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Posts Tagged ‘Alexandra Hauser-Kawaguchi’

Creating better drugs to treat breast cancer

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Alexandra Hauser-KawaguchAlexandra Hauser-Kawaguchi, a PhD candidate in Dr. Len Luyt’s lab at the London Health Science Centre’s London Regional Cancer Program, works to help breast cancer patients fight the disease, but does so from her chemistry lab.

“The drug development process that we focus on in our lab is on basic science. We carry out the first steps in the discovery of new anti-cancer drugs. As a chemist, I synthesize novel compounds, and then, I work with biologists, who screen them in cells. If it looks successful, we move onto animal models. But quite often, the outcome leads me to having to redesign and redeveloping the compounds. This is how a successful drug molecule is discovered.”

What Alexandra studies specifically has a long and complicated name – Receptor for hyaluronan mediated motility (RHAMM). “Basically, any receptor is a protein molecule that can react to chemical signals from outside the cell. When such signals arrive, and bind to the receptor, it responds in a certain way. RHAMM reacts specifically to hyaluronan (HA) signals. In breast cancer cells, their interaction increases.”

What follows is a domino effect. “The RHAMM-HA interaction activates downstream signaling pathways. Breast cancer cells, especially those of an aggressive nature, begin to rapidly exchange signals. This process, in turn, activates genes responsible for spreading the cancer to other body parts, which means that it unfortunately becomes metastatic, and this often means that it is ‘incurable’. Yet, the good news is that we can prevent this scenario if we don’t let RHAMM and HA interact.”

For a few years, Alexandra has been focused on discovering new therapeutic agents – drugs – that could block the interaction between RHAMM and HA. “We have developed peptides that act as RHAMM mimics. Proteins and peptides are very similar in structure, but peptides are smaller. RHAMM mimics bind strongly with HA and prevent it from interacting with the real RHAMM. Our studies show that these peptides can block inflammation associated with breast cancer, as well as stop metastasis from occurring.”

Recently, Alexandra’s team has created a set of such peptides and conducted preclinical evaluation in mice. “Preliminary results demonstrated that our lead compound may be successful, and it will be further investigated as a prototype drug molecule for treating RHAMM-related breast cancer.”

“In a perfect world, we hope to one day test our therapeutic agent in patients. Unfortunately, it takes years and requires funding to reach that point. Even preclinical studies are quite expensive. In our lab, we have to be very rigorous with everything leading up to the preclinical stage before we are confident enough to move forward to a clinical trial.”

Alexandra Hauser-KawaguchGoing further in describing the process of drug development, Alexandra suggests that the prospective drug would be injectable, like a vaccine. In addition, the team is thinking of the possibility for the drug to be taken orally: “We are working on designing our compounds in such a way that one day it could end up being a pill. No blood, no needles – it would be much more convenient for patients.”

In Alexandra’s opinion, the most exciting part of research is that it is all about discovering things. However, there is also a negative side. “Quite often experiments fail. You spend so long trying to solve a problem, but it often doesn’t work out like you expected. Such moments can be a bit heartbreaking and discouraging. But when something does work, it is extremely rewarding, and it reminds me why I do this.”

After graduating from University of Toronto, she chose Western University in London for her doctorate because of its reputation in health research, imaging and radiopharmaceuticals. Alexandra was actually first involved in the development of imaging agents. This is directly related to PET (positron emission tomography) or SPECT (single-photon emission computerized tomography) scan technologies. These nuclear imaging tests use very small doses of radioactive compounds that are injected into patients, which helps visualize the cancer tumor on the scan.

“Starting with work in imaging/diagnostics, I ended up working on drug molecules for therapeutic applications in cancer. I do not believe in a magical cure for everything. Each type of cancer is very different, and each patient is very different. But I definitely think it is possible to develop drugs that will treat specific types of breast cancers in the future.”

Support researchers like Alexandra Hauser-Kawaguchi and others by considering a donation to the Breast Cancer Society of Canada. Find out how you can help fund life-saving research, visit bcsc.ca/donate

 

Alexandra Hauser-Kawaguchi’s story was transcribed from interviews conducted by BCSC volunteer Natalia Mukhina – Health journalist, reporter and cancer research advocate

Natalia Mukhina - Health JournalistNatalia Mukhina, MA in Health Studies, is a health journalist, reporter and cancer research advocate with a special focus on breast cancer. She is blogging on the up-to-date diagnostic and treatment opportunities, pharmaceutical developments, clinical trials, research methods, and medical advancements in breast cancer. Natalia participated in numerous breast cancer conferences including 18th Patient Advocate Program at 38th San Antonio Breast Cancer Symposium.
She is a member of The Association of Health Care Journalists.

Receptor for Hyaluronan-Mediated Motility or RHAMM

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Hi everyone!

My name is Alexandra Hauser-Kawaguchi and I’m a PhD candidate in the Department of Chemistry at Western University. I work in Dr. Len Luyt’s lab at London Health Sciences Centre’s London Regional Cancer Program.

