Vassiliki Saloura, M.D. Ph. D.
Dr. Saloura’s laboratory investigates the role of histone and non-histone protein methylation in tumor growth, therapy resistance and immunogenicity in squamous cell carcinoma of the head and neck.
1) histone epigenetics
2) non-histone protein methylation
3) tumor immunology
4) squamous cell carcinoma of the head and neck
Protein methyltransferases (PMTs) and demethylases (PDMTs) are a class of approximately 100 enzymes that modify histone and non-histone proteins and were recently reported to be mutated, amplified and overexpressed in a significant proportion of cancers, including squamous cell carcinoma of the head and neck (SCCHN).
Dr. Saloura’s laboratory aims to elucidate the role of protein methylation mediated by PMTs and PDMTs in oncogenesis, therapy resistance and immunogenicity in squamous cell carcinoma of the aerodigestive tract, with a special focus in SCCHN. Our goal is to develop a translational research program focusing on histone and non-histone protein methylation, and to introduce novel targeted PMT and PDMT inhibitors in clinical trials for head and neck cancer patients with relevant driver molecular phenotypes.
To achieve these goals, research efforts concentrate on two main inter-related projects:
Project 1: Elucidation of the oncogenic function of specific PMTs/PDMTs in SCCHN. We plan to elucidate the function of frequently amplified and/or overexpressed PMTs/PDMTs in SCCHN, including NSD3/WHSC1L1, SUV420H1/KMT5B and SMYD3, and evaluate these as novel drug targets. This project will entail experiments aiming to assess the oncogenic function of these enzymes through identification of their downstream genes, methylation substrates and interacting proteins, and evaluation of their prognostic significance in SCCHN patients. Relevant methods include high-throughput molecular biology techniques, such as ChIP-Seq and RNA-Seq in cell lines and cancer tissue samples, as well as cytotoxicity assays, the development of doxycycline-inducible stably transformed SCCHN cell lines for knockdown and overexpression systems, mass spectrometry analysis, in-vitro methyltransferase assays, in-vivo mouse modelling and immunohistochemical (IHC) correlations using surgical specimens with clinical outcome of patients with SCCHN.
Project 2: The role of PMTs/PDMTs as immune modulators in SCCHN. The overall aim of this project is to elucidate mechanisms through which PMTs/PDMTs affect immune cell infiltration and antigen presentation in SCCHN. The main objectives are the following:
- To identify PMTs/PDMTs that epigenetically silence the expression of chemokines in SCCHN, leading to decreased T-cell infiltration.
- To identify PMTs/PDMTs that epigenetically influence the expression of HLA-I molecules, antigen presenting machinery (APM) components, and neoantigens in SCCHN.
- To identify PMTs that directly methylate HLA-I molecules and/or APM components in SCCHN and to determine the phenotypic effect of methylation on the function of these potential substrates.
Relevant experiments will include a combination of in-vitro and in-vivo experiments, such as ChIP assays, ChIP-Seq, assays to measure migration to chemokines in vitro, IFN-ELISA ELISPOT assays to evaluate the induction of activated T-cell responses to upregulated neoantigens, and in-vivo mouse modelling.
Selected Recent Publications
Characterization of the T-cell receptor repertoire and immune microenvironment in patients with locoregionally advanced squamous cell carcinoma of the head and neck.Clinical Cancer Research. 23 (16): 4897-4907, 2017. [ Journal Article ]
WHSC1L1-mediated EGFR mono-methylation enhances the cytoplasmic and nuclear oncogenic activity of EGFR in head and neck cancer.Scientific Reports. 7: 40664, 2017. [ Journal Article ]
WHSC1L1 drives cell cycle progression through transcriptional regulation of CDC6 and CDK2 in squamous cell carcinoma of the head and neck.Oncotarget. 7 (27): 42527-42538, 2016. [ Journal Article ]
WHSC1 promotes oncogenesis through regulation of NIMA-related kinase-7 in squamous cell carcinoma of the head and neck.Molecular Cancer Research. 13(2): 293-304, 2015. [ Journal Article ]
- Lancet Oncology. 16(2): 129-30, 2015. [ Journal Article ]
Dr. Saloura received her M.D. at the University of Athens. She completed her internal medicine residency training at Hahnemann University Hospital/Drexel University College of Medicine and her Hematology/Oncology Fellowship at the University of Chicago. She did her postdoctoral training at the laboratory of Yusuke Nakamura at the University of Chicago before joining the faculty as an instructor in 2014. In 2017, she joined the Thoracic and Gastrointestinal Oncology Branch at the Center for Cancer Research as an Assistant Clinical Investigator.