Shawn Li
Affiliations
Scientist, Division of Genetics & Development, Children’s Health Research Institute
Associate Professor, Departments of Biochemistry, Paediatrics and Oncology, Schulich School of Medicine & Dentistry, Western University
How my research helps children
X-linked lymphoproliferative (XLP) syndrome is a fatal immunodeficiency condition that leads to the development of malignant lymphomas in 20% of patients. The average age of onset for XLP is less than 5 years, with a mortality rate reaching 100% by age 20.
Most cases of XLP are caused by deficiency in a protein called SAP. I use cell culture and mouse models to study the molecular mechanism of the XLP syndrome. Specifically, my research team has identified certain novel functions for SAP in regulating the immune response and is researching how compromises in these functions contribute to the pathogenesis of the XLP disease.
Dr. Li’s research has the potential to pave new ways for the treatment of this rare, but fatal disease that affects children and young adults.
Research
Current Research Activities
My research team made the original discovery that SAP is involved in a process called negative or inhibitory signaling by B cells. Negative signaling is important for proper immune regulation, and I believe that it is the imbalance of positive versus negative immune response that is underpinning the XLP syndrome. My team carried out the initial biochemical analysis on the interactions between SAP and three molecules that play critical roles in the immune system.
In addition, I use an integrated approach that combines molecular, cellular, and proteomic information to obtain a comprehensive picture of how certain proteins interact and transduce signals in a cell. I am particularly interested in understanding the mechanisms of asymmetric cell division, cell polarity and adhesion, and how adaptor proteins function in facilitating immunoreceptor signaling. Moreover, my team employs peptide and protein arrays to identify protein-protein interaction networks underlying these important biological events.
Research Team
Zezhou Wang, Post-doctoral fellow
Shelley Sandiford, Post-doctoral fellow
Xing Li, Post-doctoral fellow
Thamara Dayarathna, Post-doctoral fellow
Tomonari Kaneko, Post-doctoral fellow
Bing Zhao, Post-doctoral fellow
Marek Galka, Post-doctoral fellow
Lei Li, Post-doctoral fellow
Gurpreet Dhami, Post-doctoral fellow
Huadong Liu, Post-doctoral fellow
Karen Kennedy, Graduate Student
Rena Wei, Graduate Student
Wendy Zhu, Graduate Student
Future Research Plans
I propose to test my findings in B and T cells isolated from mice. Because it is not always practical to perform biochemical analysis on human subjects, a mouse model is often created for studying the mechanism of a human disease. My team will compare B cells or T cells isolated from the SAP-deficient mice with those from normal mice to define defects in signaling by the SAP-deficient B or T cells. We will also examine the growth and survival of these cells under various immunological challenges. An understanding of precisely how SAP regulates B and T cell activation, growth, and survival should lead to new ways of treating the XLP disease.
Awards & Grants
Awards & Grants (past 5 years)
Funding in support of "Characterizing the role of Numb-interacting protein 1 in neural differentiation of stem cells"– Awarded by Natural Sciences and Engineering Research Council of Canada (NSERC)
Research Scientist Award – Awarded by National Cancer Institute of Canada
Funding in support of A Numb linkage between kinase and polarity and its role in cancer – Awarded by Canadian Cancer Society Research Institute (CCSRI)
Funding in support of Biochemical and Functional Characterization of the XLP protein SAP – Awarded by CCSRI
Funding in support of The University of Western Ontario Biomolecular NMR facility – Awarded by Canadian Institute of Health Research
Recent Publications
Publications
Loops govern SH2 domain specificity by controlling access to binding pockets
Kaneko T, Huang H, Zhao B, Li L, Liu H, Voss CK, Wu C, Schiller MR, Li SS
Sci Signal. 2010 May 4;3(120):ra34
Mammalian numb-interacting protein 1/dual oxidase maturation factor 1 directs neuronal fate in stem cells. Kennedy KA, Ostrakhovitch EA, Sandiford SD, Dayarathna T, Xie X, Waese EY, Chang WY, Feng Q, Skerjanc IS, Stanford WL, Li SS. J Biol Chem. 2010 Jun 4;285(23):17974-85.
Numb: A new player in EMT. Wang Z, Li SS. Cell Adh Migr. 2010 Apr 16;4(2).
NIP/DuoxA is essential for Drosophila embryonic development and regulates oxidative stress response. Xie X, Hu J, Liu X, Qin H, Percival-Smith A, Rao Y, Li SS Int J Biol Sci. 2010 May 11;6(3):252-67.
Regulation of cell proliferation and survival: convergence of protein kinases and caspases
Duncan JS, Turowec JP, Vilk G, Li SS, Gloor GB, Litchfield DW. Biochim Biophys Acta. 2010 Mar;1804(3):505-10
Insulin-like growth factor binding protein-6 (IGFBP-6) interacts with DNA-end binding protein Ku80 to regulate cell fate. Iosef C, Vilk G, Gkourasas T, Lee KJ, Chen BP, Fu P, Bach LA, Lajoie G, Gupta MB, Li SS, Han VK Cell Signal. 2010 Jul;22(7):1033-43
Numb regulates cell-cell adhesion and polarity in response to tyrosine kinase signaling
Wang Z, Sandiford S, Wu C, Li SS. EMBO J. 2009 Aug 19;28(16):2360-73
CelluSpots: a reproducible means of making peptide arrays for the determination of SH2 domain binding specificity. Wu C, Li SS. Methods Mol Biol. 2009;570:197-202
Using peptide array to identify binding motifs and interaction networks for modular domains
Li SS, Wu C Methods Mol Biol. 2009;570:67-76.
Retinoic acid enhances skeletal muscle progenitor formation and bypasses inhibition by bone morphogenetic protein 4 but not dominant negative beta-catenin. Kennedy K, Porter T, Mehta V, Ryan SD, Price F, Peshdary V, Karamboulas C, Savage J, Drysdale TA, Li SS, Bennett SA, and Skerjanc IS BMC Biol. 2009 Oct 8;7:67
Contact
Phone: 519-850-2910
Fax: 519-661-3175
Email: sli [at] uwo [dot] ca
Website: http://lilab.uwo.ca
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