Ted Hupp
Therapeutics; Oesophageal Cancer Progression Models; Immune-cancer Synapse; Interferon Signalling; The Endoplasmic Reticulum Secretory System
Research in a Nutshell
Cancer progression is driven in part by the mutation of genes that mediate immortality, angiogenesis, metastasis, changes in energy metabolism, and evasion of the immune system. P53 mutation is one of the most common genetic changes in cancer development that leads to a re-wiring and selective survival advantage to the developing cancer cell. This genetic re-wiring involves changes in the transciptome, the proteome, and the phenotype of the cell within a specific microenvironmental niche in vivo. The lab is using biophysical, biochemical, and proteomic approaches to develop novel molecular insights into clinically relevant cancer progression pathways; particularly cancers of unmet clinical need including oesophageal adenocarcinoma, gliomas, and sarcomas. Emerging therapeutic strategies being developed include drugging protein-protein interactions; biologics and immunotherapeutics; and proteogenomics platforms that define mutated neoantigen landscapes to facilitate cancer vaccine developments.
Biography
Ted Hupp obtained a dual BSc degree in microbiology & chemistry at the idyllically named Bowling Green State University in Ohio, USA. Following a PhD in Biochemistry at Michigan State University, enzymology principles were then applied to the cancer research field in Dundee (UK) to develop the paradigm that the tumour suppressor p53 could be activated by antibodies. His current position of Professor is as the Chair of Experimental Cancer Research at the University of Edinburgh and aims to spearhead the formation of novel, interdisciplinary research programmes in cancer biomedicine. Topics include as Drug Discovery programmes in the Ubiquitin-Proteasome system and the development of therapeutic monoclonal antibodies. It is during these European Union wide collaborations that Ted and colleagues set up the International Center for Cancer Vaccine Science (ICCVS); at the University of Gdansk forming a joint research unit with the University of Edinburgh to seed inter-disciplinary collaborations within the European Union and around the world.
Publications
1 Maurel, M. et al. Control of anterior GRadient 2 (AGR2) dimerization links endoplasmic reticulum proteostasis to inflammation. EMBO Mol Med 11, doi:10.15252/emmm.201810120 (2019).
2 Gu, X. et al. Copy number variation: A prognostic marker for young patients with squamous cell carcinoma of the oral tongue. J Oral Pathol Med 48, 24-30, doi:10.1111/jop.12792 (2019).
3 Gomez-Herranz, M. et al. The effects of IFITM1 and IFITM3 gene deletion on IFNgamma stimulated protein synthesis. Cell Signal 60, 39-56, doi:10.1016/j.cellsig.2019.03.024 (2019).
4 Coufalova, D. et al. An inter-subunit protein-peptide interface that stabilizes the specific activity and oligomerization of the AAA+ chaperone Reptin. J Proteomics 199, 89-101, doi:10.1016/j.jprot.2019.02.012 (2019).
5 Mohtar, M. A. et al. The sequence-specific peptide-binding activity of the protein sulfide isomerase AGR2 directs its’ stable binding to the oncogenic receptor EpCAM. Mol Cell Proteomics, doi:10.1074/mcp.RA118.000573 (2018).
6 O’Neill, J. R. et al. Quantitative Shotgun Proteomics Unveils Candidate Novel Esophageal Adenocarcinoma (EAC)-specific Proteins. Mol Cell Proteomics 16, 1138-1150, doi:10.1074/mcp.M116.065078 (2017)
Collaborations
The ICCVS has formed a centre of excellence in inter-disciplinary research that aims to improve human health by establishing discovery science programmes focused on the immune-cancer synapse. Several inter-disciplinary collaborations with academic and industry colleagues are focused on (i) identifying genes that regulate the expression of MHC Class I molecules, (ii) identifying oncogenic receptors at cancer-immune synapse; (iii) developing therapeutic antibodies to targets in the cancer secretory system; (iv) using proteogenomics and kinomics platforms to develop preclinical models in cancers of high unmet clinical need.
Technology expertise
Protein-protein interactions; kinase signal transduction; ubiquitination and protein degradation; synthetic monoclonal antibody and peptide bacteriophage libraries