Endocrine Oncologic Pathology
Research interests include:
Major Research Activities
- Endocrine tumor development
- Endocrine tumor progression
- Endocrine tumor detection
Thyroid cancer is the most common endocrine malignancy and one of the most common malignancies in young women. It is one of the few cancers that is increasing in incidence worldwide. Pituitary tumors are also increasingly being detected; autopsy reports and radiologic and MRI evidence from around the globe indicate that one in five people worldwide has a pituitary tumor. Neuroendocrine tumors arising in the pancreas, gut, lung and other sites are often misdiagnosed. Rare endocrine tumors affect the parathyroid glands and adrenals. These tumors that arise in endocrine tissues are unique in that they also often produce hormonal manifestations, and they respond to targeted therapies based on hormone regulation. Patients often have delayed diagnosis, and are affected by the complications of the hormonal dysregulation that can have significant social and psychological impact in addition to that of a cancer diagnosis.
Our laboratory focuses on investigating the mechanisms underlying tumor development and progression in endocrine tissues. Studies aim to identify genetic and epigenetic changes that characterize these various cancers. Mouse models of these disorders are developed and used to verify the roles of these alterations that are found in human tumors. Once characterized, tests to identify these tumorigenic factors are developed for diagnostic, prognostic and predictive application. The underlying alterations represent targets for the design of novel therapies that can be tested in our mouse models before transition to human trials.
The genetic predisposition that underlies many of these neoplasms is also being examined. Multiple endocrine neoplasia syndromes include the classical type 1 syndrome that is due to inheritance of a mutant tumor suppressor gene menin, the type 2 syndrome due to germline transmission of a unique activated oncogene RET, Cowden syndrome and Familial Polyposis Coli syndromes due to germline mutations of PTEN and AFP respectively, von Hippel Lindau disease, neurofibromatosis, and the more recently identified SDH mitochondrial mutations. The impact of these alterations and other predisposition genes is being studies in cell lines and animal models as well as in primary human tumors.
The specific role of tyrosine kinase receptors, cell adhesion molecules, and epigenetics factors that silence tumor suppressors are all examined to validate the role of primary genetic mutations in tumor development and subsequent epigenetic modulation of tumor progression.