Anne Kenworthy

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Primary Appointment

Professor, Molecular Physiology and Biological Physics

Education

  • BA, Biology, Kenyon College
  • PhD, Cell Biology, Duke University School of Medicine, Durham, NC
  • Postdoc, Biophysics, Johns Hopkins University
  • Postdoc, Cell Biology, National Institutes of Health, Bethesda, MD

Research Disciplines

Biophysics, Cell and Developmental Biology, Physiology

Research Interests

Architecture and function of biological membranes

Research Description

Research Description
One of the major goals of my research program is to understand the role of membrane microdomains such as lipid rafts and caveolae in health and disease. We address this question using a combination of live cell imaging, cell biology, biophysics, structural, and biochemical approaches. Current projects ongoing in the lab include:
1. How do proteins and lipid cooperate to build functional raft domains?
2. How do bacterial toxins exploit lipid rafts as a mechanism to enter host cells?
3. How do cholesterol and lipid rafts contribute to the progression of Alzheimer's disease?
4. How do mutations in caveolin-1 and defects in caveolae cause human diseases such as breast cancer and pulmonary arterial hypertension?
5. What is the structural basis for caveolae formation?

Training

  • Training in Cell and Molecular Biology
  • Training in Molecular Biophysics

Selected Publications

2024

Balakrishnan, M., & Kenworthy, A. K. (2024). Lipid Peroxidation Drives Liquid-Liquid Phase Separation and Disrupts Raft Protein Partitioning in Biological Membranes. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 146(2), 1374-1387. doi:10.1021/jacs.3c10132

2023

Balakrishnan, M., & Kenworthy, A. K. (2023). Lipid peroxidation drives liquid-liquid phase separation and disrupts raft protein partitioning in biological membranes.. bioRxiv. doi:10.1101/2023.09.12.557355

Kenworthy, A. K., Han, B., Ariotti, N., & Parton, R. G. (2023). The Role of Membrane Lipids in the Formation and Function of Caveolae. COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, 15(9). doi:10.1101/cshperspect.a041413

Kenworthy, A. K. (2023). What's past is prologue: FRAP keeps delivering 50 years later. BIOPHYSICAL JOURNAL, 122(18), 3577-3586. doi:10.1016/j.bpj.2023.05.016

Kenworthy, A. K. (2023). The building blocks of caveolae revealed: caveolins finally take center stage. BIOCHEMICAL SOCIETY TRANSACTIONS, 51(2), 855-869. doi:10.1042/BST20221298

Han, B., Gulsevin, A., Connolly, S., Wang, T., Meyer, B., Porta, J., . . . Kenworthy, A. K. (2023). Structural analysis of the P132L disease mutation in caveolin-1 reveals its role in the assembly of oligomeric complexes. JOURNAL OF BIOLOGICAL CHEMISTRY, 299(4). doi:10.1016/j.jbc.2023.104574

Kenworthy, A. K. (2023). Cellular sinkholes buffer membrane tension. NATURE CELL BIOLOGY, 25(1), 15-16. doi:10.1038/s41556-022-01032-5

Gulsevin, A., Han, B., Porta, J. C., Mchaourab, H. S., Meiler, J., & Kenworthy, A. K. (2023). Template-free prediction of a new monotopic membrane protein fold and assembly by AlphaFold2. BIOPHYSICAL JOURNAL, 122(11), 2041-2052. doi:10.1016/j.bpj.2022.11.011

2022

Ohi, M. D., & Kenworthy, A. K. (2022). Emerging Insights into the Molecular Architecture of Caveolin-1. JOURNAL OF MEMBRANE BIOLOGY, 255(4-5), 375-383. doi:10.1007/s00232-022-00259-5

Porta, J. C., Han, B., Gulsevin, A., Chung, J. M., Peskova, Y., Connolly, S., . . . Ohi, M. D. (2022). Molecular architecture of the human caveolin-1 complex. SCIENCE ADVANCES, 8(19). doi:10.1126/sciadv.abn7232

Fricke, N., Raghunathan, K., Tiwari, A., Stefanski, K. M., Balakrishnan, M., Waterson, A. G., . . . Kenworthy, A. K. (2022). High-Content Imaging Platform to Discover Chemical Modulators of Plasma Membrane Rafts. ACS CENTRAL SCIENCE, 8(3), 370-378. doi:10.1021/acscentsci.1c01058

2021

Kenworthy, A. K., Schmieder, S. S., Raghunathan, K., Tiwari, A., Wang, T., Kelly, C. V., & Lencer, W. I. (2021). Cholera Toxin as a Probe for Membrane Biology. TOXINS, 13(8). doi:10.3390/toxins13080543

Arumugam, S., Schmieder, S., Pezeshkian, W., Becken, U., Wunder, C., Chinnapen, D., . . . Johannes, L. (2021). Ceramide structure dictates glycosphingolipid nanodomain assembly and function. NATURE COMMUNICATIONS, 12(1). doi:10.1038/s41467-021-23961-9

Capone, R., Tiwari, A., Hadziselimovic, A., Peskova, Y., Hutchison, J. M., Sanders, C. R., & Kenworthy, A. K. (2021). The C99 domain of the amyloid precursor protein resides in the disordered membrane phase. JOURNAL OF BIOLOGICAL CHEMISTRY, 296. doi:10.1016/j.jbc.2021.100652

2020

Kabbani, A. M., Raghunathan, K., Lencer, W. I., Kenworthy, A. K., & Kelly, C. V. (2020). Structured clustering of the glycosphingolipid GM1 is required for membrane curvature induced by cholera toxin. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 117(26), 14978-14986. doi:10.1073/pnas.2001119117

Han, B., Porta, J. C., Hanks, J. L., Peskova, Y., Binshtein, E., Dryden, K., . . . Kenworthy, A. K. (2020). Structure and assembly of CAV1 8S complexes revealed by single particle electron microscopy. SCIENCE ADVANCES, 6(49). doi:10.1126/sciadv.abc6185

Kreutzberger, A. J. B., Kiessling, V., Doyle, C. A., Schenk, N., Upchurch, C. M., Elmer-Dixon, M., . . . Tamm, L. K. (2020). Distinct insulin granule subpopulations implicated in the secretory pathology of diabetes types 1 and 2. ELIFE, 9. doi:10.7554/eLife.62506

Rathinasabapathy, A., Copeland, C., Crabtree, A., Carrier, E. J., Moore, C., Shay, S., . . . West, J. D. (2020). Expression of a Human Caveolin-1 Mutation in Mice Drives Inflammatory and Metabolic Defect-Associated Pulmonary Arterial Hypertension. FRONTIERS IN MEDICINE, 7. doi:10.3389/fmed.2020.00540

Kenworthy, A. K. (2020). Choosing who can ride the raft. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 21(10), 566-567. doi:10.1038/s41580-020-00285-y

Marinko, J. T., Kenworthy, A. K., & Sanders, C. R. (2020). Peripheral myelin protein 22 preferentially partitions into ordered phase membrane domains. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 117(25), 14168-14177. doi:10.1073/pnas.2000508117

2019

Parton, R. G., del Pozo, M. A., Vassilopoulos, S., Nabi, I. R., Le Lay, S., Lundmark, R., . . . Lamaze, C. (2020). Caveolae: The FAQs. TRAFFIC, 21(1), 181-185. doi:10.1111/tra.12689

Insinna, C., Lu, Q., Teixeira, I., Harned, A., Semler, E. M., Stauffer, J., . . . Westlake, C. J. (2019). Investigation of F-BAR domain PACSIN proteins uncovers membrane tubulation function in cilia assembly and transport. NATURE COMMUNICATIONS, 10. doi:10.1038/s41467-018-08192-9

Kang, M., Day, C. A., & Kenworthy, A. K. (2019). A novel computational framework for D(t) from Fluorescence Recovery after Photobleaching data reveals various anomalous diffusion types in live cell membranes. TRAFFIC, 20(11), 867-880. doi:10.1111/tra.12690

Foegeding, N. J., Raghunathan, K., Campbell, A. M., Kim, S. W., Lau, K. S., Kenworthy, A. K., . . . Ohi, M. D. (2019). Intracellular Degradation of Helicobacter pylori VacA Toxin as a Determinant of Gastric Epithelial Cell Viability. INFECTION AND IMMUNITY, 87(4). doi:10.1128/IAI.00783-18

2018

Saito-Diaz, K., Benchabane, H., Tiwari, A., Tian, A., Li, B., Thompson, J. J., . . . Lee, E. (2018). APC Inhibits Ligand-Independent Wnt Signaling by the Clathrin Endocytic Pathway. DEVELOPMENTAL CELL, 44(5), 566-+. doi:10.1016/j.devcel.2018.02.013

Raghunathan, K., Foegeding, N. J., Campbell, A. M., Cover, T. L., Ohi, M. D., & Kenworthy, A. K. (2018). Determinants of Raft Partitioning of the Helicobacter pylori Pore-Forming Toxin VacA. INFECTION AND IMMUNITY, 86(5). doi:10.1128/IAI.00872-17

Raghunathan, K., & Kenworthy, A. K. (2018). Dynamic pattern generation in cell membranes: Current insights into membrane organization. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 1860(10), 2018-2031. doi:10.1016/j.bbamem.2018.05.002

Kenworthy, A. K. (2018). Bigger Isn't Always Better: Bulking Up Impedes Receptor Internalization. BIOPHYSICAL JOURNAL, 114(6), 1255-1256. doi:10.1016/j.bpj.2018.01.037

2017

Simunovic, M., Manneville, J. -B., Renard, H. -F., Evergren, E., Raghunathan, K., Bhatia, D., . . . Callan-Jones, A. (2017). Friction Mediates Scission of Tubular Membranes Scaffolded by BAR Proteins. CELL, 170(1). doi:10.1016/j.cell.2017.05.047

Copeland, C. A., Han, B., Tiwari, A., Austin, E. D., Loyd, J. E., West, J. D., & Kenworthy, A. K. (2017). A disease-associated frameshift mutation in caveolin-1 disrupts caveolae formation and function through introduction of a de novo ER retention signal. MOLECULAR BIOLOGY OF THE CELL, 28(22), 3095-3111. doi:10.1091/mbc.E17-06-0421

2016

Cui, Y., Kenworthy, A. K., Edidin, M., Divan, R., Rosenmann, D., & Wang, P. (2016). Analyzing Single Giant Unilamellar Vesicles With a Slotline-Based RF Nanometer Sensor. IEEE TRANSACTIONS ON MICROWAVE THEORY AND TECHNIQUES, 64(4), 1339-1347. doi:10.1109/TMTT.2016.2536021

Han, B., Copeland, C. A., Kawano, Y., Rosenzweig, E. B., Austin, E. D., Shahmirzadi, L., . . . Kenworthy, A. K. (2016). Characterization of a caveolin-1 mutation associated with both pulmonary arterial hypertension and congenital generalized lipodystrophy. TRAFFIC, 17(12), 1297-1312. doi:10.1111/tra.12452

Tiwari, A., Copeland, C. A., Han, B., Hanson, C. A., Raghunathan, K., & Kenworthy, A. K. (2016). Caveolin-1 is an aggresome-inducing protein. SCIENTIFIC REPORTS, 6. doi:10.1038/srep38681

Klaus, C. J. S., Raghunathan, K., DiBenedetto, E., & Kenworthy, A. K. (2016). Analysis of diffusion in curved surfaces and its application to tubular membranes. MOLECULAR BIOLOGY OF THE CELL, 27(24), 3937-3946. doi:10.1091/mbc.E16-06-0445

Raghunathan, K., Wong, T. H., Chinnapen, D. J., Lencer, W. I., Jobling, M. G., & Kenworthy, A. K. (2016). Glycolipid Crosslinking Is Required for Cholera Toxin to Partition Into and Stabilize Ordered Domains. BIOPHYSICAL JOURNAL, 111(12), 2547-2550. doi:10.1016/j.bpj.2016.11.008

Schlebach, J. P., Barrett, P. J., Day, C. A., Kim, J. H., Kenworthy, A. K., & Sanders, C. R. (2016). Topologically Diverse Human Membrane Proteins Partition to Liquid-Disordered Domains in Phase-Separated Lipid Vesicles. BIOCHEMISTRY, 55(7), 985-988. doi:10.1021/acs.biochem.5b01154

Kraft, L. J., Manral, P., Dowler, J., & Kenworthy, A. K. (2016). Nuclear LC3 Associates with Slowly Diffusing Complexes that Survey the Nucleolus. TRAFFIC, 17(4), 369-399. doi:10.1111/tra.12372

Kraft, L. J., Dowler, J., Manral, P., & Kenworthy, A. K. (2016). Size, organization, and dynamics of soluble SQSTM1 and LC3-SQSTM1 complexes in living cells. AUTOPHAGY, 12(9), 1660-1674. doi:10.1080/15548627.2016.1199299

Chandrasekaran, R., Kenworthy, A. K., & Lacy, D. B. (2016). Clostridium difficile Toxin A Undergoes Clathrin-Independent, PACSIN2-Dependent Endocytosis. PLOS PATHOGENS, 12(12). doi:10.1371/journal.ppat.1006070

Han, B., Copeland, C. A., Tiwari, A., & Kenworthy, A. K. (2016). Assembly and Turnover of Caveolae: What Do We Really Know?. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 4. doi:10.3389/fcell.2016.00068

Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Arozena, A. A., . . . Zughaier, S. M. (2016). Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). AUTOPHAGY, 12(1), 1-222. doi:10.1080/15548627.2015.1100356

2015

Day, C. A., Baetz, N. W., Copeland, C. A., Kraft, L. J., Han, B., Tiwari, A., . . . Kenworthy, A. K. (2015). Microtubule Motors Power Plasma Membrane Tubulation in Clathrin-Independent Endocytosis. TRAFFIC, 16(6), 572-590. doi:10.1111/tra.12269

Kenworthy, A. K. (2015). Lipid Domains. Preface.. Current topics in membranes, 75, xiii-xvii. doi:10.1016/s1063-5823(15)00033-2

Han, B., Tiwari, A., & Kenworthy, A. K. (2015). Tagging Strategies Strongly Affect the Fate of Overexpressed Caveolin-1. TRAFFIC, 16(4), 417-438. doi:10.1111/tra.12254

Kang, M., Andreani, M., & Kenworthy, A. K. (2015). Validation of Normalizations, Scaling, and Photofading Corrections for FRAP Data Analysis. PLOS ONE, 10(5). doi:10.1371/journal.pone.0127966

2014

Renard, H. -F., Simunovic, M., Lemiere, J., Boucrot, E., Garcia-Castillo, M. D., Arumugam, S., . . . Johannes, L. (2015). Endophilin-A2 functions in membrane scission in clathrin-independent endocytosis. NATURE, 517(7535), 493-+. doi:10.1038/nature14064

Prewitt, A. R., Ghose, S., Frump, A. L., Datta, A., Austin, E. D., Kenworthy, A. K., & de Caestecker, M. P. (2015). Heterozygous Null Bone Morphogenetic Protein Receptor Type 2 Mutations Promote SRC Kinase-dependent Caveolar Trafficking Defects and Endothelial Dysfunction in Pulmonary Arterial Hypertension. JOURNAL OF BIOLOGICAL CHEMISTRY, 290(2), 960-971. doi:10.1074/jbc.M114.591057

Mazerik, J. N., Kraft, L. J., Kenworthy, A. K., & Tyska, M. J. (2014). Motor and Tail Homology 1 (TH1) Domains Antagonistically Control Myosin-1 Dynamics. BIOPHYSICAL JOURNAL, 106(3), 649-658. doi:10.1016/j.bpj.2013.12.038

Kraft, L. J., Nguyen, T. A., Vogel, S. S., & Kenworthy, A. K. (2014). Size, stoichiometry, and organization of soluble LC3-associated complexes. AUTOPHAGY, 10(5), 861-877. doi:10.4161/auto.28175

2013

Song, Y., Kenworthy, A. K., & Sanders, C. R. (2014). Cholesterol as a co-solvent and a ligand for membrane proteins. PROTEIN SCIENCE, 23(1), 1-22. doi:10.1002/pro.2385

Hanson, C. A., Drake, K. R., Baird, M. A., Han, B., Kraft, L. J., Davidson, M. W., & Kenworthy, A. K. (2013). Overexpression of Caveolin-1 Is Sufficient to Phenocopy the Behavior of a Disease-Associated Mutant. TRAFFIC, 14(6), 663-677. doi:10.1111/tra.12066

2012

Kang, M., Day, C. A., Kenworthy, A. K., & DiBenedetto, E. (2012). Simplified Equation to Extract Diffusion Coefficients from Confocal FRAP Data. TRAFFIC, 13(12), 1589-1600. doi:10.1111/tra.12008

Day, C. A., Kraft, L. J., Kang, M., & Kenworthy, A. K. (2012). Analysis of protein and lipid dynamics using confocal fluorescence recovery after photobleaching (FRAP).. Current protocols in cytometry, Chapter 2, Unit2.19. doi:10.1002/0471142956.cy0219s62

Kraft, L. J., & Kenworthy, A. K. (2012). Imaging protein complex formation in the autophagy pathway: analysis of the interaction of LC3 and Atg4BC74A in live cells using Forster resonance energy transfer and fluorescence recovery after photobleaching. JOURNAL OF BIOMEDICAL OPTICS, 17(1). doi:10.1117/1.JBO.17.1.011008

Chinnapen, D. J. -F., Hsieh, W. -T., te Welscher, Y. M., Saslowsky, D. E., Kaoutzani, L., Brandsma, E., . . . Lencer, W. I. (2012). Lipid Sorting by Ceramide Structure from Plasma Membrane to ER for the Cholera Toxin Receptor Ganglioside GM1. DEVELOPMENTAL CELL, 23(3), 573-586. doi:10.1016/j.devcel.2012.08.002

Day, C. A., & Kenworthy, A. K. (2012). Mechanisms Underlying the Confined Diffusion of Cholera Toxin B-Subunit in Intact Cell Membranes. PLOS ONE, 7(4). doi:10.1371/journal.pone.0034923

2011

Lapierre, L. A., Ducharme, N. A., Drake, K. R., Goldenring, J. R., & Kenworthy, A. K. (2012). Coordinated regulation of caveolin-1 and Rab11a in apical recycling compartments of polarized epithelial cells. EXPERIMENTAL CELL RESEARCH, 318(2), 103-113. doi:10.1016/j.yexcr.2011.10.010

Kang, M., DiBenedetto, E., & Kenworthy, A. K. (2011). Proposed Correction to Feder's Anomalous Diffusion FRAP Equations. BIOPHYSICAL JOURNAL, 100(3), 791-792. doi:10.1016/j.bpj.2010.11.091

2010

Kang, M., Day, C. A., DiBenedetto, E., & Kenworthy, A. K. (2010). A Quantitative Approach to Analyze Binding Diffusion Kinetics by Confocal FRAP. BIOPHYSICAL JOURNAL, 99(9), 2737-2747. doi:10.1016/j.bpj.2010.09.013

Drake, K. R., Kang, M., & Kenworthy, A. K. (2010). Nucleocytoplasmic Distribution and Dynamics of the Autophagosome Marker EGFP-LC3. PLOS ONE, 5(3). doi:10.1371/journal.pone.0009806

Cha, B., Zhu, X. C., Chen, W., Jones, M., Ryoo, S., Zachos, N. C., . . . Donowitz, M. (2010). NHE3 mobility in brush borders increases upon NHERF2-dependent stimulation by lyophosphatidic acid. JOURNAL OF CELL SCIENCE, 123(14), 2434-2443. doi:10.1242/jcs.056713