Proteostasis and Immune Signalling in Cancer and Dementia
Research in a Nutshell
Proteostasis is a complex regulatory network which balances the cellular proteome by coordinating protein synthesis, folding, functional activity and degradation. Disruption of cellular proteostasis manifests in levels of proteotoxic stress that can compromise the immune system, initiate age related neurodegenerative conditions and predispose to cancer. We focus on defining the molecular and cellular mechanisms by which interferon regulated immune signalling and ubiquitin-mediated proteostatic mechanisms are integrated and coordinately regulated in order to protect cells and organs from aberrant protein:protein that re-purpose signal transduction pathways.
Our current focus is cancers of high unmet clinical need and dementia with synucleinopathies, for example:
- Two major obstacles in the treatment of oesophageal cancer (OAC) are metastasis and drug resistance. We are using tissue proteomics to identify novel OAC targets and dissecting pro- and anti-cancer interferon regulated proteins in order to develop novel biologics with anticancer activity. We are also exploiting interferon and proteostasis dependent immune-blockade pathways to define novel therapeutic approaches.
- Dementia with Lewy bodies (DLB) is a protein disease with a high unmet need for novel treatments and progression models. We are using iPSC derived neurons and animal models to study the role of ubiquitin pathways, proteostasis and interferon signalling in DLB.
Principal Investigator and Professor of Biochemistry and Cell Signalling
|Julia Mara Kulbe
|Visiting Postdoctoral Fellow
|Dr Filip Trcka
- Dr Tilo Kunath, CRM (University of Edinburgh)
- Professor Ted Hupp, The Institute of Genetics and Cancer (University of Edinburgh)
- Professor Malcolm Walkinshaw, CTCB (University of Edinburgh)
- Professor David Argyle, Vet School (University of Edinburgh)
- Dr Alison Hulme, Chemistry (University of Edinburgh)
- Professor Bořivoj Vojtěšek, RECAMO, Masaryk Memorial Cancer Institute
- Dr Chandra Verma, A* Singapore
- Dr Robin Fahraeus, Universite Paris
- Professor Krystyna Bieńkowska-Szewczyk, University of Gdansk
- Professor Rory Duncan, Heriot-Watt University
Partners and Funders
- RECAMO/European Union
- Medical Research Council
- Alzheimer’s Research UK
Protein structure-function relationships in vitro and in cells; cell signalling and proteomics in cancer; ubiquitin signalling and proteomics in dementia; generation of biologics for basic and translational research.
Protein structure and function; generation and use of both conventional and synthetic antibodies for basic research and translation into novel therapeutics; proteomics and mass spectrometry; interferon and antiviral cell signalling; cell and molecular biology; generation of cell models using gene editing; tissue biochemistry; imaging nano-probes and biosensors; chemical genetics.