D. Neil Hayes, MD, MPH, of the Division of Hematology and Oncology, Department of Medicine, was given a joint appointment with the Department of Otolaryngology/Head and Neck Surgery. He has been collaborating with our head and neck oncologists on projects for many years.
The Hayes Lab endeavors to bring together a collection of researchers with intersecting interests in multidisciplinary clinical cancer care, clinical trials, translational cancer research, and model systems of cancer with a focus on aerodigestive tumors.
Clinical Practice and Clinical Trials
In the clinic we provide multidisciplinary care across a spectrum of aerodigestive tumors. Our primary focus is on lung tumors and epithelial tumors of the head and neck (mouth, throat, larynx, sinuses, and salivary glands). All patient care is delivered by a full services tertiary and quaternary care facility with rich compliment of oncology care. In this context, we have endeavored to develop a palate of clinical trials serving the spectrum of disease we treat, including focused trials appropriate to every patient stage and function. The breadth and depth of our practice leads us to an expertise in rare tumors of the head, neck, and lung as well, and the treatment of rare tumors is clearly part of our expertise.
Translational cancer research and model systems
Progress in two key areas of science has provided the foundation for the work in our group. First, the advent of personal computers along with associated progress in the field of statistical computing greatly accelerated the development of data-rich models of human disease behavior. Second, collaborative efforts across the biomedical science have made available the building blocks of normal (i.e. The Human Genome Project) and adherent genomes (i.e. The Cancer Genome Atlas). To leverage the power of computers to assess alterations in the genome associated with cancer a host of molecular technologies has become commercially available in recent years. The primary targets of these assays have been nucleic acids (DNA and RNA), although a limited number of protein assays are also included. The technologies allow labs such as ours to make broad and inclusive measurements in samples of alterations in gene expression (RNA), gene dosage (DNA amplification and deletions), gene structure (normal population variants, mutations, alternate splices, fusion genes, epigenetic modifications), protein abundance and other events such as presence of a pathogen. Primary technologies in use in our lab include array based approaches (gene expression arrays, methylation profiling, SNP chips, CGH, miRNA arrays), sequencing (targeted and deep sequencing/“NextGen”), and immunohistochemistry (including tissue microarrays).
Our lab is intimately connected with the practice of clinical medicine, and as such, our interest is not simply the detection of alterations such as those described above. All alterations are placed in their clinical context, including the frequency of the event and any relevant association with cancer outcome. To accomplish these goals, our lab works equally hard to capture both clinical and molecular data for any samples we evaluate. The hypothesis of our research is that tumor-specific predictors based on high throughput nucleic acid and protein assays will offer significant advances.
Early work by Dr. Hayes, performed in collaboration with his mentor Dr. Matthew Meyerson, included a meta-analysis of approximately 500 human lung adenocarcinoma expression arrays generated by the National Cancer Institute’s Director’s Challenge Program. We successfully reconciled discordant previous reports by demonstrating three reproducible molecular tumor subtypes of lung adenocarcinoma that are otherwise indistinguishable by routine clinical evaluation. The subtypes have statistically significant survival differences, independent of disease stage and are comprised of tumors with differing underlying rates of mutations in key lung cancer genes including KRAS and EGFR. Similar reports for squamous cell carcinoma of the lung are forthcoming, as are reports of clinically applicable diagnostic tests. More recently, in collaboration with Kwok Wong and Ned Sharpless we have documented the frequent mutation of the gene STK11/LKB1 in human lung cancers, including squamous cell carcinoma. Numerous follow up reports of the clinical importance of these findings are forthcoming.
Data analysis of the type we routinely perform requires a strong set of statistical collaborators since standard methods are frequently lacking. In this way, we have been fortunate to build ties with numerous local and national statisticians, computer scientists, biostatisticians, and epidemiologists.