I recently had the pleasure of interviewing Dr. Stephen Chan for the PVRI Chronicle. Dr. Chan is an MD-PhD Clinician Scientist and Director of the University of Pittsburgh Center for Pulmonary Vascular Biology and Medicine. He is a practising cardiologist and a well funded, prolific scientist with numerous high impact publications. He also is a warm, welcoming and down-to-earth person who was happy to meet with me and answer all of my questions. The following conversation ensued:
Q: Tell me a little about your background and your career path leading to your current position.
A: I am a physician scientist and was originally interested in biomedical research that would directly impact the quality and service of patients in need. I had this desire since I was a young adult back in college and it is what drove me to pursue medical school and join the MD-PhD program at UCSF. I initially trained as a molecular biologist in virology and infectious disease. Though the training was very good, I ultimately decided to switch fields, when I became exposed to clinical cardiology and vascular disease in general. I believed I could make the most impact in this area. After graduating with both degrees, MD-PhD, I joined the internal medicine residency program in Boston at BWH followed by a fellowship in cardiology at Massachusetts General Hospital. It was during my fellowship that I became much more acquainted with the disease of pulmonary hypertension (PH). PH struck me from two perspectives: 1) our understanding of what this disease is, how it occurs and 2) how it is being treated. At the same time, I witnessed the devastating effects of this disease in our patients. This drove me, at least clinically, to delve deeper into exploration of the disease. Now, as a basic research scientist, PH became very appealing to me because I realized that we knew very little about the disease. It had been historically neglected and is also often considered an orphan disease. It was very exciting to me to feel I could make an impact in an area where there was still unmet need. That’s how I began to train as a physician scientist in pulmonary hypertension. I became a postdoctoral fellow with Joseph Loscalzo, who is the Chairman of Medicine in BWH. Dr. Loscalzo has been interested in the study of PH for decades. I also trained clinically at BWH with Aaron Waxman in the Center for Pulmonary Vascular Medicine. This was truly the start of my independent career both as a physician scientist as well as a clinician. I recently moved to the University of Pittsburgh where I now direct the Center for Pulmonary Vascular Biology and Medicine with the goal to combine both clinical and research operations to optimize patient care.
Q: Looking at the PH field right now, both from the perspective of a clinician and a physician scientist, would you consider that we have made a lot of headway in the past years and where do you see the field going in the next few years?
A: Over the past five to ten years it definitely seems that there has been an influx of new information, particularly from the molecular aspects of understanding this disease. I believe even from the clinical perspective we have now a better perspective of our patients, how they develop the disease and how it progresses. We seem to be on the upslope and I believe that we are hitting an inflection point of gaining great traction into establishing new paradigms for this disease, both from a clinical and research perspective. It has been helpful not only in terms of the interests from our trainees who embraced the tasks of pushing the field to the next level, but also by increasing community awareness. The industry and pharma are also more aware and willing to invest into PH research, as is the federal government via the NIH. We are now beginning to see the payoff of this focus, at least in small form and still have a long way to go. Certainly other fields such as cancer and atherosclerosis for instance, are light-years ahead of us in terms of disease understanding and how to best approach the complexities of patient care and pathogenesis. I am convinced we are on the right track but we still have a long way to go.
Q: What do you think is the next big thing - or should be - in terms of PH research?
A: It depends on where you look. There are still a number of holes in our understanding of how we treat PH. I will highlight a few of the ones our program is interested in. The first is about early diagnosis and our understanding of early pathogenesis of PH. For years we have been fixated on trying to understand the end stages of this chronic disease. This has given us a limited understanding of where the disease is coming from. But we now know that probably what is going to drive the next era of therapeutics and management of PH is trying to understand how to identify those patients who are at risk or those who are just developing this disease. We would love to prevent PH rather than having to treat something that has developed for many years. We may want to understand the molecular processes initiating PH. We may want to try to design new diagnostics in order to understand the beginning stages of the disease. Investigating exercise physiology, for example, is one particular notion that may be addressed this way. Also, we may want to pursue novel imaging modalities of looking at early stage disease in the context of the pathways that we have yet to discover. I believe that early diagnostics will be an important area to focus on.
