Xu Lab of Structural and Molecular Biochemistry

Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh

Research areas

Pathogen-host interactions, mechanism of signal transduction in the innate immune response, X-ray crystallography.

Research in our lab focuses on structural and mechanistic studies of protein kinases in various biological processes. Protein kinases are major signal transmitters in eukaryotic cells. There are 518 protein kinases in the Human genome, comprising about 2% of all genes. They are classified into mainly two types of protein kinases, membrane integral receptor kinases and intracellular kinases. The membrane integral receptor kinases function to receive extracellular signals and transmit them across the plasma membrane into the cells, while many intracellular kinases function to relay and amplify the signals in the cells. We chose the Leucine-Rich Repeats Receptor Kinases as an example to understand the general mechanism of ligand-induced receptor kinase activation, and investigate the activation mechanism of IkB kinase to understand the role of intracellular signalling kinases in signal transduction.

Inhibitor of κB kinase (IKK) controls the activation of nuclear factor (NF)-κB transcription factors, which are the master regulators of a wide variety of cellular processes, particularly immune and inflammatory responses. Dysregulation of the IKK/NF-κB pathway is associated with numerous diseases such as diabetes and cancer, inflammatory and autoimmune diseases; therefore IKK has become an attractive drug target for the treatment of these common human diseases. However incomplete understanding of the structure, mechanisms of activation and substrate catalysis of IKK has severely hampered inventing additional novel strategies as well as improving current strategies to target IKK for disease treatment.

IKK is a large protein complex containing the kinase subunits IKKα and IKKβ, and the regulatory subunit NF-κB essential modifier (NEMO, also known as IKKγ). IKKβ accounts for the majority of the IκB kinase activity of IKK and plays a dominant role in the canonical NF-κB pathway in response to proinflammatory stimuli. IKKκ shares more than 50% sequence identity with IKKβ and plays an indispensable role in the non-canonical NF-κB pathway in response to a subset of NF-κB-induction stimuli. The activation of IKKβ entails interaction with NEMO, while NEMO is not required for IKKα activation in the non-canonical pathway. NEMO-mediated IKKβ oligomerization and subsequent trans-autophosphorylation have been shown to be crucial for IKK activation but the underlying molecular mechanism remains to be revealed.

We are addressing two fundamental questions on IKK:

  • What is the mechanism of IKK activation?
  • What are the mechanisms of IKK substrate specificity and catalysis?

Our experimental approaches include protein expression and purification, biochemical reconstitution, biochemical and biophysical characterizations, X-ray crystallography, electron microscopy (EM), kinase assay, structure-based mutagenesis and cellular experiments.

Dr. Guozhou Xu, Assistant Professor of Biochemistry, Department of Molecular and Structural Biochemistry, North Carolina State University

Education
  • PhD: Weill Medical College of Cornell University
  • Postdoctoral: Harvard Medical School
Contact
  • Office: 26 Polk Hall
  • Phone: 919-515-0835 (Office)
  • Email: gxu3@ncsu.edu
Other members
  • Zhijie Li, Postdoctoral Fellow
  • Sayan Chakraborty, Graduate Student
  • Nour Saleh, Undergraduate Student (2014 - 2015)
  • Elizabeth Brown, Undergraduate Student (2015)
  • Veronica Emmerich, Undergraduate Student (2015)
  • Jerrin Gause, Undergraduate Student (2015)
  • Arushi Wadhwa, Undergraduate Student (2015)
  • Benton Gorre, Undergraduate Student (2015)
  • Gabriela Schroder, Rotation PhD Student

Our lab is always interested in recruiting outstanding research fellows, Postdoctoral associates, graduate students and undergraduate students.

For Postdoctoral positions and Graduate studies please contact Dr. Xu.

For undergraduate students please set up an appointment with Dr. Xu by an email.

Multiple postdoctoral fellow positions are available presently. Interested candidates can go through this advertisement and apply.