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Thyroid cancer is a common malignancy associated with substantial morbidity. Well-differentiated thyroid cancer is the most common endocrine malignancy and ranks as the seventh most common cancer diagnosed in women. While the majority of patients with well-differentiated thyroid cancer present with limited disease and become disease-free after initial treatment, 20% of patients with thyroid cancer have local or regional recurrent disease, and 5% develop distant metastases. There remains a lack of alternative treatment for patients with these poorly differentiated tumors, and these patients have a poor response to conventional treatment. Key molecules involved in the initiation of this process may prove potent targets for treatments.
Our lab focuses on translational research in thyroid cancer. The principal investigator of the lab is a thyroid surgeon interested in research in thyroid cancer that can help improve the care of all patients with thyroid cancer. We study certain key genetic and epigenetic changes seen more frequently in those patients who do poorly, and find out how exactly these genetic changes lead to more aggressive cancer behavior in those patients. In essence, we hope to use our new knowledge to predict which patients with thyroid cancer may do poorly and treat those more aggressively with novel targeted therapies directed at the specific genetic mutations that seem to worsen their prognosis.
Some patients with thyroid cancers have a single mutation in an important gene called BRAF. This gene is the most commonly mutated in papillary thyroid cancer and activation of ERK pathway by this common mutation leads to progression with more invasive local disease, lymph node involvement and distant metastases. Moreover, this single mutation is associated with both loss of radioiodine avidity and cancer recurrence. The mechanisms by which this mutation and others induce invasion and distant spread are not fully understood.
One of the major goals of our laboratory is to characterize the molecular changes that occur as a result of the BRAF mutation using human thyroid cancer cells and relevant in vivo models. The information we learn from the mechanisms involved in the development of invasive thyroid cancers will lead directly to better treatment for all patients with thyroid cancer, especially those with aggressive kinds of thyroid cancer. Studying how this mutation leads to invasiveness in the thyroid tumors will help find novel therapeutic targets for advanced papillary thyroid cancer. By analyzing this invasive pathway our eventual purpose is to look for this BRAF mutation in all thyroid cancer patients treated at Mass General, help identify those with thyroid cancers that have a higher chance for aggressive clinical behavior, and treat those particular patients with special therapies targeting this mutations.
Our lab works diligently on validating a novel assay which identifies the BRAF mutation in circulating thyroid cancer cells. We eventually hope to come fore with an easy, less invasive biomarker that will refine the workup an treatment of our patients.
One of the recent investigations in our laboratory is on the role of this immune checkpoint in the development and aggressiveness of thyroid cancer. In the last decade immunotherapy has been regaining attention as a potential strategy to fight cancer cells. The genetic variability of cancer cells causes these cell to express different kind of molecules on their surface which can be recognize as antigen by the immune cells of an individual patient. This recognition as ‘non-self’ antigen has the potential of promoting anti tumor immune response. However, there are inhibitory pathways that regulate the function of T lymphocytes and render these responses unsuccessful. These molecular interaction normally designed to modulate immune response, called “immune checkpoints”, are being used by the tumor to evade the immune system. Our laboratory focuses on the immune checkpoint PD-1/ PD-L1 in thyroid cancer. By using our novel imunocompetent in-vivo model we are trying to better understand the potential benefit of treatments aiming at blocking tumor evasion mechanisms. We are studying the potential mechanisms by which tumor cells over-express PD-L1 and the ways to interfere with this process. Our aim is to establish a firm base of preclinical data to support clinical trials using immunotherapies to treat patients with aggressive thyroid cancer.
Sareh Parangi, MD
Major projects are listed below and use not only basic molecular laboratory techniques but also a multitude of other resources, including the Mass General Endocrine Tumor Tissue Repository and the Mass General Endocrine Surgery Clinical Database under the auspices of the Codman Center for Clinical Effectiveness in Surgery.
The Thyroid Cancer Research Laboratory seeks interested individuals for one-two year research fellowships. Pre- or post-doctoral fellows or MDs from outside the United States should apply if they have funding provided by their governments or institutions by emailing their resume and two letters of recommendation to Sareh Parangi, MD
Help with obtaining Visas for accepted candidates may in some cases be processed through the Partners International Office. Surgical residents or medical students with funding from their own institutions or eligible for T32/T35 NIH funding should apply by sending their resume to Dr. Parangi.
Due to difficulty in teaching basic science techniques, periods of time less than one year cannot be spent in the lab with the exception of medical student summer projects. The lab is open to those interested in both basic/clinical and translational projects. Mass General encourages women and minority applicants to apply to this position.
View Dr. Parangi's recent publications at PubMed
Thyroid Cancer Research Laboratory
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