Molecular Profiling of Oral Squamous Cell Cancer: HNSCC Cancer Genes
John Martignetti, M.D., Ph.D.
Head and neck squamous cell carcinoma (HNSCC) is one of the most common human cancers and is a major cause of morbidity and mortality worldwide. Most strikingly, 50% of these cancers recur despite histologically proven tumor-free margins. The overall goals of this research project are to identify the genes involved in the development and progression of HNSCC; develop molecular assays for diagnosis, surveillance, and prognosis; and establish a web-based “HNSCC Molecular Profiling Directory” to provide other researchers and clinicians interactive access to these results.
Vocal Fold Vibrations in Dysphonic Patients
Peak Woo, M.D.
The visual examination of patients with dysphonia has been largely centered on videostroboscopy. The stroboscopic image is largely a composite image made of many glottal cycles. It is unable to resolve voice disorders such as voice breaks, diplophonia, and extreme rough voices. The use of high-speed cinematography has become possible with the development of high-speed CCD cameras. This opens a whole area of investigation into vocal function that this study aims to explore.
Changes in Phonatory Transglottal Flows among Patients with Spasmodic Dysphonia
Linda M Carroll, Ph.D.
This study aims to describe the trends and levels of transglottal flows associated with subglottic pressure changes and phonatory activity among spasmodic dysphonia patients and compare these patterns with a group of normal subjects. It also aims to describe the relationships between changes in transglottal flow and changes in subglottic pressure in the course of phonation.
Hyperfunctional Voice Use in Broadway Belting
Linda M. Carroll, Ph.D.; Peak Woo, M.D.
The incidence of laryngeal pathology among high-use voice professionals is of significant concern to patients, laryngologists, speech pathologists, voice trainers, and the music industry. This study on perceptual, aerodynamic, and laryngologic findings among Equity Broadway performers examines the interaction of vertical laryngeal position, degree of laryngeal hyperfunction, transglottal flow, subglottal pressure, and electroglottographic closed phase in the mid-high frequency range. It is hoped that this study may provide critical information of at risk behaviors in the Broadway belt frequency range.
The Pulsed Dye Laser (PDL) for Treatment of Upper Airway/Laryngeal Scar and Vascular Abnormalities
Peak Woo, M.D.; Kenneth Altman, M.D., Ph.D.; Stanley Shapshay, M.D.; Linda Carroll, Ph.D.
Scarring and vascular abnormalities in the upper airway and larynx have the potential to cause serious impairment in function, affecting the ability of a patient to breathe, speak, and swallow. There is no presently accepted treatment for laryngeal scarring and vascular abnormalities. This study explores whether the Pulsed Dye Laser (PDL) can be used to successfully treat laryngeal and upper airway scarring and vascular abnormalities in the office setting. Treatments will be applied through flexible fiberoptic delivery systems or through rigid or malleable hand-pieces This approach represents a paradigm shift in treatment of upper airway/laryngeal scar or vascular abnormalities since there is presently no standard of care for these problems and procedures to treat them are done in the operating room under general anesthesia.
Proton Pumps in Human Laryngeal Submucosal Glands
Kenneth Altman, M.D., Ph.D.
The H+/K+-ATPase is a membrane bound enzyme proton pump in the parietal cell of the stomach that secretes acid that is a major component of GERD/LPR. Our laboratory was the first to demonstrate the presence of the proton pump in human laryngeal submucosal glands through immunohistochemical techniques, which implies that there may be a role of the proton pump (outside the stomach) in aerodigestive tract disease. This line of research further explores the presence and activity of the proton pump and its activity in the respiratory tract.
Anatomical Specialization of the Human Pharynx
Liancai Mu, M.D.
At present, the neuromuscular characteristics of the pharynx are poorly understood. It has long been controversial regarding the formation and distribution of the pharyngeal plexus in any mammal. In addition, little is known about the structural properties of the pharyngeal muscles. Precise information about the neuromuscular organization of the human pharynx is useful for further studying muscle functions and for developing novel techniques to treat neuromuscular disorders of the upper airway. This project is funded through the National Institute on Deafness and Communication Disorders, NIH.
Laryngeal Transplantation/Immune Tolerance Models
Eric M. Genden, M.D.
We examine and define the mechanism responsible for allograft tolerance resultant from a peripheral inoculation of donor antigen and examine alternative methods for inducing immune tolerance and preventing rejection of tracheal allografts and eventually, laryngeal allografts. In our laboratory, we aim to focus on 1) determining the mechanism tolerance as a result of portal venous administration of donor antigen; 2) alternative methods of inducing donor specific tolerance to tracheal allografts; and 3) the behavior of the tracheal allograft and its effect upon the established state of tolerance.
Clinical and Basic Science Approaches to Upper Respiratory Tract Function and Disorders in Space
Patrick J. Gannon, PhD; William Lawson, M.D., D.D.S.
In the Rhinology Research Laboratory, we have pursued an investigative approach designed to improve our understanding of normal physiology and precursors to disease processes. This has involved determination of the key variables that might be involved with normal and disordered upper respiratory functions.
Head and Neck Tumor Biology, Signal Transduction, and Gene Therapy
Dianne C. Duffey, MD; Svetlana Dolgilevich, Ph.D.
The Laboratory of Head and Neck Tumor Biology and Immunology in association with the Departments of Oncological Sciences and Gene and Cell Medicine (Gene Therapy) studies mechanisms of signal transduction and apoptosis in head and neck cancers and therapeutic targeting of these mechanisms. Transcriptional control of MAPK/SAPK pathways and cytokine production by head and neck tumors has proven to be an important mechanism involved in apoptosis. Signal transduction and transcription are manipulated as a therapeutic means for controlling tumor proliferation. Cell and molecular biology techniques are developed through work on this project as well as expertise using gene therapy (siRNA, plasmid, adenoviral, and lentiviral-mediated), animal models and mammalian cell culture. This project is funded through the National Institute on Deafness and Communication Disorders, NIH.
VSV Virotherapy for Head and Neck Cancer
Edward J. Shin, M.D.; Oliver Ebert, M.D.; Savio L.C. Woo, Ph.D.
Additional therapeutics are required to further improve local regional control in the treatment of unresectable recurrent head and neck squamous cell cancers (SCC). Tumor-targeted replication-competent viruses represent a novel class of therapeutic agents for cancer therapy. Vesicular stomatitis virus (VSV) is an enveloped negative strand RNA virus that infects a wide variety of mammalian and insect cells. Infections in humans are asymptomatic in most cases or result in a mild febrile illness. Compared with other replication-competent oncolytic vectors, VSV is particularly appealing for its rapid replication rate (8-10 hours in tumor cells), such that antitumor effects would be expected within hours of injection, and significant tumor destruction would have occurred before the initiation of any potentially neutralizing antiviral immune responses (7-10 days). Using an immune-competent animal model of orthotopic floor-of-mouth squamous cell carcinoma, we are developing testing various recombinant VSVs to enhance its inherent oncolytic activity. Other strategies involving recombinant adenoviruses are also being investigated in collaboration with the laboratory of Savio Woo, MD.
Laryngeal Neurophysiology
Don Weisz, Ph.D.
In collaboration with Liancai Mu, MD, and his laboratory, we are engaged in both human and animal projects in which we are studying basic laryngeal behaviors at the neurophysiological and neuromuscular levels of analysis. In humans, we are focusing on the function of the muscle compartments in the intrinsic laryngeal muscles during swallowing, respiration, and phonation.
|
