Primary Research Focus
Through the use of novel physiologically relevant human induced pluripotent stem cell models and transgenic mouse models, Dr. Kevin Francis’ laboratory is focused on defining the biological mechanisms underlying disorders of neurodevelopment using human induced pluripotent stem cells (iPSCs) derived from rare patient populations.
As a doctoral student and postdoctoral fellow, Dr. Francis received extensive training in patch clamp electrophysiology, neurodevelopment, cellular stress, genetics, lipid biology and pluripotent stem cell biology. Using this expertise, our laboratory at Sanford Research has developed induced pluripotent stem cell (iPSC) models of rare patient populations to identify cell specific effects and signaling mediated events resulting from genetic mutations within critical genes regulating lipid metabolism, neuronal cell health and leading to patient pathology (for example, Nat Med, 2016, 22(4):388-96).
Dr. Francis has formed strong collaborations with experts in the fields of neurodevelopment, cell signaling, -omics methodology, and the development of therapeutics to define disease pathogenesis and identify novel therapies for rare 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.
Searching for an Effective Treatment for CLN6-Batten Disease
This study will explore five different therapeutic approaches for the delay or prevention of CLN6-Batten disease. Our lab’s role in this multi-disciplinary team will be to screen various small molecules, gene therapy, stem cell and gene editing approaches in both mouse and iPS cell models of CLN6-Batten disease to expedite a clinical trial for patients with this disease.