Researcher at Heart

What prompted your interest in medicine?
It started when I was in high school. I became broadly interested in research and, as that evolved, I realized that what really excited me was human research with a translational angle. I’ve been involved in research ever since I was 16 years old.

I chose pathology because it seemed like the best marriage of research and the clinic. As I finished my residency and fellowship, I found myself gravitating toward breast cancer research. At the time, I ran a DNA flow cytometry lab that principally worked on breast cancer, and my research postdoc focused on prolactin and the immune system. I told my mentor I wanted to port that research into the breast, so I could have congruence between my research and my clinical practice – and he consented.

What has been the most unexpected moment of your career?
I would say there have been two.

One is our discovery that both prolactin and its receptor can enter – and function in – the nucleus. The notion that peptide hormones could enter the nucleus was heretical at the time. People thought steroid hormones worked in the nucleus and peptide hormones worked at the cell surface – and ne’er the twain shall meet. Now, of course, we know that’s not true.

The other involved shedding new light on an old discovery. There are seven prolactin receptor isoforms; we cloned four, including an intermediate that is missing about half of its intracellular domain. We had originally shelved it; after all, why use something that only works half as well as the complete protein? But, three years ago, Schreiber and colleagues performed a STAT1 knockout mouse study in which all of the female mice got breast cancer. Their tumor DNA had one thing in common: a mutant, truncated form of the mouse prolactin receptor that strongly resembled the intermediate form of the human receptor. They also showed that it didn’t have any special properties by itself – but, when co-expressed with the wild-type receptor, it was profoundly transforming in mouse fibroblasts. I immediately recognized that this form of the receptor was very similar to the human intermediate form and wondered, “Could it be playing a similar role in the human breast?” The results of our research in that area are forthcoming!

What are your other meaningful accomplishments to date?
I think I’m most proud of my accomplishments in the realm of mentoring. When I assumed the chair position at Virginia Commonwealth University seven years ago, I was tasked with rebuilding our research division. I recruited three junior faculty into the department – and, since then, they have all published and they have all received major grant support. And that’s hugely gratifying. I’ve had the opportunity to mentor young scientists to a stage where their career is now set – not easy in the current funding environment.

I view the role of a mentor as a service – not something to micromanage. Some scientists believe that chairs and mentors should be in every aspect of people’s business, which I don’t think is successful. The model my chairs and mentors used was not to interfere with what I was doing. They gave me free rein, but they were always there when I had a problem or hit a brick wall. I view my role as chair in the same way – not as someone who directs every movement, but as someone who helps when there’s a real problem.

What do you think lies in pathology’s near future?
I think we’ll increasingly see digital pathology make inroads into our practice. Digital pathology offers us a permanent record of every slide we make; it allows us to be quantitative in ways that we haven’t been before; and – particularly relevant in today’s pandemic environment – it allows us to readily share images with colleagues around the world.

Unlike radiology, pathology can never be truly digital. We’ll always have to make a slide and scan it to obtain a digital image. But I don’t see that as a downside; if anything, it facilitates the transition, because if you have any reservations about the technology, you can still go back to the paraffin block. You can still practice pathology the “old” way.

Do you have any advice for pathologists at the start of their careers?
Find a niche. Don’t leap in and start trying to cure cancer right away; try to find a subdiscipline that you can become an expert in before you move on to bigger things.

Ask yourself constantly, “Am I still being challenged? Am I still having fun?” And, if the answer is no, do something about it. Moves are a great time-waster if you don’t have a good reason – but you’ll know when you do have a good reason. If you can’t achieve what you want in your current position, it’s time to consider a move.

If you hadn’t become a pathologist, what would you have become?
My great loves are playing the piano and cooking. In fact, my wife and I are both pretty good cooks – so it’s a great hobby to share. If I had to pick a specialty, I would say it’s baking bread – an increasingly popular pandemic hobby, but one I have pursued for many years. And I have to say, my bread is pretty darn good… So to answer your question: a baker!