Eric Ross Professor

Office: Mrb 343

Phone: (970) 491-0688

Education

  • Ph.D., Mayo Graduate School

About

Numerous diseases including Parkinson's disease, Alzheimer's disease, late-onset diabetes, and the transmissible spongiform encephalopathies are associated with the formation of ordered protein aggregates, called amyloid fibrils. Despite considerable study, relatively little is known about the forces that drive amyloid aggregation. The major focus of my lab is defining how the amino acid sequence of a protein affects its propensity to form amyloid aggregates. 

We are using yeast prions as a model to address this question.  A prion is an infectious protein.  In yeast, a number of different prions have been identified, each involving the conversion of proteins from a soluble form into an insoluble amyloid form.  The rapid growth rate and ease of genetic manipulation of yeast make yeast prions a powerful model system for studying the causes and consequences of amyloid aggregation.

All but one of the yeast prion proteins contains a region that is enriched in the amino acids glutamine and asparagine.  Such glutamine/asparagine-rich regions are common in both the yeast and human genome, but predicting whether a given glutamine/asparagine-rich protein will form amyloid aggregates has proven difficult.  We recently developed a Prion Aggregation Prediction Algorithm (PAPA) that for the first time allows accurate prediction of the aggregation propensity of glutamine/asparagine-rich proteins (this algorithm can be found at http://combi.cs.colostate.edu/supplements/papa/). 

Remarkably, when PAPA is used to scan the human genome, four of the highest scoring proteins are ones that have recently been linked to various degenerative diseases, including ALS and certain forms of dementia.  We are currently examining some of the other high-scoring proteins, as well as working to refine the prediction accuracy of PAPA.

Additional interests include using yeast prions to examine the cellular response to amyloid, to identify potential therapeutic targets for the treatment of amyloid diseases and to examine why of all of the amyloid diseases, only a small subset are infectious.

Publications

Composition-based prediction and rational manipulation of prion-like domain recruitment to stress granulesBoncella AE, Shattuck JE, Cascarina SM, Paul KR, Baer MH, Fomicheva A, Lamb AK, Ross EDProc Natl Acad Sci U S A, 117:5826-5835, 2020
The prion-like protein kinase Sky1 is required for efficient stress granule disassemblyShattuck JE, Paul KR, Cascarina SM, Ross EDNature Communications, 10:3614, 2019
Sequence features governing aggregation or degradation of prion-like proteinsCascarina SM, Paul KR, Machihara S, Ross EDPLoS Genet., 14:e1007517, 2018
Effects of Mutations on the Aggregation Propensity of the Human Prion-Like Protein hnRNPA2B1Paul KR, Molliex A, Cascarina S, Boncella AE, Taylor JP, Ross EDMol Cell Biol., 37:pii: e00652-16, 2017
The effects of glutamine/asparagine content on aggregation and heterologous prion induction by yeast prion-like domainsShattuck JE, Waechter AC, Ross EDPrion, 11:249-264, 2017
Generating new prions by targeted mutation or segment duplicationPaul KR, Hendrich CG, Waechter A, Harman MR, Ross EDProc Natl Acad Sci U S A, 112:8584-9, 2015
Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALSKim HJ, Kim NC, Wang YD, Scarborough EA, Moore J, Diaz Z, MacLea KS, Freibaum B, Li S, Molliex A, Kanagaraj AP, Carter R, Boylan KB, Wojtas AM, Rademakers R, Pinkus JL, Greenberg SA, Trojanowski JQ, Traynor BJ, Smith BN, Topp S, Gkazi AS, Miller J, Shaw CE, Kottlors M, Kirschner J, Pestronk A, Li YR, Ford AF, Gitler AD, Benatar M, King OD, Kimonis VE, Ross ED, Weihl CC, Shorter J, Taylor JPNature, 495:467-473, 2013