TCP Informational Interview: Dr. Scott Waldman

Scott Waldman MD, PhD, is a Professor and Chair of the Department of Pharmacology and Experimental Therapeutics at Thomas Jefferson University. He is trained in Internal Medicine and Clinical Pharmacology and the recipient of the 2016 Mentor Award from the American Society for Clinical Pharmacology and Therapeutics.

Questions and Answers

Could you tell me about your job history?

• PhD – Thomas Jefferson University 1979
• Postdoctoral Fellowship (4 years) – Pharmacology, University of Virginia

Two years into my fellowship, I moved to Stanford along with my mentor, who was appointed as the Chief of Medicine at the Palo Alto VA Hospital. After four years, I was appointed as a Staff Scientist at that VA Hospital. While maintaining the staff scientist position, I matriculated into Stanford Medical School. I received a VA Merit Award for my laboratory, which was competitively renewed during the entirety of my clinical training (1983-1990). Following the completion of my clinical training in 1990, I joined the Division of Clinical Pharmacology in the Department of Medicine at Thomas Jefferson University as an Assistant Professor, relocating my laboratory. In 1991, I was appointed as the Director of the Clinical Research Unit. After some time at Thomas Jefferson University, I was promoted to tenured professor, and in 1996 I took over as the Director for Division of Clinical Pharmacology. In 2005, I oversaw the transition of the Division of Clinical Pharmacology into its own independent Department of Pharmacology and Experimental Therapeutics. I am the inaugural chair of this department and I am continuing in this role along with a number of ancillary leadership positions as well. I stopped seeing patients about 10 years ago and see patients only in the context of the Jefferson Clinical Research Unit. I spend most of my time in research, administration, and teaching.

Why did you choose this career?

That's an interesting question. I meandered my way into this career. When I went to college, my goal was to become a cardiologist. However, during my senior year of college, I applied for graduate school and fell in love with research. Along the way, during my postdoctoral training, I was introduced to translational research and became enamored with it. I realized that if I intended to continue doing translational research, it would be a good idea for me to get clinical training. That's why I returned to school and completed comprehensive clinical training including medical school, residency training and clinical pharmacology fellowship training. I enjoyed it and ultimately landed my first position here in the Department of Medicine in Clinical Pharmacology, with the specific intent of building a translational research program. I think I have been modestly successful at doing that. We have had a very translational focus on bench-to-bedside discovery research. In the laboratory, our work at the bench is focused on discovering new molecular mechanisms and pathways in a variety of diseases, with the ultimate goal of advancing those discoveries into the clinic/patient setting. We have conducted a number of clinical studies based on our discoveries and have managed to get some of them into clinical trials and licensed by companies for application to patients. My career focus was forged and shaped by my educational experiences. Every time I had an educational experience, it better focused me on what I like to do and what I was interested in and ultimately how I wanted my career to take shape.

Describe a typical day in your job.

I get up at 5 AM and I am typically at my desk by 6.30 AM. I have a number of outside responsibilities, including serving as the Editor-in-Chief for Clinical Pharmacology and Therapeutics, one of the top research journals in the area of pharmacy and pharmacology. In the morning, I take care of my many extracurricular scientific activities including editorial positions, peer review positions, etc. After 9 AM, my group has daily morning meetings. I run a group of about 15 scientists that are broken up into teams. Everybody meets daily for 2 hours, where we discuss the science of that team. Around 11 AM, I go the gym or I go for a run, depending on the season (in the Spring, Summer and Fall I go for a run and in winter time I go down to the gym for an hour or so). I always squeeze in time for exercise during the day. I then have lunch at my desk for about an hour while I catch up on things that I didn't get done in the morning. I then have back to back meetings until anywhere from 6 to 11 PM at night. If I don't have late meetings, I go home and turn on my computer to catch up on things that I didn't get done during the day, starting the entire process over the next day. I typically write my grants and papers on weekends. For my approach to grants and papers, I need blocks of dedicated and uninterrupted time during which I can think and write. I work both days of the weekend.

What things do you like most about your job?

Absolutely the one thing that I like most about my job is the daily morning meeting focused on research. It's funny that I never liked working in the laboratory and I am not a good craftsman. When it comes to doing things with my hands, I don't like working on my house even and it's funny that my son does it and my father and grandfather did it, but I can't do it. I broke a lot of stuff when I was in the laboratory and was never good at doing experiments at the bench. But I loved thinking about hypotheses, figuring out explanations for observations and I love interpreting data and seeing patterns. I truly love the interaction with the folks in the laboratory. My lab tends to run heavy on graduate students and probably a little lighter than most on postdoctoral fellows. I love my trainees. We have a good time and the discussions are outstanding and there is always exciting stuff going on. In our very small way (and we are a small laboratory), we are constantly trying to push back little tiny frontiers, and every day at work is very exciting to me. I get to see what we are discovering and talk about how we would apply it. The exciting thing is everybody in the laboratory participates in writing patents and trying to think about what the next step is, not only in the discovery paradigm, but in the application and translational paradigms as well. We have a number of active clinical trials based on the discoveries that have been made in our laboratory. We provide a unique experience where the graduate students make discoveries in the laboratory and run that all the way up into a clinical trial in patients. There are not a lot of places that do that, and that is what I like the most about my job.

