Header Logo

David Lambright PhD

TitleProfessor
InstitutionUMass Chan Medical School
DepartmentProgram in Molecular Medicine
AddressUMass Chan Medical School
373 Plantation Street
Worcester MA 01605
Phone508-856-6876
vCardDownload vCard
    Other Positions
    InstitutionT.H. Chan School of Medicine
    DepartmentBiochemistry and Molecular Biotechnology

    InstitutionT.H. Chan School of Medicine
    DepartmentProgram in Molecular Medicine

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentBiochemistry and Molecular Biotechnology

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentInterdisciplinary Graduate Program

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentMD/PhD Program


    Collapse Biography 
    Collapse education and training
    University of Massachusetts Lowell, Lowell, MA, United StatesBSChemistry
    Stanford University, Palo Alto, CA, United StatesPHDChemistry

    Collapse Overview 
    Collapse overview

    Academic Background

    David Lambright received his BS from the University of Lowell in 1984 and his PhD in chemistry from Stanford University in 1992. He was a Damon Runyon-Walter Winchell postdoctoral fellow from 1992-1995 in the Department of Molecular Biophysics and Biochemistry at Yale University. He joined the University of Massachusetts Medical School as a faculty member in the Program in Molecular Medicine in 1996. He is a recipient of a Scholar Award from the Leukemia & Lymphoma Society of America.

    Structural and molecular mechanisms of cell signaling and membrane trafficking

    Photo: David G. LambrightResearch in this laboratory is concerned with structural and molecular mechanisms of cell signaling and membrane trafficking. Our approach combines a broad range of experimental methods from diverse disciplines including biochemistry, biophysics, X-ray crystallography, and bioinformatics as well as molecular, cell, and systems biology. Areas of interest include the regulation of membrane trafficking by Rab GTPases, phosphoinositide signaling, and the regulation of cell proliferation. Defects in these fundamental regulatory mechanisms play critical roles in complex disease states such as cancer and diabetes as well as genetically linked disorders.

    Rab GTPases comprise a large family of molecular switches that function in membrane trafficking and organelle biogenesis by cycling between active (GTP bound) and inactive (GDP bound) states. Activation is regulated by guanine nucleotide exchange factors (GEFs), which promote exchange of GTP for GDP in response to extracellular or intracellular signals. Inactivation is regulated by GTPase-activating proteins (GAPs), which stimulate the hydrolysis of GTP. In the active state, Rab GTPases interact with a diverse effector proteins to regulate vesicle budding, cargo sorting, and motor-dependent transport as well as the tethering, docking, and fusion of vesicles with target membranes. We seek to understand the structural basis underlying the nucleotide dependent interactions of Rab GTPases with effectors and regulatory factors and determine the mechanisms by which these interactions regulate membrane trafficking. Towards this end, we have developed a novel structural proteomic strategy to profile interactions with the Rab family and determine the underlying structural bases. High throughput microplate assays are used to quantitatively profile interactions with GEFs, effectors, and GAPs. In addition to identifying novel interaction partners, the family-wide analyses facilitate crystallographic studies of Rab-GEF, Rab-effector, and Rab-GAP complexes and are also being used to characterize interactions of Rab GTPases with viral and bacterial virulence factors.

    Lipid second messengers known as phosphoinositides regulate a broad spectrum of cellular functions including survival, membrane trafficking, cytoskeletal dynamics, and migration. Targets of phosphoinositides include pleckstrin homology (PH) and FYVE domains in modular signaling and trafficking proteins. Our goal is to understand how phosphoinositide binding domains recognize phosphoinositides and elucidate the mechanisms by which phosphoinositides regulate the assembly and activation of multiprotein signaling and trafficking complexes on intracellular membranes.

    A third area of interest concerns an evolutionarily conserved protein, Zpr1, which is required for viability, normal cell cycle progression, and cell growth. Zpr1 is retained in the cytoplasm of quiescent cells through interactions with inactive growth factor receptors and, following stimulation, assembles into cytoplasmic complexes with elongation factor 1-alpha (eEF1A) and nuclear complexes with the survival motor neurons (SMN) protein. An exon deletion in the SMN1 gene that disrupts the interaction with Zpr1 is responsible for the most severe form of spinal muscular atrophy known as Werdnig-Hoffmann syndrome. We have solved the crystal structure of Zpr1 and are working on the structural bases underlying the interactions with growth factor receptors, EF1A, and the SMN complex.

    Figures

    GTPases and phosphoinositides

    Regulation of intracellular membrane trafficking

    The trafficking of lipids, integral membrane proteins and soluble cargo between membrane delimited organelles is regulated by GTPases of the Rab, Arf, Arl and Sar families as well as mono- and polyphosphorylated derivatives of phosphatidyl inositol (PIPs).

     

    Rabs Image  

     

     

    The Rab GTPase Cycle

    As evolutionarily conserved molecular switches, Rab GTPases cycle between inactive (GDP-bound) and active (GTP-bound) states.  In the active state, Rab GTPases interact with structurally and functionally diverse effectors including cargo sorting complexes on donor membranes, motor proteins involved in vesicular transport and tethering complexes that regulate vesicle fusion with acceptor membranes.  Rab GTPases are activated by guanine nucleotide exchange factors (GEFs) and deactivated by GTPase activating proteins (GAPs), which accelerate the slow intrinsic rates of nucleotide exchange and GTP hydrolysis.  Dual prenylation of C-terminal cysteine motifs allows Rab GTPases to partition with membranes.  Transfer between membranes is facilitated by GDP dissociation inhibitor (GDI) and GDI displacement factors (GDFs).  Targeting of Rab GTPases to specific organelles also depends on GEFs, effectors and GAPs.

