Dr. Shawn S.C. Li, PhD


Children’s Health Research Institute
Scientist, Molecular Genetics Program

Lawson Health Research Institute
Scientist, Children’s Health Research Institute


University of Western Ontario
Associate Professor, Departments of Biochemistry and Paediatrics


Contact Information
Tel: (519) 850-2910
Fax: (519) 661-3175
E-mail: sli@uwo.ca
Web: http://www.biochem.uwo.ca/fac/li/li.html


Brief Biography

Dr. Shawn Li received his Bachelor of Science Degree in chemistry at Peking University, China in 1985. He earned his Master of Science degree in Biochemistry at the Shanghai Institute of Biochemistry in 1988. He then pursued his doctorate in Dr. Charles Deber’s laboratory in Biochemistry at the University of Toronto and obtained a PhD degree in 1995. From 1995-2000, he trained as a postdoctoral fellow in Dr. Tony Pawson’s laboratory at Mount Sinai Hospital in Toronto. Dr. Li became an Assistant Professor in the Departments of Biochemistry and Paediatrics at The University of Western Ontario in 2000 and was promoted to the rank of Associate Professor with Tenure in 2005. Dr. Li has received many academic honours throughout his career, including a Boeringer Ingelheim Young Investigator Award in Biological Science, a Premier’s Research Excellence Award (PREA) from the government of Ontario and a Harold E. Johns Award from the National Cancer Institute of Canada (NCIC). Dr. Li is a scientist of NCIC, and his research is currently supported by grants from CIHR, NCIC and CRS.


Research Interests

The main focus of Dr. Li’s research group is the structural and functional characterization of protein interaction modules in signal transduction. They use structural, molecular and proteomic approaches to study these modules in the context of proteins involved in important biological processes.


Research Activities

Dr. Li is a young investigator whose work focuses on the structure and function of protein interaction domains in cellular signal transduction under normal and disease conditions. His research impacts on both normal development and cancer of all ages including children. His work has been published in such high impact journals as Molecular Cell, Nature Structural Biology and the EMBO Journal.


There are currently four research projects being carried out in his laboratory.
1. Characterization of the SH2 domain protein SAP and the elucidation of the molecular mechanism of X-linked lymphoproliferative (XLP) syndrome.

XLP is an inherited immunodeficiency condition marked by increased susceptibility to Epstein-Barr virus (EBV). The gene whose truncation or mutation is associated with XLP was found to encode a small SH2 domain protein named SAP or SH2D1A. We have determined the solution structure of this SH2 domain protein and are in the process of characterizing its disease-causing mutants using various biophysical and biochemical means. Novel proteins that interact with SAP have also been identified in the lab, and the functional significance of these interactions in lymphocyte signaling is currently under investigation.


2. Biochemical and functional characterization of Numb-interacting proteins.

Numb is one of the most important cell fate determinants in asymmetric cell division, a fundamental means of generating cell diversity in multi-cellular organisms. Dr. Li’s team have recently identified a novel protein from a library screen that interacts specifically with Numb. This protein, namely NIP, may play an important role in anchoring Numb to the plasma membrane and in controlling the asymmetric localization of Numb during the division of neuroprecursor cells. Biochemical and genetic experiments are currently being conducted to elucidate the function of NIP in both Drosophila and mammals.


3. Structure and functional analysis of the IGF-binding proteins.

IGFBPs bind to the insulin-like growth factors (IGF) and modify their function. Dr. Li’s team is interested in elucidating the molecular basis of specific recognition of IGF-I and -II by IGFBPs and their roles in regulating various cellular functions. Their studies on IGFBP-6 revealed a novel nuclear localization signal that mediates its localization to the nucleus. This finding suggests that IGFBP-6 is both a secreted and a nuclear protein. The role of nuclear localized IGFBP-6 is currently under investigation.


4. Domain-mediated protein interaction networks probed by peptide arrays and bioinformatics.

The genomes of multicellular organisms are characterized by a selective enrichment of modular domains. The so-called interaction domains have the capacity of binding to proteins through recognition of specific peptide motifs. Dr. Li’s team has developed an integral approach that combines the power of peptide array and bioinformatics in an effort to map the protein-protein interaction events mediated by these domains. Pilot studies on SH3 domains have demonstrated the feasibility of this approach. The ultimate goal of this research project is to establish a database of protein-protein interactions mediated by domains such as SH3, SH2, PTB, PDZ, etc.

Representative Publications

  1. Li, S.C., Zwahlen, C., Vincent, S.J.F., McGlade, C.J., Kay, L.E., Pawson, T., and Forman-Kay, J.D. Sturcture of a Numb PTD domain-peptide complex: a basis for diverse binding specificity Nat. Struct. Biol. (1998) 5, 1075-1083.
  2. Li, S.-C., Zwalen, C., Kay, L.E., Pawson, T., and Forman-Kay, J.D. Multiple modes of peptide recognition by the PTB domain of the cell fate determinant Numb. EMBO J. (2000) 12:1505-1515.
  3. Hwang, P.M., Li, C., Morra, M., Lillywhite, J., Muhandiram, D.R., Gertler, F., Terhorst, C., Kay, L.E., Pawson, T., Forman-Kay, J.D. and Li, S.-C. A ‘three-pronged’ binding mechanism for the SAP/SH2D1A SH2 domain: structural basis and relevance to the XLP syndrome. EMBO J. (2002) 21: 314-323.
  4. Liu, Q., Berry, D., Nash, P., Pawson, T., McGlade, C.J., and Li, S.S.-C. Structural basis for specific binding of the Gads SH3 domain to an Rxxk-motif containing SLP-76 peptide - a novel mode of peptide recognition. Mol. Cell (2003) 11, 471-481.
  5. Li, C., Iosef, C., Jia, C.Y.H., Han, V.K.M., and Li, S.S.-C. Dual functional roles for the XLP syndrome gene produce SAP/SH2D1A in signaling through the SLAM family of immune receptors J. Biol. Chem. (2003) 278, 2852-3859.
  6. Qin, H., Percival-Smith, T., Li, C., Jia, C. Y.H., Gloor, G., Li, S.S.C. A novel transmembrane protein recruits Numb to the plasma membrane during asymmetric cell division. J. Biol. Chem. (2004) 279: 11304-11312.
  7. Nie, J., Li, S.S.-C., McGlade, C.J. A novel PTB-PDZ domain interaction mediates isoform-specific ubiquitylation of mammalian Numb. J. Biol. Chem. (2004) 279, 20807-20815.
  8. Rodriguez M, Li S.S.C, Harper JW, Songyang Z. An oriented peptide array library (OPAL) strategy to study protein-protein interactions. J. Biol. Chem. (2004) 279, 8802-8807.
  9. Jia, C.Y.H. Nie, J., Wu, C., Li, C. and Li, S.S.-C. Novel specificity of the SH3 domain identified from a proteomic screenof a Pro-rich region. Mol. Cell. Proteomics. (2005) 4, 1155-1166.
  10. Li, S.S.-C. (2005) Specificity and promiscuity of interaction domains- Structural basis and implications to cellular signaling transduction. Biochem. J. (2005) 390, 641-653.