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
- Direct binding of ESCRT protein Chm7 to phosphatidic acid-rich membranes at nuclear envelope herniations.Thaller 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. The Journal Of Cell Biology 2021, 220 PMID: 33464310, PMCID: PMC7816628, DOI: 10.1083/jcb.202004222.
- Nuclear accumulation of CHMP7 initiates nuclear pore complex injury and subsequent TDP-43 dysfunction in sporadic and familial ALS.Coyne 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.
- An ESCRT-LEM protein surveillance system is poised to directly monitor the nuclear envelope and nuclear transport system.Thaller 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 PMID: 30942170, PMCID: PMC6461442, DOI: 10.7554/eLife.45284.
- A Programmable DNA Origami Platform for Organizing Intrinsically Disordered Nucleoporins within Nanopore Confinement.Fisher PDE, Shen Q, Akpinar B, Davis LK, Chung KKH, Baddeley D, Saric A, Melia TJ, Hoogenboom BW, Lin C, Lusk CP. A Programmable DNA Origami Platform for Organizing Intrinsically Disordered Nucleoporins within Nanopore Confinement. ACS Nano 2018, 12: 1508-1518. PMID: 29350911, PMCID: PMC5834394, DOI: 10.1021/acsnano.7b08044.
- Congenital Heart Disease Genetics Uncovers Context-Dependent Organization and Function of Nucleoporins at Cilia.Del Viso F, Huang F, Myers J, Chalfant M, Zhang Y, Reza N, Bewersdorf J, Lusk CP, Khokha MK. Congenital Heart Disease Genetics Uncovers Context-Dependent Organization and Function of Nucleoporins at Cilia. Developmental Cell 2016, 38: 478-92. PMID: 27593162, PMCID: PMC5021619, DOI: 10.1016/j.devcel.2016.08.002.
- Surveillance of nuclear pore complex assembly by ESCRT-III/Vps4.Webster 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.