ESR 14 -Anvesh Jallapally

Hosted at UAntwerpen

ESR9 round

I have a Master's degree in Pharmaceutical Chemistry and over two years of research experience in synthesis and drug testing working as Project Junior Research Fellow in CSIR Indian Institute of Chemical Technology, Hyderabad, India. My expertise in drug discovery includes handling moisture sensitive organic reactions, analysis of 2D NMR, ESI, and HRMS spectra of synthesized compounds, invivo and invitro screening, cellular biology techniques (e.g. Realtime PCR), pharmacological techniques (e.g. dose response assesment),laboratory animal handling and conducting enzyme assays for high throughput screening.

I am pursuing my PhD as a part of ECMED network in Prof. Pieter Van der Veken's lab at University of Antwerp, Belgium. My research topic includes synthesis of fluorescent and [18]F- labeled activity based probes for Fibroblast activation proteins and Prolyl oligopeptidase proteins.


Imaging the extracellular matrix proteases MMP-9 and uPA in the development of acquired epilepsy



Background

Matrix metalloproteinase-9 (MMP-9) and urokinase-type plasminogen activator (uPA) are two of the most important extracellular matrix proteases that have been involved in epilepsy. MMP-9 and uPA are upregulated in epileptogenic lesions. In addition, MMP-9 knockout mice have been shown to be less sensitive to epileptogenesis than wild type mice while MMP-9 overexpressing rats showed an increased sensitivity to epileptogenesis compared to wild type rats. On the other hand, uPA knockout mice showed a higher sensitivity to epileptogenesis than wild types. Imaging of these ECM compounds would facilitate the investigation of their role in acquired epilepsy.

Objectives

  • to assess spatial and temporal changes of MMP-9 and uPA in animal models of posttraumatic epilepsy and temporal lobe epilepsy 
  • to determine the role of these proteases in animal models of acquired epilepsy 
  • to investigate whether these proteases can act as biomarkers/predictors of the long-term functional outcome. 

Approach

Alterations in MMP-9 and uPA in rat models of acquired epilepsy will be assessed at different time points using different post-mortem techniques: in situ/in gel zymography, immunohistochemistry, qPCR and/or ELISA. The ECM proteases will also be assessed in autoradiography experiments, making use of the recently developed ECM radiotracer 18F-UAMC-01306 targeting uPA and an MMP-9 radiotracer, which is currently under development. AMU and Vect-Horus will provide peptide vectors to which the radiotracers can be conjugated with NOTA or DOTA cages for caging of radionuclides used for SPECT and PET. In a follow-up study, rats will receive an epileptogenic insult (traumatic brain injury of status epilepticus) and be subjected to in vivo PET/SPECT imaging using radiotracers that bind the ECM proteases as well as a TSPO tracer to assess inflammation, followed by MRI scanning to assess structural changes and blood-brain barrier integrity. Both short-term and long-term functional (including motor, cognitive and seizure) outcomes of the rats will also be assessed. We will investigate whether early changes in MMP-9/uPA can predict functional outcome. Finally, we will pharmacologically interfere with these ECM proteases during a specific time window and assess whether the short-term and long-term functional outcome of the animals improves. This might identify MMP-9 and uPA as novel anti-epileptogenic drug targets.  

Collaborations

Zymography experiments will be performed in collaboration with LIN. Characterization of the Controlled Cortical Impact model of traumatic brain injury will be done in association with UEF. EEG monitoring will be done in collaboration with UCL. Evaluation of the benefit of conjugation of the radiotracers to brain penetrating peptide vectors will be done in collaboration with AMU and Vect-Horus.

Current Activity

Anvesh started his PhD later than the other ESRs, and is currently in his third year of research. He will submit his thesis in 2020. 

Page last modified on 21 may 19 11:32