Krishna C. Mudumbi, PhD
Cards
About
Titles
Associate Research Scientist in Pharmacology
Biography
Krishna is interested in exploring the kinetics of receptor tyrosine kinase (RTK) signaling through the use of biophysical techniques, with a focus on single-molecule microscopy. He gained experience in single-molecule microscopy during his Ph.D. work in the lab of Weidong Yang at Temple University studying nuclear envelope membrane proteins. During his time there, he studied the translocation of nuclear envelope transmembrane proteins into the nucleus, as well as developed a single-molecule FRAP technique to study the distribution of transmembrane proteins on the nuclear envelope.
In Mark Lemmon's lab, Krishna is using his expertise with single-molecule microscopy to understand how the dynamics of EGFR dimerization contribute to its signaling. Using single-particle tracking, his work recently revealed how the different domains of EGFR contribute to its dimerization and oligomerization on the cell surface. He continues to use advanced imaging techniques, cellular, and biochemical assays to explore how the kinetics and spatial organization of EGFR on the plasma membrane defines signaling specificity.
Appointments
Pharmacology
Associate Research ScientistPrimary
Other Departments & Organizations
Education & Training
- PhD
- Temple University, Biophysics
- BA
- Emory University
Research
Publications
2023
Distinct interactions stabilize EGFR dimers and higher-order oligomers in cell membranes
Mudumbi K, Burns E, Schodt D, Petrova Z, Kiyatkin A, Kim L, Mangiacapre E, Ortiz-Caraveo I, Rivera Ortiz H, Hu C, Ashtekar K, Lidke K, Lidke D, Lemmon M. Distinct interactions stabilize EGFR dimers and higher-order oligomers in cell membranes. Cell Reports 2023, 43: 113603. PMID: 38117650, PMCID: PMC10835193, DOI: 10.1016/j.celrep.2023.113603.Peer-Reviewed Original Research
2021
Structural basis for ligand reception by anaplastic lymphoma kinase
Li T, Stayrook SE, Tsutsui Y, Zhang J, Wang Y, Li H, Proffitt A, Krimmer SG, Ahmed M, Belliveau O, Walker IX, Mudumbi KC, Suzuki Y, Lax I, Alvarado D, Lemmon MA, Schlessinger J, Klein DE. Structural basis for ligand reception by anaplastic lymphoma kinase. Nature 2021, 600: 148-152. PMID: 34819665, PMCID: PMC8639777, DOI: 10.1038/s41586-021-04141-7.Peer-Reviewed Original Research
2020
Nucleoplasmic signals promote directed transmembrane protein import simultaneously via multiple channels of nuclear pores
Mudumbi KC, Czapiewski R, Ruba A, Junod SL, Li Y, Luo W, Ngo C, Ospina V, Schirmer EC, Yang W. Nucleoplasmic signals promote directed transmembrane protein import simultaneously via multiple channels of nuclear pores. Nature Communications 2020, 11: 2184. PMID: 32366843, PMCID: PMC7198523, DOI: 10.1038/s41467-020-16033-x.Peer-Reviewed Original ResearchConceptsMembrane proteinsInner nuclear membrane proteinCentral channelEukaryotic transmembrane proteinsNuclear membrane proteinsNuclear localization signalNuclear pore complexCertain membrane proteinsCentral outstanding questionsSingle-molecule microscopyProtein importProtein translocationLocalization signalPore complexNuclear transportBlock translocationTransmembrane proteinNuclear poresSuch proteinsProtein targetsNuclear membraneProteinTranslocationOutstanding questionsChannel transport
2019
Casting a Wider Net: Differentiating between Inner Nuclear Envelope and Outer Nuclear Envelope Transmembrane Proteins
