May 8, 2015

Discovering and developing new peptide-based drugs for breast cancer

Hi everyone! My name is Alexandra Hauser-Kawaguchi. I’m a PhD student in the Department of Chemistry at Western University and I work at London Health Sciences Centre’s London Regional Cancer Program under the supervision of Len Luyt, PhD.

Our lab focuses on peptide-based chemistry. Peptides are strands of less than 50 amino acids. When there are more than 50 amino acids arranged in a single compound, this is called a protein. I’m focused on discovering and developing new peptide-based drugs that will treat a certain type of breast cancer.

I work with the protein RHAMM. Expression of this protein increases during breast cancer, making it a good marker for aggressive and metastatic strains of the disease.

In the body, RHAMM binds hyaluronan (HA) under normal conditions, but the interaction between these two molecules increases in cancerous cells, activating a number of downstream signaling pathways that ultimately lead to metastasis. In order to prevent this from happening, I’m focused on discovering new peptide ligands that can interact with RHAMM and block HA.

This type of protein-ligand interaction is like a lock and key: the protein is the lock and the ligand is the incoming key, which can fit perfectly in the lock if it has some of the correct properties, like shape and size.

To date, it is impossible to synthesize full-length RHAMM in the lab using standard biological techniques because of its large size and complexity. As a result, I use chemical methods to synthesize a ‘mini-protein’ version of RHAMM that is 62 amino acids in length, making it more than 10 times smaller in size than the full-length protein. It is very challenging, if not impossible, to chemically synthesize a peptide of more than 30 amino acids under normal conditions. However, I use a highly specialized instrument that is equipped with a microwave irradiator to make my mini-protein. We can then analyze how my shortened RHAMM interacts with the new peptide ligands that we discover.

Thank you to BCSC for your trainee support!
– Alexandra Hauser-Kawaguchi, PhD student researcher
Pamela Greenaway-Kohlmeier Translational Breast Cancer Research Unit, London Health Sciences Centre

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