Go 
Dr. Andrew Craig

  Andrew Craig, PhD

  Email: andrew.craig@queensu.ca

  Office Phone: 613-533-2496
  Lab Phone: 613-533-6000, ext. 77540
  Fax: 613-533-6830
  Lab/Office: Rm. 315 Cancer Research
Inst.

  • Associate Professor, Dept. of Biomedical & Molecular Sciences (DBMS)
  • Cancer Biology & Genetics (CBG) division, Queen's Cancer Research Institute
  • Graduate students in my lab enrol in Biochemistry graduate program
    PDF applicants are members of DBMS & CBG
  • Applications are welcome and should include your CV and statement of interests.

Dr. Craig's Lab

Research Projects: 

Mast cell signaling and inflammation

Mast cells are granulocytic cells derived from bone marrow progenitors, and are the main mediators of allergy and asthma.  However, mast cells also play a key protective role in the innate immune response.  Therefore, proteins that regulate mast cell functions are potential therapeutic targets in allergic disease.  Mast cells are activated through binding of ligands to cell surface receptors, which cause dramatic changes in the cell including: release of granular contents; synthesis and secretion of leukotrienes, prostaglandins, and cytokines; increased cell adhesion and motility.  Our research relates to molecular mechanisms controlling mast cell activation downstream of the high affinity IgE receptor (Fc£`RI) and the c-Kit receptor tyrosine kinase.  Primary bone marrow-derived mast cells (BMMCs) are established from transgenic (knock-out, knock-in) mice, which provide valuable insights into the functions of the encoded protein in mast cell signaling and activation.  Our recent studies have focussed on Src family and Fer/Fes family tyrosine kinases.and SHP2 (PTPN11) phosphatase.  We are also establishing methods to extend our work to human mast cells using lentiviruses expressing short hairpin RNAs that can knock-down expression of these gene products in human mast cell lines.

 

F-BAR adaptor proteins in cancer

Recently, a new type of phosphoinositide-binding module has been identified (F-BAR) in the Pombe Cdc15 Homology (PCH) family of proteins (that includes the Fer/Fes kinases).  We are studying F-BAR domain functions in both the Fer/Fes kinases, as well as in adaptor proteins (CIP4 & Toca-1) that interact with Cdc42 and its effector N-WASP.  F-BAR adaptor proteins function promoting membrane invaginations through coordinated actions of their F-BAR and SH3 domains.  F-BAR domains bind membranes and induce curvature, while SH3 domain interactions recruit N-WASP (promoting actin assembly that constricts the neck) and Dynamin (that pinches off the nascent vesicle).  The F-BAR kinases may cooperate with F-BAR adaptors via phosphorylation of actin regulatory proteins (cortactin and HS1) that stabilize branched filamentous actin (F-actin).  F-BAR proteins have been implicated in contributing to inflammatory disorders, immunity and cancer.  Our lab is actively pursuing how F-BAR proteins regulate cancer progression and metastases using cell-based assays and animal models.

Recent Publications (since 2004; Craig lab trainees are underlined):

Andrew W.B. Craig (2011) FES/FER kinase signaling in hematopoetic cells and leukemias. Frontiers in Bioscience, in press.

Jinghui Hu, Alka Mukhopadhyay, Peter Truesdell, UK Mukhopahyay, Alan Mak and Andrew WB Craig (2011)  Cdc42-Interacting Protein 4 is a Src substrate that regulates invadopodia and breast tumor invasiveness via promoting MT1-MMP endocytosis, J. Cell Sci., 124: 1739-1751.

Jinghui Hu, Alka Mukhopadhyay and Andrew WB Craig (2011) Transducer Of Cdc42-dependent actin assembly promotes epidermal growth factor-induced cell motility and invasiveness, J. Biol. Chem., 286:2261-72.

Julie Smith, Lionel Samayawardhena and Andrew Craig (2010) Fps/Fes protein-tyrosine kinase regulates mast cell adhesion and migration downstream of Kit and ƒÒ1 integrin receptors, Cell. Signal, 22:427-436.

