Craig, Andrew

Andrew Craig, PhD

Email: ac15@queensu.ca
Office Phone: 613-533-2496
Lab Phone: 613-533-6000, ext. 77540
Fax: 613-533-6830

Associate Professor, Dept. of Biochemistry
CIHR New Investigator

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. 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.

Recent Publications (Craig lab trainnes are underlined):

Julie Smith, Lionel Samayawardhena and Andrew Craig (2009) Fps/Fes protein-tyrosine kinase regulates mast cell adhesion and migration downstream of Kit and ƒÒ1 integrin receptors, Cellular Signaling, in press.

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. Signaling, 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 , MCB 29:389-401.

Waheed Sangrar, Andrew W. Craig and Peter A. Greer. FES and FER: the F-BAR-containing protein-tyrosine kinases. IN Pombe Cdc15 Homology Proteins, Chapter 8., ed. Pontus Aspenstrom, June 1, 2009.

Lei Liu,Andrew W. Craig, Heather D. Meldrum, Bruce E. Elliott, and Marlys L. Koschinsky (2009) Integrin ƒÑ_VƒÒ₃is Required for Apolipoprotein(a) Stimulation of Vascular Endothelial Cell Growth and Migration, Biochemical Journal, 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, JBC, 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, Cellular Signaling, 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 Science,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. Biochemical 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.

Y.A. Senis*, A.W.B. Craig* and P.A. Greer (2003). Fps/Fes and Fer Protein-Tyrosine Kinases Play Redundant Roles in Regulating Hematopoiesis. Exp. Hematol., 31:673-81. *co-first authors

Y.A. Senis, W. Sangrar, R. Zirngibl, A.W.B. Craig, D.H. Lee and P.A. Greer (2003). Fps/Fes and Fer non-receptor protein-tyrosine kinases regulate collagen- and ADP-induced platelet aggregation. J. Thrombosis and Haemostasis, 1:1062-70.

A.W.B. Craig and P.A. Greer (2002). Fer Kinase Is Required For Sustained p38 Kinase Activation and Maximal Chemotaxis of Activated Mast Cells. MCB, 22: 6363-6374.

Last updated 3 Dec 09