I am from the Central Coast of California and prior to coming to Case, I earned my Bachelors degree in Biochemistry, Biophysics, and Molecular Biology from Whitman College in Washington. I also earned a minor in Art History and Visual Culture Studies. I came here to pursue a PhD with a focus in Molecular Biology and Genetics. What most impressed me about the Atit lab, besides their background in Cell and Molecular Biology, was their bowling abilities. When I am not in the lab, you can find me at the Cleveland Museum of Art, in evening ceramics classes, or tutoring students through the Saturday Tutoring Program in Cleveland!
My Project
Fibrosis of the skin affects nearly 5% of people worldwide annually, yet there are no effective treatments for its reversal. Your skin’s dermis is composed of fibroblasts and extracellular matrix or ECM and a prominent layer of dermal fat, composed of adipocytes. Skin fibrosis is characterized by dermal thickening caused by fibroblast activation and increased ECM deposition as well as the loss of dermal fat. This fat loss is poorly understood, but greatly impacts the function and mechanical properties of your skin. What we want to know is how dermal fat is lost? Which signals or processes are involved?
The Wnt signaling pathway stands out from other pro-fibrotic signaling pathways because it’s involved in fibroblast/adipocyte cell fate decisions. When we activate Wnt signaling in mouse skin, we can cause fibrosis including dermal fat loss. Thus, we hypothesized that, Wnt signaling induces fibrotic fat loss via lipolysis (which is the process by which lipid is broken down into fatty acids and glycerol). Within a few days of Wnt activation in mouse skin we see evidence of lipid depletion including reduction in adipocyte size, visible lipid breakdown by electron microscopy, and an increase in the active form of key lipolytic enzymes. In vitro, Wnt activation also exerts cell autonomous lipolytic effects. Though Wnt signaling is lipolytic, targeting it is challenging because it is ubiquitously expressed in healthy tissue. Thus, we conducted a screen for possible mediators of the lipolytic effect of Wnt signaling and found dipeptidyl peptidase 4 (or DPP4) to be highly Wnt responsive. In human skin samples from individuals with severe scleroderma, DPP4 was present in greater quantities. And genetic ablation and enzymatic inhibition of DPP4 are fibroprotective and promote recovery from fibrosis including lipolytic fat loss.
Figure 1: Wnt activation causes a reduction of dermal white adipose tissue (DWAT)