Alan Daugherty completed a BSc in Pharmacology at Sunderland Polytechnic and received his PhD and DSc in Pharmacology from the University of Bath.

He moved to Washington University in St. Louis for fellowship training and was subsequently appointed to the faculty. In 1997, he moved to the University of Kentucky in Lexington, Kentucky. Dr. Daugherty is the Gill Foundation Professor of Preventive Cardiology, Director of the Saha Cardiovascular Research Center and the Saha Aorta Center, and Chair of the Department of Physiology.

Dr. Daugherty has been highly committed to the cardiovascular research community. This have included many roles in the American Heart Association, including a 10-year term as Editor-in-Chief of Arteriosclerosis, Thrombosis, and Vascular Biology. He has also served for many years as a grant reviewer for the British Heart Foundation.

Dr. Daugherty’s research focuses on mechanisms leading to vascular pathologies; particularly atherosclerosis and aortopathies. This has predominantly emphasized the role of the renin angiotensin system with particular interest in angiotensinogen inhibition.

Hi Professor Daugherty and Welcome to “Pharmacologist In Phrame”!

Interviewed by Dr Aisah Aubdool _ Oct 2025

What is your background and career pathway to date?

I grew up in Liverpool in a house of non-scientists. I struggled as a school kid but was fortunate to be accepted by Sunderland Polytechnic for a BSc in Pharmacology. This was a highly transformative phase of my life. I found a real passion for learning the topic, which was strengthened by lecturers who conveyed genuine enthusiasm for the subject, and by attending with a group of students who really gelled, both professionally and personally. I then had the good fortune to move to the University of Bath for a PhD in Pharmacology with Dr. Brian Woodward, who has been a lifelong mentor and friend. My thesis focused on cyclic nucleotides in cardiac function and arrhythmias. With the goal of becoming a “real” electrophysiologist, I moved to the States for a fellowship in the Division of Cardiovascular Medicine at Washington University in St. Louis. Unfortunately, this plan was thwarted since the Divisional leadership decided I was to work on imaging of atherosclerosis, even though I had no knowledge of either topic! While originally intending to return to the UK, the postdoctoral fellowship led to a faculty position at Washington University.

After 15 years at Washington University, I had a chance meeting with Dr. Fred de Beer at a Keystone meeting, where we discussed faculty options at the University of Kentucky. The recruitment process ultimately made the decision to move quite easy. Almost 30 years later, I am still convinced I made the right decision at the right time. The University of Kentucky is referred to in the same way as my mother country - UK; which has been a source of much confusion! The UK has afforded me the opportunity for scientific growth in an outstanding research environment. It provided opportunities to engage in administration at the Center, Departmental, College, and University levels. It is also an environment that recognizes the importance of engaging with the broader scientific community and appreciates active participation in professional societies.

1. What research are you currently working on?

While at Washington University, I predominantly worked on the role of oxidation in immune mechanisms of atherosclerosis. For reasons described below, my laboratory added aortic diseases to the vascular pathology portfolio. The initial focus was on development of abdominal aortic aneurysms (AAA). This was based on an incidental finding in studies aimed at determining whether hypertension promotes atherosclerosis. To do this, we infused angiotensin II to increase blood pressure in mice lacking low-density lipoprotein (LDL) receptors. Subsequently, we replicated the studies in apolipoprotein E (ApoE)^-/- mice. After a protracted focus on this region, our studies naturally progressed to investigating aneurysms and rupture in the thoracic aortic regions. Our current studies summarise the role of the renin angiotensin system on the stability and regeneration of elastic fibres during the development of aortic aneurysms and dissections.

2. How did you choose your PhD project?

I would say that my PhD project chose me! After completing my BSc in Pharmacology, my plan was to pursue a PhD at Heriot Watt in Edinburgh. Soon after this fell through, I was fortunate to be contacted by Brian Woodward, who offered me a position in the Pharmacology Department at the University of Bath. At the time, there was a focus on the role of catecholamines in the development of ventricular arrhythmias. This was a time of great fun and exploration. Also, a time of great frustration! My first major publication from my PhD was rejected by multiple journals before it was finally accepted by the British Journal of Pharmacology. This was a second submission that was at least 2 years after the initial submission!

3. How do you balance your time as a Principal Investigator and Director of Saha Cardiovascular Research Centre?

My laboratory is of prime importance to me. Its smooth running has been greatly helped by the stability I have been fortunate to experience. I run my lab in collaboration with Dr. Hong Lu, a colleague of over 20 years. I have also benefited from long-term staff members, two of whom have been with the lab for more than two decades. This stability has helped the development of consistent protocols and practices, facilitating the productivity of trainees. My primary focus is on laboratory operations and strategies to promote successful grant and manuscript submissions.

The Saha Cardiovascular Research Center at UK is composed of intelligent, collegial faculty who run highly effective laboratories. My role is to assist in providing an environment in which they can thrive. Currently, we have space and facilities that promote productivity, supported by a talented administrative team to facilitate the burden of extraneous activities. Overall, the Center is not an unduly administratively burdensome unit to manage.

