Sofia Quinodoz
725 N. Wolfe Street
PCTB 603
Inside every human cell, six feet of DNA and thousands of RNAs and proteins are packed into a tiny nucleus. This raises the question: How is the cell able to execute various complex reactions like gene regulation, RNA splicing, and ribosome assembly in this crowded molecular environment? Importantly, these molecules are not organized as a random tangle. Instead, DNA, RNA, and proteins of shared functions organize in specialized compartments called nuclear bodies, or biomolecular condensates. The most prominent of these, the nucleolus, acts as a massive factory, bringing together thousands of genes, RNAs, and proteins for ribosome assembly.
Nuclear bodies and biomolecular condensates are dynamic—changing in size and number across cell states and in diseases like cancer and neurodegeneration. Yet, despite being discovered over 200 years ago, their roles remain mysterious. Do nuclear bodies simply store factors or actively accelerate critical cellular reactions? Does their dysregulation lead to disease? These questions have persisted because we lacked tools to measure and dissect the structure and function of condensates.
Our lab is building cutting-edge tools to tackle these questions. We combine genomics, RNA biology, and super-resolution microscopy to uncover how nuclear bodies and other condensates organize molecules in the cell to orchestrate RNA processing, gene regulation, and more. Our goal is to reveal principles underlying nuclear organization, cellular compartmentalization, and RNA metabolism—and how their disruption contributes to various diseases.
*Quinodoz SA, *Jiang L, Abu-Alfa AA, Comi TJ, Zhao H, Yu Q, Wiesner LW, Botello JF, Donlic A, Soehalim E, Bhat P, Zorbas C, Wacheul L, Košmrlj A, Lafontaine DLJ, Klinge S, Brangwynne CP. Mapping and engineering RNA-driven architecture of the multiphase nucleolus. Nature. 2025;644:557-566. *Contributed equally to this work
Becker LA, Quinodoz SA, Comi TJ, Kimchi O, Knowles DA, Brangwynne CP. Genome-wide mapping of mesoscale neuronal RNA organization and condensation. bioRxiv. 2025;doi:10.1101/2025.04.19.649570
4D Nucleome Consortium; Dekker J, Oksuz BA, Zhang Y, Wang Y, Minsk MK, Kuang S, Yang L, Gibcus JH, Krietenstein N, Rando OJ, Xu J, Janssens DH, Henikoff S, Kukalev A, Willemin A, Winick-Ng W, Kempfer R, Pombo A, Yu M, Kumar P, Zhang L, Belmont AS, Sasaki T, van Schaik T, Brueckner L, Peric-Hupkes D, van Steensel B, Wang P, Chai H, Kim M, Ruan Y, Zhang R, Quinodoz SA, Bhat P, Guttman M, Zhao W, Chien S, Liu Y, Venev SV, Plewczynski D, Azcarate II, Szabó D, Thieme CJ, Szczepińska T, Chiliński M, Sengupta K, Conte M, Esposito A, Abraham A, Zhang R, Wang Y, Wen X, Wu Q, Yang Y, Liu J, Boninsegna L, Yildirim A, Zhan Y, Chiariello AM, Bianco S, Lee L, Hu M, Li Y, Barnett RJ, Cook AL, Emerson DJ, Marchal C, Zhao P, Park P, Alver BH, Schroeder A, Navelkar R, Bakker C, Ronchetti W, Ehmsen S, Veit A, Gehlenborg N, Wang T, Li D, Wang X, Nicodemi M, Ren B, Zhong S, Phillips-Cremins JE, Gilbert DM, Pollard KS, Alber F, Ma J, Noble WS, Yue F. An integrated view of the structure and function of the human 4D nucleome. bioRxiv. 2024;doi:10.1101/2024.09.17.613111
Chang YC, Quinodoz SA, Brangwynne CP. Live imaging of Alu elements reveals non-uniform euchromatin dynamics coupled to transcription. eLife. 2024;13:RP97537.
Bhat P, Chow A, Emert B, Ettlin O, Quinodoz SA, Strehle M, Takei Y, Burr A, Goronzy IN, Chen AW, Huang W, Ferrer JLM, Soehalim E, Goh ST, Chari T, Sullivan DK, Blanco MR, Guttman M. Genome organization around nuclear speckles drives mRNA splicing efficiency. Nature. 2024;629(8014):1165-1173.
Riback JA, Eeftens JM, Lee DSW, Quinodoz SA, Donlic A, Orlovsky N, Wiesner L, Beckers L, Becker LA, Strom AR, Rana U, Tolbert M, Purse BW, Kliener R, Kriwacki R, Brangwynne CP. Viscoelasticity and advective flow of RNA underlies nucleolar form and function. Mol Cell. 2023;83(17):3095-3107.
*Goronzy I, *†Quinodoz SA, Jachowicz JW, Ollikainen N, Bhat P, Guttman M. Simultaneous mapping of 3D structure and nascent RNAs argues against nuclear compartments that preclude transcription. Cell Rep. 2022;41(9):111730. *Contributed equally to this work, order listed alphabetically; † Co-corresponding author
Quinodoz SA, Guttman M. Essential roles for RNA in shaping nuclear organization. In Pombo A, Hetzer MW, Misteli T (eds). The Nucleus. 2nd Ed. Cold Spring Harbor Laboratory Press. 2022.
Quinodoz SA, Bhat P, Chovanec P, Jachowicz JW, Ollikainen N, Detmar E, Soehalim E, Guttman M. SPRITE: A genome-wide method for mapping higher-order 3D interactions in the nucleus using combinatorial split-and-pool barcoding. Nat Protoc. 2022;17(1):36-75.
Boninsegna S, Yildirim A, Polles G, Zhan Y, Quinodoz SA, Finn EH, Guttman M, Zhou XJ, Alber F. Integrative genome modeling platform reveals essentiality of rare contact events in 3D genome organizations. Nat Methods. 2022;19(8):938-949.
Arrastia MV, Jachowicz JW, Ollikainen N, Curtis MS, Lai C, Quinodoz SA, Selck DA, Ismagilov RF, Guttman M. Single-cell measurement of higher-order 3D genome organization with scSPRITE. Nat Biotechnol. 2022;40(1):64-73.
Quinodoz SA, Jachowicz JW, Bhat P, Ollikainen N, Banerjee AK, Goronzy IN, Blanco MR, Chovanec P, Chow A, Markaki Y, Thai J, Plath K, Guttman M. RNA promotes the formation of spatial compartments in the nucleus. Cell. 2021;184(23):5775-5790.
Vangala P, Murphy R, Quinodoz SA, Gellatly K, McDonel P, Guttman M, Garber M. High-resolution mapping of multiway enhancer-promoter interactions regulating pathogen detection. Mol Cell. 2020;80(2):359-373.
Quinodoz SA, Ollikainen N, Tabak B, Palla A, Schmidt JM, Detmar E, Lai M, Shishkin A, Bhat P, Takei Y, Trinh V, Aznauryan E, Russell P, Cheng C, Jovanovic M, Chow A, Cai L, McDonel P, Garber M, Guttman M. Higher-order inter-chromosomal hubs shape 3D genome organization in the nucleus. Cell. 2018;174(3):744-757.
Quinodoz S, Guttman M. Long noncoding RNAs: an emerging link between gene regulation and nuclear organization. Trends Cell Biol. 2014;24(11):651-663.