Dorit Hanein

Professor
Joint Appt: Biological Engineering (BioE)

Contact Phone

(805) 708-5700

Office Location

PSNB 4619
Labs: CHEM 1126, 1135A

Specialization

Developing and employing protocols for correlative light and electron cryogenic microscopy and in situ cellular tomography

Education

Professor Hanein received her doctoral degree at the Weizmann Institute, Israel. She completed training as a Fulbright postdoctoral fellow at Brandeis University with Professor David DeRosier, one of the founding fathers of three-dimensional image reconstruction techniques via electron microscopy. Professor Hanein holds a joint appointment with Institut Pasteur and the Scintillon Institute and is a PEW Innovation Fund Investigator. She holds a "Habilitation à Diriger des Recherches" (HDR, Accreditation to Direct Research) from Sorbonne University, France.  

 

Research

Professor Hanein's research is at the interfaces between structural biology, cell biology, systems biology, and engineering science.  She is leading efforts in combining light microscopy with cellular tomography to permit the placement of dynamics multimolecular protein complexes into their functional context in mammalian cells.  Through these efforts, she made seminal contributions to our knowledge of the structure, assembly and regulation of the actin cytoskeleton and its associated macromolecular assemblies, to the development of  techniques and protocols for correlative light and in-situ cellular tomography of protein structures in intact hydrated mammalian cells at cryogenic temperatures, and to the evolution of quantitative  cryogenic electron  microscopy.  This workflow is tied to high-resolution, live-cell fluorescence imaging techniques that are used to pinpoint the location of single proteins. With the advent of the new generation of electron cryo-microscopy equipment, including direct detection technology, phase plate devices, and automation capabilities, these efforts place Professor Hanein's research at the forefront of exciting new developments at the interface between electron microscopy, cell biology, and systems biology. The resulting quantitative integration of scales between macroscopic cellular behavior and high-resolution structural changes carries high impact in both medicinal and basic biological research.

Sanford Burnham Prebys, cryo-EM Facility (La Jolla CA): Professor Hanein built the facility at Sanford Burnham Prebys Medical Discovery Institute (SBP) in 1999 and supervised its operation until 2020. She commissioned three high-end cryo-TEMs. A Tecnai Spirit T12, a Tecnai F20 with PostGIF Biofilter, and a Titan Krios with Falcon C3E direct detector and phase plate. She also commissioned all dedicated hardware and sample preparation resources, including cryo-CLEM and high-pressure freezer instruments in preparation for acquiring an Aquilos cryo-FIB. In 2018, Professor Hanein was selected to be highlighted by the Office of Research Infrastructure of NIH.

Institut Pasteur Nanoimaging Core Facility (Paris, France): Professor Hanein designed and built the entire setup of the Nanoimaging facility at Institut Pasteur. This includes the design of the building which houses the facility, the purchase and commissioning of four high-end instruments (Titan Krios G3, two Glacios and one Aquilos cryo-FIB ). In parallel, she set up a complete workflow for interfacing the facility with cell biology such as novel cryo-CLEM setups including micro-patterning approaches and methodologies to push the technology beyond cell culture towards handling organoids and tissues.

 

 

Publications

Dow LP, Gaietta G, Kaufman Y, Swift MF, Lemos M, Lane K, Hopcroft M, Bezault A, Sauvanet C, Volkmann N, Pruitt BL, Hanein DMorphological control enables nanometer-scale dissection of cell-cell signaling complexesNat Commun. (2022) 



Gaietta G, Kai F, Swift MF, Weaver VM, Volkmann N, Hanein DNovel cryo-tomography workflow reveals nanometer-scale responses of epithelial cells to matrix stiffness and dimensionalityMol Biol Cell. (2022) 



Rodríguez de Francisco B, Bezault A, Xu XP, Hanein D, Volkmann N. MEPSi: A tool for simulating tomograms of membrane-embedded proteinsJ Struct Biol. (2022) 



Vilela F, Bezault A, Rodriguez de Francisco B, Sauvanet C, Xu XP, Swift MF, Yao Y, Marrasi FM, Hanein D, Volkmann N. Characterization of heterogeneity in nanodisc samples using Feret signaturesJ Struct Biol. (2022) 



Kai F, Ou G, Tourdot RW, Stashko C, Gaietta G, Swift MF, Volkmann N, Long AF, Han Y, Huang HH, Northey JJ, Leidal AM, Viasnoff V, Bryant DM, Guo W, Wiita AP, Guo M, Dumont S, Hanein D, Radhakrishnan R, Weaver VM. ECM dimensionality tunes actin tension to modulate endoplasmic reticulum function and spheroid phenotypes of mammary epithelial cellsEMBO J. (2022) 



Courtney KC, Wu L, Mandal T, Swift M, Zhang Z, Alaghemandi M, Wu Z, Bradberry MM, Deo C, Lavis LD, Volkmann N, Hanein D, Cui Q, Bao H, Chapman ER. The complexin C-terminal amphipathic helix stabilizes the fusion pore open state by sculpting membranesNat Struct Mol Biol. (2022) 



Gaietta G, Swift MF, Volkmann N, Hanein DRapid tool for cell nanoarchitecture integrity assessmentJ Struct Biol. (2021) 

(2021-2016; beyond PubMed)

Robert-Paganin J, Xu XP, Swift MF, Auguin D, Robblee JP, Lu H, Fagnant PM, Krementsova EB, Trybus KM, Houdusse A, Volkmann N, and Hanein D. The Actomyosin interface contains an evolutionary conserved core and an ancillary interface involved in specificity. Nat Commun, (2021).