What is the most challenging part in your job?

There are two particularly challenging parts of my job. One of them is keeping the research funded, which I suspect is a challenge for everybody. It doesn't seem to matter whether you are doing cutting edge research or not or if you are putting out lots of intellectual property or doing a lot of translation, it's always challenging to keep the boat afloat. I spend an enormous amount of time trying to keep the machine oiled and make sure we keep doing what we are doing. It is what it is and I don't think we are unique in that respect, but it is challenging. It's unfortunate because writing grants sucks up an enormous amount of time and takes my focus off of the part that I like the most, which is the creative part (i.e., creating new hypotheses and following/developing them). So, I find myself spending a lot of time on things that are not going to actually be remarkable in the field, but it's the only way to keep the laboratory funded.

The other most challenging part of my job is people management. I figured out pretty early on that it is hard to manage people and get them to do what you need them to do. And there is really no point along the training continuum where anybody ever takes you aside and says “look, let me give you a little insight into human resources and how you manage people.” You sort of get thrown into it and you learn on the job by doing. I have managed a lot of people over the last 30-40 years, and it's still not my favorite thing to do. I find it to be difficult, challenging and occasionally disappointing. But I do it because it's a part of running a successful department and a successful laboratory. These are the most challenging parts of my job.

What are the duties in your job that are essential but least enjoyable?

As I said, it's the people management and human resources aspects. In that regard, there are two pieces of it. There is the human resources/people piece and there is the managing of the upper management/institute leadership and organizational expectations. These are the least enjoyable aspects of the job because it's not the thing I like to do. It's political and I don't like politics. I like data, hypotheses and experiments. But in order to have a successful enterprise in that respect you have to be able to work within the organization. So, I find that I spend an inordinate amount of my time on organizational and enterprise-level activities trying to keep my department healthy in a funding environment that is pretty challenging. Not a fun thing to do and if I had to do all over again, I don't know if I would choose that particular aspect of my career to focus on. In retrospect, I prefer spending my time on the research side of things.

Looking back over the years of job experience in your field, what do you think you should have done differently?

I love what I do, but if I could do it all over again, I would want to shorten the training period. I completed my training in series rather than in parallel (separate Ph.D. and M.D. with full post-doctoral fellowship and full clinical residency). I was thirty-eight years old when I took my first post-training, fully independent position. Thirty-eight years is a long time, and I already had kids who were in school by the time I got my first job. Making my family wait and essentially deferring adulthood and earning power by completing both degrees independently was a difficult thing to do. Additionally, I was an older faculty member and grant applicant, which meant I was near or beyond the age limit of many funding opportunities afforded to new independent investigators. So if I could go back, I would shorten the training period, "telescoping" the years.

In retrospect, I would also more closely align my research and clinical expertise. I didn't settle on my research focus until several years after I took my first faculty position. I found it to be a disjointed situation that my clinical expertise was in internal medicine and clinical pharmacology, but my laboratory and translational interests were in gastrointestinal malignancies and colorectal cancer. From the perspective of integrating the clinical, faculty, and research time, it would have been much easier if I had clinical training in fields such as gastroenterology or oncology, allowing me to integrate my clinical and research activities.

Those are the things I would go back and do again, but because my training meandered I didn't have all of the opportunities I wanted. In hindsight, I think I made the best out of what I had on my plate over the years.

What advice do you have for new graduates looking for postdoctoral jobs? Should he/she work in a field similar to their PhD work or branch out into a new research area?

I think that getting your Ph.D. is like getting your learner's permit. You are just learning how to think scientifically, how to form answerable hypotheses/experiments and how to interpret and present data, among other skills. The Ph.D. is simply a vehicle to learn the basic skills, and you learn how to do science after you get your Ph.D. and get a little more independence in a postdoctoral position. I believe the broader your research base, the more tools at your disposal, and the more nuances of the fundamental paradigm you get to see the better off you will be. This requires you to go into different research areas. I interviewed in a few labs that were doing very similar things to what I was doing in my Ph.D., and then I interviewed with my postdoctoral advisor, who was in a completely different universe to what I did as a Ph.D. In my opinion, my career would have taken a less satisfying turn if I had continued working in the same field in which I earned my Ph.D. There's certainly something comforting in staying in the same field, but it was a much richer experience for me to move off into a completely new area, learn new tools, and a new perspective on science. It was this experience that primed me for the path my career now follows, so my personal experience tells me to do something that is not in the field of your Ph.D.

