The Henne Lab is interested in how cells spatially organize their metabolism. This includes understanding how cells adapt to nutritional stress, and remodel their organelles to survive. Armed with this knowledge, we also hope to deeply understand molecular mechanisms that govern human physiology and disease. In particular, we are currently focused on understanding how different organelles contact one another at so-called Membrane Contact Sites (MCSs), and how these MCSs are used as biological platforms for the exchange of nutrients and biological information.
Recently, we characterized a new protein family (the PXA domain-containing family) that play critical roles in lipid metabolism and neurological disease (see Henne, JCB, 2015). In yeast, this protein is called Mdm1, and acts as a "molecular bridge" connecting the lysosome to the endoplasmic reticulum (ER). Using a combination of cell biology and genetics, we have discovered that Mdm1 coordinates the production of lipid droplets (LDs) at a sub-region of the ER adjacent to the lysosome (Hariri, EMBO Reports, 2017). These LDs serve as nutrient reserviors, and are eventually delivered to lysosomes during starvation to promote survival. Our findings suggest a previously unappreciated level of spatial orgnaization to lipid droplet biology and cellular energetics. Indeed, this function is highly conserved in metazoans, and we find together with our clinical collaborator Dr. Phil Stanier (UCL, London) that human Mdm1 homolog SNX14 also functions in ER-lipid droplet crosstalk, the loss of which contributes to pediatric cerebellar ataxia (Bryant & Liu, HMG, 2018).
Background: Dr. Henne received his B.S. in Cellular and Molecular Biology from Texas Tech University in Lubbock, Texas, and then accepted a MRC Scholarship from the UK to pursue graduate studies at the MRC Laboratory of Molecular Biology at Cambridge University. As a student in the lab of Harvey McMahon, Ph.D., he studied how membrane sculpting BAR and F-BAR domain-containing proteins promote clathrin-mediated endocytosis. He characterized the F-BAR proteins FCHo1/2, and showed that they play crucial roles initiating clathrin vesicle biogenesis. Mike was awarded the Max Perutz Prize for his graduate work.
Following graduate school, Dr. Henne began a postdoctoral position in the laboratory of Scott Emr, Ph.D., at Cornell University as a Sam and Nancy Fleming Research Fellow. There, he continued to study endolysosomal trafficking, and how endosomes can be reshaped by the ESCRT (Endosomal Sorting Complexes Required for Transport) pathway. His work has focused on reconstituting and imaging ESCRT protein assemblies, and dissecting how they shape multi-vesicular endosomes. More recent projects involve global screens in yeast to identify novel proteins involved in endolysosomal trafficking.
Dr. Henne uses cell biology, biochemistry, structural biology, and genetics to understand the molecular mechanisms of membrane reshaping and trafficking.
- inter-organelle communication
- lipid metabolism
- membrane sculpting
- SNX14 mutations affect endoplasmic reticulum associated neutral lipid metabolism in autosomal recessive spinocerebellar ataxia 20.
- Bryant D, Liu Y, Datta S, Hariri H, Seda M, Anderson G, Peskett E, Demetriou C, Sousa S, Jenkins D, Clayton P, Bitner-Glindzicz M, Moore GE, Henne WM, Stanier P Hum. Mol. Genet. 2018 Apr
- Lipid droplet biogenesis is spatially coordinated at ER-vacuole contacts under nutritional stress.
- Hariri H, Rogers S, Ugrankar R, Liu YL, Feathers JR, Henne WM EMBO Rep. 2017 Nov
- Mdm1/Snx13 is a novel ER-endolysosomal interorganelle tethering protein.
- Henne WM, Zhu L, Balogi Z, Stefan C, Pleiss JA, Emr SD J. Cell Biol. 2015 Aug 210 4 541-51
- Organelles in metabolism and stress responses.
- Ferguson SM, Henne WM Mol. Biol. Cell 2018 Mar 29 6 691
- Discovery and Roles of ER-Endolysosomal Contact Sites in Disease.
- Henne WM Adv. Exp. Med. Biol. 2017 997 135-147
- Inter-organelle ER-endolysosomal contact sites in metabolism and disease across evolution.
- Hariri H, Ugrankar R, Liu Y, Henne WM Commun Integr Biol 2016 May-Jun 9 3 e1156278
- ESCRT-III activation by parallel action of ESCRT-I/II and ESCRT-0/Bro1 during MVB biogenesis.
- Tang S, Buchkovich NJ, Henne WM, Banjade S, Kim YJ, Emr SD Elife 2016 Apr 5
- Structural basis for activation, assembly and membrane binding of ESCRT-III Snf7 filaments.
- Tang S, Henne WM, Borbat PP, Buchkovich NJ, Freed JH, Mao Y, Fromme JC, Emr SD Elife 2015 Dec 4
- Molecular mechanisms of inter-organelle ER-PM contact sites.
- Henne WM, Liou J, Emr SD Curr. Opin. Cell Biol. 2015 May 35 123-130
- Essential N-terminal insertion motif anchors the ESCRT-III filament during MVB vesicle formation.
- Buchkovich NJ, Henne WM, Tang S, Emr SD Dev. Cell 2013 Oct 27 2 201-14
Honors & Awards
- Searle Scholar
- Sam & Nancy Fleming Research Fellowship
- The Max Perutz Prize
awarded for Graduate work at MRC, Cambridge, UK (2009)