     

    Rab Cycle Image  

     

    Membrane targeting mechanisms

    Lipid binding domains including those that recognize phosphoinositides utilize ligand-specific and/or non-specific mechanisms for partitioning with lipid bilayers.

     

    LBD Image  

    For additional information, see:

    http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=14679290&query_hl=1&itool=pubmed_docsum

    http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16807090&query_hl=1&itool=pubmed_docsum

     

    Rab family-wide interaction analyses

    Quantitative profiling of interactions with the Rab GTPase family

    Quantitative high throughput microplate assays are used to profile interactions of GEFs, GAPs and effectors with Rab GTPases.  Applications include determination of family-wide specificity profiles, identification of novel interaction partners and mutational analyses of specificity determinants.

     

    HTP Image  

    Activation of Rab GTPases by Vps9 domain GEFs

    Rab specificity profile for the Rabex-5 catalytic core

    Rab5 is an essential regulator of endosomal trafficking and endosome biogenesis.  Rabex-5 is a Rab5 GEF with a Vps9 domain homologous to the yeast Vps9 protein implicated in vacuolar protein sorting.  A profile of the Rab specificity of the catalytic core of Rabex-5 revealed equivalently high exchange activity for Rabs 5 and 21, weak activity for Rab22 and no detectable activity for 29 other Rab GTPases.  Rabs 5, 21 and 22 comprise a small phylogenetic subfamily of endosomal Rab GTPases.

     

    Rabex Profile Image  

    For additional information, see:

    http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15339665&query_hl=1&itool=pubmed_docsum

     

    Rabex-5 structure and mutational analyses of recognition determinants

    The crystal structure of the Rabex-5 catalytic core revealed a tandem architecture consisting of a Vps9 domain stabilized by a helical bundle.  Conserved exchange determinants map to a common surface of the Vps9 domain, which recognizes invariant aromatic residues in the switch regions of Rab GTPases and selects for the Rab5 subfamily by requiring a small nonacidic residue preceding a critical phenylalanine in the switch I region.

    Rabex Structure Image  

     

    For additional information, see:

    http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15339665&query_hl=1&itool=pubmed_docsum

     

    Structural basis for Rab GTPase activation by Vps9 domain GEFs

    The crystal structure of the RABEX-5 helical bundle-Vps9 tandem in complex with nucleotide free RAB21 (a key intermediate in the exchange reaction pathway) revealed how the VPS9 domain recognizes Rab5 subfamily GTPases  (Rabs 5, 21 and 22), accelerates GDP release by destabilizing the magnesium binding site and subsequently stabilizes the high energy nucleotide free intermediate via an aspartic acid finger that simultaneously engages the P-loop lysine and switch II backbone.

     

    Rabex Rab21 Image  

     

    For additional information, see:

    http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17450153&query_hl=1&itool=pubmed_docsum

     

    Rab-effector recognition

    Structural genomic survey of the Rab family

    To understand how structural similarity and diversity in the active conformation of Rab GTPases contributes to effector recognition, we conducted a structural genomic survey of the mammalian Rab GTPase family.  The results revealed non-phylogenetic similarity and variability in the active conformations of Rab GTPases.

     

    SG Survey Image  

    For additional information, see:

    http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16034420&query_hl=1&itool=pubmed_docsum

     

    Rab specificity profile of the multivalent effector Rabensoyn-5

    Surface plasmon resonance (SPR) was used to profile the interaction of the central and C-terminal Rab binding domains (RBDs) of the multivalent endosomal effector Rabenosyn-5 with the active form of 33 Rab GTPases.  Despite similar tertiary structures, the central and C-terminal RBDs recognize distinct subsets of Rab GTPases (Rabs 4 and 14 vs. Rabs 5, 22 and 24).

     

    Rbsn Profile Image  

    For additional information, see:

    http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16034420&query_hl=1&itool=pubmed_docsum

     

    Structural basis for Rab GTPase recognition by Rabenosyn-5

    A truncation analysis of the multivalent Rab GTPase and PI3P effector Rabenosyn-5 mapped the central and C-terminal Rab binding domains (RBDs) to homologous regions.  Structures of the RBDs in complex with Rab4 and Rab22 revealed a common binding modality in which a structurally similar helical hairpin core in the RBDs engages a structurally similar active conformation of the switch and interswitch regions in the respective Rab GTPases.  Mutational analyses further revealed that the differential specificity of the RBDs is due in part to a non-conserved N-terminal extension (NTE) in RDB1 and in part to compositional differences within the conserved helical hairpin cores.

     

    r4r22rbsn Image  

     

    For additional information, see:

    http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16034420&query_hl=1&itool=pubmed_docsum

     

    Conceptual model for Rab-effector recognition

    The model shown here is based on known structures of Rab GTPases alone and in complex with effectors and takes into account the results of mutational analyses.  Structural variability influences the spatial disposition and exposure of the conserved residues, sub-dividing the Rab family into non-phylogenetic subsets that satisfy the structural requirements for effector recognition.  Compositional diversity within the switch/interswitch regions (and in certain cases CDRs) further refines the specificity through enhanced affinity for Rab GTPases with compatible compositions (positive selection) and/or reduced affinity for Rab GTPases with incompatible compositions (negative selection).  The family-wide nature of the recognition process is underscored by the conservation of positive determinants in interacting subsets and negative determinants in non-interacting Rab GTPases.  This model is also applicable to interactions with regulatory/accessory factors.

