Sylvia L Asa, PhD, MD

Endocrine tumour development, progression and detection

Major Research Activities
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 tumours are also increasingly being detected; autopsy reports and radiologic and magnetic resonance imaging (MRI) evidence from around the globe indicate that one in five people worldwide has a pituitary tumour. Neuroendocrine tumours arising in the pancreas, gut, lung and other sites are often misdiagnosed. Rare endocrine tumours affect the parathyroid glands and adrenals. These tumours 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 tumour 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 tumours. Once characterized, tests to identify these tumourigenic 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 tumour 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 succinate dehydrogenase (SDH) mitochondrial mutations. The impact of these alterations and other predisposition genes is being studied in cell lines and animal models as well as in primary human tumours.
The specific role of tyrosine kinase receptors, cell adhesion molecules and epigenetics factors that silence tumour suppressors are all examined to validate the role of primary genetic mutations in tumour development and subsequent epigenetic modulation of tumour progression.
Virchows Arch. 2015 Mar 24;
Hernandez KG, Ezzat S, Morel CF, Swallow C, Otremba M, Dickson BC, Asa SL, Mete O
Oncogene. 2015 Feb 2;
Wei W, Liu W, Serra S, Asa SL, Ezzat S
Endocrinol Diabetes Metab Case Rep. 2015;2015:140105
Dinesen PT, Dal J, Gabrovska P, Gaustadnes M, Gravholt CH, Stals K, Denes J, Asa SL, Korbonits M, Jørgensen JO
J Clin Endocrinol Metab. 2014 Oct 30;:jc20142521
Gomez Hernandez K, Hafezi-Bakhtiari S, Pierre A, Szentgyorgyi E, Brown DH, Krzyzanowska MK, Brierley J, Ezzat S, Asa SL, Mete O
Endocr Relat Cancer. 2014 Aug;21(4):R331-44
Monsalves E, Juraschka K, Tateno T, Agnihotri S, Asa SL, Ezzat S, Zadeh G
Endocrinol Nutr. 2014 Jul 5;
Gonzalez B, Vargas G, Ramirez C, Asa S, Cheng S, Sandoval C, Mercado M
Endocr Pract. 2014 Aug 1;20(8):e145-50
Lebowitz-Amit R, Mete O, Asa SL, Ezzat S, Joshua AM
Mol Endocrinol. 2014 Apr;28(4):525-33
Nakano-Tateno T, Tateno T, Hlaing MM, Zheng L, Yoshimoto K, Yamada S, Asa SL, Ezzat S


Professor, Department of Laboratory Medicine and Pathobiology, University of Toronto​