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Halfmann Lab

We seek to understand aging, the inexorable decline in cellular and bodily function that results from the unidirectional nature of self-assembly by supersaturated proteins.

Research Summary

What drives protein self-assembly?

Research Areas

Molecular and Cell Biology, Development and Regeneration, Evolutionary Biology, Systems Biology


Human cell lines, Yeast, Mice

The Halfmann Lab uses genetic, biochemical, and biophysical approaches to better understand the processes that cause certain proteins like prions to aggregate, or cluster together. Historically, prions have had a bad reputation and have been implicated in Creutzfeldt-Jakob disease, ALS, Alzheimer's, and Parkinson's. However, the lab’s research has discovered that prions are also important for normal cellular processes including immune responses that fight off viruses.

Halfmann’s work has done much to deepen our understanding of prions, illustrating that they can allow yeast cells to coordinate their metabolism and cooperate like more complex organisms. The lab has demonstrated that prions function as part of innate immune responses in humans.

At the heart of the Halfmann Lab's research is the metastable state of molecules called supersaturation, where a solution exceeds its normal limit of concentration for those molecules.

The Halfmann Lab uses cutting-edge microscopy and flow cytometry technology to look inside living cells and “see” what happens when supersaturated proteins transition from a liquid to a solid state. Their mission is to understand how these phase transitions are regulated in cells and how this form of signaling is involved in various healthy and disease-causing processes including inflammation and aging.

Principal Investigator

Randal Halfmann

Associate Investigator

Stowers Institute for Medical Research

Portrait of Randal Halfmann

Get to know the lab


The central tenet of our research holds that nucleation barriers render living proteomes perpetually high energy, or supersaturated, with respect to ordered protein assemblies such as amyloids, and this provides a driving force for inevitable and irreversible declines in cellular phenotypic potential.

Group of people posing on a bridge

Our Team

Featured Publications

Pathologic polyglutamine aggregation begins with a self-poisoning polymer crystal

Kandola T, Venkatesan S, Zhang J, Lerbakken B, Schulze AV, Blanck JF, Wu J, Unruh J, Berry P, Lange JJ, Box A, Cook M, Sagui C, Halfmann R. eLife 2023;12:RP86939. doi: 10.7554/eLife.86939.

A nucleation barrier spring-loads the CBM signalosome for binary activation

Rodriguez Gama A, Miller T, Lange JJ, Unruh JR, Halfmann R. eLife. 2022;11:e79826. doi: 10.7554/eLife.79826.

Quantifying nucleation in vivo reveals the physical basis of prion-like phase behavior

Khan T, Kandola TS, Wu J, Venkatesan S, Ketter E, Lange JJ, Rodriguez Gama A, Box A, Unruh JR, Cook M, Halfmann R. Mol Cell. 2018;71:155-168.e157.

A self-perpetuating repressive state of a viral replication protein blocks superinfection by the same virus

Zhang XF, Sun R, Guo Q, Zhang S, Meulia T, Halfmann R, Li D, Qu F. PLoS Pathog. 2017;13:e1006253. doi: 1006210.1001371/journal.ppat.1006253.

Prion-like polymerization underlies signal transduction in antiviral immune defense and inflammasome activation

Cai X, Chen J, Xu H, Liu S, Jiang QX, Halfmann R, Chen ZJ. Cell. 2014;156:1207-1222.

Heritable remodeling of yeast multicellularity by an environmentally responsive prion

Holmes DL, Lancaster AK, Lindquist S, Halfmann R. Cell. 2013;153:153-165.

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