Lina Dagnino

Genetics & Development Dr. Lina Dagnino
Scientist
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Affiliations

Scientist, Division of Genetics & Development, Children’s Health Research Institute
Associate Professor, Departments of Physiology and Pharmacology, Paediatrics,
Schulich School of Medicine & Dentistry, Western University
Scientist, Lawson Health Research Institute

How my research helps children

Children born with genetic defects that cause skin diseases such as Epidermolysis bullosa (an inherited connective tissue disease) develop blisters in areas subjected to high friction, such as hands and feet. This severe, generalized blistering remains throughout life, and can progress into chronic wounds that greatly reduce the general health and quality of life of affected individuals. Our research focuses on understanding how the skin and its derivatives, such as hair and hair follicles, are formed and repaired. We are also working to identify the factors responsible for skin integrity and ability to repair after wounding, and to understand how they function.

Research

Current Research Activities

My research interests involve the elucidation of the mechanisms that regulate epidermal keratinocyte (KT) proliferation and maturation. My group has demonstrated that genes encoding the family of E2F transcription factors are differentially expressed in developing epidermis, and that expression of E2F-1 is essential for proper KT proliferation and migration, and for normal wound healing. A second research theme in my program is the characterization of integrin-linked kinase (ILK) in differentiating KTs and its role in epidermal homeostasis and acquisition of barrier function. I have demonstrated novel, tissue-specific mechanisms that control the formation of ILK complexes associated with cell-cell junctions in differentiated KTs and with cell-extracellular matrix contact points in undifferentiated cells, as well as a fundamental role for ILK in the formation and developmet of hair follicles. Recently, I have generated an animal model to study skin blistering disorders and develop better therapies. Children born with genetic defects that cause Epidermolysis bullosa develop blisters in areas subjected to high friction, such as hands and feet, and can present with severe, generalized blistering that progresses into chronic wounds.

Research Team

My research team currently includes a post-doctoral fellow, five graduate students, one undergraduate student and a research technician. Opportunities for additional graduate students and post-doctoral fellows to join my research group are available. My trainees have been very successful after finishing their work in our laboratory, and have gone on to a variety of institutions and organizations, as post-doctoral fellows and faculty members in academia, officers at government organizations such as Health Canada, research managerial positions in private industry settings, and continuing their education in professional schools.

Future Research Plans

I have generated several mouse models that will allow us to study skin stem cells, their basic biology and potential in various therapies for skin diseases.

Awards & Grants

Awards and Grants

Funding in support of Regulation of TGF-beta signaling by focal adhesion proteins – Awarded by Natural Science and Engineering Research Council (NSERC)

Funding in support of Maintenance of Mouse Colony – Awarded by Schulich School of Medicine & Dentistry, Western University

Funding in support of Focal adhesion proteins and epidermal integrity – Awarded by Canadian Institutes of Health Research (CIHR)

Funding in support of Integrin-linked kinase in epidermal stem cells – Awarded by Canadian Institutes of Health Research (CIHR)

Funding in support of The role of periostin in promotin epithelialmyofibroblast transition and incidence of apoptosis in cutaneous wound healing – Awarded by Canadian Institutes of Health Research (CIHR)

Funding in support of Mechanisms of melanosome phagocytosis in keratinocytes – Awarded by National Science and Engineering Research Council (NSERC)

Funding in support of ILK and Elmo in cell migration – Awarded by Heart and Stroke Foundation

Funding in support of Integrin-linked kinase in epidermal formation and regeneration – Awarded by Canadian Institutes of Health Research (CIHR)

Funding in support of Molecular mechanisms of epidermal formation and regeneration (ILK) – Awarded by Canadian Institutes of Health Research (CIHR)

Funding in support of Molecular mechanisms of hair follicle morphogenesis – Awarded by National Cancer Institute of Canada (NCIC)

Funding in support of Integrin-linked kinase in epidermal morphogenesis and regeneration – Awarded by Institute of Musculoskeletal Health and Arthritis (CIHR)

Funding in support of Role of Integrin-linked kinase in melanosome uptake in keratinocytes – Awarded by Natural Sciences and Engineering Research Council of Canada (NSERC)

Funding in support of E2F1 target genes in epidermal repair – Awarded by CIHR

Funding in support of London Strategic Training Initiative in Cancer Research and Technology Transfer – Awarded by CIHR

Funding in support of Integrin-linked kinase in epidermal stem cells – Awarded by The Cancer Research Society

Recent Publications

Publications

Integrins and small GTPases as modulators of phagocytosis
Sayedyahossein S, Dagnino L
Int Rev Cell Mol Biol. 2013; 302:319-352