Tingey M, Mudumbi KC, Schirmer EC, Yang W. Casting a Wider Net: Differentiating between Inner Nuclear Envelope and Outer Nuclear Envelope Transmembrane Proteins. International Journal Of Molecular Sciences 2019, 20: 5248. PMID: 31652739, PMCID: PMC6862087, DOI: 10.3390/ijms20215248.Peer-Reviewed Original ResearchConceptsNuclear envelope transmembrane proteinsEnvelope transmembrane proteinsInner nuclear membraneOuter nuclear membraneNuclear envelopeTransmembrane proteinDouble membraneNuclear membraneInner nuclear envelopeGenome architectureNuclear organizationNuclear positioningEukaryotic cellsCellular functionsDNA replicationEndoplasmic reticulumCorrect localizationProteinVital functionsMembraneNuclear structureImportant roleSplicingEpigeneticsNuclear stability
2017
Determination of Membrane Protein Distribution on the Nuclear Envelope by Single‐Point Single‐Molecule FRAP
Mudumbi K, Yang W. Determination of Membrane Protein Distribution on the Nuclear Envelope by Single‐Point Single‐Molecule FRAP. Current Protocols In Cell Biology 2017, 76: 21.11.1-21.11.13. PMID: 28862339, PMCID: PMC5879780, DOI: 10.1002/cpcb.27.Peer-Reviewed Original ResearchConceptsNuclear envelope transmembrane proteinsInner nuclear membraneOuter nuclear membraneNuclear membraneEnvelope transmembrane proteinsEukaryotic cellsTransmembrane proteinEndoplasmic reticulumHuman diseasesFluorescence recoveryTranslocation rateTranslocation dynamicsMembraneAbnormal distributionProteinReticulumMicroscopy techniquesCellsVivoSpatial distribution
2016
Single-point single-molecule FRAP distinguishes inner and outer nuclear membrane protein distribution
Mudumbi K, Schirmer E, Yang W. Single-point single-molecule FRAP distinguishes inner and outer nuclear membrane protein distribution. Nature Communications 2016, 7: 12562. PMID: 27558844, PMCID: PMC5007294, DOI: 10.1038/ncomms12562.Peer-Reviewed Original ResearchConceptsNuclear envelope transmembrane proteinsInner nuclear membraneOuter nuclear membraneNuclear membraneEnvelope transmembrane proteinsMembrane protein distributionTranslocation rateTransmembrane proteinEndoplasmic reticulumProtein distributionHuman diseasesMembraneProteinReticulumMicroscopy techniquesDetermination of distributionVivoProbing Protein Distribution Along the Nuclear Envelope In Vivo by Using Single-Point FRAP
Mudumbi K, Yang W. Probing Protein Distribution Along the Nuclear Envelope In Vivo by Using Single-Point FRAP. Methods In Molecular Biology 2016, 1411: 113-122. PMID: 27147037, PMCID: PMC10099394, DOI: 10.1007/978-1-4939-3530-7_6.Peer-Reviewed Original ResearchConceptsNuclear envelope transmembrane proteinsNuclear membrane proteinsEnvelope transmembrane proteinsInner nuclear membraneNuclear envelope membranesWeeks-long processEnvelope membraneMembrane proteinsTransmembrane proteinNuclear envelopeNuclear membraneProtein distributionFluorescence recoveryStaining of cellsProteinMembraneElectron microscopy
2013
The Pathogenic A391E Mutation in FGFR3 Induces a Structural Change in the Transmembrane Domain Dimer
Mudumbi K, Julius A, Herrmann J, Li E. The Pathogenic A391E Mutation in FGFR3 Induces a Structural Change in the Transmembrane Domain Dimer. The Journal Of Membrane Biology 2013, 246: 487-493. PMID: 23727984, DOI: 10.1007/s00232-013-9563-6.Peer-Reviewed Original ResearchConceptsFGFR3 transmembrane domainFibroblast growth factor receptor 3Transmembrane domainA391E mutationSingle-pass membrane proteinCytosolic kinase domainTransmembrane domain dimerReceptor tyrosine kinase familyTyrosine kinase familyGrowth factor receptor 3TMD dimersCytosolic domainKinase familyTransmembrane proteinMembrane proteinsKinase domainDomain dimerExtracellular domainGenetic studiesDistinct domainsActivity assaysStable dimerCranial dysplasiaMutationsMotif