Donna-Marie McCafferty, PhD

Associate Professor, Department of Physiology & Pharmacology

Gastrointestinal Research Group
CIHR New Investigator
Office: Room 1753, Health Sciences Centre
Phone Office: (403) 210-9714
Phone Lab: (403) 220-8681
Fax: (403) 283-3028
Email: dmmccaff [at] ucalgary [dot] ca

 

I currently have an opening for a graduate student. Please contact me.

Curriculum Vitae

BSc, University of Glasgow, Scotland
PhD, University of Strathclyde, Scotland

Research Interests

The infiltration of white blood cells into tissue is a key factor in the development of gastrointestinal inflammation. My laboratory investigates the role of white blood cells in causing macroscopic/histological and epithelial permeability changes in various inflammatory models e.g. in response to bacterial products (LPS) and in experimental models of colitis. We also investigate the mechanisms (adhesion molecules) used by leukocytes to leave the blood stream and enter gut tissue. In these studies we investigate the role of the LPS receptor molecules CD14 and TLR4 as well as group IV non receptor protein tyrosine kinases (fer and fps/fes) using genetically modified mice.

In addition, chronic inflammatory conditions such as Ulcerative colitis predispose individuals to an enhanced risk of developing colon cancer.  In addition, animal models such as the IL-10-deficient mouse (IL-10^-/- ), which develop a spontaneous chronic colitis have also been shown to develop adenocarcinomas later in life.  A potential molecule implicated in the induction of cancer is the nitric oxide (NO).  NO is a free radical which can regulate a range of physiological functions, including vascular homeostasis, immune responses and neurotransmission.  However, the sustained high levels of NO produced in chronic inflammatory conditions has also implicated this radical in tumor biology.  NO has been detected in high concentrations both in clinical colitis as well as in many experimental models, including the IL-10^-/- model.  We have developed a double mutant mouse (IL-10^-/- /iNOS^-/- ).  This mouse develops a spontaneous chronic inflammation in the colon to a similar degree as the IL-10^-/- single mutant without the chronic production of NO.  These mice can now be studied to ask the role of chronic NO production on the development of adenocarcinoma.  We have also developed , IL-10^-/- /TLR4^-/- deficient mice and are currently examining the role of TLR4 in the development of colitis associated adenocarcinoma.

Publications

Zhang R, Y. Li, P. L. Beck, McCafferty, D-M. (2007) Toll Like Receptor 4 regulates Colitis-Associated Adenocarcinoma Development in Interleukin-10 Deficient (IL-10 (-/-)) Mice. Biochemical Society Transactions 35 (5): 1375-6 [IF 2.962]

Beck, P.L., Li, Y., Chen CW., Keenan, C.M., Sharkey, K.A., McCafferty, D-M., (2007) Inducible nitric oxide synthase from bone marrow-derived cells plays a critical role in regulating colonic inflammation.  Gastroenterology, May; 132 (5):1778-90. Epub 2007 Jan 25. [IF 12.386]

Zhang, R., Ma, A., Urbanski, S. & McCafferty, D-M. (2007). Induction of Inducible Nitric Oxide synthase: A protective Mechanism in Colitis-Induced Adenocarcinoma. Carcinogenesis. 2007 May; 28 (5):1122-30. Epub 2006 Nov 20 [IF 5.108]

Nasser Y., Kennan, C.M., Ma A.C., McCafferty, D-M., Sharkey, K.A. (2007). Expression of a functional metabotropic glutamate receptor 5 on enteric glia is altered in states of inflammation. Glia, June; 55 (8): 859-72 (Epub 2007 April 2) [IF 4.276]

Li, Y., Liu, H., Gaskari, S.A., McCafferty, D-M. and Lee, S.S. (2006). Hepatic venous dysregulation contributes to blood volume pooling in cirrhotic rats. Gut, Jul; 55 (7): 1030-1035 Epub 2006 Jan 9. [IF 7.692]

Qi, W., Ebbert, K.V.J., Greer, P.A., Craig, A. and McCafferty, D-M (2005). Absence of Fer protein-tyrosine kinase exacerbates endotoxin-induced intestinal epithelial barrier dysfunction in vivo. Gut 54 (8): 1091-7 [IF 7.692]

Additional Publications

Personnel

Graduate Trainees
Mark Gillrie (Ph.D. student) Co-supervisor
Misha Bawa (M.Sc. student)
Manar Mutardi (MSc Student)

Postdoctoral Fellows
Ying Gao

Research Staff
Ronald Chan

Administrative Assistant
Jennifer McCarty