Genetics and Genomics of Squamous Cell Carcinoma:
We are interested in understanding the identity and function of the events that reprogram normal cells into tumor cells. Head and neck squamous cell carcinoma (HNSCC) is a morbid and frequently lethal disease. Despite years of research, the rate of survival following treatment of this disease has not substantially improved in the past 50 years. As a consequence, new approaches to treatment of this disease are necessary to improve patient outcomes. Together with our collaborators, we have identified a set of genes which when mutated contribute to the initiation and progression of HNSCC. However, our understanding of how these events arise and interact genetically and biochemically is far from complete. Our lab uses a combination of techniques including high throughput sequencing, computational biology, molecular biology, and biochemistry, to better understand the function of these mutations in the initiation, progression, and maintenance of HNSCC. We use in vitro models, in vivo models, and clinical samples in our analyses. We are particularly interested in the following questions:
1. In what order do mutations arise in HNSCC?
2. How many events are required for the transition from a normal cell to cancer?
3. Which events are required for the maintenance of the cancer state?
4. What is the nature of the alterations in cellular machinery and metabolism downstream of these mutations?
5. Which molecular events predict poor outcomes in HNSCC?
6. What is the identity and function of driver mutations in other tumors arising in the head and neck?
The Auditory System:
We are also interested in the development and maintenance of function in the auditory system. In particular, we are applying modern genomic technologies including single cell RNA sequencing, multiplex RNA in situ hybridization, in vivo lineage tracing, immunohistochemistry, immunofluorescence, and organoid cultures to the following questions:
1. What is the cellular composition of the inner ear, middle ear, tympanic membrane, and external auditory canal?
2. How are cells specified and maintained within the inner ear, middle ear, tympanic membrane, and external auditory canal?
3. What are the lineage dynamics of cells within the inner ear, middle ear, tympanic membrane, and external auditory canal?
4. What is are the cellular and molecular events involved in the response to injury in the inner ear, middle ear, tympanic membrane, and external auditory canal?
5. How do these processes go awry in human diseases of the ear?
6. Can we harness biological knowledge of the processes listed above to improve treatments and regenerative medicine approaches to these problems?
High Throughput Technologies:
We have expertise and an interest in leveraging high throughput biological techniques including whole genome sequencing, exome sequencing, RNA sequencing, and single cell RNA sequencing.
1. How can we best analyze single cell RNA-sequencing data in order to identify novel cell populations?
2. Can we identify biologically relevant signalling pathways from single cell RNA-sequencing data?
3. How can we best dissociate samples to give robust and representative data for use in single cell RNA-sequencing?
Clinical Otology, Neurotology, and Skull Base Surgery:
We are interested in questions with direct clinical application to patients with disorders of the auditory system, temporal bone, skull base, and surrounding structures including:
1. Can we improve surgical approaches to the structures of the temporal bone and skull base (i.e. endoscopic ear surgery, eustachian tube dilation etc.)?
2. What are the optimal treatment approaches to tumors of the skull base including vestibular schwannomas and meningiomas?
3. How can we use pharmacologic approaches to augment surgical managment of disorders of the auditory system?