As part of our “Meet Yale Internal Medicine” series, today’s Q&A is with William Chang, MD, PhD, assistant professor of medicine (nephrology).
Q: Tell me your path to Yale School of Medicine (YSM). ![]()
A: I grew up in Charleston, W.V., where my academic interests gravitated towards science and math. While at Harvard as an undergraduate, I developed interests in biology, physics, and basic research. After graduating from Harvard with a bachelor's degree in Biology in 1998, I did a combined MD/PhD program at NYU School of Medicine. At NYU, my PhD research focused on basic telomere biology. I was specifically interested in how different proteins regulate telomerase access to the ends of chromosomes called telomeres (read more in Genes & Development), which act like a biologic clock that defines the number of times that a cell can divide. Telomere biology has significance to both aging and cancer. During the pre-clinical years of my MD training, I was most interested in physiology and its quantitative rigor. During the clinical years of medical school training, I decided to pursue a career path in internal medicine. So, after medical school graduation, I came to the Yale School of Medicine (YSM) to join the internal medicine house staff in 2006.
Q: What brought you to YSM?
A: After medical school, I wanted to continue down both the research and clinical pathways. In deciding where to do my training next, Yale really stood out me. It was a really good fit for me professionally and personally. Yale is obviously an incredible place to do research, but I was also very impressed by the friendly and approachable faculty. I saw enormous potential in working with and learning from world-class researchers in a great collaborative environment. Personally, it also made sense to me because my future wife, Grace [Lee, MD], was still at NYU as a medical student at the time. The commute from New Haven to NYC is quite convenient.
Q: Why specialize in nephrology?
A: I find the kidneys incredibly interesting and complex. I enjoy thinking about electrolyte disorders and find kidney pathology fascinating. The fundamental function of the kidneys is to act as a vascularized filtration system that clears away toxins and tightly regulates electrolytes, acids, bases, and volume. Because of these critical functions, severe renal dysfunction can lead to life-threatening clinical situations. One of the truly great biomedical engineering accomplishments has been the development of hemodialysis. Nephrologists are often called in to assist with some of the most critically ill patients in the hospital.
Another really remarkable aspect of nephrology is how other organ systems can have profound effects on kidney function. If the heart or liver do not work, then renal function can be compromised. These disorders are called cardiorenal and hepatorenal syndromes. Diabetes and high blood pressure which are very common medical disorders can also cause kidneys to fail. I am also particularly interested in the intersections of rheumatology, immunology, and nephrology. The immune system can attack the kidney in many different ways. Fortunately, when we do a kidney biopsy, we can see all the parts of the functional units of the kidney, called nephrons. With the help of renal pathologists, we determine how the different parts of the kidney are damaged by hemodynamics, immune cells, antibodies, or even medications themselves.
Q: What drove your research interests?
A: When thinking about my research focus during my nephrology fellowship, I really wanted to do basic science research that could benefit the kidney patients that I see. I became interested in the field of vascular tissue engineering while working as a nephrology research fellow in the Yale laboratory of Jordan Pober, MD, PhD. Jordan has made important basic discoveries in vascular immunology, and in the process of his lab's work, developed a system to tissue-engineer human microvascular networks in an animal models system. Remarkably, under the right conditions, dissociated human blood vessel cells can re-assemble into functional, perfusable microvessels in an immunodeficient mouse in vivo. After developing a system to build more complex microvessels (read more in Cardiovascular Research), I moved towards trying to incorporate components of the kidneys.
In collaboration with Alessia Fornoni, MD, PhD, at the University of Miami, I learned to microdissect out the vascular tuft of nephrons called the glomerulus, and found that human vascular cells can self-assemble into microvasculature that can re-perfuse this specific part of the nephron.
In my own lab here at Yale, we focus on both vascular and kidney tissue engineering. Although we still use animal model systems, we have now moved towards microfluidic technologies to generate perfusable human microvascular networks on a chip (read more in npj Regenerative Medicine). With microfluidic chip technology, we are currently trying to model diabetic microangiopathy with the hope of better understanding disease pathogenesis and advance the development of therapeutics. In collaboration with my other research mentor, Laura Niklason, PhD, MD, we are also developing tissue-engineered vascular constructs as therapeutic delivery platforms. For kidney tissue engineering, we are using inducible pluripotent stem cell-derived kidney organoids to explore how to generate functional kidney tissue.
My hope is that discoveries that we make will one day significantly improve the lives of patients.