PUBLICATIONS:

Pulupa J*, McArthur NG*, Stathi O, Wang M, Zazhytska M, Pirozzolo ID, Nayar A, Shapiro L, Lomvardas S. Solid phase transitions as a solution to the genome folding paradox. Nature. 2025 May 14; 629(8012):820-829. doi: 10.1038/s41586-025-09043-6. PMCID: PMC40369073

This paper presents a solution to a fundamental mystery in genome organization: how regulatory DNA sequences make highly specific, stable contacts across vast genomic distances that persist throughout a cell’s lifespan. The discovery that transcription factors forming stable condensates with specific enhancer sequences in vivo has broad implications for understanding genome architecture, gene regulation, and diseases caused by chromosomal rearrangements. This discovery represents a paradigm shift in how we understand genome organization— moving from a focus primarily on DNA and histone modifications to recognizing that solid phase transitions are essential for creating stable, sequence-specific gene regulatory networks in longlived, post-mitotic cells like neurons.

Pourmorady AD, Bashkirova EV, Chiariello AM, Belagzhal H, Kodra A, Duffié R, Kahiapo J, Monahan K, Pulupa J, Schieren I, Osterhoudt A, Dekker J, Nicodemi M, Lomvardas S. RNA-mediated symmetry breaking enables singular olfactory receptor choice. Nature. 2023 Dec 23; 625(7995):181–188. doi:10.1038/s41586-023-06845-4. PMCID: PMC10765522

Pulupa J, Prior H, Johnson DS, Simon SM. Conformation of the nuclear pore in living cells is modulated by transport state. Elife. 2020 Dec 21;9. doi: 10.7554/eLife.60654. PMCID: PMC7752133

I developed polarized-total internal reflection microscopy (pol-TIRFM) as a superresolution technique to detect conformational changes in the nuclear pore complex (NPC) in living cells. With this technique, I provided the first in vivo evidence of a biologically relevant conformational change to the NPC scaffold upon cargo engagement. Although most super-resolution imaging techniques are applied to fixed cells and none provided information about the orientational dynamics of proteins, my technique has the potential to achieve mechanistic insight into the function of macromolecular complexes in vivo.

Pulupa J, Rachh M, Tomasini MD, Mincer JS, Simon SM. A coarse-grained computational model of the nuclear pore complex predicts Phe-Gly nucleoporin dynamics. J Gen Physiol. 2017 Oct 2;149(10):951966. doi: 10.1085/jgp.201711769. PMCID: PMC5694938

I used coarse-grained computational modeling to predict FG-Nucleoporin (FG-Nup) dynamics in nuclear pore complexes (NPCs), providing crucial insights into the mechanism of nuclear transport. In my model, FG-Nups formed different organizational states depending on FG-FG binding strength—from gel-like meshworks to liquid-crystal arrangements. Regardless of FG-FG binding strength, individual FG-Nup filaments translocated through the NPC at rates matching cargo translocation.

Takacs CN, Andreo U, Belote RL, Pulupa J, Scull MA, Gleason CE, Rice CM, Simon SM. Green fluorescent protein-tagged apolipoprotein E: A useful marker for the study of hepatic lipoprotein egress. Traffic. 2017 Mar;18(3):192-204. doi: 10.1111/tra.12467. PMCID: PMC5334657

Abrahamsson S, Ilic R, Wisniewski J, Mehl B, Yu L, Chen L, Davanco M, Oudjedi L, Fiche JB, Hajj B, Jin X, Pulupa J, Cho C, Mir M, El Beheiry M, Darzacq X, Nollmann M, Dahan M, Wu C, Lionnet T, Liddle JA, Bargmann CI. Multifocus microscopy with precise color multi-phase diffractive optics applied in functional neuronal imaging. Biomed Opt Express. 2016 Mar 1;7(3):855-69. doi: 10.1364/BOE.7.000855. PMCID: PMC4866461