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, 2018; 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; Datta, PNAS, 2020). 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.
Our work also dissects new and non-canonical roles of yeast nucleus-vacuole junctions (NVJs) as "metabolic platforms" that spatial organize metabolism. We find that NVJs act as sites of LD biogeneis (Hariri, EMBO reports, 2018; Hariri, JCB, 2019), as well as sites for the compartmentalization of mevalonate synthesis by HMG-CoA Reductases (Rogers, in revision). We also discovered that the expansion of NVJ contacts can be used to predict cell fates in response to nutrient stress. Yeast which expand their NVJs when faced with glucose starvation become quiescent, whereas yeast which fail to expand their NVJs become senescent (Wood, Cell Reports, 2020). These findings reveal NVJ inter-organelle contacts as important metabolic platforms for the organization of metabolism and cellular decision-making.
See more at our lab website: https://www.utsouthwestern.edu/labs/henne/
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
- Snx14 proximity labeling reveals a role in saturated fatty acid metabolism and ER homeostasis defective in SCAR20 disease.
- Datta S, Bowerman J, Hariri H, Ugrankar R, Eckert KM, Corley C, Vale G, McDonald JG, Henne WM, Proc Natl Acad Sci U S A 2020 Dec
- Nutrient Signaling, Stress Response, and Inter-organelle Communication Are Non-canonical Determinants of Cell Fate.
- Wood NE, Kositangool P, Hariri H, Marchand AJ, Henne WM, Cell Rep 2020 Dec 33 9 108446
- Drosophila Snazarus Regulates a Lipid Droplet Population at Plasma Membrane-Droplet Contacts in Adipocytes.
- Ugrankar R, Bowerman J, Hariri H, Chandra M, Chen K, Bossanyi MF, Datta S, Rogers S, Eckert KM, Vale G, Victoria A, Fresquez J, McDonald JG, Jean S, Collins BM, Henne WM, Dev. Cell 2019 Aug
- Mdm1 maintains endoplasmic reticulum homeostasis by spatially regulating lipid droplet biogenesis.
- Hariri H, Speer N, Bowerman J, Rogers S, Fu G, Reetz E, Datta S, Feathers JR, Ugrankar R, Nicastro D, Henne WM J. Cell Biol. 2019 Feb
- Cerebellar ataxia disease-associated Snx14 promotes lipid droplet growth at ER-droplet contacts.
- Datta S, Liu Y, Hariri H, Bowerman J, Henne WM J. Cell Biol. 2019 Feb
- 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
- Spastin joins LDs and peroxisomes in the interorganelle contact ballet.
- Henne WM, J. Cell Biol. 2019 Aug 218 8 2439-2441
- Classification of the human phox homology (PX) domains based on their phosphoinositide binding specificities.
- Chandra M, Chin YK, Mas C, Feathers JR, Paul B, Datta S, Chen KE, Jia X, Yang Z, Norwood SJ, Mohanty B, Bugarcic A, Teasdale RD, Henne WM, Mobli M, Collins BM, Nat Commun 2019 Apr 10 1 1528
- The assembly of lipid droplets and their roles in challenged cells.
- Henne WM, Reese ML, Goodman JM EMBO J. 2018 May
Honors & Awards
- NIGMS R35/MIRA Award
- Searle Scholar
- Sam & Nancy Fleming Research Fellowship
- The Max Perutz Prize
awarded for Graduate work at MRC, Cambridge, UK (2009)