As part of our “Meet Yale Internal Medicine” series, today’s Q&A is on Whitney Besse, MD, instructor (nephrology).
Q: What brought you to Yale School of Medicine (YSM) and why did you choose nephrology?
A: I came to Yale in 2009 for its highly regarded Internal Medicine Residency Program. Yale also happened to be both where my now-husband was finishing training in the Yale Physician Associate Program and beginning on the YNHH Hospitalist service, and near my family in Guilford, Conn.
I began residency with a strong suspicion that I would want to select a medicine subspecialty, but was entirely undecided as to which. Yale’s residency program provided excellent exposure to inpatient care by nearly all the subspecialties. In fact, I worked with inspiring individuals that had me considering cardiology, oncology/hematology and pulmonary/critical care. Then, while on rotation on the nephrology teaching service, the Peters team, with attendings Ursula Brewster, MD and William Asch, MD, PhD, I saw how nephrology had daily discussions of physiology and electrolytes, an effective albeit suboptimal intervention of dialysis, and patient continuity all of which interested me.
Q: What was your YSM fellowship experience?
A: I began the busy first year of Yale Nephrology Fellowship following residency in 2012. This was intense, but tremendously educational. The faculty have quite a diversity of strengths and they, as well as my co-fellows, were very supportive. I enjoyed learning from all the different perspectives provided by clinician educators and the research faculty rotating through the inpatient clinical service. I chose to pursue the research track option of the fellowship based on my enjoyment of past research experiences I had prior to medical school, and the brief Research-in-Residency at Yale with successful female physician scientist Erica Herzog, MD, PhD, in the pulmonary section.
I chose to do my fellowship research with mentor and Section Chief Stefan Somlo, MD, who studies polycystic kidney disease (PKD), the most common genetic kidney disease. I have always had an interest in genetics and also liked Dr. Somlo’s mentoring style. I began in his lab during the second year of fellowship.
The Yale’s Nephrology Fellowship maintains an NIH T32 training grant that funds fellows research training for up to three years. This enabled me, an MD, not a PhD, the time to get up to speed on the basic science techniques needed to produce the results needed to move ahead. I was fortunate to also get a two-year fellowship grant from the PKD Foundation to give me a total of five years of research training. During this time, I made some exciting progress with my projects. I also began attending on the clinical service, working with the next generations of clinical fellows.
I was promoted to faculty in July 2018 and continue to greatly enjoy working with my mentors and colleagues.
Q: In your research now you're actively studying PKD? What are you trying to solve for?
While on rotation on the nephrology teaching service, the Peters team, with attendings Ursula Brewster, MD and William Asch, MD, PhD, I saw how nephrology had daily discussions of physiology and electrolytes, an effective albeit suboptimal intervention of dialysis, and patient continuity all of which interested me.
Dr. Whitney Besse
A: My research focuses primarily on autosomal dominant polycystic kidney disease (ADPKD), the most common genetic kidney disease. About 1 in 1000 people experience ADPKD. These patients develop kidney and liver cysts that typically lead to kidney failure by age 60. The liver cysts are benign unless they get so big and are painful. ADPKD is caused by mutations in PKD1, which encodes polycystin-1, or PKD2. We seek to learn how to compensate for the genetic defect in ADPKD by either increasing the functional amount of the missing proteins or blocking the effects resulting from loss of the mutant proteins. Besides PKD1 and PKD2, many additional human genes are required for the function of the ADPKD proteins. Mutations in these gene can be rare causes of kidney or liver cysts, and studying them can shed light on the pathways we need to target for treatment.
We published our discovery and investigation of five additional disease genes for ADPKD or its liver-limited form known as isolated polycystic liver disease (PCLD). Our study of these genes has contributed to knowledge of how the ADPKD protein polycystin-1 matures, and which chaperone molecules it requires. Numerous additional disease genes exist to be found.
Mutations in one of the genes we identified lead to an overlap of ADPKD and kidney fibrosis, so another goal will be to use this model to study more general chronic kidney disease mechanisms as well.
Q: What led you into PKD research?
A: During my clinical year of fellowship, I met with every researcher in our section. My decision to work with Dr. Somlo studying PKD was both a project-based and a mentor-based decision. I have always had an interest in genetics.
My motivation to study PKD was also affected by a patient I took care of in my first year of clinical fellowship. He was younger than me, and I took care of him for three weeks as an inpatient before he unexpectedly passed away from bleeding complications that can accompany ADPKD. During this time, I saw the effects ADPKD can have on families, and the frustration of having a disease with no cure.
Q: What are your goals for your career in the future, and do you hope to continue working in PKD?
A: My goal is to become a successful physician scientist to contribute to future treatments for genetic kidney diseases, and to contribute to my section at Yale. I have developed some expertise in the field of PKD research and have a project that I believe continues to have great potential to make further contributions to the field, so yes, I do hope to at least partially continue in the PKD field. Because some of my findings thus far have led me to also investigate other non-cystic forms of genetic kidney disease as well, I plan to pursue some of each in the short term and see which turns out to be a more successful direction for me.