4. How would you choose a mentor and what are on your thoughts on mentorship?

I was fortunate to have excellent mentors in my early career. Dr. Geoffrey Hall was Head of Pharmacology at Sunderland Polytechnic when I was pursuing my BSc. He was such a positive force that I am sure he contributed to a very large number of my classmates going on to successful research careers. As mentioned above, I then had the good fortune to have Dr. Brian Woodward as my PhD advisor. Brian was approachable and enjoyed discussing science, often tossing out unconventional, innovative ideas. In retrospect, one of the best things he did was give me enough leeway to foster development of independence. I have subsequently realized that an overly intrusive style of mentorship can hinder the potential development of independence. Following my PhD, I had mentors with whom my interactions were quite different and sometimes not as favourable. However, with the advantage of the rear-view mirror, I recognize that these challenging experiences were fundamental in shaping my skills and perseverance to succeed in research.

The judicious, and maybe fortuitous, selection of a mentor is an incredibly important facet of career development in research. It is unlikely that a single mentor is sufficient in today’s complex environment of research. It is also important to have mentors among peers, in addition to those with more seniority. Effective mentors are most likely to be individuals whose lived experiences offer a valuable perspective on a mentee’s unique situation. Ideally, mentors maintain a select number of mentees that can provide objective opinions that they provide in the best interest of the mentees to whom they can offer objective advice, even when that advice is difficult to hear. True mentors are willing to be candid with an appropriate strategy! An example from my own career illustrates this: many years ago, Dr. Jan Breslow, the chair of the Research Committee at the American Heart Association took the time to discuss a failed grant application with me. A key theme of the conversation was that my research direction at that time was not serving my career well. It was not easy to hear, but in hindsight, I realise it was accurate. Following that conversation, I changed my focus which I now recognise as the correct decision!

5. What do you enjoy the most about your current position?

Being a research scientist is a privileged life, full of intellectual curiosity, stimulating conversations, and insightful networking. Many facets of my current position are deeply enjoyable. The constant evolution of science encourages me to continually explore new ideas that integrate and maximize the benefits from the ongoing technological advances. The development of my research has been facilitated by formal and informal interactions with colleagues at local, national, and international forums. This is an environment that makes it easy and rewarding to get up and go to work each morning!

6. What are you looking forward to in terms of research?

Scientists are always thinking about how to advance their research, driven by the excitement of seeing their data published in a manuscript and being able to present the studies from a podium. It is also exciting to witness others take an interest in your research, especially when they replicate major findings to build on their own research. For these reasons, I am looking forward to the privilege of conducting research that I hope will have a meaningful impact on cardiovascular diseases.

7. What are your views on experimental models in pre-clinical studies?

The focus of pharmacology is to develop drugs that prevent or reduce the burden of human disease. This complex process requires a spectrum of approaches to generate relevant information. Appropriate preclinical models are an important component of providing insight into understanding disease mechanisms and evaluating drug efficacy. Assessing how faithfully these preclinical models recapitulate human disease is of paramount importance. However, in my research area of aortic disease, this evaluation is hampered by our lack of knowledge of the human disease process. This limitation has led some to advocate performing every study in two animal models. Yet, with currently available models of abdominal aortic aneurysms (AAA), we have little idea whether drug efficacy observed in any model would translate to human disease. Therefore, requiring consistent responses in two models is only meaningful if both models are subsequently shown to recapitulate the human disease. It is also important to note that the human disease is complex, and treatment often begins at different stages in different patients. While it is unlikely that pre-clinical models recapitulate all facets of the human diseases, I think there are potential translational benefits of carefully interpreted experimental studies.

The extrapolation of preclinical models would likely benefit from mimicking, as closely as possible, the reality of human disease. For example, a recurrent feature in experimental designs assessing drug efficacy in aortic diseases is that interventions are commonly administered prior to, or simultaneously with the initiation of the pathology. This contrasts with the clinical situation, in which drug therapy is typically provided following the detection of established disease. Performing studies on interventions in established aortic disease is much more arduous and time-consuming, but it is necessary to identify efficacious therapies.

Overall, I think that rigorously performed preclinical studies that show major effects sizes of an intervention can have profound impact on insights into human diseases.

8. What has been your most important scientific finding to date?

If citation and importance are equated, my most important finding is the notion that angiotensin II infusion promotes the development of aortic diseases. My initiation into these studies was based on my interactions with vascular surgeons while I was at Washington University, who provided me with human tissues for atherosclerosis studies. The major theme of these studies was to determine whether myeloperoxidase could be detected in atherosclerosis. This was an era of open aortic aneurysm repair, so my surgical colleagues were incredibly helpful in providing human samples. They also spent time educating me on aortic diseases. Two issues that arose in conversation with my surgical colleagues at the time were the rather modest amount of research on these diseases and the lack of suitable animal models to perform preclinical studies. Upon moving to the University of Kentucky, Lisa Cassis and I initiated studies on hypertension-induced atherosclerosis. We made the serendipitous observation that angiotensin II infusion into hypercholesterolemia mice led to bulges in the abdominal aorta. These findings were published in the June issue of JCI in 2000. Adjacent to our article was a publication by my former Washington University surgical colleague, Dr Robert Thompson, who described a model of abdominal aortic aneurysm provoked by direct application of elastase to mouse abdominal aortas. The availability of these two initial preclinical models has facilitated the entry of other laboratories into this research area.

9. What advice will you give to a young person interested in studying pharmacology? [e.g. studies, career, networking]

My constant advice to early-career individuals is to think about a profession that they will enjoy in the long term. My own career as an academic researcher has certainly been challenged along the road, particularly in the early phase of my career when insecurities can often be more difficult to cope with. Now that I have moved much further along, I still go to work each day with enthusiasm. Research is an ever-evolving field, providing a continually stimulating and dynamic work environment.

Rapid-Fire Round with Professor Alan Daugherty.