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University of Colorado Department of Biochemistry and Molecular Genetics

Biochemistry and Molecular Genetics
 

Changwei Liu, PhD

Associate Professor


Ph.D., Chinese Academy of Sciences

Contact Information:

Phone: (303) 724-3208
E-mail: Changwei.Liu@ucdenver.edu

Postdoctoral Positions Available


Graduate Program Memberships

Molecular Biology​
Biomedical Sciences
MSTP
Structural Biology & Biochemistry

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Our group has two major research interests: 1) investigate the biochemical mechanisms by which proteasomal activities are regulated in cells; and 2) determine new functions of the spinal muscular atrophy protein – survival motor neuron.  We use biochemical, cell biological and proteomics approaches for our studies.     

Regulating proteasomal activities      The 26S proteasome is an approximately 3 Mega Dalton large protease that is responsible for degradation of the majority of intracellular proteins in eukaryotic cells. Usually, protein substrates of the 26S proteasome are modified with a polyubiquitin chain through a cascade of enzymatic reactions requiring a ubiquitin activating enzyme (E1), a ubiquitin conjugating enzyme (E2) and a ubiquitin ligase (E3). In human cells there are more than one thousand enzymes that are involved in mediating protein ubiquitination and deubiquitination. The 26S proteasome is consisted of 33 different proteins that catalyze multiple activities. 1) Binding of polyubiquitin chains by which the proteasome recruits substrates. 2) Deubiquitinating substrates by which ubiquitin is recycled. 3) Hydrolysis of ATP that promotes unfolding and translocation of substrates for degradation. 4) Hydrolysis of polypeptides by which substrate proteins are degraded. The biochemistry of proteasome-mediated protein degradation is fascinating, which requires coordinated actions of all proteasomal activities. Moreover, proteasomal degradation is highly regulated by factors that control proteasome assembly and/or proteasomal activities. Currently, we are investigating how human 26S proteasome-associating proteins regulate proteasomal activities. Mechanistically, proteasome-associating proteins may regulate processing of substrates, modification of proteasomal subunits or conformation, which in turn could regulate proteasomal degradation.  

Determining new functions of survival motor neuron        Spinal muscular atrophy (SMA) is the leading genetic disorder for causing infant death with an incidence of 1/10,000 in living births.  SMA is caused by low levels of survival motor neuron (SMN) protein, it is unknown why low protein levels of SMN cause a specific motor neuron disease. Studies using mice have suggested that increase of SMN protein levels can ameliorate the disease symptom and significantly extend the life span of SMA mice. Thus, means that increase SMN protein levels are potential therapies for SMA. One of our goals is to identify modulators that play critical roles in mediating SMN protein levels at the posttranscriptional level. For instance, we are identifying ubiquitin ligases and deubiquitinating enzymes that mediate proteasomal degradation of SMN. Therapeutically, we expect that some of the SMN protein stability modulators are potential drug targets of SMA. The other goal is to explore new functions of SMN, especially its roles in mediating neuron growth and signaling events.  Understanding of SMN functions may help us to uncover the pathogenesis of SMA.




Current Lab Colleagues​

 Results From Research : Selected site and subsites
PicturesLast NameFirst NameJob TitleEmailBio Page
HanKe-JunPostdoctoral FellowKe-Jun.Han@UCDenver.edu  
JacobsonAndrewPostdoctoral FellowAndrew.Jacobson@UCDenver.edu  
MacFaddenAndreaProfessional Research AssistantAndrea.MacFadden@UCDenver.edu  
TianWenminPostdoctoral FellowWenmin.Tian@UCDenver.edu