Welcome to SCCP’s Research Spotlight! Here, we seek to learn more about what our school of pharmacy professors are doing outside the classroom. Our first spotlight goes to Dr. Benjamin Van Tassell, a professor, clinical pharmacist, and research investigator all in one!
Describe your primary research interests.
Primarily, I work with heart failure (HF), trying to come up with better ways to treat the condition. Often, we live in a space between having a heart attack and developing HF. We know that patients who have had a heart attack are at a really high risk of developing HF. But even if we give everybody the gold standard medications, there is still about a 30%–40% risk of developing HF within the first year after having a heart attack. As we get better at keeping our patients with heart attack alive, we’re increasing the number of patients with sicker and sicker hearts and therefore increasing the number of patients at risk of developing HF. We want to know: what are we missing with current treatments? What pathophysiologic pathways are still active or becoming activated after the heart attack, and how does this lead to HF? This has primarily led us to looking at inflammation. We know that inflammation is present in a lot of the patients who develop HF, but just because it is there and predicts risk does not mean it is necessarily causing the HF. We also know that once you develop HF, you have more inflammation, and as a result, your symptoms quickly become worse and hospitalization frequency increases, which makes us think that we need to look into this. Is the inflammation actually causing some of these problems? If so, how do we interrupt it in a way that gives us positive outcomes? From 60% to 70% of what we are currently doing is looking at inflammation in heart disease. We begin by testing these mechanisms in animal models, particularly mice. We then try to take the treatments and therapies that look the best and test them in people.
How did you become interested in this?
It's hard to look back and pin it to a certain day or event, but I think everybody knows someone with heart disease. This fact is not unique. Maybe just this familiarity with it and seeing so many people with heart disease gets a person interested in it. I would also say that what sets cardiology apart from a lot of the other areas is that it is a very number-heavy discipline. There is a lot we can measure objectively. Not to pick on other areas, but if you are studying patients who have anxiety, how do you measure that? How do you measure pain? Cardiology has, for whatever reason, always been very metric heavy; there are a lot of things you can measure, and I am a numbers guy, so I like things you can put a number to. Maybe this attracted me to it, but ultimately, it chose me! I did not start pharmacy school knowing that I wanted to go into cardiology. As residents in San Francisco, we all had to go to the ASHP Midyear Clinical Meeting to recruit for the next year’s group of residents; I remember sitting down with one of my co-residents on the shuttle between San Francisco General and UCSF hospital, and we were looking through the Midyear program. After I had circled eight or nine of the topics that interested me, my friend pointed out that I had circled all of the cardiology topics. That was really the first time anyone had ever pointed that out to me. From then on, I did start paying more attention to the things that were interesting to me, and I noticed that these were cardiology related. I then started looking into cardiology training programs and decided to apply to a fellowship after my PGY1 residency. My PGY1 was a general pharmacy practice residency, and the fellowship was a 2-year program in cardiovascular research, after which I came to VCU.
The fellowship training consisted of conducting a research project from start to finish. As a fellow, you work on several different projects and learn all about the process. When I was interviewing for faculty positions after that, part of the process involved finding an institution that had good research and collaborators already in place so that I could come and join a team, because I still did not have a solid idea of what I wanted to focus on. Modern research is about collaboration, not doing things on your own. We have learned that people are generally more productive when they are on a team working together. Therefore, I was looking for a team that already had a well-established group working in cardiology and a medical center that had a lot of patients with HF and academic cardiologists who would be interested in this type of work. I viewed my role in the beginning as being the bridge between the basic science work and the early stages of clinical practice. I spent my first 2 years mostly working with the basic scientists to observe the drug development process and trying to predict the outcomes of these drugs in actual heart disease.
