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About Sickkids
About SickKids

Aleksander Hinek, MD, PhD, DSc

Research Institute
Senior Scientist
Translational Medicine

University of Toronto
Professor
Department of Laboratory Medicine & Pathobiology

Professor
Institute of Medical Science


Phone: 416-813-6725
Fax: 416-813-7480
Email: aleksander.hinek@sickkids.ca

Research Interests

  • Elastin and other components of extracellular matrix
  • Atherosclerosis/vascular Injury
  • Inherited cardiovascular diseases
  • Tissue regeneration
  • Bioengineering

Research Activities

My previous research interests were scattered through a broad spectrum of subjects, centred around structure and function of connective tissue cells and the extracellular matrix, in the development of disease. I studied problems arising with cartilage and bone transplantation and bioengineering of cartilage from human cells. I have addressed pathomorphology of vascular diseases including atherosclerosis and diabetic arteriopathies, protection of cardiac muscle against cytotoxicity induced by anticancer drugs, and role of proteinases in cancer spreading and metastasis. Many of my studies were aimed at ultrastructure of elastic fibers, and role of impaired elastogenesis in pathological processes ranging from cancer spreading and wound healing to atherosclerosis. They lead to the discovery of the 67-kD elastin binding protein (EBP), which is the alternatively spliced variant of beta-galactosidase (S-GAL) and serves as a major subunit of the cell surface "elastin receptor" propagating multiple intracellular signals. EBP also serves as a recyclable intracellular chaperone facilitating secretion of tropoelastin and assembly of elastic fibers.

My research team and I found that primary or secondary deficiencies in the EBP can be linked to impaired elastin deposition that directly contributes to the development of cardiovascular defects, supravalvular aortic stenosis, occlusions of coronaries, and skeletal deformities in children with such inherited conditions as GM1-gangliosidosis, Morquio B disease, Costello syndrome, Hurler disease, and Williams-Beuren syndrome. Another set of recent results indicates that the second components subunit of the elastin receptor (Neuraminidase-1) also facilitates elastic fiber assembly and may modulate mitogenic response of arterial SMC to mitogenic growth factors IGF-II and PDGF.

We have also verified that a third component of cell surface elastin receptor, called Protective Protein, has deamidase activity that may inactivate a potent SMC mitogen and vasoconstrictor, Endothelin 1, thereby controling arterial blood pressure. Recently we have discovered that aldosterone also induces elastin production in cardiac fibroblasts through activation of IGF-1 receptor and explained why inhibition of mineralo-corticosteroid receptors triggers the beneficial remodeling of the injured heart.

Future Research Interests

Pursuing our discovery that subunits of elastin receptor modulate normal production of elastic fibers and control cellular proliferation, we will determine whether overexpression of the EBP and activation of other sub-units of elastin receptor could be used in future therapies of children with inherited elastinopathies, including Williams-Beuren disease and Costello Syndrome. We will also therapeutically apply results our recent research indicating that low concentration of iron is a prerequisite for the transcription of elastin gene and that polyphenols, ellagic and tannic acids protect elastic fibers present in skin, lungs and arteries from enzymatic degradation.

We have also started new research aimed at pharmacological treatments of children with Marfan disease and Loyes-Dietz syndrome that are characterized with development or aortic aneurysms.

External Funding

  • Canadian Institutes for Health Research (CIHR)
  • Heart and Stroke Foundation of Ontario

Achievements

Career Investigator Award, Canadian Heart and Stroke Foundation, since 1993.

Publications

Hinek A, Bodnaruk T, Bunda S, Wang Y, Liu K. Neuraminidase-1, a subunit of the cell surface elastin receptor, desialylates and functionally inactivates adjacent receptors interacting with the mitogenic growth factors, PDGF-BB and IGF-II. Am. J. Pathol. 173(4): 1042-1056, 2008

Hinek A, Jain S, Taylor G, Nykanen D, Chitayat D. High copper levels and increased elastolysis in a patient with cutis marmorata teleangiectasia congenita. Am J Med Genet A. 2008 Sep 15;146A(19):2520-2527

Bunda S, Liu P, Wang Y, Liu K, Hinek A. Aldosterone induces elastin production in cardiac fibroblasts through activation of IGF-1 receptor in MR-independent manner. Am. J. Pathol. 171:809-819, 2007

Hinek A, Pshezhetsky AV, von Itzstein M, Starcher B. Lysosomal sialidase Neu1 is targeted to cell surface in the multiprotein complex that facilitates elastic fiber assembly. J. Biol. Chem. 281: 3698-3710, 2006

Jimenez F, Mitts TF, Liu K, Wang Y, Hinek, A. Ellagic and tannic acids protect newly synthesized elastic fibers from premature enzymatic degradation in dermal fibroblast cultures. J. Investig. Dermatol. 126(6):1272-80, 2006

Hinek A, Titell M, Schoyer L, Allen W, Gripp KW, Hamilton R, Weksberg R, Lin AE. Myocardial storage of chondroitin sulfate-containing moieties in Costello syndrome patients with severe hypertrophic cardiomyopathy. Am. J. Med. Genet. 133A: 1-12, 2005

Hinek A, Braun KR, Liu K, Wang Y, Wight TN. Retrovirally mediated overexpression of versican v3 reverses impaired elastogenesis and heightened proliferation exhibited by fibroblasts from Costello syndrome and Hurler disease patients. Am. J. Pathol 164 (1):,119-131, 2004.

Mochizuki S, Brassart B, Hinek A. Signaling pathways transduced through the elastin receptor facilitate proliferation of arterial smooth muscle cells. J. Biol.Chem. 277 (47) 44854-44863, 2002.

Urbán Z, Riazi S, Seidl TL, Katahira J, Smoot LB, Chitayat D, Boyd CD, Hinek A. Connection between elastin haploinsufficiency and increased cell proliferation in patients with supravalvular aortic stenosis and Williams-Beuren syndrome. Amer. J. Hum.Genet. 71 (1), 30-44. 2002.

Nakamura T, Lozano PR, Ikeda Y, Iwanaga Y, Hinek A, Minamisawa S, Cheng C-F, Kobuke K, Dalton N, Takada Y, Tashiro K, Ross J, Honjo T, Chien KR. Fibulin-5/DANCE is essential for elastogenesis in vivo. Nature 415, 171-175, 2002.