     

    RR Model Image

    Structural basis for recruitment of FIP3 to recycling endosomes

    Rab11 regulates recycling of internalized plasma membrane receptors and is essential for completion of cytokinesis.  A family of Rab11 interacting proteins (FIPs) that conserve a C-terminal Rab-binding domain (RBD) selectively recognize the active form of Rab11.  Normal completion of cytokinesis requires a complex between Rab11 and FIP3.  Shown here is the structure of a heterotetrameric complex between constitutively active (GTP-bound) Rab11 and a FIP3 construct that includes the RBD.  Two Rab11 molecules bind to dyad symmetric sites at the C terminus of FIP3, which forms a non-canonical coiled-coiled dimer with a flared C terminus and hook region.  The RBD overlaps with the coiled coil and extends through the C-terminal hook.  Although FIP3 engages the switch and interswitch regions of Rab11, the mode of interaction differs from that of other Rab-effector complexes. In particular, the switch II region undergoes a large structural rearrangement that facilitates the interaction with FIP3.

     

    r11fip3 Image

     

    For additional information, see:

    http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17007872&query_hl=1&itool=pubmed_docsum

     

    De-activation of Rab GTPases by TBC domain GAPs

    Rab specificity profile of the Gyp1p TBC domain GAP

    TBC (Tre-2, Bub2 and Cdc16) domains are broadly conserved in eukaryotes and function as GAPs for Rab GTPases as well as GTPases that control cytokinesis.  A profile of the specificity of the Gyp1p TBC domain revealed high GAP activity for Rab33 in addition to Rab1 (the mammalian homologue of the in vivo Gyp1p substrate Ypt1p).  The identification of Rab33 as a Gyp1p substrate facilitated determination of the structure of a TBC domain-Rab GTPase complex.

     

    gyp2 Profile Image  

     

    For additional information, see:

    http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16855591&query_hl=1&itool=pubmed_docsum

     

    TBC domains accelerate GTP hydrolysis by a dual finger mechanism     

    In the crystal structure of the Gyp1p TBC-domain-Rab33-aluminium fluoride complex, which approximates the transition-state intermediate for GTP hydrolysis, the TBC domain supplies two catalytic residues in trans, an arginine finger analogous to Ras/Rho family GAPs and a glutamine finger that substitutes for the glutamine in the DxxGQ motif of the GTPase.  The glutamine from the Rab GTPase does not stabilize the transition state as expected but instead interacts with the TBC domain.  Strong conservation of both catalytic fingers suggests that most TBC-domain GAPs will accelerate GTP hydrolysis by a similar dual-finger mechanism.  These conclusions are supported by mutational and complementation analyses.

     

    gyp1r33 Image  

               

    For additional information, see:

    http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16855591&query_hl=1&itool=pubmed_docsum

     

    Phosphoinositide recognition and membrane targeting

    Structural basis for 3-phosphoinositide recognition by PH domains

    The pleckstrin homology (PH) domain of Grp1, a PI 3-kinase-activated exchange factor for Arf GTPases, selectively binds PIP3 with high affinity.  The structure of the Grp1 PH domain bound to the head group of PIP3 (IP4) revealed a novel mode of phosphoinositide recognition involving a 20-residue beta hairpin insertion within the beta6/beta7 loop.   The observed mode of recognition involving residues from a conserved basic motif as well as the variable loops surrounding the phosphoinositide binding site explains the high affinity and specificity of the Grp1 PH domain and the promiscuous 3-phosphoinositide binding typical of several PH domains that lack the hairpin insertion.

     

    grp1 Image  

     

    For additional information, see:

    http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=10983985&query_hl=1&itool=pubmed_DocSum

     

    Structural determinants of phosphoinositide selectivity in splice variants of Grp1 family PH domains

    The PH domains of the homologous proteins Grp1, ARNO and Cytohesin-1 bind PIP3 with unusually high selectivity.  Remarkably, splice variants that differ only by the insertion of a single glycine residue in the beta1/beta2 loop exhibit dual specificity for PIP2 and PIP3.  Crystal structures for the dual specificity 'triglycine' variant of the ARNO PH domain in complex with the head groups of PIP2 (IP3) and PIP3 (IP4) revealed the structural basis underlying this dramatic selectivity switch.  Loss of contacts with the beta1/beta2 loop with no significant change in head group orientation accounts for the significant decrease in PIP3 affinity observed for the dual specificity variants.  Conversely, a small increase rather than decrease in affinity for PIP2 is explained by a novel 'rotated' binding mode, in which the glycine insertion alleviates unfavorable interactions with the beta1/beta2 loop. These and other observations supported by systematic mutational analyses suggested a general model for phosphoinositide recognition by PH domains that conserve a 'signature' basic motif.

     

    arno Image  

     

    For additional information, see:

    http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15359279&query_hl=1&itool=pubmed_docsum

     

    Structural basis for PI3P recognition and multivalent endosome targeting by FYVE domains

    The localization of the early endosomal marker and tethering factor EEA1 is mediated by a C-terminal region that includes a calmodulin binding motif, a Rab5 binding site and a FYVE domain that selectively binds PI3P.  The crystal structure of the C-terminal region bound to the head group of PI3P (IP2) revealed an organized quaternary assembly consisting of a parallel coiled coil and a dyad-symmetric FYVE domain homodimer. Structural and biochemical observations support a multivalent mechanism for endosomal targeting in which domain organization, dimerization and quaternary structure amplify the weak affinity and modest specificity of head group interactions with conserved residues.

     

    eea1 Image 

     

    For additional information, see:

    http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11741531&query_hl=1&itool=pubmed_docsum

     


    Collapse Rotation Projects

    Lab Rotations

    Our lab takes an interdisciplinary approach to the study of fundamental problems in cell biology, signal transduction and membrane trafficking. Rotation projects are available in any of the areas of interest to the lab. Projects are tailored to the individual interests of the students and often involve a combination of molecular, biochemical, biophysical, structural and/or cell based analyses to investigate signaling and trafficking mechanisms.


    Collapse Post Docs

    A postdoctoral position is available to study in this laboratory. Contact Dr. Lambright for additional details.


