November 29, 2016
Lue Zhi Pi Mao, a Chinese idiom, translates literally to “only knowing a little about skin and hairs.” It's used when someone only has superficial knowledge of a subject—seeing the skin and hair but not what's underneath. Hao Chang, PhD, who joined the Department of Dermatology faculty as an Assistant Professor in September of 2016, studies skin and hair in mice, but hopes to use this superficial knowledge to help us understand what happens deeper in the body.
Professor Chang researches Planar Cell Polarity--abbreviated to PCP (“not that kind of PCP,” jokes Chang)--a genetic mechanism that controls epithelial cell alignments along body and tissue axes. In simpler terms, “skin cells need to know which way is the front and which way is the rear so they can grow hair in the correct direction.”
The PCP pathway is used by many cells and organs, not just in hair and skin. For example, in the fetal neural tube, which develops into the brain and spinal cord, cells need to know in which direction to move in order to seal the neural tube as it develops. An error in the PCP pathway in the developing neural tube causes craniorachischisis and spina bifida; likewise, an error in the PCP pathway in the developing oral palate causes a maturing fetus to develop a cleft palate.
Chang’s exploratory research studies the genetic pathways that control PCP in mouse skin, particularly the gene Frizzled6. Mouse skin has thousands of hair follicles, and on a mouse’s back, all hair follicles grow in a front-to-back direction, parallel to the body’s axis. In Frizzled6-mutant mice, hair follicles exhibit random orientations relative to the body’s axis. By studying the genes of mice with the naturally occurring “ridge” pattern (see below), Chang has identified a novel PCP modifier gene that controls hair orientation, Astrotactin2. This is the same genetic mechanism that controls the direction in which your own hair grows—and any curious intersections or “cowlicks” would be a result of PCP signals in your genes.
Applying his mouse models to cancer studies, Dr. Chang also investigates how PCP affects tumorigenesis in melanoma. “There is increasing evidence that PCP is involved in tumor progression,” says Chang. “Melanoma interests me not only because it is deadly—therefore important in terms of clinical outcomes—but it shows high expression of Frizzled6, the focus of my research.”
Chang uses mouse models, which means his studies take longer to complete (two to three months) when compared with common laboratory organisms such as microscopic C. elegans and Drosophila (one to two weeks). All of these organisms have been widely used to study PCP, but Astrotactin2—the new gene Chang discovered—exists only in vertebrates. “You can’t rush the process, but,” says Chang, putting things in perspective, “after talking with plant geneticists, I can’t complain—their subjects take years sometimes to reproduce!”
Before accepting a faculty position at UW-Madison, Chang spent seven years as a postdoctoral researcher at Johns Hopkins, and six years completing his PhD in Texas. While his postdoctoral research was exclusively in the developmental area of PCP, his PhD research was on the tumorigenesis of testicular cancer in mice. The ability to integrate his interests in both basic science and translational research was what drew Chang to UW’s School of Medicine and Public Health, particularly the ability to work alongside physicians. “The physicians are doing their own research, and I can attend Grand Rounds to learn, observe, and find opportunities to collaborate with physicians on clinical or translational studies, all while conducting my own exploratory research in the basic science labs.”
Already, after just over two months with the department, he is impressed by what he hears at Dermatology Grand Rounds. “I can see the clinical patterns of thinking: it’s very scientific. I like it. It’s like when we [basic scientists] encounter a new phenomenon, how we try to examine and study it differentially, that’s how they approach their diagnoses. A very similar scientific thinking process is always going on over in the clinics. I’m glad I get to witness it firsthand.”
Chang and his wife—a neuroscientist now in Madison’s private sector—have two sons aged four and seven and are currently settled in downtown Middleton. “We like Madison so far. It’s very peaceful, and it’s nice to have a short commute.”
When asked whether he looks forward to his first Wisconsin winter, the Game of Thrones fan replied, “’Winter is coming.’ I’m ready. Of course, I spend most of my time in the lab, in the car commuting, or at home, so not much time out-of-doors! Still, my seven-year-old just had his first ice-skating lesson. He’s ready for winter too.”
If you would like more information on Dr. Chang's research program, email him here.