Dr Olivera Grubisha
Lecturer
- grubishao@cardiff.ac.uk
- +44 (0)29 2251 1071
- Main Building, Park Place, Cardiff, CF10 3AT
Overview
Overview
Building on 10 years of pharmaceutical experience in industry (Eli Lilly & Co), and more recently in academia, my research involves drug discovery in the therapeutic areas of unmet medical need, primarily psychiatric and neurodegenerative disorders. Using biophysical, biochemical and cellular imaging methods, I study protein-ligand interactions and their functional effects in cellular model systems. Current projects include:
- LIMK1 inhibitors for the treatment of Fragile X syndrome
- SR inhibitors as novel therapeutics for treatment-resistant depression
- SR positive allosteric modulators – a novel approach for the treatment of schizophrenia
New potential drug targets are continually being reviewed internally, and as Head of Biology for the New Targets Team, I coordinate this process and help drive decisions and shape the new project portfolio. If you would like to propose a target, discuss ways to collaborate or simply would like to learn more about drug discovery, please feel free to contact me.
Interested in joining my research team?
I enjoy having students and providing them with opportunities for hands-on learning and immersion into an interdisciplinary environment. Several projects are available for undergraduate, Master’s and self-funded PhD students. Motivated individuals interested to be part of the team, please contact me by email.
Biography
I completed my studies in the USA, receiving a BSc degree in Microbiology from Arizona State University (Tempe, Arizona) and a PhD degree in Microbiology and Molecular Genetics from the Medical College of Wisconsin (Milwaukee, Wisconsin). I was interested in disease and medicine from a very early age and decided to study virus biology because I was fascinated by the ingenious ways that these microorganisms evolved to usurp the host machinery. Pursuing doctoral research in Prof. Paula Trakman’s lab, I studied the life cycle of vaccinia virus, the prototypic member of the poxvirus family. The highlight of this work was uncovering the role of the viral I6 protein in viral genome packaging into the virus particle. Prof. Traktman was one of the people who had a tremendous influence on my life, she shaped me into a scientist and has remained, through the years, one of my biggest role models.
I became interested in signal transduction pathways and understanding how enzymes work, which brought me to Prof. John Denu’s lab at the Department of Biomolecular Chemistry at the University of Wisconsin-Madison, where I stayed as a post-doc for 2 years. With a team of chemists and biologists, the lab studied histone/protein deacetylases (HDACs), their catalytic mechanism, specificity and physiological function using an incredibly wide breath of disciplines. This was an extremely enriching experience where I gained valuable knowledge about signal transduction, enzyme kinetics and learned many biochemical and biophysical techniques. Seeking to demonstrate more independence, I identified an opportunity and was successfully awarded a 3-year research fellowship from the Pasteur Foundation, to conduct research at the Pasteur Institute in Paris, France. Working in the Department of Structural Biology and Chemistry, I successfully crystalized a regulatory domain of the IKK gamma protein and helped characterize its interaction with ubiquitin, demonstrating a downstream effect on NF-kB signalling. These data facilitated a research agreement between Servier Pharmaceuticals and the host lab and led to joint patent filling. It was also was my first interaction with the pharmaceutical industry, which opened new possibilities and led me towards the drug discovery path.
In November 2009, I decided to transition into industry and joined Eli Lilly & Company in Windlesham, UK. During the 9 years as a research scientist at Lilly, I contributed to projects across the Neuroscience Division, in therapeutic areas such as pain, cognition, psychiatry, and neurodegeneration, particularly Alzheimer’s disease. I was involved in biochemical and cellular assay development, pharmacological profiling of compounds, and measuring target engagement biomarkers in pre-clinical models. Most of all, I enjoyed managing different aspects of the projects, interacting with colleagues across disciplines and contributing to the drug discovery process from target validation to candidate selection. However, perpetual downsizing, meant limited possibilities for career progression. I was seeking a role with more leadership and the ability to shape the portfolio at a strategic level. This opportunity opened to me at the newly formed Medicines Discovery Institute at Cardiff University. I joined as Lecturer in August 2018 and have been enjoying the team effort of building the Institute, leading the new targets team and creating collaborations with researchers across the university.