    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    Newest   |   Oldest   |   Most Cited   |   Most Discussed   |   Timeline   |   Field Summary   |   Plain Text
    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Perica T, Mathy CJP, Xu J, Jang G?, Zhang Y, Kaake R, Ollikainen N, Braberg H, Swaney DL, Lambright DG, Kelly MJS, Krogan NJ, Kortemme T. Systems-level effects of allosteric perturbations to a model molecular switch. Nature. 2021 11; 599(7883):152-157. PMID: 34646016.
      Citations: 1     Fields:    Translation:AnimalsCells
    2. Duan J, Lambright DG. Propelling COPII vesicle biogenesis at the endoplasmic reticulum. Structure. 2021 08 05; 29(8):779-781. PMID: 34358462.
      Citations:    Fields:    Translation:HumansCells
    3. Mishra AK, Lambright DG. High-Throughput Assay for Profiling the Substrate Specificity of Rab GTPase-Activating Proteins. Methods Mol Biol. 2021; 2293:27-43. PMID: 34453708.
      Citations:    Fields:    Translation:Humans
    4. Li J, Lambright DG, Hsu VW. Coordination of Grp1 recruitment mechanisms by its phosphorylation. Mol Biol Cell. 2020 12 01; 31(25):2816-2825. PMID: 33026967.
      Citations: 1     Fields:    Translation:AnimalsCells
    5. Struck MW, Pazour GJ, Lambright DG. X Caps the Phosphate for Phospho-Rab GTPase Recognition in Ciliogenesis and Parkinson's Disease. Structure. 2020 04 07; 28(4):385-387. PMID: 32268075.
      Citations:    Fields:    Translation:HumansCells
    6. Das S, Malaby AW, Nawrotek A, Zhang W, Zeghouf M, Maslen S, Skehel M, Chakravarthy S, Irving TC, Bilsel O, Cherfils J, Lambright DG. Structural Organization and Dynamics of Homodimeric Cytohesin Family Arf GTPase Exchange Factors in Solution and on Membranes. Structure. 2019 12 03; 27(12):1782-1797.e7. PMID: 31601460.
      Citations: 3     Fields:    Translation:AnimalsCells
    7. Sztul E, Chen PW, Casanova JE, Cherfils J, Dacks JB, Lambright DG, Lee FS, Randazzo PA, Santy LC, Schürmann A, Wilhelmi I, Yohe ME, Kahn RA. ARF GTPases and their GEFs and GAPs: concepts and challenges. Mol Biol Cell. 2019 05 15; 30(11):1249-1271. PMID: 31084567.
      Citations: 64     Fields:    Translation:HumansAnimalsCells
    8. Duan J, Lambright DG. TRAPPing a Rab GTPase by the Tail. Dev Cell. 2019 01 07; 48(1):9-11. PMID: 30620905.
      Citations:    Fields:    
    9. Malaby AW, Das S, Chakravarthy S, Irving TC, Bilsel O, Lambright DG. Structural Dynamics Control Allosteric Activation of Cytohesin Family Arf GTPase Exchange Factors. Structure. 2018 01 02; 26(1):106-117.e6. PMID: 29276036.
      Citations: 3     Fields:    Translation:HumansAnimalsCells
    10. Das S, Lambright DG. Membrane Trafficking: An Endosome Tether Meets a Rab and Collapses. Curr Biol. 2016 10 24; 26(20):R927-R929. PMID: 27780062.
      Citations: 2     Fields:    Translation:Cells
    11. Kahn RA, Lambright D, De Matteis A. Special Issue: GTPases in trafficking, autophagy, and disease (FASEB SRC). Small GTPases. 2016 10; 7(4):187. PMID: 27880519.
      Citations:    Fields:    
    12. Mishra AK, Lambright DG. Invited review: Small GTPases and their GAPs. Biopolymers. 2016 Aug; 105(8):431-48. PMID: 26972107.
      Citations: 30     Fields:    Translation:HumansAnimalsCells
    13. Kahn RA, Lambright DG. A PH Domain with Dual Phospholipid Binding Sites Regulates the ARF GAP, ASAP1. Structure. 2015 Nov 03; 23(11):1971-3. PMID: 26536378.
      Citations: 2     Fields:    Translation:Cells
    14. Malaby AW, Chakravarthy S, Irving TC, Kathuria SV, Bilsel O, Lambright DG. Methods for analysis of size-exclusion chromatography-small-angle X-ray scattering and reconstruction of protein scattering. J Appl Crystallogr. 2015 Aug 01; 48(Pt 4):1102-1113. PMID: 26306089.
      Citations:    
    15. Mishra AK, Lambright DG. High-throughput assay for profiling the substrate specificity of Rab GTPase-activating proteins. Methods Mol Biol. 2015; 1298:47-60. PMID: 25800831.
      Citations: 4     Fields:    Translation:Cells
    16. Priya A, Kalaidzidis IV, Kalaidzidis Y, Lambright D, Datta S. Molecular insights into Rab7-mediated endosomal recruitment of core retromer: deciphering the role of Vps26 and Vps35. Traffic. 2015 Jan; 16(1):68-84. PMID: 25367362.
      Citations: 32     Fields:    Translation:HumansCells
    17. Stockler S, Corvera S, Lambright D, Fogarty K, Nosova E, Leonard D, Steinfeld R, Ackerley C, Shyr C, Au N, Selby K, van Allen M, Vallance H, Wevers R, Watkins D, Rosenblatt D, Ross CJ, Conibear E, Wasserman W, van Karnebeek C. Single point mutation in Rabenosyn-5 in a female with intractable seizures and evidence of defective endocytotic trafficking. Orphanet J Rare Dis. 2014 Sep 20; 9:141. PMID: 25233840.
      Citations: 13     Fields:    Translation:Humans
