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TCP Informational Interview Series: James Crowe, MD

April 18, 2016

TCP Informational Interview Series: James Crowe, MD

Dr. Crowe received his MD from the University of North Carolina at Chapel Hill, and conducted five years of post-doctoral training in Dr. Robert Chanock's laboratory at the National Institute of Allergy and Infectious Diseases (NIAID). He currently holds the Ann Scott Carell Endowed Chair position and is the acting director of the Vanderbilt Vaccine Center. He has also been the recipient of investigator awards from the March of Dimes, American Society for Microbiology, Pediatric Infectious Diseases Society, and Society for Pediatric research. Other high honors include the American Philosophical Society's Judson Infectious Daland Prize, the Infectious Diseases Society of America's Oswald Avery Award, the Mead Johnson Award for Excellence in Pediatrics, the American Pediatric Society's Norman J. Siegel Award, and the American Federation for Medical Research's Outstanding Investigator Award.

Dr. Crowe has a research interest in the prevention and treatment of viral infections using antibodies. His lab's current research interests focus on three main areas: 1. antiviral antibodies, 2. vaccine development and testing, and 3. cell biology of respiratory syncytial virus.

Question and Answers

What experiences led you to choose this career and successfully transition from a clinical degree to research in the basic sciences?

I started as a pediatrician and was planning on becoming a medical missionary in sub-Saharan Africa. Along the way I married my wife, a physician who was also interesting in helping the developing world, particularly Haiti, and she spent some time there. Eventually, as a couple, we decided it was not for us to live in the developing world. At that point I had an established interest and passion for children's health in the developing world, especially Africa. I sought career advice from a few of my mentors and considered studying epidemiology mainly because it was popular at my institution at [UNC] Chapel Hill, however, my mentors convinced me to move toward vaccine research to directly benefit those children. At the time, the most common cause of hospitalization around the world was RSV (respiratory syncytial virus) infections, so I entered a RSV research lab and started a postdoc, without seeing any patients, just working in the lab like a Ph.D. researcher. I trained in a lab under the lab chief Robert Chanock (NIAID) who had trained with Albert Sabin (who developed the oral polio virus vaccine), both of whom had contributed to a number of influential vaccine studies. Two years into the postdoc, I realized I was only getting started, so I ended up staying for 5 years. At that point I became excited about science because instead of seeing 80 patients a day in a clinic in Africa, I saw a vision for contributing to a vaccine that might affect millions of people over time. I had an interest in RSV from my medical background and I saw that there's potentially greater impact through developing vaccines to solve the problem rather than treating the disease.

What is the most challenging aspect of your job and how do you address this challenge?

There's a tremendous amount of administrative and logistical overhead to running a large research operation. There's also a lot of oversight and regulation over what we do. For example we have chemical safety, biohazard, radiation safety, immunization policies, export/import of hazardous materials, intellectual property rights, human resources, and on and on. A lot of the management and administrative responsibilities are also required to maintain the federal money that supports us: monthly reports, annual reports, end of grant reports, et cetera. So there's a lot of administrative work that requires my attention that keeps me away from the scientific work. The real work is doing immunology or virology in the lab, but to make that happen I do a lot of things that are not that pleasant and may not be that interesting on a day-to-day basis.

This does introduce the more interesting aspect of the management and strategic planning of a group of people. I understand everyone has strengths and weaknesses and nobody can do everything, so I try to surround myself with people who have talents in management and administration. Increasingly over my career I'm trying to learn to delegate to those people who are more talented and better suited to execute these tasks at a higher level than I can. Then I try to figure out what I'm supposed to be doing, which is figuring out the strategy behind our lab's science. So, I try to address this challenge through a team of administrators, regulation people, statisticians, and many other people around me who have a lot of unique talents.

How is your lab successfully able to balance a diverse research focus, including research into multiple viruses? What advice do you have to other young researchers who want to develop similar research pursuits?

Although I am particularly interested in diseases in Africa, the way that our lab's research interests were developed was because as an academic in a university you have to pay your bills. Usually our money comes through the NIH, which emphasizes certain areas of research at certain times. After 9/11 and the anthrax scare, Congress directed a lot of money into biodefense and emerging infectious diseases. There were basically three categories of infectious diseases: (1) HIV, (2) general infectious diseases, and (3) biodefense and emerging infectious diseases. Considering that a third of the funding was set aside for emerging infectious diseases, I pursued funding in that field. So, adapting our knowledge and skillsets toward addressing funding concerns brought about the current research focus of my lab. Actually, many of the emerging infectious diseases and bioterrorism agents are naturally occurring in locations like Africa, so looking back, my current research focus came full circle.

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?

In my case, we are a large group currently with 11 graduate students pursuing a Ph.D., so lab members need to be highly independent. They must know when things are not going well and be willing to ask for help. We are fortunate to have many talented scientists in our lab, so they don't necessarily need to get the answers from me, but most know when and who to ask for help. The environment in our particular group is a combination of free-form chaos that at the same time has a very rigid structure. For instance, I may only be able to meet with my graduate students once every two weeks, which may be very little interaction by conventional means, but I expect them before our meetings to send me an agenda. That agenda should be populated with various sections that include all of their data, their plans for future experiments, what I need Jim [Dr. Crowe] to do for me, and figures for their next paper. So this becomes a very structured encounter that allows me to go over everything before we meet, and this allows me to mentor them through their thought processes, conclusions from the data, and experimental design. In our system, graduate students and postdocs must be very organized, because although I'm available electronically 24 hour a day 7 days a week, in between meetings we may not have direct contact. As opposed to having a Principal Investigator micromanaging and solving problems for them, I have found this structure helps my graduate students and postdocs develop into successful scientists at whatever endeavors they pursue next. That is one of the most gratifying aspects of this job.

How have translational technologies (e.g., RNA-seq, DNA-seq, proteomics from patient samples) aided in some of your current research pursuits?

It's an amazing time to be in our field. When I started as a postdoc, the first human antibodies were being isolated and people were amazed if you could get one antibody. Now with all of the technologies including sequencing, the flow cytometer, accessibility to immune volunteers who have been infected by various infectious diseases, and other advances, we routinely make hundreds of antibodies from a single specimen. This allows us to find very rare antibodies that may have desirable properties, and honestly that excitement is why I enjoy research this much.

In your opinion where is your field of translational research moving toward in the near future?

We're at a threshold in antibody research where available techniques are allowing us to develop more antibodies, and those antibodies are becoming less costly to patients. Over the past 10 years many antibodies have been licensed as drugs, but mostly for cancer. In the case of cancer, the perceived health benefits often outweigh the monetary cost of these antibodies, however, in the case of viral infectious diseases the costs have historically been prohibitive, leading to a reliance on other treatment options. So until now our research has been seen as interesting, but has not necessarily been considered a viable treatment option because of the cost to patients. With technical advances leading to increased throughput and output, we believe we are currently at the threshold where the price-point may no longer be prohibitive in using therapeutic antibodies to fight viral infections. In fact, this is the first time in my career when we have 4 different programs in which antibodies are being developed to give to humans in clinical trials. So, translational studies have allowed us to perform academic basic science work, while producing hundreds of fully human antibodies that each represents drug candidates that can be licensed to drug companies as medical interventions. This type of research is truly translational now that we are on the precipice of being able to describe the basic scientific processes that are occurring, while creating products that can benefit people in a large way.

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