Alexandra Hauser-Kawaguchi - BCSC Breast Cancer ResearcherFor the past few years, I have been studying the protein RHAMM (Receptor for Hyaluronan-Mediated Motility). RHAMM levels increase in response to fragmentation of the compound hyaluronan (HA), which ultimately results in the spread of cancer and thus poorer outcomes for breast cancer patients.

We have recently been developing stapled peptides as RHAMM mimics. “Stapled” peptides are compounds that have been partially cyclized, giving them the appearance of having a “stapled” backbone. This “stapling” allows the peptide to circulate through the body longer than it would otherwise. This is ideal, as our RHAMM mimics are part of a drug discovery initiative, in which we have shown that they are able to block inflammation associated with breast cancer relating to fragmented HA. The RHAMM mimics could also help stop the disease from spreading to other parts of the body.

In September of 2016, I had the opportunity to attend the 34th European Peptide Symposium and 8th International Peptide Symposium in Leipzig, Germany. I was one of eight chosen to give an oral presentation in front of 700 scientists. This experience was frightening but also thrilling, and the high point of my graduate student career to date. After meeting with and learning from experts in the field, I returned to the lab full of new ideas on how to make our compounds better drugs for treating breast cancer.

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

Attempting to inhibit breast cancer proliferation

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Hauser-Kawaguchi

Alexandra Hauser-Kawaguchi in the lab

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

You may remember seeing my blog post last year.

Since then, I’ve continued to study the interactions between the mini-protein known as 7 kDa RHAMM and the molecules called peptide ligands. If we can discover a peptide that has better binding to 7 kDa RHAMM than the natural ligand, we can potentially inhibit the actions that lead to breast cancer proliferation.

It’s taken a while, but we’ve finally found that the best way to study these interactions is by using the technique called surface plasmon resonance, which studies the binding interactions in real time.

This past year has been an exciting one outside the lab as well. I presented my work at the Boulder Peptide Symposium in September, where I also learned about some interesting new techniques. I’ve already started using some of them in the lab … updates to come in my next blog post!

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

Breast cancer trainees honoured at London’s Oncology Research & Education Day

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London’s 12th annual Oncology Research & Education Day was held on June 26, 2015. This city-wide event showcases the breadth of oncology research at Western University, ranging from basic research through to translational and clinical research. More than 285 investigators and trainees attended the day, with eight oral presentations and 98 poster presentations from trainees.

The oral and poster presentations were judged by a panel of scientists and clinicians – and current and former trainees at the Pamela Greenaway-Kohlmeier Translational Breast Cancer Research Unit (TBCRU) took home 5 of the 14 awards!

Winners of Poster Presentation awards, afternoon session: Jessica Tong, Bart Kolendowski, Michael Thwaites and Tom Hrinivich, with Dr. David Rodenhiser (far left).

Winners of Poster Presentation awards: Jessica Tong, Bart Kolendowski, Michael Thwaites and Tom Hrinivich, with Dr. David Rodenhiser (far left).

Winners of Oral Presentation awards: Natasha Caminsky and Mohammad Hassan, with award presenter Dr. Jim Koropatnick (left).

Winners of Oral Presentation awards: Natasha Caminsky and Mohammad Hassan, with award presenter Dr. Jim Koropatnick (left).

Winners of Poster Presentation awards, morning session (left to right): Carolina Batista, Adrienne Borrie, Emily Rodrigues (accepting on behalf of Alexandra Hauser-Kawaguchi, shown separately), with Dr. Trevor Shepherd.

Winners of Poster Presentation awards (L to R): Carolina Batista, Adrienne Borrie, Emily Rodrigues (on behalf of Alexandra Hauser-Kawaguchi), with Dr. Trevor Shepherd.

Alexandra Hauser-Kawaguchi

Alexandra Hauser-Kawaguchi

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

The TBCRU trainee winners are:

  • Natasha Caminsky, MSc student, Dept. of Biochemistry. Supervisor: Dr. Peter Rogan.
  • Adrienne Borrie, PhD student, Dept. of Clinical Pharmacology. Supervisor: Dr. Richard Kim.
  • Alexandra Hauser-Kawaguchi, MSc student, Dept. of Chemistry. Supervisor: Dr. Len Luyt.
  • Bart Kolendowski, PhD student, Dept. of Biochemistry. Supervisor: Dr. Joe Torchia.
  • Lori Lowes, PhD student, Dept. of Anatomy & Cell Biology. Supervisor: Dr. Alison Allan.

Congratulations to all the award winners – well done!

Thank you to BCSC for your support of our award-winning TBCRU trainees!
Pamela Greenaway-Kohlmeier Translational Breast Cancer Research Unit, London Health Sciences Centre

Discovering and developing new peptide-based drugs for breast cancer

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Dr. Len Luyt and Alexandra Hauser-Kawaguchi

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