Sara and Frank McKnight Fellow
Randal Halfmann, Ph.D., is the current holder of the Sara and Frank McKnight Fellowship, which supports postdoctoral fellows who choose to conduct independent research within the Department of Biochemistry.
Dr. Halfmann, a native of Coleman, Texas, received his bachelor's in genetics from Texas A&M University and his doctorate in biology at the Massachusetts Institute of Technology, under the guidance of Susan Lindquist, Ph.D.
His research centers on prions: misfolded, self-perpetuating proteins. Prions are notoroious for their involvement in fatal brain infections such as bovine spongiform encephalopathy – "mad cow disease" – in cattle and variant Creutzfeldt-Jakob Disease (vCJD) in humans. But research, including a recent study at UT Southwestern that shows a role for prions in immune response, is beginning to reveal a benevolent side of prions.
Dr. Halfmann studies prions in yeast, focusing on the processes that regulate prion formation, and how prions change the way cells behave. "Despite tons and tons of work, we're only chipping away at understanding protein folding," he said. "There are underexplored areas of protein folding – including how and when proteins aggregate. There are lots of reasons to think aggregation, and prion formation, has important functions that we haven’t yet discovered.”
Dr. Halfmann has also received the NIH’s Early Independence Award, which is geared to “provide a mechanism for exceptional, early career scientists to omit traditional post-doctoral training, and move into independent research positions at US institutions directly upon completion of their graduate degrees.”
The McKnight Fellowship and Early Indepence award allow Dr. Halfmann to begin working as a principal investigator, without working under a faculty member advisor as in a traditional postdoctoral position.
(† denotes corresponding author, *equal author)
Holmes DL, Lancaster AK, Lindquist S, and Halfmann R†. (2013). Heritable remodeling of yeast multicellularity by an environmentally responsive prion. Cell 153(1), 153-165.
Wang G, Wang X, Yu H, Wei S, Williams N, Holmes DL, Halfmann R, Naidoo J, Wang L, Li L, Chen S, Harran P, Lei X, Wang X. (2013). Small-molecule activation of the TRAIL receptor DR5 in human cancer cells. Nature Chemical Biology 9, 84–89.
Halfmann R†*, Wright J*, Alberti S, Lindquist S, Rexach M. (2012). Prion formation by a yeast GLFG nucleoporin. Prion 6(4).
Halfmann R*, Jarosz DF*, Jones SK, Chang A, Lancaster AK, Lindquist S. (2012). Prions are a common mechanism for phenotypic inheritance in wild yeasts. Nature 482(7385), 363-8.
Halfmann, R.*, Alberti, S.*, Krishnan, R., Lyle, N., Pappu, R., Lindquist, S. (2011). Opposing effects of glutamine and asparagine govern prion formation by intrinsically disordered proteins. Molecular Cell 43(1), 72-84.
O'Donnell, C.W., Waldispühl, J., Lis, M., Halfmann, R., Devadas, S., Lindquist, S., Berger, B. (2011). A method for probing the mutational landscape of amyloid structure. Bioinformatics 27(13):i34-42.
Halfmann, R., Lindquist, S. (2010). Epigenetics in the extreme: Prions and the inheritance of environmentally acquired traits. Science 330(6004), 629-32.
Alberti, S., Halfmann, R., and Lindquist, S. (2010). Biochemical, cell biological and genetic assays to analyze amyloid and prion aggregation in yeast. For: Guide to Yeast Genetics: Functional Genomics, Proteomics, and Other Systems Analysis, 2nd Ed. Methods in Enzymology 470, 709-731.
Halfmann, R., Alberti, S., Lindquist, S. (2010). Prions, protein homeostasis, and phenotypic diversity. Trends in Cell Biology 20, 125-33.
Alberti, S.*, Halfmann, R.*, King, O., Kapila, A., and Lindquist, S. (2009). A systematic survey identifies prions and illuminates sequence features of prionogenic proteins. Cell 137, 146-58.