The Andrulis lab: Uncovering the genes and pathways associated with breast cancer

Cancer is genetic, meaning that it is triggered by alterations or mutations in the genes making up an individual’s genome.  Some cancers are inherited, in which a mutation carried in reproductive cells is passed on from one generation to the next, and is present in cells throughout the body. These mutations reduce the natural defenses of cells and significantly increase the risk of cancer and/or other illnesses.

 

Dr. Irene Andrulis, a molecular biologist and Senior Investigator at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital, is world-renowned for her pioneering work in hereditary breast cancer. Dr. Andrulis is collaborating with researchers internationally who are conducting genome-wide analyses of genes that impact the risk of breast cancer.

 

A major goal of Dr. Andrulis’ team is to identify and characterize genetic alterations or mutations in cancer, and apply this knowledge to clinical practice.

 

For example, her team is involved in a study as part of the CIMBA group (Consortium of Investigators of Modifiers of BRCA1/2), a collaborative group of researchers assessing genetic abnormalities and cancer risk—including environmental factors—in women who carry the BRCA1/BRCA2 genetic mutation.

 

“We are studying women who carry genes that increase the risk of breast cancer, to better understand the factors triggering onset of the disease and, ultimately, finding ways to prevent these triggers,” says Dr. Andrulis.    

 

As well, Andrew Seto is a PhD student in Dr. Andrulis’ lab who is working to identify mutations in genes that put women at risk of developing breast cancer.  His work focuses on breast cancer patients who developed the disease at an early age and who also have a family history of breast cancer. 

 

“I hope to find new mutations that can be used in the future as a tool to identify women at an increased risk of developing the disease,” says Andrew.

 

Others in Dr. Andrulis’ team are focused on these and other aspects of breast cancer development and progression.

 

For example, Dr. Andreas Evangelou, a post-doctoral fellow in Dr. Andrulis’ lab, is studying the mechanisms associated with the growth and metastasis of breast cancer cells. Specifically, he is studying two cellular communication pathways called Notch and fibroblast growth factor (FGF), and their role in breast cancer progression.  These pathways control intracellular communication mechanisms that help regulate cell growth and differentiation.  Faulty FGF and Notch signaling have been implicated in breast cancer progression, as well as the development of other human cancers.

 

“We have demonstrated a novel interplay between Notch and FGF pathways in breast cancer cells that may be associated with poorer prognosis in breast cancer patients,” says Dr. Evangelou. “This knowledge will help lead to earlier, more effective diagnostic techniques as well as more specific, targeted and/or combined therapies.”

 

Dylan Ehman, a Master’s student who recently joined the Andrulis lab, is exploring a relatively new area of cancer genetics that investigates the role of ‘micro’ ribonucleic acids (miRNAs), which are short regions of non-coding genetic material that regulate genes and affect their level of expression.

 

Dylan explains that because there are many subtypes of breast cancer that vary in prognosis, response to treatment, metastasis and chance of recurrence, finding new ways of classifying and discriminating between subtypes can help lead to more individualized therapies.

 

“I hope that investigating these miRNA expression profiles will potentially help develop improved methods of breast cancer detection, diagnosis and prognosis in the clinical setting,” says Dylan. “Additionally, identifying specific miRNAs could reveal diagnostic biomarkers or novel therapeutic targets, providing new avenues for future research.”

 

Other trainees in Dr. Andrulis’ lab are also focused on the genetics of breast cancer, as well as molecular factors underlying the development and progression of osteosarcoma, the most common form of bone cancer.

 

 

miRNAs: Small but mighty

 

Researchers suspect miRNAs are involved in the regulation of immunity, the development and differentiation of immune cells, antibody production and the release of chemicals involved in the inflammatory response.

 

Aberrant expression of miRNAs has been implicated in several complex illnesses including cardiovascular disease, hepatitis C, Alzheimer’s disease, as well as various forms of cancer.

 

miRNAs may help explain certain connections in the cell, and facilitate cross-talk between two cellular communication pathways inside a cell. For example, though the research is unpublished to date, the Notch and FGF signaling pathways may be connected through the effects of miRNAs.