A New Signal to Halting T1D
Type 1 diabetes (T1D) is a disease of the insulin-producing, pancreatic beta cells. As the beta cells progress from normal, to inflamed, to diabetic, there are many structural changes that occur which lead to impaired insulin secretion. We have determined these transport structures (primary cilium) impact beta-cell function. Our research is designed to characterize how changes in the wave-like motion of primary cilia may contribute to, or cause, the onset of T1D.
Primary cilia are hair-like tiny organs (organelles) that protrude from the surface of most cells. They act as antennae to receive information from the environment or neighboring cells. Each beta cell has a single primary cilium composed of a tiny tube-like structure that transports proteins and provides signals to other molecules. Mutations in cilia genes cause human disease, including childhood-onset obesity and diabetes. Diabetic islets have abnormal cilia gene expression. We do not know whether primary cilia loss causes diabetes, or results from the disease.
We hypothesize primary cilia regulate communications between the beta cells in the pancreatic islet cells. As a first step to address whether cilia cause the destruction of beta cells, we will determine when cilia loss occurs during the progression of T1D and determine if cilia loss accompanies the functional loss of beta-cell insulin secretion.
Our research group is a multidisciplinary team of scientists with expertise in islet biology, immunology, and endocrinology. We will examine primary cilia in normal and diabetic islets from T1D animal models. The results are expected to reveal new roles of primary cilia in beta-cell function and endocrine-immune cell crosstalk which may cause the onset of T1D in humans.
As a physician, I see patients with T1D in the clinic and witness the progression of the disease. While the scientific goal of my research is to understand how cilia maintain beta-cell function, my goal is to improve the quality of life for individuals with T1D. I envision our work may lead to the development of cilia-based therapy which will promote beta-cell survival and reduce insulin requirements for those living with T1D, and possibly delay or avoid the onset of the disease.