Randal Halfmann, PhD
Associate Investigator
Faculty, The Graduate School of the Stowers Institute for Medical Research
Adjunct Professor, Department of Molecular and Integrative Physiology, University of Kansas School of Medicine

BS, Genetics, Texas A&M University
PhD, Biology, Massachusetts Institute of Technology

Areas of Interest 
Aging, Protein Biophysics, Innate Immunity, Prions, Synthetic Biology

As a genetics major at Texas A&M University, Randal Halfmann, PhD, attempted to create a new species of cotton. Manipulating the plant’s genetic material sent his scientific curiosity into overdrive. “I would wake up and literally almost spring out of bed with an idea like, ’Aha! This is the experiment I want to do!’”

While that experience helped cement Halfmann’s career path in research, Halfmann traces his enthusiasm for science back even further, to his upbringing in the rural west Texas town of Coleman (population 4,518). “There weren’t the usual entertainment options, so I spent a lot of time outside and with plants and animals,” he says. In high school, Halfmann was active in Future Farmers of America (FFA) and went to Texas A&M on an agriculture scholarship, graduating with a degree in genetics in 2004. Halfmann embarked on his doctorate degree at the Massachusetts Institute of Technology (MIT) and joined the lab of Susan Lindquist, PhD, who was studying particles of misfolded proteins known as prions. He bypassed traditional postdoctoral training for an independent position at the University of Texas Southwestern Medical Center. In 2015, he became an assistant investigator at the Stowers Institute.

Halfmann relishes the day-to-day work of running his lab at Stowers and all that it entails, from training students and planning experiments to keeping up with the latest scientific literature and brainstorming with his team. He credits the Institute’s unique environment, untethered from the demands of securing funding, for giving him the freedom to take risks and conduct inventive research.

“Science has a lot in common with art because you’re creating something new, and you’re trying to communicate a new idea. As a scientist, finding one’s source of creativity and nurturing that is critical,” he says.

When he’s not making new discoveries in the lab, Halfmann enjoys gardening, foraging for wild mushrooms, and spending time with his wife and twin daughters.

Research Summary 

The Halfmann Lab is using 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 — probably best known for accumulations in the brain that cause mad cow disease and its human counterpart Creutzfeldt-Jakob disease. Prion aggregates have also been implicated in devastating neurodegenerative diseases, including ALS, Alzheimer's, and Parkinson's. However, the lab’s research has discovered that prions are important for normal cellular processes as well, including immune responses that fight off viruses.

Halfmann’s work has done much to deepen our understanding of prions — both their bad and good sides. Two of his publications from the Lindquist Lab, a 2009 Cell paper and a 2012 Nature paper, demonstrated that prions aren’t “all bad” and that several proteins in normal yeast can aggregate into prion forms that help yeast adapt to environmental change. Before these studies, which identified nineteen new prions, few prions were known. And during his time at the University of Texas Southwestern Medical Center, Halfmann showed that prions can allow yeast cells to coordinate their metabolism and cooperate like more complex organisms. He also collaborated with Zhijian (James) Chen, PhD, on studies showing that prions function as part of innate immune responses in our own cells. Since joining the Stowers Institute in 2015, Halfmann continues to study prions in both yeast and human cells.

At the heart of the Halfmann Lab's research is an unstable state of molecules called supersaturation -- wherein a solution is more concentrated than normally possible. A familiar example of this phenomenon is honey in a jar. It is normally liquid, but given enough time, the sugar will spontaneously crystallize and solidify the honey.

This type of transition fascinates Halfmann. His lab is using 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 crystal state, releasing energy. They want to understand how these phase transitions are regulated in cells and how this newly identified form of signaling is involved in various healthy and disease-causing processes including inflammation and aging.

Featured Publications 
Rodriguez Gama A, Miller T, Lange JJ, Unruh JR, Halfmann R. eLife. 2022;11:e79826. doi: 10.7554/eLife.79826.
Kandola T, Venkatesan S, Zhang J, Lerbakken B, Blanck JF, Wu J, Unruh J, Berry P, Lange LL, Von Schulze A, Box A, Cook M, Sagui C, Halfmann R. Preprint. bioRxiv 458132; doi: https://doi.org/10.1101/2021.08.29.458132
Khan T, Kandola TS, Wu J, Ketter E, Venkatesan S, Lange JL, Gama AR, Box A, Unruh JR, Cook M, and Halfmann R. Molecular Cell. 2018;7(1):155-168.
Zhang XF, Sun R, Guo Q, Zhang S, Meulia T, Halfmann R, Li D, Qu F. PLoS Pathogens. 2017;13(3):e1006253.
Cai X, Chen J, Xu H, Liu S, Jiang QX, Halfmann R, Chen ZJ. Cell. 2014;156:1207-1222.
Holmes DL, Lancaster AK, Lindquist S, Halfmann R. Cell. 2013;153:153-165.

American Cancer Society Research Scholar

Basil O’Connor Starter Scholar

National Institute of Health Director’s Early Independence Award

Sara and Frank McKnight Fellow, UT Southwestern Medical Center

National Science Foundation Graduate Research Fellow

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