Shirin Bahmanyar, PhD
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Research Summary
Our lab is focused on understanding mechanisms that control membrane dynamics at the nuclear envelope to ensure genome protection during early embryogenesis and somatic cell division.
Extensive Research Description
Our lab is interested in mechanisms that drive organelle structure, identity, and dynamics. In particular, we study the nuclear envelope - a specialized compartment that surrounds and protects the genome. The nuclear envelope is highly dynamic in both interphase and mitotic cells. Defects in nuclear envelope dynamics cause DNA damage and disrupt nuclear functions and as such are highly relevant to disease, yet little is known about mechanisms that control membrane dynamics at the NE.
Membrane dynamics at nearly all membrane bound organelles depend on the composition of bilayer lipids. Almost nothing is known about the membrane lipid composition of the nuclear envelope. This is in part because the nuclear envelope is not a stand-alone organelle but is continuous with the expansive endoplasmic reticulum (ER) making it difficult to biochemically distinguish between their lipid content. The ER serves as a platform for de novo lipid synthesis. Because lipids diffuse rapidly in the two dimensional network of the ER and nuclear envelope it has long been assumed that their lipid composition is the same. However, emerging evidence suggests that the nuclear envelope harbors distinct regulators of phospholipid metabolism that may lead to its unique lipid composition.
Our lab harnesses the powerful tools to identify genetic pathways and gene function in C. elegans and cutting-edge microscopy approaches amenable to live imaging of mammalian cells to define mechanisms that control nuclear envelope dynamics. We study nuclear envelope reformation in mitosis and interphase nuclear rupture and repair - two specialized processes that require local and global changes in membrane structure and protein recruitment and as such provide tractable systems to dissect the molecular mechanisms underpinning lipid-mediated regulation of nuclear envelope dynamics in genome protection.
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Research Interests
Endoplasmic Reticulum; Molecular Biology; Nuclear Envelope; Organelles; Caenorhabditis elegans; Lamins; Lipid Metabolism; Diseases
Public Health Interests
Cancer
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Selected Publications
- Ndc1 drives nuclear pore complex assembly independent of membrane biogenesis to promote nuclear formation and growthMauro MS, Celma G, Zimyanin V, Magaj MM, Gibson KH, Redemann S, Bahmanyar S. Ndc1 drives nuclear pore complex assembly independent of membrane biogenesis to promote nuclear formation and growth ELife 2022, 11: e75513. PMID: 35852146, PMCID: PMC9296133, DOI: 10.7554/elife.75513.
- Cell cycle regulation of ER membrane biogenesis protects against chromosome missegregationMerta H, Carrasquillo Rodríguez JW, Anjur-Dietrich MI, Vitale T, Granade ME, Harris TE, Needleman DJ, Bahmanyar S. Cell cycle regulation of ER membrane biogenesis protects against chromosome missegregation Developmental Cell 2021, 56: 3364-3379.e10. PMID: 34852214, PMCID: PMC8692360, DOI: 10.1016/j.devcel.2021.11.009.
- Coupling lipid synthesis with nuclear envelope remodelingBarger SR, Penfield L, Bahmanyar S. Coupling lipid synthesis with nuclear envelope remodeling Trends In Biochemical Sciences 2021, 47: 52-65. PMID: 34556392, PMCID: PMC9943564, DOI: 10.1016/j.tibs.2021.08.009.
- Lipid and protein dynamics that shape nuclear envelope identityBahmanyar S, Schlieker C. Lipid and protein dynamics that shape nuclear envelope identity Molecular Biology Of The Cell 2020, 31: 1315-1323. PMID: 32530796, PMCID: PMC7353140, DOI: 10.1091/mbc.e18-10-0636.
- The Endoplasmic Reticulum Regulates Membraneless Organelles through Contact SitesLee S, Bahmanyar S. The Endoplasmic Reticulum Regulates Membraneless Organelles through Contact Sites Biochemistry 2020, 59: 1716-1717. PMID: 32324384, PMCID: PMC10026189, DOI: 10.1021/acs.biochem.0c00232.
- Regulated lipid synthesis and LEM2/CHMP7 jointly control nuclear envelope closurePenfield L, Shankar R, Szentgyörgyi E, Laffitte A, Mauro MS, Audhya A, Müller-Reichert T, Bahmanyar S. Regulated lipid synthesis and LEM2/CHMP7 jointly control nuclear envelope closure Journal Of Cell Biology 2020, 219: e201908179. PMID: 32271860, PMCID: PMC7199858, DOI: 10.1083/jcb.201908179.
- Dynamic nanoscale morphology of the ER surveyed by STED microscopySchroeder LK, Barentine AES, Merta H, Schweighofer S, Zhang Y, Baddeley D, Bewersdorf J, Bahmanyar S. Dynamic nanoscale morphology of the ER surveyed by STED microscopy Journal Of Cell Biology 2018, 218: 83-96. PMID: 30442642, PMCID: PMC6314542, DOI: 10.1083/jcb.201809107.
- The Inner Nuclear Membrane Takes On Lipid MetabolismMerta H, Bahmanyar S. The Inner Nuclear Membrane Takes On Lipid Metabolism Developmental Cell 2018, 47: 397-399. PMID: 30458132, DOI: 10.1016/j.devcel.2018.11.005.
- Dynein-pulling forces counteract lamin-mediated nuclear stability during nuclear envelope repairPenfield L, Wysolmerski B, Mauro M, Farhadifar R, Martinez MA, Biggs R, Wu HY, Broberg C, Needleman D, Bahmanyar S. Dynein-pulling forces counteract lamin-mediated nuclear stability during nuclear envelope repair Molecular Biology Of The Cell 2018, 29: mbc.e17-06-0374. PMID: 29386297, PMCID: PMC5905298, DOI: 10.1091/mbc.e17-06-0374.