Primary Research Focus
The Francis laboratory is currently using a molecular, biochemical, cellular, and in vivo animal models to answer three major questions surrounding the impact of lipid metabolism on human health:
- How sterol biochemistry regulate protein localization and signaling pathways of interest?
- How does sterol metabolism regulate cell function?
- What are the developmental impacts of sterol metabolism?
Dr. Francis has formed strong collaborations with experts in the fields of neurodevelopment, cell signaling, -omics methodology, and the identification of therapeutic targets to delineate the impact of lipid metabolism on human health.
These studies will answer questions regarding the importance of specific lipid species to basic cell biology while providing insight into the contribution of lipid metabolism to a variety of diseases.
About the Francis Lab
Lab Projects and News
Regulation of Cell Fate & Function By Sterol Homeostasis
The goal of this study is to define the effects of altered sterol biochemistry on neural fate choice and functional activity in iPSC derivatives and to determine the effects of Wnt signaling on neural function in cholesterol synthesis disorders.
Regulation of Tissue Development by Lipid Homeostasis
As evidenced by clinical phenotypes, disrupted lipid homeostasis has dramatic effects on human development. Using transgenic mouse models and human iPSC differentiation models, we are defining how lipid homeostasis regulates cell fate and function.
Protein-Protein Interactions & Cellular Cholesterol
Cholesterol constitutes a critical component of cellular membranes and plays a vital role in the organization of proteins within the membrane. Using CRISPR/Cas9 genome editing, molecular modeling and advanced protein-lipid interaction analyses, we are determining the selectivity and dependence of protein localization and binding patterns on cholesterol content.
Defining the Metabolic Requirements of Neuron-Glia Interactions
Glial support of neurons is critical for proper organization and functional activity of the nervous system. Using both primary and differentiated cultures of mouse and human astrocytes, microglia, and neurons, we are determining how cholesterol transport and cholesterol levels across cell types mediates developmental processes such as synaptogenesis and functional activity within defined neuronal populations.
Identification of Genetic & Pharmacological Regulators of Neuronal Health & Function
Identifying genes and small molecules which can stabilize neuronal health and function is critical for the treatment of rare diseases affecting the nervous system. Using high-content screening in multiwell plates using CRISPR libraries and commercially available small molecule libraries, we are attempting to identify novel genetic modifiers or small molecules to rescue or slow neuronal disease progression.