Ross Buchan

Associate Professor, Molecular and Cellular Biology

The Buchan lab studies diverse topics related to RNA biology and proteostasis, spanning both basic and translational topics of research. We utilize yeast (S.cerevisiae) and various human cell line models, and apply a variety of genetic, cell biology and biochemical approaches in our work.

Historically, we have focused on characterizing the dynamics, composition and function of stress granules and P-bodies, which are membraneless biomolecular condensates enriched in non-translating mRNA-protein complexes (mRNPs), as well as a range of other non-coding RNAs and proteins of diverse function. An ongoing project is in studying the clearance mechanisms of these granules, dysregulation of which has been suggested to play an important role in the pathological mechanisms in Amyotrophic Lateral Sclerosis (ALS), other related neurodegenerative diseases and various cancers. Other related projects include compositionally assessing stress granules and P-bodies under conditions of interest, and determining the consequences of various biomolecules being sequestered in these condensates.

More recently, we have characterized a novel endolysosomal degradation mechanism by which TDP-43, an RNA-binding aggregation prone protein implicated in ALS pathology, is cleared in eukaryotic cells. Ongoing work here focuses on the precise molecular mechanisms of such clearance. We are also interested in how various TDP-43 proteostatic mechanisms interface under distinct conditions to limit the cytoplasmic mislocalization, accumulation and aggregation that is typically seen in ALS patients, and patients of other TDP-43 proteinopathies.

Finally, we have an interest in novel functions of mRNA 3’UTR sequences, in particular a means by which 3’UTRs may help scaffold nascently translated protein interactions by recruiting binding partner proteins.

Publications

2021

Bearss, J. J., S. Kr Padi, N. Singh, M. Cardo-Vila, J. H. Song, G. Mouneimne, N. Fernandes, Y. Li, M. R. Harter, J. Mc Gard, et al., "EDC3 phosphorylation regulates growth and invasion through controlling P-body formation and dynamics.", EMBO Rep, pp. e50835, 2021 Feb 15. PMID: 33586867

2020

Eshleman, N., X. Luo, A. Capaldi, and J.R. Buchan, "Alterations of signaling pathways in response to chemical perturbations used to measure mRNA decay rates in yeast.", RNA, vol. 26, issue 1, pp. 10-18, 2020 01. PMCID: PMC6913126 PMID: 31601735
Fernandes, N., L. Nero, S. M. Lyons, P. Ivanov, T. M. Mittelmeier, T. A. Bolger, and J.R. Buchan, "Stress Granule Assembly Can Facilitate but Is Not Required for TDP-43 Cytoplasmic Aggregation.", Biomolecules, vol. 10, issue 10, 2020 Sep 25. PMCID: PMC7650667 PMID: 32992901
Fernandes, N., and J.R. Buchan, "RPS28B mRNA acts as a scaffold promoting cis-translational interaction of proteins driving P-body assembly.", Nucleic Acids Res, vol. 48, issue 11, pp. 6265-6279, 2020 06 19. PMCID: PMC7293044 PMID: 32396167
Liu, G., A. Byrd, A. N. Warner, F. Pei, E. Basha, A. Buchanan, and J.R. Buchan, "Cdc48/VCP and Endocytosis Regulate TDP-43 and FUS Toxicity and Turnover.", Mol Cell Biol, vol. 40, issue 4, 2020 01 30. PMCID: PMC6996276 PMID: 31767634

2018

Fernandes, N., N. Eshleman, and J.R. Buchan, "Stress Granules and ALS: A Case of Causation or Correlation?", Adv Neurobiol, vol. 20, pp. 173-212, 2018. PMID: 29916020

2017

Liu, G., C. Lanham, J.R. Buchan, and M. E. Kaplan, "High-throughput transformation of Saccharomyces cerevisiae using liquid handling robots.", PLoS One, vol. 12, issue 3, pp. e0174128, 2017. PMCID: PMC5358765 PMID: 28319150
Liu, G., F. Pei, F. Yang, L. Li, A. Dipak Amin, S. Liu, J.R. Buchan, and W. C. Cho, "Role of Autophagy and Apoptosis in Non-Small-Cell Lung Cancer", Int J Mol Sci, vol. 18, issue 2, 2017 Feb 10. PMCID: PMC5343902 PMID: 28208579
Liu, G., A. N. Coyne, F. Pei, S. Vaughan, M. Chaung, D. C. Zarnescu, and J.R. Buchan, "Endocytosis regulates TDP-43 toxicity and turnover.", Nat Commun, vol. 8, issue 1, pp. 2092, 2017 12 12. PMCID: PMC5727062 PMID: 29233983

2016

Eshleman, N., G. Liu, K. McGrath, R. Parker, and J.R. Buchan, "Defects in THO/TREX-2 function cause accumulation of novel cytoplasmic mRNP granules that can be cleared by autophagy.", RNA, vol. 22, issue 8, pp. 1200-14, 2016 08. PMCID: PMC4931113 PMID: 27251550

2014

Buchan, J.R., "mRNP granules. Assembly, function, and connections with disease.", RNA Biol, vol. 11, issue 8, pp. 1019-30, 2014. PMCID: PMC4615263 PMID: 25531407

2013

Buchan, J.R., R-M. Kolaitis, P. J Taylor, and R. Parker, "Eukaryotic stress granules are cleared by autophagy and Cdc48/VCP function.", Cell, vol. 153, issue 7, pp. 1461-74, 2013 Jun 20. PMCID: PMC3760148 PMID: 23791177

2012

Buchan, J.R., A. P. Capaldi, and R. Parker, "TOR-tured yeast find a new way to stand the heat.", Mol Cell, vol. 47, issue 2, pp. 155-7, 2012 Jul 27. PMID: 22841000

2011

Buchan, J.R., J-H. Yoon, and R. Parker, "Stress-specific composition, assembly and kinetics of stress granules in Saccharomyces cerevisiae.", J Cell Sci, vol. 124, issue Pt 2, pp. 228-39, 2011 Jan 15. PMCID: PMC3010191 PMID: 21172806

2010

Buchan, J.R., T. Nissan, and R. Parker, "Analyzing P-bodies and stress granules in Saccharomyces cerevisiae.", Methods Enzymol, vol. 470, pp. 619-40, 2010. PMID: 20946828

2009

Buchan, J.R., and R. Parker, "Eukaryotic stress granules: the ins and outs of translation.", Mol Cell, vol. 36, issue 6, pp. 932-41, 2009 Dec 25. PMCID: PMC2813218 PMID: 20064460

2008

Buchan, J.R., D. Muhlrad, and R. Parker, "P bodies promote stress granule assembly in Saccharomyces cerevisiae.", J Cell Biol, vol. 183, issue 3, pp. 441-55, 2008 Nov 03. PMCID: PMC2575786 PMID: 18981231

2007

Buchan, J.R., and R. Parker, "Molecular biology. The two faces of miRNA.", Science, vol. 318, issue 5858, pp. 1877-8, 2007 Dec 21. PMID: 18096794
Buchan, J.R., and I. Stansfield, "Halting a cellular production line: responses to ribosomal pausing during translation.", Biol Cell, vol. 99, issue 9, pp. 475-87, 2007 Sep. PMID: 17696878

2006

Buchan, J.R., L. S. Aucott, and I. Stansfield, "tRNA properties help shape codon pair preferences in open reading frames.", Nucleic Acids Res, vol. 34, issue 3, pp. 1015-27, 2006. PMCID: PMC1363775 PMID: 16473853