    18. Rahman M, Nirala NK, Singh A, Zhu LJ, Taguchi K, Bamba T, Fukusaki E, Shaw LM, Lambright DG, Acharya JK, Acharya UR. Drosophila Sirt2/mammalian SIRT3 deacetylates ATP synthase ? and regulates complex V activity. J Cell Biol. 2014 Jul 21; 206(2):289-305. PMID: 25023514.
      Citations: 37     Fields:    Translation:AnimalsCells
    19. Hubber A, Arasaki K, Nakatsu F, Hardiman C, Lambright D, De Camilli P, Nagai H, Roy CR. The machinery at endoplasmic reticulum-plasma membrane contact sites contributes to spatial regulation of multiple Legionella effector proteins. PLoS Pathog. 2014 Jul; 10(7):e1004222. PMID: 24992562.
      Citations: 30     Fields:    Translation:HumansAnimalsCells
    20. Del Campo CM, Mishra AK, Wang YH, Roy CR, Janmey PA, Lambright DG. Structural basis for PI(4)P-specific membrane recruitment of the Legionella pneumophila effector DrrA/SidM. Structure. 2014 Mar 04; 22(3):397-408. PMID: 24530282.
      Citations: 22     Fields:    Translation:Cells
    21. Malaby AW, van den Berg B, Lambright DG. Structural basis for membrane recruitment and allosteric activation of cytohesin family Arf GTPase exchange factors. Proc Natl Acad Sci U S A. 2013 Aug 27; 110(35):14213-8. PMID: 23940353.
      Citations: 25     Fields:    Translation:Cells
    22. Mishra AK, Del Campo CM, Collins RE, Roy CR, Lambright DG. The Legionella pneumophila GTPase activating protein LepB accelerates Rab1 deactivation by a non-canonical hydrolytic mechanism. J Biol Chem. 2013 Aug 16; 288(33):24000-11. PMID: 23821544.
      Citations: 14     Fields:    Translation:HumansCells
    23. Mannstadt M, Harris M, Bravenboer B, Chitturi S, Dreijerink KM, Lambright DG, Lim ET, Daly MJ, Gabriel S, Jüppner H. Germline mutations affecting G?11 in hypoparathyroidism. N Engl J Med. 2013 Jun 27; 368(26):2532-4. PMID: 23802536.
      Citations: 32     Fields:    Translation:Humans
    24. Tan SX, Ng Y, Burchfield JG, Ramm G, Lambright DG, Stöckli J, James DE. The Rab GTPase-activating protein TBC1D4/AS160 contains an atypical phosphotyrosine-binding domain that interacts with plasma membrane phospholipids to facilitate GLUT4 trafficking in adipocytes. Mol Cell Biol. 2012 Dec; 32(24):4946-59. PMID: 23045393.
      Citations: 34     Fields:    Translation:AnimalsCells
    25. Davey JR, Humphrey SJ, Junutula JR, Mishra AK, Lambright DG, James DE, Stöckli J. TBC1D13 is a RAB35 specific GAP that plays an important role in GLUT4 trafficking in adipocytes. Traffic. 2012 Oct; 13(10):1429-41. PMID: 22762500.
      Citations: 19     Fields:    Translation:HumansAnimalsCells
    26. Nottingham RM, Pusapati GV, Ganley IG, Barr FA, Lambright DG, Pfeffer SR. RUTBC2 protein, a Rab9A effector and GTPase-activating protein for Rab36. J Biol Chem. 2012 Jun 29; 287(27):22740-8. PMID: 22637480.
      Citations: 17     Fields:    Translation:HumansAnimalsCells
    27. Li J, Malaby AW, Famulok M, Sabe H, Lambright DG, Hsu VW. Grp1 plays a key role in linking insulin signaling to glut4 recycling. Dev Cell. 2012 Jun 12; 22(6):1286-98. PMID: 22609160.
      Citations: 28     Fields:    Translation:AnimalsCells
    28. Navaroli DM, Bellvé KD, Standley C, Lifshitz LM, Cardia J, Lambright D, Leonard D, Fogarty KE, Corvera S. Rabenosyn-5 defines the fate of the transferrin receptor following clathrin-mediated endocytosis. Proc Natl Acad Sci U S A. 2012 Feb 21; 109(8):E471-80. PMID: 22308388.
      Citations: 35     Fields:    Translation:HumansAnimalsCells
    29. Nottingham RM, Ganley IG, Barr FA, Lambright DG, Pfeffer SR. RUTBC1 protein, a Rab9A effector that activates GTP hydrolysis by Rab32 and Rab33B proteins. J Biol Chem. 2011 Sep 23; 286(38):33213-22. PMID: 21808068.
      Citations: 32     Fields:    Translation:HumansAnimalsCells
    30. DiNitto JP, Lee MT, Malaby AW, Lambright DG. Specificity and membrane partitioning of Grsp1 signaling complexes with Grp1 family Arf exchange factors. Biochemistry. 2010 Jul 27; 49(29):6083-92. PMID: 20527794.
      Citations: 6     Fields:    Translation:HumansAnimalsCells
    31. Zhou QL, Jiang ZY, Mabardy AS, Del Campo CM, Lambright DG, Holik J, Fogarty KE, Straubhaar J, Nicoloro S, Chawla A, Czech MP. A novel pleckstrin homology domain-containing protein enhances insulin-stimulated Akt phosphorylation and GLUT4 translocation in adipocytes. J Biol Chem. 2010 Sep 03; 285(36):27581-9. PMID: 20587420.
      Citations: 20     Fields:    Translation:HumansAnimalsCells
    32. Mishra A, Eathiraj S, Corvera S, Lambright DG. Structural basis for Rab GTPase recognition and endosome tethering by the C2H2 zinc finger of Early Endosomal Autoantigen 1 (EEA1). Proc Natl Acad Sci U S A. 2010 Jun 15; 107(24):10866-71. PMID: 20534488.
      Citations: 46     Fields:    Translation:HumansCells
