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.
One current focus is understanding how cells store lipids in lipid droplets (LDs), and use LDs to maintain homeoatasis. LDs do not work in isolation, and much of the lab is dedicated to chatacterizing how LDs form contacts with other cellular organelles. We are also interested in how cells spatially and functionally organize their LD stores to balance long-term lipid storage with efficient mobilization during energetic crises.
Recently, we characterized a new protein family (the PXA domain-containing family) that plays critical roles in LD biogenesis and LD spatial organization within the cell. Budding yeast encode a PXA domain-containing protein called Mdm1 that we found acts as a "molecular tether" connecting LDs to the yeast lysosome/vacuole (Henne, JCB, 2015; Hariri, EMBO reports, 2017; Hariri, JCB, 2019). Mdm1 is highly conserved in metazoans, and we also found that its human homolog SNX14 regulates LD growth and homeostasis, which is perturbed in the genetic neurological disease SCAR20 (Bryant, HMG, 2018; Datta, JCB, 2019). The Drosophila fruit fly also encodes a Mdm1 homolog called Snazarus (Snz), which we discovered localizes to ER-PM contact sites in Drosophila adipocytes and regulates a sub-population of peripheral LDs (Ugrankar, Dev Cell, 2019). Thus, PXA domain-containing proteins appear to function as "metabolic tethers" that regulate LD biogenesis as well as LD attachment to other cellular compartments, thus controlling LD spatial organization and the interactions LDs have with other organelles.
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 LD dynamics, and the spatial organization of cellular lipid metabolism.
- inter-organelle communication
- lipid metabolism
- membrane sculpting
- The ESCRT pathway.
- Henne WM, Buchkovich NJ, Emr SD Dev. Cell 2011 Jul 21 1 77-91
- FCHo proteins are nucleators of clathrin-mediated endocytosis.
- Henne WM, Boucrot E, Meinecke M, Evergren E, Vallis Y, Mittal R, McMahon HT Science 2010 Jun 328 5983 1281-4
- Structure and analysis of FCHo2 F-BAR domain: a dimerizing and membrane recruitment module that effects membrane curvature.
- Henne WM, Kent HM, Ford MG, Hegde BG, Daumke O, Butler PJ, Mittal R, Langen R, Evans PR, McMahon HT Structure 2007 Jul 15 7 839-52
- AMPA-induced excitotoxicity increases nuclear levels of CAD, endonuclease G, and acinus and induces chromatin condensation in rat hippocampal pyramidal neurons.
- Henne WM, Oomman S, Attridge J, Finckbone V, Coates P, Bliss R, Strahlendorf H, Strahlendorf J Cell. Mol. Neurobiol. 2006 May 26 3 321-39
Honors & Awards
- Searle Scholar
- Sam & Nancy Fleming Research Fellowship
- The Max Perutz Prize
awarded for Graduate work at MRC, Cambridge, UK (2009)