Integrins as modulators of TGF-beta signaling in skin regeneration after injury
Boo S, Dagnino L
Adv Wound Care. 2013; 2:225-237

Essential role of integrin-linked kinase in regulation of phagocytosis in keratinocytes
Sayedyahossein S, Nini L, Irvine TS, Dagnino L
FASEB J. 2012; 26:4218-4229

Emerging role of ILK and ELMO2 in the integration of adhesion and migration pathways
Ho E, Dagnino L
Cell Adhesion and Migration. 2012; 6(3):168-172

Multiple roles of integrin-linked kinase in epidermal development, maturation and pigmentation revealed by molecular profiling
Judah D, Rudkouskaya A, Wilson R, Carter DE, Dagnino L
PLoS One. 2012; 7(5):e36704

Epidermal growth factor induction of front-rear polarity and migration in keratinocytes is mediated by integrin-linked kinase and ELMO2
Ho E, Dagnino L
Mol Biol Cel. 2012; 23:492-502

Integrin-linked kinase: A scaffold protein unique among its ilk
Dagnino L
J Cell Commun Signal. 2011; 5:81-83

Targeted inactivation of integrin-linked kinase in hair follicle stem cells reveals an important modulatory role in skin repair after injury
Nakrieko KA, Rudkouskaya A, Irvine TS, D'Souza SJA, Dagnino L
Mol Biol Cell. 2011; 14:2532-2540

Integrin-linked kinase is essential for transforming growth factor-beta induced myofibroblast differentiation
Vi L, deLasa C, DiGuglielmo G, Dagnino L
J Invest Dermatol. 2011; 131: 586-593

Differential expression of specific microRNA and their targets in acute myeloid leukemia
Cammarata G, Augugliaro L, Salemi D, Agueli C, La Rosa M, Dagnino L, Civiletto G, Messana F, Marfia A, Bica MG, Cascio L, Floridia PM, Mineo AM, Russo M, Fabbiano F, Santoro A
Am J Hematol. 2010 May; 85(5):331-9

Accurate and reproducible measurements of RhoA activation in small samples of primary cells
Nini L, Dagnino L
Anal Biochem. 2010 Mar 1; 398(1):135-7

Expression and analysis of exogenous proteins in epidermal cells
Dagnino L, Ho E, Chang WY
Methods Mol Biol. 2010; 585:93-105

Altered mRNA expression of PAX5 is a common event in acute lymphoblastic leukaemia
Santoro A, Bica MG, Dagnino L, Agueli C, Salemi D, Cannella S, Veltroni M, Cetica V, Giarin E, Fabbiano F, Basso G, Arico M
Br J Haematol. 2009 Sep; 146(6):686-9

Integrin-linked kinase interactions with ELMO2 modulate cell polarity
Ho E, Irvine T, Vilk GJ, Lajoie G, Ravichandran KS, D'Souza SJ, Dagnino L
Mol Biol Cell. 2009 Jul; 20(13):3033-43

Phosphorylation by p38 MAP kinase is required for E2F1 degradation and keratinocyte differentiation
Ivanova IA, Nakrieko KA, Dagnino L
Oncogene. 2009 Jan 8; 28(1):52-62

Modulation of integrin-linked kinase nucleo-cytoplasmic shuttling by ILKAP and CRM1
Nakrieko KA, Vespa A, Mason D, Irvine TS, D'Souza SJ, Dagnino L
Cell Cycle. 2008 Jul 15; 7(14):2157-66

Impaired hair follicle morphogenesis and polarized keratinocyte movement upon conditional inactivation of integrin-linked kinase in the epidermis
Nakrieko KA, Welch I, Dupuis H, Bryce D, Pajak A, St Arnaud R, Dedhar S, D'Souza SJ, Dagnino L
Mol Biol Cell. 2008 Apr; 19(4):1462-73

A novel mechanism of E2F1 regulation via nucleocytoplasmic shuttling: determinants of nuclear import and export
Ivanova IA, Vespa A, Dagnino L
Cell Cycle. 2007 Sep 1; 6(17):2186-95

Differentiation and injury-repair signals modulate the interaction of E2F and pRB proteins with novel target genes in keratinocytes
Chang WY, Andrews J, Carter DE, Dagnino L
Cell Cycle. 2006 Aug; 5(16):1872-9

Additional publications

Contact

Contact

Phone: (519) 661-4264
Fax: (519) 661-3827
Email: ldagnino [at] uwo [dot] ca
Website: www.uwo.ca/physpharm/faculty/dagnino_lina.html

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