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KOÇ UNIVERSITY

GRADUATE SCHOOL OF SCIENCES & ENGINEERING

BIOMEDICAL SCIENCES AND ENGINEERING

PhD THESIS DEFENSE BY MOHAMMAD HAROON QURESHI

 

Title: Roles of Protocadherins in Mammalian Cells

Speaker: Mohammad Haroon Qureshi

Time: October 30, 2018, 15:00

Place: ENG 208

Koç University

Rumeli Feneri Yolu

Sariyer, Istanbul

Thesis Committee Members:

Assoc. Professor Nurhan Özlu (Advisor, Koç University)

Assist. Professor Tuğba Bağcı Önder (Koç University)

Assist. Professor Elif Nur Fırat Karalar (Koç University)

Assoc. Professor Umut Şahin (Boğaziçi Üniversity)

Assist. Professor Halil Bayraktar (Istanbul Technical University)

Abtract:

Cancer is one of the leading causes of morbidity and mortality around the globe. It is a complex disease characterized by hyperproliferation, genetic instability, and cumulative mutations, and at advanced stages, a spread to secondary sites, through a process known as metastasis. Metastasis is directly dependent on cancer cells’ ability to migrate and, for an intervention in metastasis, it is pertinent to understand the molecular details of cell migration. In the current thesis, we attempted to understand the roles of a cell surface protein protocadherin-7 (PCDH7) in cell migration.

Previous work from our group has shown PCDH7 as a cell-cycle regulated membrane protein. For the current project, we characterized the effects of perturbation of PCDH7 expression on cell migration of mammalian cells using RNA interference based knockdown and CRISPR/Cas9 based knockout. We also characterized its sub-cellular localization using immunofluorescence and live-cell imaging, which highlighted its association with cellular compartments directly involved in cell migration dynamics.

To further characterize molecular mechanisms behind PCDH7’s role in cell migration, we used a quantitative proteomics approach to compare global changes upon PCDH7’s knockout, which in turn outlined a plethora of upregulated and downregulated proteins. Many of these proteins have previously been shown to be associated with cellular compartments involved in cell migration or have a molecular function characterized in the regulation of cell migration.

Taken together, we have described a critical role of PCDH7 in cell migration in mammalian cells. We showed PCDH7’s correlation with subcellular compartments that are associated with cell migration and invasion and found possible molecular players mediating its role in cell migration. Our work is a step towards recognizing PCDH7 as a promising therapeutic target for the control of cancer metastasis.

 

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