Division of Physician-Scientists Spotlight

Division of Physician-Scientists Spotlight on Stephen Stone, MD

Reprint from the Division of Physician-Scientists’ newsletter.

May 2021 Newsletter interview with Dr. Stone

What does it mean to be a Dean’s Scholar?

I vividly remember opening the email where I found out about being accepted to the Dean’s Scholar’s program. I had fully expected to get a rejection email saying that “there were too many qualified applicants…” However, the email started saying, “It is my great pleasure to inform you…” I really couldn’t believe it, I had been accepted! I had to read it at least 3 times before it started to register.

It truly means the world to me that I was selected to represent the Division of Physician-Scientists for the first year of the Dean’s Scholars program. From my personal experience, it can be very intimidating embarking on a career in basic science research, when you only have an MD degree. The fact that the university has developed these programs, really demonstrates their commitment to developing a pipeline of physicians devoting their careers to research.

Specifically, the Dean’s Scholars program has provided me with additional mentorship and institutional support for my research. Additionally, it is a great boost of confidence to have a team of people who are deeply invested in your success, constantly cheering you on! This along with the incredible support that I have received from the Department of Pediatrics and the Division of Pediatric Endocrinology & Diabetes has been instrumental in the successes that I have had in the last year.

What drew you to your field?

During my 3rd year pediatrics clerkship I had the opportunity to complete a 2-week subspecialty rotation in pediatric endocrinology. I was instantly hooked on taking care of kids with diabetes or other endocrine problems! Obviously I am biased, but pediatric endocrinology is such a cool field. An endocrinologist gets to see all of the amazing aspects of endocrine physiology come to life. For example, it is truly amazing to me that a difference of a few micrograms of thyroid hormone could result in anything from myxedema coma to thyroid storm. Beyond the fascinating academic aspects of endocrinology, there is a huge humanistic component to the work. We follow many of our patients every 3–6 months, giving us the opportunity to build physician-patient relationships and watch our patients grow up. I have had the honor to see this happen, as I have followed many of my same patients since joining Washington University.

My clinical practice has two main focuses. I take care of many patients with either type 1 or type 2 diabetes. I am a big proponent of using technology to augment diabetes care – including continuous glucose monitors, insulin pumps, and closed-loop systems. I worked with my colleagues to modernize our insulin pump curriculum, and develop online courses and resources for our patients. Additionally, I am very interested in understanding how genetics influences diabetes. In recent years, several discoveries have identified syndromes and monogenic conditions which result in diabetes. I helped develop a genetic testing panel for monogenic and syndromic forms of diabetes which is done on campus at Genome & Pathology Services. Learning from patients with genetic or syndromic forms of diabetes can help us understand more about the basic biology of diabetes. This had led me to have clinical research experiences working with the Wolfram Syndrome Research Clinic, the Rare and Atypical Diabetes Network (RADIANT), and the Undiagnosed Diseases Network (UDN).

Tell us about your research and what’s next?

My current research project studies an extremely rare syndrome called insulin-mediated pseudoacromegaly (IMPA). This condition results in obesity, tall stature, and acromegalic features. Patients with IMPA appear as if they have growth hormone excess (acromegaly). However, their growth hormone secretion is completely normal. Rather, patients with IMPA have extremely elevated insulin levels. There are less than 12 cases of IMPA in the literature and a genetic or molecular mechanism had yet to be described.

A couple of years ago, I would be fortunate to make this diagnosis in one of my patients, a 12-year old girl. She set the record for highest insulin level every measured at St. Louis Children’s Hospital. I was very fortunate to collaborate with many investigators on campus. Eventually, we performed research exome sequencing and identified that she carries digenic missense mutations in two genes responsible for FGF21 signaling (FGFR1 and KLB). After reading more about these genes, we began to realize that resistance to FGF21 would be a great explanation for what is going on in IMPA. We have since performed in vitro functional studies demonstrating that the variants found in my patient, reduce FGF21 signaling. Most recently, we have created transgenic knock-in mice, harboring the same exact mutations as my patient. The goal will be to understand the underlying metabolic defects in this condition, and hopefully use these models to test new treatments for my patient, and hopefully others, with IMPA.

I always try to remind myself that my #1 most important job is to be a dad. This helps me try to strike the right balance between my patients, my experiments, and my family. Although, it can be a huge challenge sometimes, the great part of being a physician-scientist is that is can be flexible. Every day, I am reminded why I truly love what I do! It is so cool to be able make clinical observations and run with them all the way back to the lab. With the help of my mentors and the Dean’s Scholars Program, I have been working towards independence. I recently received some good news regarding my K08 (career development award) from the NIDDK, and will be starting that this spring. My goal is to use this time to continue to grow as a parent, person, physician, and scientist.

What has mentorship meant to you?

Mentorship is critical to career development in so many ways. I have been so fortunate to have so many great mentors along the way. Of course mentors provide subject matter expertise. However that is only the tip of the iceberg. At different times, my mentors have filled roles as educators, role models, rock-stars, advocates, cheerleaders, and close friends. As I have moved further along, I have found that my mentors have become more and more invested in ensuring my success. Particularly, I want to recognize my current mentoring team including Dr. David Ornitz in Developmental Biology and Dr. Fumihiko Urano in Endocrinology & Metabolism who have both been incredibly supportive of my career. I am also extremely thankful for the tremendous support that I have been receiving from Ana Maria Arbelaez (Division Chief of Pediatric Endocrinology) and Gary Silverman (Chair of Pediatrics).