I worked with an investigator who did a lot of work with myocardial infarction (MI), stimulating heart attacks in mice, which was used as a platform to evaluate potential treatments. At the time, they were evaluating phosphodiesterase inhibitors as a potential treatment for MI. A lot of the damage that occurs after an MI can be prevented with sildenafil – and although this has never translated into practice (we don’t completely know why not), it was clear from the studies that inflammation was really driving a lot of the damage. Right as I was interviewing for my position at VCU, a cardiologist (Antonio Abbate) had been hired a few months before, and he was looking at a different inflammatory pathway. I got to know him a little better, and we really connected. That is how my research really kicked off. One of the struggles with current research is that, because are all so specialized, it is difficult to know what you don’t know. A lot of the basic science is fantastic basic science, but sometimes, the models are not very representative of what we do in clinical practice. For example, many treatments have been proposed for heart disease. When you use them in mice, they are very effective, but only if you give the drug before the heart attack, which conceptually tells you that this chemical pathway is certainly involved in the damage. Scientifically, that’s valid and good to know, but if your only opportunity is to pretreat, that is clinically irrelevant. This is more of an issue when trying to select primary prevention drugs and weighing the risk-benefit of implementing these drugs in patients. Most of our work has involved repurposing old drugs rather than finding new drugs because the older drugs are already on the market.
What is the focus of your current research?
Right now, we are focusing on the IL-1 inflammatory pathway. This is the molecule that causes fever and activates a lot of factors downstream in the immune response. We have been using Anakinra, approved for rheumatoid arthritis as a subcutaneous injection with a specific mechanism of action that targets the IL-1 pathway. In the heart, damage is caused by IL-1; therefore, we have been using Anakinra in some patients to mitigate this. We are also working with drug companies that have potential molecules for treatment, on which we can do phase I studies to get a concept of efficacy and potential outcomes. This is the fun stuff!
What have been some of the most rewarding moments in your career so far?
Ultimately helping patients, especially when you can see people getting better. In one of our early studies when we were testing the IL-1 strategy, two patients participated and did exceptionally well. One of the local news places came and did a story on a patient who had done so well in recovery that he was able to participate in a 10K run. The way we recruited for this particular study involved talking to patients admitted with a STEMI. For many of these patients, this is the scariest moment in their lives. When they arrive at the hospital, we talk with them about our clinical trial and ask whether they would be interested. We can’t guarantee it will make them better, but it may reduce the risk of HF. It’s a tough conversation to have, and not everybody wants to do it.
This is reasonable, and we try to respect that, but we offer it to everybody. Most of our studies are fairly short; whenever doing a new treatment, we have to make sure it is safe and providing positive outcomes. We do not often keep in touch with our patients for extended periods, but some do come back and request to see us in the clinic. This was a double-blind study in which we did not know what the patients were receiving, so we didn’t know whether they were getting better because of the drug or because of the placebo. However, this was revealed at the end of the study, and we saw that the previously mentioned patient was getting the drug. Unblinding the study is one of the most intense moments because years of work are tested.
Can you explain what makes your job unique?
My job requires me to have a foot in many places, including pathophysiology, clinical practice, pharmacology, and research design/evidence-based medicine. Where do all of these places overlap? Pharmacy! A pharmacy background is an ideal training to get into this line of work. I feel that I am still practicing pharmacy every day, but in a slightly different context. I do not work in a pharmacy or on a particular cardiology team, but rather on a research team where we do things to exercise these projects and go wherever we need to go. As a faculty member, I am evaluated on grants and publications, and at least half of my job is research. It is a fun but chaotic job. If you want everything to be planned out and to know exactly what you’re going to do every day, this may not be the role for you. The research side of things is very unpredictable but allows me to be perpetually innovating!
Do you have any opportunities for students to work with you?
Even though I have a practice site, I do not have an APPE rotation spot yet because of the variability of patient participation in research trials. This does not fit into the typical APPE requirements, but I hope to change this. We do welcome students to come and shadow, but these research projects are very time-consuming and not very realistic for a student. This is not intentional but just a natural consequence. Most trainees are residents and fellows. If you want to shadow, just shoot me an e-mail. At any given time, we may be running five or six clinical trials, so the experience can be a little unpredictable, but there is always something to do!
Are you affiliated with ACCP?
I am a member of ACCP and a Fellow! ACCP is my home professional organization. By going to the meetings and networking within the PRNs, I found that I fit the most here. This is where a lot of academic people congregate, and I find the different PRN subgroups an appealing feature. Our own Dr. Dixon is the newly elected chair of the Cardiology PRN, which has 1000+ members!
If you have questions about the information presented, or if you want to get in contact with Dr. Van Tassell, feel free to e-mail him at [email protected] or [email protected].