Dieter Egli, PhD
The pancreas and the brain are two important organs involved regulating energy homeostasis. The key relevant cell types, beta cells in the pancreas and hypothalamic neurons in the brain, can be made from pluripotent stem cells. Our lab has made important contributions to establishing and improving differentiation protocols and to using the cells made for the study of metabolic disease. Human pluripotent stem cells are an extraordinarily powerful tool, allowing the study of human genomes in the disease relevant cell type, and the grafting into animals for testing of cell therapies and for functional interrogation of genotypes in a physiologically relevant context. The goal of these studies in the Egli lab is to develop novel therapeutic approaches for diabetes. We welcome inquiries about available projects.
- González, B. J., Zhao, H., Niu, J., Williams, D. J., Lee, J., Goulbourne, C. N., Xing, Y., Wang, Y., Oberholzer, J., Blumenkrantz, M. H., Chen, X., Leduc, C. A., Chung, W. K., Colecraft, H. M., Gromada, J., Shen, Y., Goland, R. S., Leibel, R. L. & Egli, D.* Reduced calcium levels and accumulation of abnormal insulin granules in stem cell models of HNF1A deficiency. Commun Biol, 5, 779. 2022. PMID:35918471
- This study established a model of diabetes caused by HNF1A deficiency, a transcription factor. We used a variety of tools, including Cas9 genetic engineering, single cell RNA seq, beta cell differentiation and grafting into mice. Using patient cells, we show the ability to correct the disease-causing mutation and associated phenotypes.
- We are currently using such models to identify new diabetes-disease candidates.
- Sui L, Xin Y, Du Q, Georgieva D, Diedenhofen G, Haataja L, Su Q, Zuccaro MV, Kim J, Fu J, Xing Y, He Y, Baum D, Goland RS, Wang Y, Oberholzer J, Barbetti F, Arvan P, Kleiner S, Egli D. Reduced replication fork speed promotes pancreatic endocrine differentiation and controls graft size. JCI Insight. 2021. PMID: 33529174
- This study shows an improved differentiation protocol from pluripotent stem cells and reveals new mechanisms regarding how limitations in cell proliferation are conferred during cell differentiation.
- Wang L, Egli D, Leibel RL. Efficient generation of hypothalamic neurons from human pluripotent stem cells. Curr Protoc Hum Genet. 2016 Jul 1;90:21.5.1-21.5.14. doi: 10.1002/cphg.3. PMID: 27367166, PMCID: PMC4963463
- This study is the first report of efficient differentiation of hypothalamic neurons from pluripotent stem cells. These cells are thought to regulate energy homeostasis. We are currently using these cells to understand obesity caused by Prader-Willi syndrome.