Assistant Professor of Biochemistry
B.S. Brigham Young University
Ph.D. Brigham Young University
Peter Shen's Lab Page
Peter Shen's PubMed Literature Search
Molecular Biology Program
Biological Chemistry Program
Protein Homeostasis, Protein Structure, cryo-EM, Image Processing, Protein quality control, Proteopathy, Protein Complexes
Protein quality control
Protein homeostasis is critical to maintaining a healthy cellular environment. All proteins rely on quality control mechanisms to ensure proper synthesis, folding, function, and turnover. Dysregulation along these pathways contribute to some of the most devastating diseases in humans, including cancer and neurodegeneration. My lab seeks to resolve the molecular mechanisms that are responsible for ensuring proper protein quality control. The mechanisms that we uncover will become the basis of developing therapeutics to rescue quality control failure.
My lab studies one of the central players in regulating eukaryotic protein homeostasis: the AAA+ Cdc48/p97 molecular machine. Cdc48 is involved in targeting ubiquitinated substrates for proteasomal degradation and in mediating cell cycle progression. It is one of the most abundant proteins in the cytosol and its regulation is mediated by dozens of co-factors. Mutations in Cdc48 cause degeneration of the brain, muscles, and bones (known as IBMPFD). How Cdc48 functions is an open mystery and my lab is developing the tools to purify, visualize, and characterize these complexes.
Seeing is Believing
All cellular processes depend on atomic-scale interactions. In order to understand molecular mechanism, my lab specializes in cryo-EM to resolve high-resolution 3D structures. Cryo-EM is uniquely suited for working with structurally heterogeneous samples because a single sample often reveals a range of structural states that can then be pieced together to deduce mechanism and dynamics. The ability to directly visualize these biological molecules will enable us to understand how multiple components come together to carry out their evolutionarily tuned functions.
Sinha NK, Iwasa J, Shen PS*, Bass BL*. Dicer uses distinct modules for recognizing dsRNA termini.Science. 2018 Jan 19:359(6373):329–34. (*co-corresponding author)
Han H, Monroe N, Sundquist WI*, Shen PS*, Hill CP*. The AAA ATPase Vps4 Binds ESCRT-III Substrates Through a Repeating Array of Dipeptide-binding Pockets.Elife. 2017 pii: e31324. (*co-corresponding author)
Shen PS*, Yang X*, DeCaen PG, Liu X, Bulkley D, Clapham DE, Cao E. The Structure of Polycystic Kidney Disease Channel PKD2 in Lipid Nanodiscs. Cell. 2016 Oct 20:167(3):763–73.
Shen PS, Park J, Qin Y, Parsawar K, Li X, Larson M, Cox J, Cheng Y, Lambowitz AM, Weissman JS, Brandman O, Frost A. Rqc2p and the 60S ribosome mediate mRNA-independent elongation of nascent chains. Science. 2015 Jan 2;347(6217):75–8.
Brandman O, Stewart-Ornstein J, Wong D, Larson A, Williams CC, Li GW, Zhou S, King D, Shen PS, Weibezahn J, Dunn JG, Rouskin S, Inada T, Frost A, Weissman JS. A ribosome-bound quality control complex triggers degradation of nascent peptides and signals translation stress. Cell. 2012 Nov 21;151(5):1042–54.