Josh Riback

1/ Excited to share a new preprint from the lab! We identify NSD3 as a novel regulator of chromatin 3D structure. 🧵

Check out this fun thread on the visual story of #RibackLab 's collaborative work with #Goodell_Lab. Excited to see it in print today in @cp-cell.bsky.social. Thanks again to all team members, especially @gandhardatar.bsky.social and @sciencyelmira.bsky.social .

It’s hard to imagine the lab without you @evdokiiap.bsky.social. As my first postdoc, you built the cell-biology foundation and pushed into new biophysics to reveal how nucleolar thermodynamics is regulated. Can’t wait for your manuscript to be released. Wishing you the best in what’s next!

Setting up tomorrow’s phase transition. Holiday lab party imminent! #RibackLab #CellularPhysicalChemistryGroup

Biomolecular Phase Boundaries are Described by a Solubility Product That Accounts for Variable Stoichiometry and Soluble Oligomers The solubility product is a rigorous description of the phase boundary for salt precipitation and has previously been shown to qualitatively describe the condensation of biomolecules. Here we present a derivation of the solubility product showing that the solubility product is also a robust description of biomolecule phase boundaries if care is taken to account for soluble oligomers and variable composition within the dense phase. Our calculation describes equilibrium between unbound monomers, the dense phase, and an ensemble of oligomer complexes with significant finite-size contributions to their free energy. The biomolecule phase boundary very nearly resembles the power law predicted by the solubility product when plotted as a function of the monomer concentrations. However, this simple form is concealed by the presence of oligomers in the dilute phase. Accounting for the oligomer ensemble introduces complexities to the power law phase boundary including re-entrant behavior and large shifts for stoichiometrically matched molecules. We show that allowing variable stoichiometry in the dense phase expands the two phase region, which appears as curvature of the phase boundary on a double-logarithmic plot. Furthermore, this curvature can be used to predict variations in the dense phase composition at different points along the phase boundary. Finally, we show how the solubility product power law can be identified in experiments by using dilute phase dissociation constants to account for the oligomer ensemble.

New publication! How to read the curves in biomolecular phase diagrams! A collaboration between the Schmit Group and Jonathon Ditlev, Les Loew, and @ani-chattaraj.bsky.social. 1/7 pubs.acs.org/doi/10.1021/...

🧪 Geometry beats chemistry: we show that self-assembly can be controlled by tuning large-scale geometric parameters rather than molecular binding energies.
PNAS: doi.org/10.1073/pnas...
Video summary: www.youtube.com/watch?v=6FS3...
#SelfAssembly #Biophysics #PhysicsOfLife

Our review on the physics of phase separation in cells has been published by Rep. Prog. Phys. 🎉 doi.org/10.1088/1361...

We hope that the text and citations are helpful for anyone interested in physical descriptions of condensates in cells!

Thank you so much Allan!

Thank you @leukemiaresearch.bsky.social ! This discovery would not have been possible without your support!

Disparate leukemia mutations converge on nuclear phase-separated condensates Mutant NPM1 and various leukemia oncofusions form biophysically indistingishable nuclear condensates, termed C-bodies, which orchestrate leukemogenic gene expression. These findings consolidate diverse genetic lesions into a shared pathogenic mechanism in AML.

Now online! Disparate leukemia mutations converge on nuclear phase-separated condensates

Scientists uncover nuclear droplets that link multiple leukemias revealing new therapeutic target A hidden structure inside the cell is rewriting how scientists understand leukemia. Beneath the microscope, what looked like disorder turned out to follow...

Scientists uncover nuclear droplets that link multiple #leukemias revealing new #therapeuticTarget.
@gandhardatar.bsky.social @sciencyelmira.bsky.social @goodell-lab.bsky.social @superscijew.bsky.social et al
@cellcellpress.bsky.social @bcmhouston.bsky.social www.bcm.edu/news/scienti...

Thrilled to share that my third year as a postdoc in the Goodell Lab at BCM begins with a paper published in @cellpress.bsky.social.

Grateful for an opportunity to be a part of this incredible multidisciplinary project.

Thanks so much, Ben! Looking forward to catching up in person in a few days!

Thank you, Vikram!!

I'm so appreciative that you joined and played such a vital part in the story! We wouldn’t have achieved this without you showing that the principles seen in cell lines are also present in patient samples and mouse models.

Thank you, Jason!!!

Thanks, Kyle!!

Thanks, Jorine!

(10/10) Thank you to everyone in the #RibackLab and @goodell-lab.bsky.social lab, especially to @gandhardatar.bsky.social and @sciencyelmira.bsky.social for this amazing work, and to NCI, CPRIT, @leukemiaresearch.bsky.social, Searle Scholars, and Ted Nash Long Life Foundation.

(9/10) In summary, our work establishes a convergent mechanism for gene regulation in the most common forms of adult leukemia and introduces C-bodies as a promising therapeutic target.

(8/10) Do other mutations follow the same strategy? We find that KMT2A and Nucleoporin oncofusions leverage the same protein networks to form biophysically indistinguishable C-bodies, pointing towards a shared mechanism across leukemia subtypes.

(7/10) Unexpectedly, we find that C-bodies – and not cytoplasmic NPM1c – are essential for maintaining cell growth and expansion in vivo, highlighting a new role for condensate-driven nuclear organization in disease.

(6/10) Through extensive in vitro studies, we show that modifying C-body formation and/or composition – through targeted degradation of NPM1c or inhibition of XPO1 or MENIN – can halt HOXA gene expression and prevent cell growth.

(5/10) How do these network interactions contribute to C-body formation? Our quantitative microscopy and biophysical approaches demonstrate that NPM1c forms C-bodies through multi-component phase separation, similar to its WT counterpart in the nucleolus.

(4/10) NPM1c condensates recruit a network of proteins - including XPO1, NUP98, and chromatin remodelers like KMT2A and MENIN - and coordinate their assembly at the HOXA chromatin. We termed this new condensate the coordinating body (C-body).

(3/10) We focused on NPM1c – the most common driver of AML – which is aberrantly exported to the cytoplasm. Endogenous protein tagging showed NPM1c in nuclear condensates distinct from WT NPM1, despite few amino acid differences.

Disparate leukemia mutations converge on nuclear phase-separated condensates Mutant NPM1 and various leukemia oncofusions form biophysically indistingishable nuclear condensates, termed C-bodies, which orchestrate leukemogenic gene expression. These findings consolidate divers...

(2/10) We found that disparate drivers of acute myeloid leukemia (AML) – including NPM1c, KMT2A-r, and nucleoporin oncofusions – form nuclear condensates with a shared set of proteins including XPO1 and MENIN to drive leukemic gene expression (e.g. HOXA). www.cell.com/cell/fulltex...

(1/10) How do diverse leukemia mutations converge on the same molecular program? In #RibackLab first manuscript @cp-cell.bsky.social, collaboration with @goodell-lab.bsky.social shows that disparate mutations rewire shared protein networks to form nuclear condensates called C-bodies.

Patrick's paper is finally out, a label-free method to measure the composition of multicomponent biomolecular condensates!

Brisket served! Look at that smoke ring; Physical Chemistry is in action!