What advice do I have? This actually isn't for new graduates but more for people who are still in graduate school. First, decide on what career path you want to go into: R01-funded principle investigator, pharmaceutical industry, regulatory sciences, intellectual property, etc. You have to make some decisions early on about what path you want your career to take because there are things you have to do to achieve success in each of those pathways. There's some overlap, and it helps to establish your credentials for success as an investigator. That comes down to the fundamental metrics that everybody uses, you need to establish a track record of publications and fundability. As early as possible you want to start contributing to publications, better to have first authored publications, but you certainly want to show you can contribute to a finished scientific product. I review lots of applicants to our laboratory, and I go straight to their funding (e.g., fellowships, training grants, travel awards). If they've ever received any peer-reviewed funding it shows that they have the fundaments to put something together that is successful. Then publications--you have to show that you are capable of completing a scientific task that is worthy of being published. If you are early in your career, contributing to somebody else's manuscript demonstrates that you understand it and have contributed to the interpretable data that is peer-reviewed and considered worthy of being published. This should be what you do every day that you're in the laboratory and working towards your Ph.D. because I expect everybody looks at funding and publication records when making a hiring decision.

My advice for postdocs is exactly the same, even before the first day you set foot in a new position you should be writing an individual NIH postdoctoral fellowship proposal. The moment you enter the laboratory start thinking what your first publication is going to be and what needs to be done to accomplish it.

In your opinion where is your translational research going in the near future?

These are very project-specific directions, but I can define this in the 4 different projects we have that are translational:

1. We are looking at novel chemoprevention approaches for colorectal cancer. We have a paradigm in which colorectal cancer is initiated as a disease of paracrine hormone insufficiency in the intestine. Certain hormones can activate tumor-suppressive pathways, and when the hormones are deficient these tumor suppressive activities are lost, allowing tumors to become more likely to develop. Our hypothesis is that we can prevent colorectal cancer by treating this deficiency just like any other endocrine deficiency with hormone replacement therapy. In collaboration with NCI, that translational project is currently in phase I clinical trials to show that replacement therapy activates identified tumor suppressive signaling pathways.
2. Another project is focused on antibody-drug conjugates to target metastatic colorectal cancer, and I'm hoping that research can make it into phase II and III clinical trials, ultimately leading to remission of patients with metastatic colorectal cancers.
3. We also have a new project developing around a newly discovered novel gut-brain axis that regulates appetite in the setting of obesity. We are trying to develop that project into a clinical trial for hormone replacement therapy to control appetite and reduce obesity and metabolic disease.
4. Finally, we have a vaccine program for metastatic colorectal cancer in a phase I trial, which is close to being transitioned into phase II. We want to know if this vaccine is immunologically and clinically effective in preventing metastatic conditions in patients. Although this is a very focused area of research, this is where I see my translational research moving in the future.

With obtaining funding becoming increasingly challenging, what advice do you have for young investigators?

I have a 3 pieces of advice for those seeking funding:

1. Get back to the fundamentals; get a track record of productivity and fundability to demonstrate you can do what it is you are proposing. I am a reviewer for NCI individual training grants, and if I see an applicant with no record of either, in my experience, those applications are not successful. Therefore, I believe track record is really important to myself and other reviewers.
2. Select projects that have a large effect on public health and are novel and innovative. Your odds of receiving funding will decrease significantly if you are researching a topic that already has an effective and well-tolerated therapy and/or contributes minimally to population morbidity and mortality. In other words, ensure that your project targets a condition where the unmet knowledge gap and medical needs are clearly identifiable and self-evident. From there, take an innovative and knowledgeable approach to meeting those unmet knowledge deficits, with a compelling plan so that the reader of a grant recognizes your plan has the traction to ultimately get translated to solve a problem.
3. The last piece is to write grants, write grants, write grants. At the end of the day, everybody who continues to write grants and has the intestinal fortitude to just keep trying can ultimately become successful. It may not happen immediately and it may take time, but those who persist are the only ones with a chance of being successful.

How do you suggest that a young scientist develop a mentoring style if they are transitioning to a position like independent investigator?

This used to be an aspect of the career that was not recognized. What I did in my first faculty position, which is now more or less a requirement at our institution, is set up a mentoring team. Now every young faculty member that comes into my department has a faculty mentoring team set up for them. The team includes three or four senior investigators who are aligned from a research or clinical perspective. The young faculty are required to meet quarterly with this team and get advice and constructive critique. Additionally, the team can assist in the review of mentoring activities, manuscripts, and grants ad libitum, so there is always a source of advice. We found that process to be reasonably successful. That being said, if this option is not available to you, set up your own informal mentoring team.

We thank Dr. Waldman for his time and insights.