Tarannum Ara - PhD Scholarship 2023
Project summary:
Targeting the novel HCO3 – sensor RPTPγ for neuroprotection in ischemic stroke
Neurons, microvascular endothelial cells, and immune cells express the proposed HCO3 – sensor protein RPTPγ. We propose that RPTPγ translates acid-base disturbances in the extracellular environment of stroke lesions into altered intracellular signaling events that may confer neuroprotection.
Project Title
Targeting the novel HCO3 – sensor RPTPγ for neuroprotection in ischemic stroke
Background
Stroke is a leading cause of death and disability. Inadequate cerebral blood flow relative to the metabolic demand lowers tissue oxygenation and causes acute ischemic damage followed by delayed secondary injury due to vasospasm and inflammation. Under physiological conditions, the local acid-base triggered mechanisms match cerebral blood flow to metabolic demand. These mechanisms are compromised during stroke.
Aim
It is the aim of this proposal to identify novel strategies for next-generation drugs that specifically target the still salvageable ischemic penumbra to facilitate innate protective mechanisms.
Methods
It is our objective to elucidate the fundamental impact of RPTPγ on cerebrovascular, immune cell, and neuronal function and identify new approaches that can exploit these observations to the benefit of patients. I will use mouse models and a series of sophisticated experimental techniques to evaluate the influence of RPTPγ on stroke severity and explore the involved neuroprotective mechanisms.
Preliminary results
The molecular mechanisms whereby RPTPγ regulates cardiovascular function remain largely unknown, however there are some identified targets from other cell types that are known mediators of cerebral ischemic damage. Loss-of-function RPTPγ variants are associated with a 7-fold increased stroke risk in humans
Tarannum Ara
- MSc
- Aarhus University
Main supervisor:
Ebbe Bødtkjer, Professor, Department of Biomedicine, Aarhus University
Co-supervisors:
Claus Ziegler Simonsen, Professor, Department of Clinical Medicine-Neurology, Aarhus University
Walter F. Boron, Professor, Department of Physiology and Biophysics Case Western Reserve University Cleveland, Ohio
Vladimir Matchkov, Associate professor, Department of Biomedicine, Aarhus University