Shawn Li

Genetics & Development Dr. Shawn Li
Scientist
Photo

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

Dynamic methylation of Numb by Set8 regulates its binding to p53 and apoptosis
Dhami GK, Liu H, Galka M, Voss C, Kaneko T, Muranko K, Cregan SP, Li L, Li SSC
Mol Cell. 2013 May 23; 50(4):565-76

A method for systematic mapping of protein lysine methylation identifies new functions for HP1beta in DNA damage response
Liu H, Galka Liu X, Lin Y-F, Pittock P, Voss C, Dhami G, Li X, Lajoie G, Chen B, Li SSC
Mol Cell. 2013 May 22

Systematic charcterization of the specificity of the SH2 domains of cytoplasmic tyrosine kinases
Zhao B, Tan P, Li SSC, Pei D
J Proteomics. 2013; 81:56-69

Structural basis for endosomal trafficking of diverse transmembrane cargos by PX-FERM proteins
Ghai R, Bugarcic A, Liu H, Norwood SJ, Li SSC, Teasdale RD, Collins BM
Proc Natl Acad Sci USA. 2013; 110(8):E643-52

The binding properties of the RasGEF Sos1/Grb2 complex define timing and selectivity in embryonic stem cell lineage commitment
Findlay GM, Smith MJ, Lanner F, Hsiung MS, Gish GD, Kaneko T, Huang H, Bagshaw TD, Ketela T, Moffat J, Ikura M, Li SSC, Sidhu S, Rossant J, Pawson T
Cell. 2013; 152(5):1008-20

Phosphotyrosine recognition domains: the typical, the atypical and the versatile
Kaneko T, Joshi R, Feller SM, Li SSC
Cell Commun Signal. 2012 Nov 7; 10(1):32

Secondary structure, a missing component of sequence-based minimotif definitions
Sargeant DP, Gryk MR, Maciejewski MW, Thapar V, Kundeti V, Rajasekaran S, Romero P, Dunker K, Li SC, Kaneko T, Schiller MR
PLoS One. 2012; 7(12):e49957

SH2 superbinders act as antagonists to cell signaling
Kaneko T, Huang H, Voss C, Sidhu SS, Li SSC
Science Signaling. 2012; 5(243):ra68

Differential regulation of the RhoGAP activity of DLC1 by tensins controls mammary cell migration and transformation
Proc Natl Acad Sci USA. 2012; 109(5):1455-60

The human phosphotyrosine signaling network: evolution and hot spots of hijacking in cancer
Li L, Fu C, Tibiche C, Kaneko T, Schiller MR, Li SSC, Wang E
Genome Research. 2012 Jan 26

Insights into high affinity small ubiquitin-like modifier (SUMO) recognition by SUMO-interacting motifs (SIMs) revealed by a combination of NMR and peptide array analysis
Namanja AT, Li YJ, Su Y, Wong S, Lu J, Colson LT, Wu C, Li SS, Chen Y
J Biol Chem. 2012; 287(5):3231-40

Reactive oxygen species in neuronal differentiation
Kennedy KM, Sandiford S, Li SSC
Mol Cell Life Sci. 2012; 69(2):215-21

Building specificity on variability for protein interaction domains
Kaneko T, Zhao B, Li SSC
Trends Biol Sci. 2011; 36:183-90

Systematic prediction of modular domain-peptide interactions from proteomic data
Li L, Zhao B, Du J, Jiang X, Zhang K, Ling CX, Li SSC
PLOS One. 2011; 6(10):e25528

Identification of Dermcidin as a novel binding protein of Nck1 and characterization of its role in promoting cell migration
Shen SL, Qiu FH, Dayarathna TK, Wu J, Kuang M, Li SS, Peng BG, Nie J
Biochim Biophys Acta. 2011; 1812:703-10

Quantitative prediction of PDZ domain-peptide interactions from primary sequence
Shao X, Tan CHT, Voss C, Li SSC, Deng N, Bader G
Bioinformatics. 2011; 27(3):383-90

Deciphering cellular decisions of life and death: Convergence of protein kinases and caspase signaling
Duncan JS, Duncan KE, Turowec JP, Wu C, Luscher B, Li SSC, Gloor GB, Litchfield DW
Science Signaling. 2011; 4:ra30

Systematic Identification of Methyllysine-Driven Interactions for Histone and Nonhistone Targets
Liu H, Galka M, Iberg A, Wang Z, Li L, Voss C, Jiang X, Lajoie G, Huang Z, Bedford MT, Li SSC
J Proteome Res. 2010; 29 (11), 5827–5836

Bing of different histone marks differentially regulates the activity and specificity of polycomb repressive complex 2 (PRC2)
Xu C, Bian C, Yang W, Galka M, Ouyang H, Chen C, Qiu W, Liu H, Jones AE, Mackenzie
F, Pan P, Li SSC, Wang H, Min J
Proc Natl Acad Sci USA. 2010; 107:19266-71

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

Additional publications

Contact

Contact

Phone: (519) 850-2910
Fax: (519) 661-3175
Email: sli [at] uwo [dot] ca
Website: http://lilab.uwo.ca

(Please note: CHRI is not responsible for the content of any external sites - links will open in new window)