    33. Chotard L, Mishra AK, Sylvain MA, Tuck S, Lambright DG, Rocheleau CE. TBC-2 regulates RAB-5/RAB-7-mediated endosomal trafficking in Caenorhabditis elegans. Mol Biol Cell. 2010 Jul 01; 21(13):2285-96. PMID: 20462958.
      Citations: 42     Fields:    Translation:HumansAnimalsCells
    34. Barr F, Lambright DG. Rab GEFs and GAPs. Curr Opin Cell Biol. 2010 Aug; 22(4):461-70. PMID: 20466531.
      Citations: 202     Fields:    Translation:HumansAnimals
    35. Fang Z, Takizawa N, Wilson KA, Smith TC, Delprato A, Davidson MW, Lambright DG, Luna EJ. The membrane-associated protein, supervillin, accelerates F-actin-dependent rapid integrin recycling and cell motility. Traffic. 2010 Jun; 11(6):782-99. PMID: 20331534.
      Citations: 39     Fields:    Translation:HumansAnimalsCells
    36. Lee MT, Mishra A, Lambright DG. Structural mechanisms for regulation of membrane traffic by rab GTPases. Traffic. 2009 Oct; 10(10):1377-89. PMID: 19522756.
      Citations: 60     Fields:    Translation:HumansAnimalsCells
    37. Leonard D, Hayakawa A, Lawe D, Lambright D, Bellve KD, Standley C, Lifshitz LM, Fogarty KE, Corvera S. Sorting of EGF and transferrin at the plasma membrane and by cargo-specific signaling to EEA1-enriched endosomes. J Cell Sci. 2008 Oct 15; 121(Pt 20):3445-58. PMID: 18827013.
      Citations: 65     Fields:    Translation:AnimalsCells
    38. DiNitto JP, Delprato A, Gabe Lee MT, Cronin TC, Huang S, Guilherme A, Czech MP, Lambright DG. Structural basis and mechanism of autoregulation in 3-phosphoinositide-dependent Grp1 family Arf GTPase exchange factors. Mol Cell. 2007 Nov 30; 28(4):569-83. PMID: 18042453.
      Citations: 86     Fields:    Translation:AnimalsCells
    39. Ingmundson A, Delprato A, Lambright DG, Roy CR. Legionella pneumophila proteins that regulate Rab1 membrane cycling. Nature. 2007 Nov 15; 450(7168):365-9. PMID: 17952054.
      Citations: 172     Fields:    Translation:HumansAnimalsCells
    40. Sklan EH, Serrano RL, Einav S, Pfeffer SR, Lambright DG, Glenn JS. TBC1D20 is a Rab1 GTPase-activating protein that mediates hepatitis C virus replication. J Biol Chem. 2007 Dec 14; 282(50):36354-61. PMID: 17901050.
      Citations: 61     Fields:    Translation:HumansCells
    41. Mukhopadhyay A, Pan X, Lambright DG, Tissenbaum HA. An endocytic pathway as a target of tubby for regulation of fat storage. EMBO Rep. 2007 Oct; 8(10):931-8. PMID: 17762880.
      Citations: 33     Fields:    Translation:AnimalsCells
    42. Mishra AK, Gangwani L, Davis RJ, Lambright DG. Structural insights into the interaction of the evolutionarily conserved ZPR1 domain tandem with eukaryotic EF1A, receptors, and SMN complexes. Proc Natl Acad Sci U S A. 2007 Aug 28; 104(35):13930-5. PMID: 17704259.
      Citations: 20     Fields:    Translation:AnimalsCells
    43. Delprato A, Lambright DG. Structural basis for Rab GTPase activation by VPS9 domain exchange factors. Nat Struct Mol Biol. 2007 May; 14(5):406-12. PMID: 17450153.
      Citations: 66     Fields:    Translation:HumansCells
    44. Hayakawa A, Hayes S, Leonard D, Lambright D, Corvera S. Evolutionarily conserved structural and functional roles of the FYVE domain. Biochem Soc Symp. 2007; (74):95-105. PMID: 17233583.
      Citations: 18     Fields:    Translation:HumansAnimalsCells
    45. Eathiraj S, Mishra A, Prekeris R, Lambright DG. Structural basis for Rab11-mediated recruitment of FIP3 to recycling endosomes. J Mol Biol. 2006 Nov 24; 364(2):121-35. PMID: 17007872.
      Citations: 57     Fields:    Translation:HumansCells
    46. Morrison AR, Moss J, Stevens LA, Evans JE, Farrell C, Merithew E, Lambright DG, Greiner DL, Mordes JP, Rossini AA, Bortell R. ART2, a T cell surface mono-ADP-ribosyltransferase, generates extracellular poly(ADP-ribose). J Biol Chem. 2006 Nov 03; 281(44):33363-72. PMID: 16931513.
      Citations: 10     Fields:    Translation:AnimalsCells
    47. Murata T, Delprato A, Ingmundson A, Toomre DK, Lambright DG, Roy CR. The Legionella pneumophila effector protein DrrA is a Rab1 guanine nucleotide-exchange factor. Nat Cell Biol. 2006 Sep; 8(9):971-7. PMID: 16906144.
      Citations: 188     Fields:    Translation:AnimalsCells
    48. Hayakawa A, Leonard D, Murphy S, Hayes S, Soto M, Fogarty K, Standley C, Bellve K, Lambright D, Mello C, Corvera S. The WD40 and FYVE domain containing protein 2 defines a class of early endosomes necessary for endocytosis. Proc Natl Acad Sci U S A. 2006 Aug 08; 103(32):11928-33. PMID: 16873553.
      Citations: 28     Fields:    Translation:HumansAnimalsCells
    49. Pan X, Eathiraj S, Munson M, Lambright DG. TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual-finger mechanism. Nature. 2006 Jul 20; 442(7100):303-6. PMID: 16855591.
      Citations: 146     Fields:    Translation:AnimalsCells