Victor A. McPherson,  Namit Sharma, Stephanie Everingham, Julie Smith, Helen H. Zhu, Gen-Sheng Feng and Andrew W.B. Craig (2009) SHP2 Protein-Tyrosine Phosphatase Promotes Fc£`RI-induced Activation of Fyn and Erk Pathways Leading to TNF£\ Release from Bone Marrow-derived Mast Cells, J. Immunol., 183:4940-4947.

Jinghui Hu, Flavia Troglio , Alka Mukhopadhyay, Stephanie Everingham, Ester Kwok, Giorgio Scita, and Andrew W.B. Craig (2009) F-BAR-containing adaptor CIP4 localizes to early endosomes and regulates Epidermal Growth Factor Receptor trafficking and downregulation, Cell. Signal, 21, 1686-1697.

Victor McPherson, Stephanie Everingham, Robert Karisch, Julie Smith, Chris Udell, Jimin Zheng, Zongchao Jia, and Andrew W.B. Craig (2009) Contributions of F-BAR and SH2 Domains of FES Protein-Tyrosine Kinase For Coupling to the FcƒÕRI Pathway in Mast Cells, Mol. Cell. Biol. 29:389-401.

Lei  Liu, Andrew W. Craig, Heather D. Meldrum, Bruce E. Elliott, and Marlys L. Koschinsky (2008) Integrin aVb3 is Required for Apolipoprotein(a) Stimulation of Vascular Endothelial Cell Growth and Migration, Biochem. J., 418:325-36.

Lionel A. Samayawardhena, Reuben Kapur and Andrew W.B. Craig (2007) Involvement of Fyn kinase in c-Kit and integrin-mediated Rac activation, cytoskeletal reorganization and chemotaxis of mast cells, Blood, 109:3679-3686.

C.M. Udell, L.A. Samayawardhena, Y. Kawakami, T. Kawakami, and A.W.B. Craig (2006) Fer and Fps/Fes participate in a Lyn-dependent pathway from Fc£`RI to Platelet-Endothelial Cell Adhesion Molecule-1 to limit mast cell activation, J. Biol. Chem., 281:20949-20957.

L. Samayawardhena, J. Hu, P. Stein, and A.W.B. Craig (2006) Fyn kinase acts upstream of Shp2 and p38 mitogen-activated protein kinase to promote chemotaxis of mast cells towards stem cell factor, Cell. Signal, 18: 1447-54.

W. Qi, K.V.J. Ebbert, A.W.B. Craig, P.A. Greer and D.M. McCafferty (2005) Absence of Fer protein-tyrosine kinase exacerbates endotoxin-induced intestinal epithelial barrier dysfunction in vivo, Gut, 54:1091-97.

G. Xu, A.W.B. Craig, P. Greer, M. Miller, P.Z. Anastasiadis, J. Lilien and J. Balsamo (2004).  An Epigenetic Loop Regulating the Tyrosine Phosphorylation of Beta-Catenin and Cadherin Function.  J. Cell Sci,117:3207-3219.

L. Fan, C. Di Ciano-Oliviera, S.A. Weed, A.W.B. Craig, P.A. Greer, O.D. Rotstein and A. Kapus (2004). Actin Depolymerization-Induced Tyrosine Phosphorylation of Cortactin: The Role of Fer Kinase. Biochem. J.,380:581-591.

A. Vultur, J. Cao, R. Arulanandam, J. Turkson, R. Jove, P. Greer, A. Craig, B. Elliot and L. Raptis (2004) Cell to cell adhesion modulates Stat3 activity in normal and breast carcinoma cells. Oncogene, 23:2600-2616.

Last updated 2 June 2011

 

Admin | © Cancer Research Institute at Queen's University 2012 | Privacy Policy | Site Map | Website Powered by SiteMajic
Site Meter