X.;Howatt, D.A.;Balakrishnan, A.;Moorleghen, J.J.;Wu, C.;Cassis, L.A.;Daugherty, A.;Lu, H. "Angiotensin-Converting Enzyme in Smooth Muscle Cells Promotes Atherosclerosis-Brief Report." Arteriosclerosis, thrombosis, and vascular biology 36, 6 (2016): 1085-9. [PubMed Link] | [ Full text ]
  • Daugherty, A.;Hegele, R.A.;Mackman, N.;Rader, D.J.;Schmidt, A.M.;Weber, C. "Complying With the National Institutes of Health Guidelines and Principles for Rigor and Reproducibility: Refutations." Arteriosclerosis, thrombosis, and vascular biology 36, 7 (2016): 1303-4. [PubMed Link] | [ Full text ]
  • Lu, H.;Cassis, L.A.;Kooi, C.W.;Daugherty, A. "Structure and functions of angiotensinogen." Hypertension research : official journal of the Japanese Society of Hypertension 39, 7 (2016): 492-500. [PubMed Link] | [ Full text ]
  • Sheppard, M.B.;Daugherty, A.;Lu, H. "Insights into ascending aortic aneurysm pathogenesis using in vivo and ex vivo imaging systems in angiotensin II-infused mice." Journal of thoracic disease 8, 8 (2016): E822-4. [PubMed Link] | [ Full text ]
  • Chen, X.;Rateri, D.L.;Howatt, D.A.;Balakrishnan, A.;Moorleghen, J.J.;Cassis, L.A.;Daugherty, A. "TGF-β Neutralization Enhances AngII-Induced Aortic Rupture and Aneurysm in Both Thoracic and Abdominal Regions." PloS one 11, 4 (2016): e0153811. [PubMed Link] | [ Full text ]