Brian Raught, PhD

Ubiquitin, a small and ancient signaling protein, is chemically attached to other proteins in the cell to mark them for destruction (in addition to other critical functions). Malfunctions in the ubiquitin system have been implicated in many disease states, including neurodegenerative disorders (e.g. Alzheimer's and Parkinson's diseases) and cancer.

The ubiquitin-like modifiers (ULMs) comprise a diverse group of small polypeptides (SUMO, ISG15, NEDD8/RUB1, URM1, FAT10, etc.) which, like ubiquitin, are also covalently conjugated to 'target' proteins (or other biomolecules) in a reversible manner. While these modifiers appear to play many critical roles in cell function, most of them remain very poorly understood.

Mass spectrometry (MS) has emerged as an extremely powerful tool to screen complex biological samples for many different types of post-translational modifications. Using a combination of MS and a novel software tool (SUMmOn), my colleagues and I developed the first automated approach for the identification of ULM target proteins and ULM attachment sites.
  • Using this technology, along with high throughput and quantitative proteomics approaches, my laboratory is focused on:
    1. defining ubiquitin and ULM target protein populations in normal cells, and characterizing how these target populations differ between cell types, how they change throughout the cell cycle, and how they are altered in response to extracellular stress or stimuli. These data will help us to better define the cellular processes modulated by each of the different ULMs.
    2. defining how ubiquitin and ULM target protein populations are altered in various disease states. This information will shed light on how ubiquitin and the ULMs are affected by, or contribute to, various types of pathologies.
    3. characterizing how modification by ubiquitin or a ULM alters the activity of specific proteins involved in vital cellular processes. This will provide us with more specific knowledge regarding how a particular modification alters the function of an individual protein.
    4. better understanding the amino acid sequence or structural elements that define the recognition sites for ubiquitin or ULM attachment. This information will help us to better understand and predict ubiquitin/ULM modification sites.
By shedding light on these critically important, yet poorly understood, signaling proteins, we hope to better understanding their roles in neurological diseases, cancer and viral infection.
 
Nat Struct Mol Biol. 2019 Nov 04;:
Wei Y, Resetca D, Li Z, Johansson-Åkhe I, Ahlner A, Helander S, Wallenhammar A, Morad V, Raught B, Wallner B, Kokubo T, Tong Y, Penn LZ, Sunnerhagen M
Theranostics. 2019;9(23):7003-7015
Mangé A, Coyaud E, Desmetz C, Laurent E, Béganton B, Coopman P, Raught B, Solassol J
Science. 2019 10 25;366(6464):460-467
Lu Y, Zheng Y, Coyaud É, Zhang C, Selvabaskaran A, Yu Y, Xu Z, Weng X, Chen JS, Meng Y, Warner N, Cheng X, Liu Y, Yao B, Hu H, Xia Z, Muise AM, Klip A, Brumell JH, Girardin SE, Ying S, Fairn GD, Raught B, Sun Q, Neculai D
Proteomics. 2019 Oct 16;:e1900139
Botham A, Coyaud E, Nirmalanandhan VS, Gronda M, Hurren R, Maclean N, St-Germain J, Mirali S, Laurent E, Raught B, Schimmer A
Nat Microbiol. 2019 Oct 14;:
D'Costa VM, Coyaud E, Boddy KC, Laurent EMN, St-Germain J, Li T, Grinstein S, Raught B, Brumell JH
Mol Cell Proteomics. 2019 Nov;18(11):2285-2297
Chan CJ, Le R, Burns K, Ahmed K, Coyaud E, Laurent EMN, Raught B, Melançon P
J Biol Chem. 2019 Nov 01;294(44):16172-16185
Frendo-Cumbo S, Jaldin-Fincati JR, Coyaud E, Laurent EMN, Townsend LK, Tan JMJ, Xavier RJ, Pillon NJ, Raught B, Wright DC, Brumell JH, Klip A
Sci Rep. 2019 Aug 28;9(1):12471
Dho SE, Silva-Gagliardi N, Morgese F, Coyaud E, Lamoureux E, Berry DM, Raught B, McGlade CJ
EMBO J. 2019 Jul 15;38(14):e101109
Gheiratmand L, Coyaud E, Gupta GD, Laurent EM, Hasegan M, Prosser SL, Gonçalves J, Raught B, Pelletier L
EMBO J. 2019 Jun 03;:
Gheiratmand L, Coyaud E, Gupta GD, Laurent EM, Hasegan M, Prosser SL, Gonçalves J, Raught B, Pelletier L

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Canada Research Chair in Proteomics and Molecular Medicine