Queen’s University PhD student Caitlin Miron makes groundbreaking discovery that may prevent spread of cancer (with brief technical details)

20171121 CTV News interview of Caitlin Miron

Caitlin Miron, a PhD student in the chemistry department at Queen’s University, interviewed on CTV News. Image credit: CTV News, image composite from screen captures.

Congrats to Ms. Caitlin Miron, Ph.D. Candidate, Queen’s University for making a groundbreaking discovery that may have the potential to prevent cancer cells from spreading. Have a watch and read of the CTV news report, “(with video) PhD student makes groundbreaking discovery that may prevent spread of cancer“. According to Miron’s interview with CTV news, “85% of cancers” may benefit from this discovery and while it is too early to talk about the time frame of a commercially available drug, about 5-8 years was mentioned.

Here is an excerpt (with emphasis and links added) from the CTV report,

Studying at the European Institute of Chemistry and Biology in Bordeaux, France, Miron was able to use advanced screening technology to examine a number of compounds from the Petitjean lab at Queen’s University. During her internship, she was able to discover one compound that binds well to four-stranded DNA structure, or guanine quadruplex [G4], which has been linked to the development of cancer and other diseases.

She explained her discovery by comparing a single-stranded DNA to a necklace with beads that move along it until they hit a knot. The beads are the cell machinery that move along the necklace processing the DNA, she said.

“You can go in and untangle that knot, but in this case someone has gone in there first and they’ve used superglue to hold it together,” Miron said. “What we’ve discovered in that case is that glue.”

By binding the newly discovered compound or “superglue” to the quadruplex to secure the “knot” in the chain, scientists may be able to prevent the cell machinery from reaching a particular section of DNA to process it, which would, in turn, prevent the growth and spread of cancer cells, Miron said.

Scientists have been researching quadruplex binders as a possible treatment for cancer for approximately 20 to 30 years, the PhD student explained. However, many of the known binders haven’t yielded results as promising as the one Miron has identified.

“It’s really exciting. It’s exciting to be on the forefront of this field,” she said. “There are other quadruplex binders out there, but what we’re seeing is that ours is very high-performing.”

P.S. Here are some additional references.

Ref 1: Miron is scheduled to have an upcoming Queen’s University Grad Chat “November 28th, 2017 – Caitlin Miron (Chemistry)” that I’m very much looking forward to listen to.

Ref 2: Here is an excerpt from Queen’s University 2017, November 21st, “Caitlin Miron – Recipient of the 2017 Mitacs Award for Outstanding Innovation (PhD)“, (emphasis and links added)

Caitlin Miron is the recipient of the 2017 Mitacs Award for Outstanding Innovation. This award is given to a PhD student who has made a significant achievement in research and development innovation during Mitacs-funded research. Last year, Caitlin received a Mitacs Globalink Research Award which funded a collaboration with Dr. Jean-Louis Mergny at the Institut Européen de Chimie et Biologue in Bordeaux, France. This collaboration was the second of two with Dr. Jean-Louis Mergny, and collectively, these collaborations have not only propelled Caitlin’s PhD thesis forward but also merited the receipt of the Mitacs Outstanding Innovation award. […]

 Caitlin’s doctoral dissertation is titled: Dynamic recognition of unusual nucleic acid architectures by cation-responsive switches and other metallo-organic platforms. In sum, DNA has been found to adopt unusual architectures. One type of architecture, called a guanine quadruplex, has been shown to form in the promoter regions of oncogenes (cancer genes), and is implicated in cancer. Caitlin’s research involves finding molecules that stabilize quadruplexes, thereby blocking the expression of these oncogenes, in the hopes that these molecules can be used as anticancer therapeutic agents, either alone or in combination with other treatments. In her first internship in Dr. Mergny’s lab, Caitlin tested a library of potential binders originating from the Petitjean lab and identified a compound that shows some of the best stabilization of quadruplexes that has been seen over the past 30 years. During her second internship (funded by the Mitacs Globalink program), Caitlin explored the effects that small modifications of the lead compound’s structure might have on guanine quadruplex recognition. By taking these compounds from expert to expert, she was able to identify suitable biophysical techniques that she has since brought back to her lab at Queen’s to further her research. Since then, preliminary results suggest that these compounds inhibit cell growth in several human cancer cell lines, and earlier this month, a patent was filed on the novel compounds Caitlin first investigated in France. These results serve as but a case example of rewards made possible by the financial support of funding agencies such as Mitacs.

When I asked Caitlin what skills have helped her during her PhD, she listed good communication, time management and perseverance. “Research doesn’t always go smoothly, so you need to be able to sit back and figure out how to fix things.” Caitlin also recommends ensuring you select a supervisor that will support you throughout the process of graduate school, and pursing opportunities that meet your needs – for example, Caitlin didn’t focus on maximizing her opportunity to teach in the undergraduate course setting during her PhD because she knew she did not want to pursue an academic career. […]

As a final note, Caitlin recommends getting into labs with big names in their respective fields, if possible. Dr. Mergny is one of the top researchers in Caitlin’s field. For Caitlin, conducting research in Dr. Mergny’s lab and having access to experts has enabled her to develop a better understanding of her work and accelerate her research.

After completing her PhD, Caitlin is looking to complete an industrial post-doctoral research position in order to bridge her experience between academia and industry. Caitlin’s long-term goal is to pursue an industrial research career, one slanted towards health applications or perhaps the development of pharmaceuticals. Given Caitlin’s positive attitude and astounding success thus far, I have no doubt she will continue to make great contributions to health-care oriented research in the future.

Ref 3: From Dr. Jean-Louis Mergny’s IECB “Unusual nucleic acid structures” team page,

G-quadruplexes: Friends or foes?
Comparison of sequencing data with theoretical sequence distributions suggests that there is a selection against G-quadruplex prone sequences in the genome, probably as they pose real problems during replication or transcription and generate genomic instability (see below). Nevertheless, “G4-hot spots” have been found in certain regions of the genome: in telomeres, in repetitive sequences such as mini and microsatellite DNAs, in promoter regions, and in first exons of mRNAs. There might be a specific positive role for these sequences that compensates for the general selection against G4 forming sequences. Our goals are to understand the factors that modulate these effects. A number of proteins that interact with these unusual structures have been identified, including DNA binding proteins, helicases, and nucleases. We are currently developing a fluorescent-based assay to follow the activity of helicases in real time (Mendoza, Nucleic Acids Res. 2015).

G-quadruplex ligands: Treats or tricks?
One may achieve structure-specific rather than sequence-specific recognition of DNA. Because of their particular geometric configuration and electrostatic potential, G-quadruplexes may indeed specifically accommodate small artificial ligands, such as planar molecules, and an impressive number of candidates have been evaluated. Together with chemists we successfully identified a variety of G4 ligands and we wish to improve and functionalize these compounds, analyse their biological effects, and ultimately find new classes of anti-proliferative agents with anticancer properties.

Ref 4: Miron’s 2016 Mitacs project, “Building on an Innovative Platform: Tuning Guanine Quadruplex Recognition for Anticancer Applications

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

%d bloggers like this: