C. Patrick Lusk, PhD
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Research Summary
The Lusk lab focuses on understanding the molecular mechanisms that control the organization, structure and function of the nuclear envelope: the membrane system that encapsulates the genome of all eukaryotes.
At the heart of this pursuit is the examination of the function of membrane proteins that selectively enrich at the nuclear envelope. Mutation or deletion of several genes encoding these proteins have profound effects on cellular processes that result in the loss of nuclear envelope structure along with changes in gene expression and an increase in genome instability. These phenotypes often lead to cell death or the manifestation of specific diseases termed nuclear envelopathies. To fully understand the mechanisms that contribute to these essential processes, we have identified conserved integral membrane proteins in the budding yeast S. cerevisiae. Using yeast as a model system allows us to use a myriad of genetic, biochemical and cell biological methodology to directly examine how membrane proteins affect various aspects of nuclear envelope physiology. Ongoing projects in the lab include (a) defining mechanisms of nuclear pore complex assembly and distribution (b) understanding membrane protein traffic to the inner nuclear membrane (c) investigating the role of membrane proteins in controlling transcription, gene recruitment and genome stability at the nuclear periphery.
Specialized Terms: Nuclear pore complex; Nuclear periphery; Membrane proteins; Chromatin structure
Coauthors
Research Interests
Nuclear Envelope; Nuclear Pore; Nuclear Pore Complex Proteins
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Selected Publications
- An ESCRT grommet cooperates with a diffusion barrier to maintain nuclear integrityAder N, Chen L, Surovtsev I, Chadwick W, Rodriguez E, King M, Lusk C. An ESCRT grommet cooperates with a diffusion barrier to maintain nuclear integrity. Nature Cell Biology 2023, 25: 1465-1477. PMID: 37783794, DOI: 10.1038/s41556-023-01235-4.
- Changing the guard—nuclear pore complex quality controlVeldsink A, Gallardo P, Lusk C, Veenhoff L. Changing the guard—nuclear pore complex quality control. FEBS Letters 2023, 597: 2739-2749. PMID: 37715940, DOI: 10.1002/1873-3468.14739.
- The capsid lattice engages a bipartite NUP153 motif to mediate nuclear entry of HIV-1 coresShen Q, Kumari S, Xu C, Jang S, Shi J, Burdick R, Levintov L, Xiong Q, Wu C, Devarkar S, Tian T, Tripler T, Hu Y, Yuan S, Temple J, Feng Q, Lusk C, Aiken C, Engelman A, Perilla J, Pathak V, Lin C, Xiong Y. The capsid lattice engages a bipartite NUP153 motif to mediate nuclear entry of HIV-1 cores. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2202815120. PMID: 36943880, PMCID: PMC10068764, DOI: 10.1073/pnas.2202815120.
- Modeling HIV-1 nuclear entry with nucleoporin-gated DNA-origami channelsShen Q, Feng Q, Wu C, Xiong Q, Tian T, Yuan S, Shi J, Bedwell G, Yang R, Aiken C, Engelman A, Lusk C, Lin C, Xiong Y. Modeling HIV-1 nuclear entry with nucleoporin-gated DNA-origami channels. Nature Structural & Molecular Biology 2023, 30: 425-435. PMID: 36807645, PMCID: PMC10121901, DOI: 10.1038/s41594-023-00925-9.
- Functionalized DNA-Origami-Protein Nanopores Generate Large Transmembrane Channels with Programmable Size-SelectivityShen Q, Xiong Q, Zhou K, Feng Q, Liu L, Tian T, Wu C, Xiong Y, Melia T, Lusk C, Lin C. Functionalized DNA-Origami-Protein Nanopores Generate Large Transmembrane Channels with Programmable Size-Selectivity. Journal Of The American Chemical Society 2022, 145: 1292-1300. PMID: 36577119, PMCID: PMC9852090, DOI: 10.1021/jacs.2c11226.
- Kap-β2/Transportin mediates β-catenin nuclear transport in Wnt signalingHwang WY, Kostiuk V, González DP, Lusk CP, Khokha M. Kap-β2/Transportin mediates β-catenin nuclear transport in Wnt signaling. ELife 2022, 11: e70495. PMID: 36300792, PMCID: PMC9665845, DOI: 10.7554/elife.70495.
- Quality control mechanisms that protect nuclear envelope identity and functionMannino PJ, Lusk CP. Quality control mechanisms that protect nuclear envelope identity and function. Journal Of Cell Biology 2022, 221: e202205123. PMID: 36036741, PMCID: PMC9442147, DOI: 10.1083/jcb.202205123.
- Atg39 selectively captures inner nuclear membrane into lumenal vesicles for delivery to the autophagosomeChandra S, Mannino PJ, Thaller DJ, Ader NR, King MC, Melia TJ, Lusk CP. Atg39 selectively captures inner nuclear membrane into lumenal vesicles for delivery to the autophagosome. Journal Of Cell Biology 2021, 220: e202103030. PMID: 34714326, PMCID: PMC8575018, DOI: 10.1083/jcb.202103030.
- Nuclear accumulation of CHMP7 initiates nuclear pore complex injury and subsequent TDP-43 dysfunction in sporadic and familial ALSCoyne AN, Baskerville V, Zaepfel BL, Dickson DW, Rigo F, Bennett F, Lusk CP, Rothstein JD. Nuclear accumulation of CHMP7 initiates nuclear pore complex injury and subsequent TDP-43 dysfunction in sporadic and familial ALS. Science Translational Medicine 2021, 13 PMID: 34321318, PMCID: PMC9022198, DOI: 10.1126/scitranslmed.abe1923.
- Direct binding of ESCRT protein Chm7 to phosphatidic acid–rich membranes at nuclear envelope herniationsThaller DJ, Tong D, Marklew CJ, Ader NR, Mannino PJ, Borah S, King MC, Ciani B, Lusk CP. Direct binding of ESCRT protein Chm7 to phosphatidic acid–rich membranes at nuclear envelope herniations. Journal Of Cell Biology 2021, 220: e202004222. PMID: 33464310, PMCID: PMC7816628, DOI: 10.1083/jcb.202004222.
- An ESCRT-LEM protein surveillance system is poised to directly monitor the nuclear envelope and nuclear transport systemThaller DJ, Allegretti M, Borah S, Ronchi P, Beck M, Lusk CP. An ESCRT-LEM protein surveillance system is poised to directly monitor the nuclear envelope and nuclear transport system. ELife 2019, 8: e45284. PMID: 30942170, PMCID: PMC6461442, DOI: 10.7554/elife.45284.
- Surveillance of Nuclear Pore Complex Assembly by ESCRT-III/Vps4Webster BM, Colombi P, Jäger J, Lusk CP. Surveillance of Nuclear Pore Complex Assembly by ESCRT-III/Vps4. Cell 2014, 159: 388-401. PMID: 25303532, PMCID: PMC4194032, DOI: 10.1016/j.cell.2014.09.012.
- Karyopherin-mediated import of integral inner nuclear membrane proteinsKing MC, Lusk C, Blobel G. Karyopherin-mediated import of integral inner nuclear membrane proteins. Nature 2006, 442: 1003-1007. PMID: 16929305, DOI: 10.1038/nature05075.