Secondly, it would be interesting to develop personalized medicine for PH. We are certainly behind the times compared to other areas in medicine, such as cancer or atherosclerosis, where “big data” are already in play in trying to allow for individualized management and patient care. I’m not just focused on genomics, but also other types of high throughput analyses, be it at the molecular level, such as metabolomix or expression data, or in the clinical realm where clinical analytics can be utilized to understand big population type data from electronic health patient. This is going to be a very important concept. I believe the integration of computational methods, bioinformatics, high throughput molecular understanding is going to allow us to drive that particular phase forward.
Third, we would be happy to usher in the next generation of therapeutics, be it small molecule inhibitors or otherwise, that would allow us to treat PH in a better fashion. This will also entail understanding the disease at a much finer level in order to target pathways other than the big three that we already have drugs for (prostacyclin, endothelin, and nitric oxide).
Q: Can you tell us a little about the PH program here at the University of Pittsburgh?
A: I arrived about 7 months ago as the Director for the Center for Pulmonary Vascular Biology and Medicine. It was an added bonus for me was that this program already had such phenomenal basic scientists and clinicians in place. This is an exciting time for us here at the University of Pittsburgh because we feel that we have a critical mass of scientists and clinicians that will allow us to integrate those disciplines to optimize patient care. We focus on innovation and research and we pride ourselves on research opportunities at the basic, translational and clinical levels. We believe we have the manpower as well as the commitment from the institution in order to pursue those types of endeavors. Several of our investigators are looking at many different pathways that we think are important in PH. At the molecular level, we are thinking not only of vasomotor tone, proliferation and survival mechanisms (all important in pulmonary vasculature and right ventricle), but also of other pathways that have not been previously studied. This includes metabolism, vascular stiffness, other phenotypes that we think are also playing an important role in this disease.
We also have a number of translational components that we are very proud of in terms of making sure that our basic science is really translated to the clinical realm not only in the therapeutic arm but also diagnostically. Accomplishing this doesn’t happen just by accident and oftentimes in the field of PH it really relies upon the individual investigator to establish those types of collaborations. Because we have a critical mass of investigators who will be here long term, we have instituted a number of structural modalities to allow for that type of collaboration to occur. One of those, certainly, is the idea that we are very intent on building a very unique database of centralized information not only from our electronic health records system but also in combination with high throughput molecular data directly from bio-banked patient samples. This includes blood, plasma, tissue and cells. We believe that that will be a very prominent resource for what we think is going to be important in personalized medicine in pulmonary hypertension. We also have a very strong understanding that in order for our home-grown science to be translated to patient care we need to be on the forefront of that effort, rather than simply making the discovery and leaving it up to others who may or may not want to take it on. In that sense we’ve also put in a lot of infrastructure and resources in order to ensure that we have the ability to act as our own facility of developing drugs from the ground up, i.e. from the pre-clinical modeling, pharmacodynamics and pharmacokinetics all the way to first-in-human studies. We believe we have an opportunity to really take it from soup to nuts. So that’s another very big push not only for our center but also for the institution in general to ensure that drug discovery remains a very high priority.
We also would like to ensure that the integration of multiple different disciplines continues to be prioritized here. We pride ourselves on having a very integrated program at least between pulmonary and cardiology clinicians for the care of pulmonary hypertension. We also partner with a number of other disciplines such as rheumatology, sickle cell disease, interstitial lung disease, transplant, surgery and so on. That’s a very big component of what we pride ourselves on and we want to train the next generation of investigators, both clinicians and researchers, in order to allow for them to have that type of training. Right now, we have both pulmonary and cardiology fellows training in PH in a number of different regards. We want to make sure that’s a real dedicated program. That will take a little bit of institutional and/or philanthropic money to do so but we are intent on making sure that we prioritize the training and mentorship of our physician scientists going forward.
Finally, one of the things that we also want to ensure is that we have a very meaningful relationship with our community of patients and advocacy groups in order to make sure that we offer the most holistic care to our patients. We have a very large program of physician and patient outreach locally, nationally and internationally. We are interested in determining whether new innovative techniques such as telemedicine services may also be something that we could offer not only in the region but also to patients perhaps in resource-poor environments throughout the world. We think that our expertise may actually have an impact there as well. So those are some examples of where our program is going in addition to the individual efforts of our investigators to really advance the care of these patients.
