Obesity and Type 2 diabetes mellitus (T2D) are highly prevalent metabolic diseases that afflict a large proportion of the aging population in the United States. Nearly 40 percent of adults are obese, and about 10 percent of individuals over 65 have T2D. These diseases, together with cardiovascular disease, should be viewed as aspects of a metabolic syndrome that is a result of the interaction of many genes, rather than a collection of separate entities. To illustrate the complexity of the issue, there are approximately 500 to 1,000 genes in mice that may lead to obesity when mutated. Our program aims to identify new obesity and type 2 diabetes mutations and their genetic modifiers and to determine how the underlying mutations cause the disease phenotype.
One focus of our investigations are ciliopathies (diseases caused by impaired function of primary cilia), which combine aspects of metabolic syndrome with sensory loss. Our laboratory identified a human gene, ALMS1, that is mutated in patients with Alström syndrome, a rare inherited condition characterized by childhood obesity, retinal and cochlear (inner ear) degeneration, type 2 diabetes, proliferative and dilated cardiomyopathy, hepatosteatitis, and kidney disease.