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LMCB - MRC Laboratory for Molecular Cell Biology

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Chris Stefan's picture

LMCB Group Leader, MRC Investigator, UCL Associate Professor


c.stefan@ucl.ac.uk
+44 (0)20 7679 7208
LMCB Room 3.01


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Organelle cross talk and membrane dynamics

Research synopsis

Cell growth and integrity require membrane growth and integrity. We are using cross-disciplinary approaches to elucidate vital roles of inter-organelle contacts in membrane biogenesis and homeostasis at the molecular, ultra-structural, cellular, and tissue levels. Inter-organelle contacts serve as key sites for the coordinated regulation of membrane lipid metabolism and transport. Our studies have focused on contacts between the endoplasmic reticulum and the plasma membrane (ER-PM contacts), providing new understanding of membrane lipid and calcium dynamics during regulated exocytosis and polarised secretion. We are currently examining ER-PM contact architecture and function in hepatocytes, polarised epithelial cells of the liver. These investigations are suggesting new strategies to control biliary secretion that may prove beneficial in the treatment of liver disease. 

Furthermore, we are probing how alterations in inter-organelle contacts and membrane lipid homeostasis result in organelle damage. These studies are revealing novel protective pathways that sense and respond to membrane stress conditions to ensure membrane integrity and organelle homeostasis. Numerous diseases are caused by imbalances in membrane lipid homeostasis including cancer, diabetes, and neurodegenerative disorders. We expect our investigations will identify new targets and strategies for the treatment of diseases caused by disruptions in membrane lipid and organelle homeostasis. 

Stefan lab research image

Stefan lab research image

Selected publications

Chung G, et al (2020). ER-PM contacts regulate apical domain formation in hepatocytes. DOI: 10.1101/2020.04.23.057521
Nishimura T and CJ Stefan (2020). Specialized ER Membrane Domains for Lipid Metabolism and Transport. BBA Mol and Cell Biol of Lipids, 1865: 158492. DOI: 10.1016/j.bbalip.2019.07.001.
CJ Stefan (2020). Endoplasmic Reticulum-Plasma Membrane Contacts: Principals of Phosphoinositide and Calcium Signaling. Curr Opin Cell Biol. 63:125-34. DOI: 10.1016/j.ceb.2020.01.010
Omnus D, et al (2020). A Heat Sensitive Osh Protein Controls PI4P Polarity. BMC Biology. 18:28. DOI: 10.1186/s12915-020-0758-x
Collodo D, et al (2019). Tricalbins Control ER Curvature to Maintain PM Integrity. Developmental Cell. 18: 476-487.e7. DOI: 10.1016/j.molcel.2019.06.037
Nishimura T, et al (2019). Osh Proteins Control Nanoscale Lipid Organization Necessary for PI(4,5)P2 Synthesis. Molecular Cell, 75: 1043-1057. DOI: 10.1016/j.molcel.2019.06.037
 

 

 

Funders

Medical Research Council

Research themes

Membrane organisation
Organelle homeostasis
 

Technology

Electron microscopy
Super-resolution microscopy
Optical biology and spectroscopy
Quantitative lipidomics and proteomics
Bioinformatics and computational modelling
Translational research
 

People

Ioanna Sevastou (Research Fellow)
Gary Chung (Research Fellow)
Ffion Thomas (PhD Student)
Bailey Hewlett (PhD Student)

Collaborators

Jemima Burden (LMCB, UK)
Robin Ketteler (LMCB, UK)
Franck Pichaud (LMCB, UK)
Luigi Aloia (LMCB, UK)
Andela Saric (LMCB/IPLS, UK)
Paul Gissen (LMCB/ICH, UK)
Sara Mole (LMCB/ICH, UK)
Emily Eden (UCL IoO, UK)
Frances Brodsky (UCL BioSci, UK)
Tim Bartels (UCL/UKDRI, UK)
Sonia Gandhi (UCL/FCI, UK)
Christian Ungermann (Osnabruck Univ, Germany)
David Teis (Innsbruck Med Sch, Austria)
Ruben Busnadiego-Fernandez (Univ Med Gottingen, Germany)
Roberto Covino (Frankfurt Inst Adv Studies, Germany)
Nozomu Kono (Tokyo Univ, Japan)
Maya Schuldiner (Weizmann Inst, Israel)