    50. DiNitto JP, Lambright DG. Membrane and juxtamembrane targeting by PH and PTB domains. Biochim Biophys Acta. 2006 Aug; 1761(8):850-67. PMID: 16807090.
      Citations: 76     Fields:    Translation:HumansCells
    51. Eathiraj S, Lambright DG. ESCRT complexes assembled and GLUEd. Structure. 2006 Apr; 14(4):631-2. PMID: 16615903.
      Citations: 1     Fields:    Translation:AnimalsCells
    52. Eathiraj S, Pan X, Ritacco C, Lambright DG. Structural basis of family-wide Rab GTPase recognition by rabenosyn-5. Nature. 2005 Jul 21; 436(7049):415-9. PMID: 16034420.
      Citations: 102     Fields:    Translation:HumansAnimalsCells
    53. Cronin TC, DiNitto JP, Czech MP, Lambright DG. Structural determinants of phosphoinositide selectivity in splice variants of Grp1 family PH domains. EMBO J. 2004 Oct 01; 23(19):3711-20. PMID: 15359279.
      Citations: 55     Fields:    Translation:HumansCells
    54. Delprato A, Merithew E, Lambright DG. Structure, exchange determinants, and family-wide rab specificity of the tandem helical bundle and Vps9 domains of Rabex-5. Cell. 2004 Sep 03; 118(5):607-17. PMID: 15339665.
      Citations: 95     Fields:    Translation:HumansAnimalsCells
    55. DiNitto JP, Cronin TC, Lambright DG. Membrane recognition and targeting by lipid-binding domains. Sci STKE. 2003 Dec 16; 2003(213):re16. PMID: 14679290.
      Citations: 75     Fields:    Translation:HumansAnimalsCells
    56. Hayakawa A, Hayes SJ, Lawe DC, Sudharshan E, Tuft R, Fogarty K, Lambright D, Corvera S. Structural basis for endosomal targeting by FYVE domains. J Biol Chem. 2004 Feb 13; 279(7):5958-66. PMID: 14594806.
      Citations: 56     Fields:    Translation:HumansAnimalsCells
    57. Lawe DC, Sitouah N, Hayes S, Chawla A, Virbasius JV, Tuft R, Fogarty K, Lifshitz L, Lambright D, Corvera S. Essential role of Ca2+/calmodulin in Early Endosome Antigen-1 localization. Mol Biol Cell. 2003 Jul; 14(7):2935-45. PMID: 12857876.
      Citations: 14     Fields:    Translation:AnimalsCells
    58. Merithew E, Stone C, Eathiraj S, Lambright DG. Determinants of Rab5 interaction with the N terminus of early endosome antigen 1. J Biol Chem. 2003 Mar 07; 278(10):8494-500. PMID: 12493736.
      Citations: 17     Fields:    Translation:Cells
    59. Weston CR, Lambright DG, Davis RJ. Signal transduction. MAP kinase signaling specificity. Science. 2002 Jun 28; 296(5577):2345-7. PMID: 12089430.
      Citations: 41     Fields:    Translation:Cells
    60. Merithew E, Lambright DG. Calculating the potential of C2 domains for membrane binding. Dev Cell. 2002 Feb; 2(2):132-3. PMID: 11832238.
      Citations: 1     Fields:    Translation:Cells
    61. Zhu Z, Delprato A, Merithew E, Lambright DG. Determinants of the broad recognition of exocytic Rab GTPases by Mss4. Biochemistry. 2001 Dec 25; 40(51):15699-706. PMID: 11747446.
      Citations: 5     Fields:    Translation:AnimalsCells
    62. Dumas JJ, Merithew E, Sudharshan E, Rajamani D, Hayes S, Lawe D, Corvera S, Lambright DG. Multivalent endosome targeting by homodimeric EEA1. Mol Cell. 2001 Nov; 8(5):947-58. PMID: 11741531.
      Citations: 91     Fields:    Translation:Cells
    63. Lawe DC, Chawla A, Merithew E, Dumas J, Carrington W, Fogarty K, Lifshitz L, Tuft R, Lambright D, Corvera S. Sequential roles for phosphatidylinositol 3-phosphate and Rab5 in tethering and fusion of early endosomes via their interaction with EEA1. J Biol Chem. 2002 Mar 08; 277(10):8611-7. PMID: 11602609.
      Citations: 59     Fields:    Translation:AnimalsCells
    64. Zhu Z, Dumas JJ, Lietzke SE, Lambright DG. A helical turn motif in Mss4 is a critical determinant of Rab binding and nucleotide release. Biochemistry. 2001 Mar 13; 40(10):3027-36. PMID: 11258916.
      Citations: 11     Fields:    Translation:AnimalsCells
    65. Merithew E, Hatherly S, Dumas JJ, Lawe DC, Heller-Harrison R, Lambright DG. Structural plasticity of an invariant hydrophobic triad in the switch regions of Rab GTPases is a determinant of effector recognition. J Biol Chem. 2001 Apr 27; 276(17):13982-8. PMID: 11278565.
      Citations: 43     Fields:    Translation:Cells
    66. Lietzke SE, Bose S, Cronin T, Klarlund J, Chawla A, Czech MP, Lambright DG. Structural basis of 3-phosphoinositide recognition by pleckstrin homology domains. Mol Cell. 2000 Aug; 6(2):385-94. PMID: 10983985.
      Citations: 97     Fields:    Translation:Cells
    67. Lawe DC, Patki V, Heller-Harrison R, Lambright D, Corvera S. The FYVE domain of early endosome antigen 1 is required for both phosphatidylinositol 3-phosphate and Rab5 binding. Critical role of this dual interaction for endosomal localization. J Biol Chem. 2000 Feb 04; 275(5):3699-705. PMID: 10652369.
