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

Tuesday, 21 November, 2017
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

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Jann Arden: My mom ‘will forget me at some point’ because of Alzheimer’s

Monday, 20 November, 2017

I watched Jann Arden‘s interview on CBC National last night and was very touched and found it informative. From CBC Tweet, ““She will forget me at some point.” Singer-songwriter @jannarden sat down with @adriearsenault and opened up about caring for her mother who has Alzheimer’s.

This Q&A at timecode 7:37 was especially moving.

“Q: You asked her [your mom] at one point if she thought she would forget you?

Jann: “She said, ‘My mind might but my heart won’t.‘”

Full interview: Jann Arden: My mom ‘will forget me’ because of Alzheimer’s

Over the years, the following three movies dealing with Alzheimer’s/Dementia have informed & touched me deeply about the challenges faced by those affected and their families and friends.
1) The Notebook (2004) [K: I LOVE this movie so much in so many ways!]
2) Away from Her (2006) [K: This is a less well known film starring  Julie Christie and Gordon Pinsent that I really like and enjoy. It was expertly directed by star turned director Sarah Polley.]
3) Still Alice (2014) [K:  Julianne Moore won an Academy Award as best actress for this film and Julianne really did an amazing job.]


Canadians will be able to identify sex as ‘X’ on their passports beginning Aug 31

Friday, 25 August, 2017

Good move by the Canadian government in announcing the news to implementing the change, “Canadians will soon be able to identify sex as ‘X’ on their passports Transgender travellers and those who do not identify as male or female, can check off an ‘X’ box“.

It is time for Canada to catch up with up-to-date science. Similar to what some other countries (Australia, New Zealand, Malta, Nepal, Denmark, India and Pakistan (Ref The Economist video)) have ALREADY been doing!

Too many people commenting on this news on CBC Facebook page need to update their science knowledge from decades old invalidated science. Quoting World Health Organization, United Nation re “Gender and Genetics”:

Most women are 46XX and most men are 46XY. […] In addition, some males are born 46XX due to the translocation of a tiny section of the sex determining region of the Y chromosome. Similarly some females are also born 46XY due to mutations in the Y chromosome.

P.S. Don’t choose to remain ignorant in face of science from reputable source like World Health Organization, United Nation.

Screen Shot 2017-08-25 at 10.44.37 AM - Canadians can choose gender as X

Reference: (The Economist, July 11, 2017) Which countries allow an option other than male or female on passports?


U of Toronto engineering researchers mend broken hearts with expanding tissue bandage

Friday, 25 August, 2017

Screen Shot 2017-08-25 at 9.56.43 AM - New biomaterial developed by U of T engineering researchers could be delivered through minimally invasive surgery

Very cool news. Excerpts from University of Toronto news “New biomaterial developed by U of T engineering researchers could be delivered through minimally invasive surgery” (emphasis, extra note & links added) (for an in-depth look, see technical article, Nature Materials “Flexible shape-memory scaffold for minimally invasive delivery of functional tissues” ),

A team of U of T engineering researchers is mending broken hearts with an expanding tissue bandage a little smaller than a postage stamp.

Repairing heart tissue destroyed by a heart attack or medical condition with regenerative cells or tissues usually requires invasive open-heart surgery. But now biomedical engineering Professor Milica Radisic [K’s note: including links to PubMed listed articles] and her colleagues have developed a technique that lets them use a small needle to inject a repair patch, without the need to open up the chest cavity.

Radisic’s team are experts in using polymer scaffolds to grow realistic 3D slices of human tissue in the lab. One of their creations, AngioChip, is a tiny patch of heart tissue with its own blood vessels – the heart cells even beat with a regular rhythm. Another one of their innovations snaps together like sheets of Velcro™.

Such lab-grown tissues are already being used to test potential drug candidates for side-effects, but the long-term goal is to implant them back into the body to repair damage.

“If an implant requires open-heart surgery, it’s not going to be widely available to patients,” says Radisic.

She says that after a myocardial infarction – a heart attack – the heart’s function is reduced so much that invasive procedures like open-heart surgery usually pose more risks than potential benefits.

“It’s just too dangerous,” she says.

Miles Montgomery, a PhD candidate in Radisic’s lab, has spent nearly three years developing a patch that could be injected, rather than implanted. [K’s note: more news on Miles]

“At the beginning, it was a real challenge,” he says. “There was no template to base my design on, and nothing I tried was working. But I took these failures as an indication that I was working on a problem worth solving.”

