Mak | Biomedical and Molecular Sciences | School of Medicine

Alan S. Mak PhD

Position(s)

Emeritus Professor

Contact Info

maka@queensu.ca

613-533-2989

Faculty Bio

Research Interests

Arteriosclerosis and atherosclerosis are vascular diseases that are primary causes of heart attack and stroke. These diseases are characterized by abnormal thickening of the walls of blood vessels that lead to impairment of blood flow and increase in blood pressure, eventually leading to heart failure. It is becoming clear that abnormal migration of smooth muscle cells from their normal locations in the interior of the arterial wall to the inner layer close to the lumenal wall and subsequent division of newly accumulated smooth muscle cells are key events in the pathogenesis of atherosclerosis and arteriosclerosis. However, we are far from understanding the factors controlling the migration of smooth muscle cells, why and how this control mechanism may break down in pathological situations, for example, due to injury to blood vessels during surgery.

We are interested in the mechanisms by which vascular smooth muscle cells migration is inhibited in healthy arteries, but stimulated under pathological conditions. Specifically, we study the roles of an organelle called podosome that is known to play a critical role in cell movement and invasion. Before a cell can move out of its normal habitat in the blood vessel, it needs to develop feet-like podosomes to allow it to crawl. Thus, development of podosome is the first step for a smooth muscle cell to invade its surrounding by excavating a 'tunnel' into which it can move.

In our studies, we employ a combination of biochemical, biophysical, cell imaging, and molecular biology techniques. This integrated approach is possible due to the establishment at Queen’s University of a Protein Function Discovery (PFD) infrastructure equipped with cutting-edge equipment for the study of protein function in the cell, including mass spectrometry, 2-D gel electrophoresis, confocal and epifluorescence microscopy, microcalorimetry, analytical ultracentrifugation, Biacore surface plasmon resonance, circular dichroism and fluorescence spectroscopy, X-ray crystallography and NMR spectrometry.

Selected Publications Funded by CIHR and Ontario Heart and Stroke Foundation.

Hu J, Mukhopadhyay A, Truesdell P, Chander H, Mukhopadhyay UK, Mak AS, Craig AW.

Cdc42-interacting protein 4 is a Src substrate that regulates invadopodia and invasiveness of breast tumors by promoting MT1-MMP endocytosis.

J.Cell Sci. (2011) 124, 1739-1751.

Mak, A.S.

p53 regulation of podosome formation and cellular invasion in vascular smooth muscle cells.

Cell Adh Mgr (2011) 5, 144-149. Review.

Poon JS, Eves R, Mak AS.

         Both lipid- and protein-phosphatase activities of PTEN contribute to the p53-PTEN anti-invasion pathway

         Cell Cycle  (2010) 9, 4450-4454.

Mukhopadhyay UK, Mooney P, Jia L, Eves R, Raptis L, Mak AS.

          Doubles game: Src-Stat3 versus p53-PTEN in cellular migration and invasion.

          Mol Cell Biol (2010) 30, 4980-4995.

Xiao H, Bai XH, Kapus A, Lu WY, Mak AS, Liu M.

         The protein kinase C cascade regulates recruitment of matrix metalloprotease 9 to podosomes and its release and activation.

          Mol Cell Biol (2010) 30, 5546-5561.

Mukhopadhyay UK, Eves R, Jia L, Mooney P, Mak A.S.

            p53 suppresses Src-induced podosome and rosette formation and cellular invasiveness through the upregulation of caldesmon.

            Mol Cell Biol (2009)29(11): 3088-3098.

Mukhopadhyay UK, Mak AS.

            p53: is the guardian of the genome also a suppressor of cell invasion?

            Cell Cycle (2009) 8(16):2481.

Xiao H, Eves R, Yeh C, Kan W, Xu F, Mak AS, Liu M.

Phorbol ester-induced podosome in human epithelial cells.

J. Cell Physiol (2009)218(2) 366-375.

Webb, B.A., Jia, L., Eves, R. and Mak, A.S.

Dissecting the functional domain requirements of cortactin in invadopodia formation.

Eur J Cell Biol (2007) 86 189-206.

Eves, R. Webb, B.A., Zhou, S. and Mak, A.S.

Caldesmon is an integral component of podosomes in vascular smooth muscle cells.

J. Cell Sci. (2006)119 1691-1702.

Webb, B.A., Zhou, Z., Eves., R., Shen, L., Jia, L. and Mak, A.S.

Phosphorylation of cortactin by p21-activated kinase.

Arch Biochem Biophys (2006) 456 183-193.

Webb,B.A. Eves,R. and Mak,A.S.

Cortactin regulates podosome formation in A7r5 vascular smooth muscle cells: the roles of functional domains.

Exp Cell Res (2006) 312:760-769.

Team

Faculty Bio

Research Interests

Selected Publications Funded by CIHR and Ontario Heart and Stroke Foundation.

Faculty