      Citations: 78     Fields:    Translation:AnimalsCells
    68. Dumas JJ, Zhu Z, Connolly JL, Lambright DG. Structural basis of activation and GTP hydrolysis in Rab proteins. Structure. 1999 Apr 15; 7(4):413-23. PMID: 10196122.
      Citations: 32     Fields:    Translation:Cells
    69. Dumas JJ, Lambright DG. Gs alpha meets its target--shedding light on a key signal transduction event. Structure. 1998 Apr 15; 6(4):407-11. PMID: 9562564.
      Citations:    Fields:    Translation:Cells
    70. Lambright DG, Sondek J, Bohm A, Skiba NP, Hamm HE, Sigler PB. The 2.0 A crystal structure of a heterotrimeric G protein. Nature. 1996 Jan 25; 379(6563):311-9. PMID: 8552184.
      Citations: 324     Fields:    Translation:HumansAnimalsCells
    71. Sondek J, Bohm A, Lambright DG, Hamm HE, Sigler PB. Crystal structure of a G-protein beta gamma dimer at 2.1A resolution. Nature. 1996 Jan 25; 379(6563):369-74. PMID: 8552196.
      Citations: 242     Fields:    Translation:HumansAnimalsCells
    72. Sondek J, Lambright DG, Noel JP, Hamm HE, Sigler PB. GTPase mechanism of Gproteins from the 1.7-A crystal structure of transducin alpha-GDP-AIF-4. Nature. 1994 Nov 17; 372(6503):276-9. PMID: 7969474.
      Citations: 132     Fields:    Translation:AnimalsCells
    73. Balasubramanian S, Lambright DG, Simmons JH, Gill SJ, Boxer SG. Determination of the carbon monoxide binding constants of myoglobin mutants: comparison of kinetic and equilibrium methods. Biochemistry. 1994 Jul 12; 33(27):8355-60. PMID: 8031769.
      Citations: 4     Fields:    Translation:HumansCells
    74. Lambright DG, Noel JP, Hamm HE, Sigler PB. Structural determinants for activation of the alpha-subunit of a heterotrimeric G protein. Nature. 1994 Jun 23; 369(6482):621-8. PMID: 8208289.
      Citations: 128     Fields:    Translation:HumansAnimalsCells
    75. Lambright DG, Balasubramanian S, Decatur SM, Boxer SG. Anatomy and dynamics of a ligand-binding pathway in myoglobin: the roles of residues 45, 60, 64, and 68. Biochemistry. 1994 May 10; 33(18):5518-25. PMID: 8180174.
      Citations: 7     Fields:    Translation:HumansCells
    76. Petrich JW, Lambry JC, Balasubramanian S, Lambright DG, Boxer SG, Martin JL. Ultrafast measurements of geminate recombination of NO with site-specific mutants of human myoglobin. J Mol Biol. 1994 May 06; 238(3):437-44. PMID: 8176734.
      Citations: 11     Fields:    Translation:HumansCells
    77. Lambright DG, Balasubramanian S, Boxer SG. Dynamics of protein relaxation in site-specific mutants of human myoglobin. Biochemistry. 1993 Sep 28; 32(38):10116-24. PMID: 8399137.
      Citations: 10     Fields:    Translation:HumansCells
    78. Balasubramanian S, Lambright DG, Boxer SG. Perturbations of the distal heme pocket in human myoglobin mutants probed by infrared spectroscopy of bound CO: correlation with ligand binding kinetics. Proc Natl Acad Sci U S A. 1993 May 15; 90(10):4718-22. PMID: 8506324.
      Citations: 11     Fields:    Translation:Humans
    79. Balasubramanian S, Lambright DG, Marden MC, Boxer SG. CO recombination to human myoglobin mutants in glycerol-water solutions. Biochemistry. 1993 Mar 09; 32(9):2202-12. PMID: 8443162.
      Citations: 12     Fields:    Translation:Humans
    80. Hubbard SR, Hendrickson WA, Lambright DG, Boxer SG. X-ray crystal structure of a recombinant human myoglobin mutant at 2.8 A resolution. J Mol Biol. 1990 May 20; 213(2):215-8. PMID: 2342104.
      Citations: 17     Fields:    Translation:HumansCells
    81. Lambright DG, Balasubramanian S, Boxer SG. Ligand and proton exchange dynamics in recombinant human myoglobin mutants. J Mol Biol. 1989 May 05; 207(1):289-99. PMID: 2544737.
      Citations: 13     Fields:    Translation:Humans
    82. Varadarajan R, Lambright DG, Boxer SG. Electrostatic interactions in wild-type and mutant recombinant human myoglobins. Biochemistry. 1989 May 02; 28(9):3771-81. PMID: 2751994.
      Citations: 16     Fields:    Translation:HumansCells
    83. Johnson DR, Lambright DG, Wong SS. Lactose synthase: effect of alpha-lactalbumin on substrate activity of N-acylglucosamines. Biochim Biophys Acta. 1985 Dec 20; 832(3):373-7. PMID: 3935175.
      Citations: 1     Fields:    Translation:AnimalsCells
    84. Lambright DG, Lee TK, Wong SS. Association-dissociation modulation of enzyme activity: case of lactose synthase. Biochemistry. 1985 Feb 12; 24(4):910-4. PMID: 3922406.
      Citations:    Fields:    Translation:AnimalsCells
    Lambright's Networks
    Click the
    Explore
    buttons for more information and interactive visualizations!
    Concepts (307)
    Explore
    _
    Co-Authors (17)
    Explore
    _
    Similar People (60)
    Explore
    _
    Same Department Expand Description
    Explore
    _
    Physical Neighbors
    _