Tissue maintenance requires stem and progenitor cells to respond to a wide range of signals. We want to understand, on a molecular level, what these signals are, how they inform cell fate, and how alterations drive pathogenesis. We use cell and molecular biology techniques, biochemistry, mouse genetics, and multi-omic technologies.
Fat Differentiation and Metabolic Health
We are deeply interested in studying fat differentiation and white adipose tissue expansion. Obesity has reached pandemic levels and its comorbidities, including diabetes and cancer, pose a significant challenge to public health. Adipose tissue expands by generating more fat cells and storing more lipids in existing fat cells. The balance between these two mechanisms has a profound effect on metabolic health: Larger fat cells are associated with insulin resistance and inflammation leading to diabetes, while white adipose tissue containing smaller fat cells, even if greater in number, is considered metabolically healthy. We want to identify the physiological and endocrine signals that regulate how white adipose tissue expands and how we can shift the balance to healthy white adipose tissue expansion.
Obese Fat Tissue and Breast Cancer
Obesity is a known risk factor for 13 types of cancer, including post-menopausal breast cancer. We are studying the localized, reciprocal interaction between breast cancer cells and cells in mammary fat. We want to identify the paracrine signals secreted by breast cancer cells to remodel its microenvironment and the paracrine signals secreted by the mammary fat to support breast cancer growth.
The Primary Cilium
The primary cilium is a central sensory organelle of the cell. Mesenchymal stem and progenitor cells, which give rise to fat, muscle, bone, and cartilage, are all ciliated. Research shows that loss of ciliation on mesenchymal progenitor cells impairs tissue maintenance, repair, and expansion. Human genetic mutations leading to dysfunctional cilia (ciliopathies) can manifest obesity, diabetes, hypotonia, and skeletal dysplasia. We want to understand how primary cilia on stem and progenitor cells regulate differentiation. This includes which physiological signals they sense, how these get communicated to the transcriptional machinery of the cell, and how dysfunctional ciliary signaling contributes to pathogenesis.
A complete and up-to-date publication list is available on Pubmed.