Q: Being part of the PVRI you have probably seen the great contribution they make to the field. Where do you see the PVRI going in the future and what is an area that you would think this institute can have an instrumental role in pushing the field forward?
A: The PVRI is a great group and institution because I believe, at least from my work with them, two things are very apparent. One of which it is a very international program and I think that one of the key areas from what I’ve heard from the leadership of the PVRI is that they want to maintain true international collaboration and not just be dominated by the same groups in the developed regions such as the US, Europe and some of the countries in Asia but certainly everywhere else including resource poor environments. That is a huge unmet need for this disease in terms of making the appropriate diagnosis and treatment of patients. Again, as I mentioned, we would love to be able to partner with someone like the PVRI in order to institute a program of telemedicine of sorts in order for us to really allow for communication between experts in the field as well as patients throughout the world. That will allow for a much more connected group and I think it would optimize the care of those patients that really deserve better treatment then what they are getting right now. I think that is one very laudable goal of the PVRI that speaks to why we would love to partner with them.
Secondly I noticed that the PVRI is very invested in research and innovation and that it is very apparent when going to their meetings. Their research component is a very big priority and we appreciate that here in our program because innovation is probably our top priority in terms of research and development. We would love to work in concert and conjunction with the PVRI as it goes forward. I think that the PVRI also has a great opportunity to really invest more resources for research in general. I think that that program is still getting off the ground in terms of it but I think that it really puts itself in a good position to do so and we’d love to partner in that realm as well.
Q: For the young junior faculty and post-docs, given the current environment of difficult funding and limited resources not just here in the US but worldwide, what advice do you have for them and what do you think they should focus on the most in securing a transition to the next step and having a successful future as researchers and physician scientists?
A: It certainly it is a very difficult time for everybody in terms of getting funding. Oftentimes it is difficult for a person, especially at a young stage, to be optimistic if they hear all of the stories of difficulties in funding and how hard a road it really is. On the flip side, however, I actually feel quite a bit of optimism being in this field at this stage of the game. I think that there are two reasons for that. One of which, is that it is a phenomenal time to be a scientist and a research investigator in pulmonary hypertension. The technologies have gotten so much better than they had been ten or fifteen years ago. There are so many more opportunities for a young investigator to really sink their teeth into and truly make an impact. Around fifteen years ago, there had been a very limited amount of research, so you’re going to have to start from scratch. At this stage, I feel there is so much technology and advancement, not just in the PH field, but also in other disciplines that we can learn from and leverage in order to make important discoveries in this field. I think there is great excitement and optimism to be had in terms of making profound discoveries at this stage in the next five to ten years. I like the direction in that regard. In terms of raising money I think that ironically, even though financial investment in research and research endeavors in general throughout the world has decreased, the PH field is actually on an upswing. If you were to look at the amount of money that is being invested and is available to the PH researcher and the young investigator included, I think that it is actually more than it was fifteen years ago. Fifteen years ago, there was less awareness and there was less interest from industry and federal partners to understand this disease better. Now I think we have critical mass and an inflection point of interest and persona in order to make this happen. I think that it is actually a really good time for a young investigator to be in this field. Even though we don’t get as much money on an absolute level as say cancer or other types of cardiovascular disease, I still feel the ratio of really good investigators to the amount of money that is being spent is very favorable for the person who is doing very strong science and making very strong discoveries. If you are to compare it to some of the other fields where there is a lot more saturation in terms of the competition, I feel perhaps even the competition is less in this regard and that, if you are well trained and you have really good ideas, you will have a very viable outlet for raising money for yourself in this purpose. Now with that being said, I don’t think that it is easy to do by any means. I think that one of the things that I would certainly advise any young investigator at any stage of their career is to ensure that they have a very strong, devoted and committed mentor who knows how the system works and understands how to train young investigators in order to usher them through this particular time of their career. This is a very fragile time in any person’s career when they are trying to make the step from a trainee to an independent investigator. You do not want to have too many missteps or mistakes in that line. I think having mentor-ship and having a person who you really can trust is paramount to making sure you have that success. That success is very available to you if you put in the time, effort and strategize well.