The Art of Scientific Discovery: How to Creatively Communicate the Biology and Chemistry of Cancer

In plain language, what is your project about? What questions are you trying to answer by doing this research?

Multiple myeloma is the second most common type of blood cancer mostly affecting the elderly. Myeloma patients are often treated with chemotherapy and sometimes by bone marrow transplants. While the existing chemotherapy treatments work and maintain remission, there is still no cure for multiple myeloma. Current drugs or treatment approaches create undesirable side effects. An important goal of myeloma research is to find new treatments that not only improve patients’ survival, but also their quality of life.

At our cancer research laboratory at UNBSJ, we aim to target the cancer cells using novel approaches, where our pre-clinical validations could potentially lead to new drug discoveries. One compound that we have extensively tested is CAPE (Caffeic Acid Phenethyl Ester). CAPE is an active compound from propolis or bee glue, made by honey bees to cement their hives, and is currently marketed as a dietary supplement for its antioxidant and immune-boosting properties. Our pre-clinical research evaluation dealt with specific questions such as:
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1. Can CAPE and its derivatives kill human myeloma cells and not impact normal bone marrow cells?
   
   
2. How do the CAPE derivatives compare with a widely used anti-myeloma chemotherapy drug such as lenalidomide?
   
   
3. What is the mechanism of action of the CAPE derivatives in human myeloma cells? 

In summary, through a systematic compound screening process, we have identified the CAPE derivative with the most potent anti-myeloma activity. We demonstrated that the potent CAPE derivative with appropriate drug-likeness surpassed CAPE and lenalidomide in its anti-myeloma activity, showing no adverse effect on normal bone marrow cells. We have also found its novel mechanism of action. Our findings reveal the promising application of a CAPE derivative to target the so-called "Achilles heel" of myeloma (interferon regulatory IRF4 protein addiction) for better treatment outcomes.

Looking at your research team members, there are people from other departments and institutions. Have you worked together before this project? 

As a passionate scientist, I am keen on evaluating the novel therapeutic potential of natural and nature-inspired compounds for treating blood cancers and its associated bone diseases. My research work ranges from testing several molecules including peptides from shrew venom to CAPE from propolis.

​This project is a continuation of the work I had started as a postdoctoral fellow with Dr. Tony Reiman, CCS research chair at UNB, Saint John.  Ever since, many summer students such as Elise, Min Ji, Lauren and Katie have had the opportunity to have hands-on experience in conducting basic research projects, from bench to the final publication.

Dr. Alli Murugesan

We connected with the UdeM team of Dr. Mohamed Touaibia during my first postdoctoral fellowship. Initially, we selected a few of his compounds for testing. Later in 2017-2018, in order to protect our inventions as patents, we strengthened our collaboration with Dr. Touaibia through an inter-institutional agreement between UNB and UdeM and tested a series of CAPE derivatives.

How – if at all – has the COVID-19 pandemic changed your research project and/or collaboration?

Restrictions related to the COVID-19 pandemic changed the nature of conducting lab-based research significantly. This brought newer challenges, making it difficult, if not impossible, to start or continue experiments already in progress. Yet, it led to unexpected opportunities in knowledge translation and scientific communication for the team. Similar to many other global research teams, we leaned on technology to connect with each other and coordinate efficiently, thereby making a significant progress. Regular online meetings among the Saint John team members and prompt e-mail conversations with the UdeM team enabled us to finalize our experimental results, draft and revise a manuscript for publication.

Converting restrictions to opportunities, I brought out my artistic talent to communicate the scientific discovery. Specifically, I designed cover art using Adobe Photoshop, showcasing the key findings from my lead authored article and submitted to the ACS publications/media selection team. Not only is the article now published, it is a pleasure to announce that it got selected as the American Chemistry Society’s Editors’ Choice article, and my supplementary cover art graces the journal.

What advice would you give to others on building a successful research collaboration?

I feel fortunate to have the valuable support of my talented and dedicated team members during this research collaboration. Projects with multi-disciplinary approaches are fascinating and challenging - on one hand, I had the great opportunity to make use of clinical specimens from our biobank and on the other, several new molecules synthesized by the chemists from another university. Open communications helped us make quicker progress. Our patience paid off in having a streamlined inter-institutional collaboration process with the help of UNB ORS. I personally believe that the respect and regard we have for the diverse talents of each other is key for building a successful research collaboration.

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This study, Antimyeloma Potential of Caffeic Acid Phenethyl Ester and Its Analogues through Sp1 Mediated Downregulation of IKZF1-IRF4- MYC Axis, was supported by a Springboard Innovation and Mobilization Program grant and Canadian Institutes of Health Research and New Brunswick Health Research Foundation grants of A.M. and T.R. and Terry Fox Research Institute and the Canadian Cancer Society Chair grants of T.R. M.T. was supported by the Natural Sciences and Engineering Research Council of Canada. The study was published online in the Journal of Natural Products (2020, Nov 19).

Alli Murugesan, PhD
Department of Biology, University of New Brunswick, Saint John
Faculty of Medicine, Halifax, NS, Dalhousie Medicine NB

Gregoire Lassalle-Claux
Department of Chemistry and Biochemistry, Université de Moncton

Lauren Hogan
Department of Biology, University of New Brunswick, Saint John

Elise Vaillancourt
Department of Biology, University of New Brunswick, Saint John

Ayyoub Selka
Department of Chemistry and Biochemistry, Université de Moncton

Katie Luiker
Department of Biology, University of New Brunswick, Saint John

Min Ji Kim
Department of Biology, University of New Brunswick, Saint John

Mohamed Touaibia, PhD
Department of Chemistry and Biochemistry, Université de Moncton

Tony Reiman, MD, FRCPC​
Department of Biology, University of New Brunswick, Saint John
Faculty of Medicine, Halifax, NS, Dalhousie Medicine NB
Department of Oncology, Saint John Regional Hospital, Horizon Health Network