Xu XP, Pokutta S, Torres M, Swift MF, Hanein D, Volkmann N, and Weis WI. Structural basis of αE-catenin-F-actin catch bond behavior. Elife, 9, (2020)

Poothong J, Pottekat A, Siriin M, Campos AR, Paton AW, Paton JC, Lagunas-Acosta J, Chen Z, Swift M, Volkmann N, Hanein D, Yong J, Kaufman RJ. Factor VIII exhibits chaperone-dependent and glucose-regulated reversible amyloid formation in the endoplasmic reticulumBlood, 135, 1899-1911. (2020

López CA, Swift MF, Xu XP, Hanein D, Volkmann N, Gnanakaran S . Biophysical Characterization of a Nanodisc with and without BAX: An Integrative Study Using Molecular Dynamics Simulations and Cryo-EMStructure27, 988-999.e4 (2019)

Engel L, Gaietta G, Dow LG, Swift MF, Pardon G, Volkmann N, Weis WI, Hanein D and Pruitt BL. Extracellular matrix micropatterning technology for whole cell cryogenic electron microscopy studiesJ Micromech Microeng29, 115018 (9pp) (2019).

Metlagel Z, Krey JF, Song J, Swift MF, Tivol WJ, Dumont RA, Thai J, Chang A, Seifikar H, Volkmann N, Hanein D, Barr-Gillespie PG, Auer M. Electron cryo-tomography of vestibular hair-cell stereociliaJ Struct Biol206, 149-155. (2019). PMC6684322 

Marston DJ, Anderson KL, Swift MF, Rougie M, Page C, Hahn KM, Volkmann N, Hanein DHigh Rac1 activity is functionally translated into cytosolic structures with unique nanoscale cytoskeletal architectureProc Natl Acad Sci U S A. 116, 1267-1272 (2019). 

Anderson KL, Swift MF, Hanein D, Volkmann N. Does self-organized criticality drive leading edge protrusion? Biophys Rev. 10, 1571-1575 (2018). 

Kumar A, Anderson KL, Swift MF, Hanein D, Volkmann N, Schwartz MA. Local Tension on Talin in Focal Adhesions Correlates with F-Actin Alignment at the Nanometer Scale. Biophys J.  115, 1569-1579 (2018). 

Hanein D, Volkmann N. Conformational Equilibrium of Human Platelet Integrin Investigated by Three-Dimensional Electron Cryo-Microscopy. Subcell Biochem87, 353-363 (2018).

Anderson KL, Page C, Swift MF, Hanein D, Volkmann N. Marker-free method for accurate alignment between correlated light, cryo-light, and electron cryo-microscopy data using sample support features. J Struct Biol 201, 46-51 (2018). PMC5748349
Bottini M, Mebarek S, Anderson KL, Strzelecka-Kiliszek A, Bozycki L, Simão AMS, Bolean M, Ciancaglini P, Pikula JB, Pikula S, Magne D, Volkmann N, Hanein D, Millán JL, Buchet R. Matrix vesicles from chondrocytes and osteoblasts: Their biogenesis, properties, functions and biomimetic models. Biochim Biophys Acta. 1862, 532-546 (2018). PMC5801150

Ariazi J, Benowitz A, De Biasi V, Den Boer ML, Cherqui S, Cui H, Douillet N, Eugenin EA, Favre D, Goodman S, Gousset K, Hanein D, Israel DI, Kimura S, Kirkpatrick RB, Kuhn N, Jeong C, Lou E, Mailliard R, Maio S, Okafo G, Osswald M, Pasquier J, Polak R, Pradel G, de Rooij B, Schaeffer P, Skeberdis VA, Smith IF, Tanveer A, Volkmann N, Wu Z, Zurzolo C. Tunneling Nanotubes and Gap Junctions-Their Role in Long-Range Intercellular Communication during Development, Health, and Disease Conditions. Front Mol Neurosci10, 333. (2017). PMC5651011

Chen Z, Sun L, Zhang Z, Fokine A, Padilla-Sanchez V, Hanein D, Jiang W, Rossmann MG, Rao VB. Cryo-EM structure of the bacteriophage T4 isometric head at 3.3-Å resolution and its relevance to the assembly of icosahedral viruses. Proc Natl Acad Sci U S A. 114, E8184-E8193 (2017)

Anderson KL, Page C, Swift MF, Suraneni P, Janssen ME, Pollard TD, Li R, Volkmann N, Hanein DNano-scale actin-network characterization of fibroblast cells lacking functional Arp2/3 complex. J Struct Biol197, 312-321 (2016). 

Fabre L, Santelli E, Mountassif D, Donoghue A, Biswas A, Blunck R, HaneiD, Volkmann N, Liddington R, Rouiller IStructure of anthrax lethal toxin prepore complex suggests a pathway for efficient cell entry. J Gen Physiol.148, 313-24 (2016). 

Xu XP, Kim E, Swift M, Smith JW, Volkmann N, Hanein D. Three-Dimensional Structures of Full-Length, Membrane-Embedded Human α(IIb)β(3) Integrin Complexes. Biophys J,110, 798-809 (2016).

Bibliography