Research
The Spiotto Laboratory is addressing how HPV alters the carcinogenesis, metastasis and immune response through three distinct research areas.
Project 1
Identify regulators of differentiation programs to promote HPV tumor growth
HPV cancers are enriched for non-coding RNAs and epigenetic factors that are known regulators of squamous epithelial differentiation. This project seeks to better understand the mechanism by which HPV subvert epithelial differentiation programs to facilitate malignant progression. Here, we utilize dual inducible mouse models coupled with deep sequencing and other multiplexed technologies to better elucidate these pathways.
Project 2
Define prognostic lymph node metastasis subtypes in head and neck squamous cell cancer patients
We have recently identified novel molecular subtypes of lymph node metastasis (LNM) in HPV-negative head and neck squamous cell cancers (HNSCC), one of which was associated with up to 10-fold worse locoregional control. We hypothesize that identification of a high risk LNM subtype will predict locoregional control in HPV-negative and HPV-associated HNSCCs. We will test this hypothesis by identifying molecular subtypes of LNMs in HPV-associated oropharyngeal cancers and dissecting pathways enriched in these distinct phenotypes.
Project 3
Define novel radiation combined with immunotherapy to enhance anti-tumor immune responses
Conventional radiation therapy induces immunogenicity by increasing immunogenic cancer cell death and novel tumor antigen presentation through transient suppression of repressor lymphocyte lineages. While stimulating immunogenic cell death, conventional RT approaches also potentially suppress anti-tumor immune responses and deplete circulating lymphocytes as well as alterations in the microenvironment that prevent effective immune responses. In collaboration with the Schueler Lab, we are studying how FLASH-RT represents a new RT paradigm to treat multiple cancer types while limiting many tissue toxicities. We utilize FLASH-RT to enhance anti-tumor immune responses in HPV cancers. In addition, we are studying how radiotherapy can induce abscopal responses against systemic leukemias.