GWIMRes alums have had outstanding achievements in their varied careers. In this edition of our newsletter, we shine a spotlight on physician-scientist Dr. Danielle Townsley (Res'09). After completing undergraduate studies at University of California San Diego and obtaining a Master of Science in Epidemiology from University of Edinburgh in Scotland, Dr. Townsley came to GW for both medical school and residency. She completed hematology fellowship at the National Institutes of Health – National Heart, Lung and Blood Institute (NIH-NHLBI). She is now a board-certified hematologist with ten years of experience in clinical research. She began her career as a PI on numerous Phase 1-2 trials in the hematology branch of NIH-NHLBI. She directed the investigation of eltrombopag, a small molecule hematopoietic growth factor, which led to FDA approval for its use to treat aplastic anemia. In 2017, Dr. Townsley joined the oncology division of AstraZeneca’s subsidiary Medimmune, and she currently serves as a Director in the AstraZeneca’s Oncologic Research and Development unit.
We sat down with Dr. Townsley to learn more about her career.
Q: You have pursued a somewhat rare career path for a GWIMRes alum. Tell us about your path and what prepared you for this career? A: I didn’t know this was my career plan. As an undergrad, I had strong experience in an immunology lab, where I did molecular immunology as a technician and Lab Manager before completing a Masters degree and attending med school. That experience set me up to have an appreciation for research, both clinical and basic science. During residency, I was fortunate to get to see a couple of patents undergo bone marrow transplants with Dr. Imad Tabbara and I was fascinated by the immunology surrounding BMT. The NIH offered a unique hematology fellowship at the National Heart Lung and Blood Institute during which I could mostly focus on highly experimental hematologic therapies for malignant and benign disorders using BMT and other cutting edge cell therapeutic such as adoptive NK and T cell therapies; e.g. the NIH pioneered the use of CAR-T cells for cancer and BMT for sickle cell disease.
Q: Tell us about your path through fellowship and how you got started on your research career? A: While at the NHLBI as a fellow, I had to decide on a research project. Again, I didn’t have a vision of my path, but I just looked at the options and chose the research project that I thought was most exciting professionally and would have impact. The ones offered were not cellular therapy or BMT-based, but there was one project that was an opportunity to further investigate the biology of cancer, specifically telomere biology, with a renowned physician-scientist who has published a lot in pivotal journals like NEJM, and has made tremendous impact in the field of bone marrow failure – Dr. Neal Young. I knew the importance of strong mentorship that Dr. Young could provide and I was fascinated by the role of telomeres in human diseases, so I joined the project (Townsley et al. Danazol Treatment for Telomere Diseases. NEJM 2016).
I had to learn how to pivot into new skills. I learned how to write scientifically, how to read the literature more critically, and think deeply in a given area of medicine. Within just a few years, I was able to publish exciting results from clinical studies in top journals, like NEJM. I was invited to international meetings and to review manuscripts for journals. Perhaps the work I am most proud of, is the study I led that shifted the standard treatment paradigm for newly diagnosed aplastic anemia that demonstrated how repurposing a drug for immune thrombocytopenia was capable for stimulating hematopoietic stem cells in an otherwise fatal disorder, severe aplastic anemia (Townsley et al. Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia, NEJM 2017). This study inspired me to learn more about drug development and how we can identify and develop new therapeutics.
Q: Your career has taken you from being a physician-investigator at the NIH to being one in private industry. What can you tell us about some of the differences between them? A: NIH-NHLBI is a very unique and special place to be a physician-investigator. It was set up so you can run back and forth easily between the laboratory, clinic and hospital for true bench-to-bedside research. On a daily basis, I could check in on my hospitalized patients in the morning, then spend time in my office doing research, then oversee my lab technicians, then go to clinic and see a few patients, and then back again. We had fellows and PAs to help with inpatient clinical care so I did not have to write notes and could maintain protected time for research and writing. Furthermore, I was able to keep up my clinical skills by spending a couple of months per year rotating as attending on the hematology transplant ward. It was a phenomenal set up. After eight years, it was time for me to try something new.
The driving factor for industry is largely pragmatic -it doesn’t matter if you can get this published, it matters if you can find a new compound that is going to be useful for patients. Sometimes you can feel like you are rushed too quickly because “time is money”, the company has shareholders, and there is competition. That’s the part I find the hardest as it may limit the ability to pontificate more thoroughly about disease pathophysiology like you might in academia. However, patients ultimately do benefit from drugs being made available more quickly.
