ESR 8 - Mehwish Anwer

Hosted at UEF

ESR6 round

I am an Early Stage Researcher and a Doctoral student at the A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland. Before joining the ECMED H2020-MSCA-ITN project, I have been working as a Researcher in Neuroanatomy at College of Medicine and Health Sciences, United Arab Emirates University. I was investigating mechanisms underlying neuropathic pain after peripheral nerve injury. I completed my Masters (MPhil) in Molecular Biology from Centre for Research in Molecular Medicine, The University of Lahore, Pakistan. My current project investigates the role of SRPX2 protein in uPAR-interactome and post-traumatic epileptogenesis. 

uPAR-interactome and post-traumatic epileptogenesis



Objectives

  • To identify regional and cellular location of SRPX2 expression during post-TBI epileptogenesis
  • To identify signaling mechanisms by which SRPX2 regulates post-TBI axonal plasticity
  • To measure the circulating levels of SRPX2 during epileptogenesis
  • To assess the suppression of SRPX2 expression on neurodegeneration and axonal plasticity
  • To assess whether the treatment effect on synaptic plasticity can be monitored with in vivo MRI imaging and multielectrode arrays

Approach

Our molecular profiling study of epileptogenesis done about 15 years ago led us to investigate urokinase-type plasminogen activator (uPA). uPA is part of the uPAR-interactome which is composed of its receptor, uPAR, and other extracellular ligands such as sushi-repeat protein X-linked SRPX2. Studies in cancer have shown that uPAR-interactome is a major player in cancer cell adhesion, proliferation, differentiation and migration; extracellular matrix degradation; invasion and clearance of inflammatory cells; apoptosis, and tumor angiogenesis. 

The reason why we became interested in uPAR-interactome is that many of these plastic processes taking place in cancer tissue also occur in the brain during epileptogenesis. Moreover, mice lacking uPAR have epilepsy that is associated with abnormal migration of GABAergic interneurons in the frontal cortex and the hippocampus, and patients with Rolandic epilepsy with speech impairment or bilateral perisylvian polymicrogyria have a mutation in a gene encoding uPAR ligand, SRPX2. However, very little is known about the expression and function of SRPX2 in the brain. Our recent preliminary studies showed that it has a very interesting distribution in the brain. We also discovered that traumatic brain injury, a major cause for epilepsy, induces SRPX2 expression in the perilesional cortex after TBI. 

The objective of this ETN project is to explore in details the distribution and function of SRPX2 during epileptogenesis, and assess the potential of this novel target for biomarker and therapy discovery. 

Collaborations

We will collaborate with UCL to produce viral constructs with shRNA for SRPX2, and with ITT in MEA technology and analysis.

Current Activity

Mehwish is currently wokring at UEF and finishing her PhD thesis in the same laboratory.

Page last modified on 21 may 19 11:21