Publications
2022
- An, H., Elvers, K. T., Gillespie, J. A., Jones, K., Atack, J. R., Grubisha, O. and Shelkovnikova, T. A. 2022. A toolkit for the identification of NEAT1_2/paraspeckle modulators. Nucleic Acids Research 50(20), article number: e119. (10.1093/nar/gkac771)
- Collins, R. et al. 2022. Comparative analysis of small-molecule limk1/2 inhibitors: chemical synthesis, biochemistry, and cellular activity. Journal of Medicinal Chemistry (10.1021/acs.jmedchem.2c00751)
- Koulouris, C. R. et al. 2022. Tyrosine 121 moves revealing a ligandable pocket that couples catalysis to ATP-binding in serine racemase. Communications Biology 5(1), article number: 346. (10.1038/s42003-022-03264-5)
2017
- Hufgard, J. R. et al. 2017. Phosphodiesterase-1b (Pde1b) knockout mice are resistant to forced swim and tail suspension induced immobility and show upregulation of Pde10a. Psychopharmacology 234 (10.1007/s00213-017-4587-8)
2014
- Ursu, D. et al. 2014. Gain and loss of function of P2X7 receptors: Mechanisms, pharmacology and relevance to diabetic neuropathic pain. Molecular Pain 10(37), pp. 1744-8069. (10.1186/1744-8069-10-37)
- Grubisha, O. et al. 2014. Pharmacological profiling of the TRPV3 channel in recombinant and native assays. British Journal of Pharmacology 171(10), pp. 2631-2644. (10.1111/bph.12303)
2013
- Sanger, H. et al. 2013. Pharmacological profiling of native group II metabotropic glutamate receptors in primary cortical neuronal cultures using a FLIPR. Neuropharmacology 66, pp. 264-273. (10.1016/j.neuropharm.2012.05.023)
2010
- Grubisha, O. et al. 2010. DARPin-assisted crystallography of the CC2-LZ domain of NEMO reveals a coupling between dimerization and ubiquitin binding. Journal of Molecular Biology 395(1), pp. 89-104. (10.1016/j.jmb.2009.10.018)
2009
- Cordier, F., Grubisha, O., Traincard, F., Véron, M., Delepierre, M. and Agou, F. 2009. The zinc finger of NEMO is a functional ubiquitin-binding domain. Journal of Biological Chemistry 284(5), pp. 2902-2907. (10.1074/jbc.M806655200)
2006
- Grubisha, O. et al. 2006. Metabolite of SIR2 reaction modulates TRPM2 Ion channel. Journal of Biological Chemistry 281(20), pp. 14057-14065. (10.1074/jbc.M513741200)
2005
- Grubisha, O., Smith, B. C. and Denu, J. M. 2005. Small molecule regulation of Sir2 protein deacetylases. FEBS Journal 272(18), pp. 4607-4616. (10.1111/j.1742-4658.2005.04862.x)
2003
- Grubisha, O. and Traktman, P. 2003. Genetic analysis of the vaccinia virus I6 telomere-binding protein uncovers a key role in genome encapsidation. Journal of Virology 77(20), pp. 10929-10942. (10.1128/JVI.77.20.10929-10942.2003)
2001
- Punjabi, A., Boyle, K., DeMasi, J., Grubisha, O., Unger, B., Khanna, M. and Traktman, P. 2001. Clustered charge-to-alanine mutagenesis of the vaccinia virus A20 gene: Temperature-sensitive mutants have a DNA-minus phenotype and are defective in the production of processive DNA polymerase activity. Journal of Virology 75(24), pp. 12308-12318. (10.1128/JVI.75.24.12308-12318.2001)
1999
- Derrien, M., Punjabi, A., Khanna, M., Grubisha, O. and Traktman, P. 1999. Tyrosine phosphorylation of A17 during vaccinia virus infection: involvement of the H1 phosphatase and the F10 kinase. Journal of Virology 73(9), pp. 7287-7296.