Ultimately, it has been a fantastic career decision for me. I do miss the patient care that I used to get to do while at NHLBI because it gave me an opportunity to think about things conceptually and see the clinical outcomes of interventions. Now I just see the data rather than the personal outcomes and that’s not as rewarding.
Q: The pharmaceutical industry typically gets a bad rap, including from physicians. Was it hard for you to join the industry? A: The pharmaceutical industry is a fascinating world with physicians all over. Most med students and doctors don’t know about this world, which is a shame. When I was a student I only knew of pharmaceutical sales reps, but that’s a separate division, that's the commercial side that is maintained very separately from the research and development division in pharmaceutical companies. The commercial side is concerned with how to get a drug used once it is approved. Most physicians hired into pharma are on the research and development side working to develop drugs and ensure they are safe. Unfortunately, that’s the side that’s hidden more from everyday medical practice, and it is a separate universe from the commercial units.
Interestingly, you see the same specialization amongst doctors in industry as you do in the clinical world. I currently work in developing new drugs for cancers and this involves early phase studies, such as phase 1 first in human studies. Some physicians support late stage development and large phase 3 randomized studies. Other physicians support regulatory or patient safety divisions. I am in early phase studies because I like the pathophysiology and the science in identifying how we proceed with new compounds using data in animals or cell lines to try to determine if the compound will be useful in humans. There’s lots of science in that! The late phase folks don’t have to deal with the preclinical science as much -the compound is already proven safe, they already have a dose and some evidence that it is efficacious. They are more involved in large phase 3s, which include coordinating all of the sites and huge amounts of patients.
Q: What do you think are the special contributions of physician-scientists to research and development, compared to scientists who are not physicians? A: I think it is absolutely critical to have physicians because they understand toxicity and can interpret clinical data to know what may or may not be safe and acceptable to patients, like, “rashes we can deal with, skyrocketing LFTs are not acceptable!” Others don’t know clinical terms, let alone the underlying disease pathophysiology. Physicians have a true appreciation for the complexity of the human body. Sometimes, physicians can bring real-world knockout models to the conversation, for example we can say there is a disease where people are born with a mutation in X, so we know what would happen if you knock out that pathway, and they are doing just fine, so a drug that targets that pathway may be ok. Or, conversely, those people have serious health consequences so you can’t hit that pathway. Or you see something happen in a petri dish with certain cell lines, and you can think through what type of cells they are, and where those cells are found and what role they play. Only physicians can question, “I remember seeing many patients who had X disease and we would give them other compounds with a similar mechanism to this, but they never worked, so why would this one work?” A physician is also well trained to say, “if this compound caused those cardiac problems in a monkey, then for first-in-human testing we are going to have to do echos, EKGs, troponins, etc. for surveillance monitoring.”
Q: You talked about the importance of mentorship in your career. What words of advice do you have for residents about mentorship? A: One of most important things someone told me along the way is it’s important to have multiple mentors, including mentors who are not conflicted and who are outside of your institution. And I’ve learned the value of routine, occasional mentorship from multiple people. For example, Neal Young was an outstanding mentor but by definition was conflicted because I was working for him. Many times our interests were aligned, but not always. Another important mentor I have had is Dr. Janis Abkowitz at the Fred Hutchinson Cancer Research Center in Seattle, who is in academia at another institution and was not conflicted. Someone like that can say, “I don't think that’s a good idea for you,” or give you a different perspective than a mentor who you work for. Now, I have physician mentors in industry at other companies who I ask, “what should I do next? What skills should I develop?”
Sometimes people wonder how to find mentors outside of their institution. It turns out, people are usually flattered if you ask them to mentor you by just approaching someone saying, “I would love to have some mentorship from you, and I’m really in awe of your accomplishments, so I wonder if you’d be willing to have phone conversations with me periodically.” It can be small things, like “I’m going to be at this conference. If you’ll be there, can we get coffee?” I think people are scared to do this, but you can definitely figure it out and find people, and you really should!
Q: Any last reflections on your career path? A: I never thought “I know for sure I want to do that,” but I’ve remained open to turns in my career path and who knows where it will take me in the future? I never had a plan 5-10 years ahead and I still to this day don’t do that. I always wanted to go where my passion led me