After dozens of attempts, Montgomery found a design that matched the mechanical properties of the target tissue and had the required shape-memory behaviour: as it emerges from the needle, the patch unfolds itself into a bandage-like shape.

[…]

The scaffold is built out of the same biocompatible, biodegradable polymer used in the team’s previous creations. Over time, the scaffold will naturally break down, leaving behind the new tissue.

The team also showed that injecting the patch into rat hearts can improve cardiac function after a heart attack: damaged ventricles pumped more blood than they did without the patch.

“It can’t restore the heart back to full health, but if it could be done in a human, we think it would significantly improve quality of life,” says Radisic.

There is still a long way to go before the material is ready for clinical trials. Radisic and her team are collaborating with researchers at the Hospital for Sick Children to assess the long-term stability of the patches, as well as whether the improved cardiac function can be maintained.

They have also applied for patents on the invention and are exploring the use of the patch in other organs, such as the liver.

“You could customize this platform, adding growth factors or other drugs that would encourage tissue regeneration,” says Radisic. “I think this is one of the coolest things we’ve done.”

Injectable tissue patch could help repair damaged organs – U of T Engineering


The Good Doctor from the creator of House with a Korean connection

Tuesday, 6 June, 2017

The Good Doctor - U.S. remake and South Korean original

I’m looking forward to watch The Good Doctor, an upcoming American medicaldrama television series, developed by David Shore (creator of House and U of Toronto law grad) and Daniel Dae Kim, starring Freddie Highmore, based on the 2013 South Korean series of the same name. See below for trailers of both series.

I’ve watched the first few episodes of the South Korean series and found it fascinating but also recognize there needs to be lots of changes in this remake to turn it something more to the taste of North American audiences. There are a lot of screen time spent on hospital politics in the South Korean series that it endanger patients so much that will be rather unbelievable. Shore created a great in House and I expect and hope he and his team would be able to create something interesting to watch with his own creativity and sensibility.

News report: Deadline, May 11, 2017, “‘The Good Doctor’ Drama Starring Freddie Highmore Picked Up To Series By ABC

The Good Doctor centers on Shaun Murphy (Highmore), a young surgeon with autism and savant syndrome who relocates from a quiet country life to join a prestigious hospital’s surgical unit. Alone in the world and unable to personally connect with those around him, Shaun uses his extraordinary medical gifts to save lives and challenge the skepticism of his colleagues.

The series also stars Antonia Thomas as Dr. Claire Brown, Nicholas Gonzalez as Dr. Neal Melendez, Chuku Modu as Dr. Jared Kalu, Irene Keng as Dr. Sarah Chen, Beau Garrett as Jessica Preston, Hill Harper as Dr. Marcus Andrews and Richard Schiff as Dr. Aaron Glassman.

Deadline, Jan 23, 2017, “ABC Orders Drama Pilots ‘The Good Doctor’ & ‘Doomsday’ From David Shore, Daniel Dae Kim & Carol Mendesohn

Written by Shore based on a South Korean format, The Good Doctor centers on a young surgeon with Savant syndrome who is recruited into the pediatric surgical unit of a prestigious hospital. The question will arise: Can a person who doesn’t have the ability to relate to people actually save their lives?

Shore executive produces via his Sony TV-based Shore Z alongside Kim, Sebastian Lee & David Kim. Shore Z’s Erin Gunn co-executive produces, along with Lindsay Goffman of Daniel Dae Kim’s 3 AD.

The original series, written by Park Jae-bum, aired on Korean Broadcasting System’s KBS2 in 2013. The Shore-created House, starring Hugh Laurie as the brilliant but flawed Dr. Gregory House, was one of the biggest medical dramas of the past two decades. It ran on Fox for eight seasons.

Deadline, Oct 6, 2016, “ABC Lands ‘The Good Doctor’ Medical Drama From David Shore & Daniel Dae Kim

Here is a trailer of the South Korean series

Here is a trailer of the ABC series.


The Usefulness of Useless Knowledge

Tuesday, 30 May, 2017

I’m watching this great talk thanks to Yann LeCun’s FB post. I’m also planning to read “The Usefulness of Useless Knowledge” by Abraham Flexner (PDF via IAS). Fascinating stuff.

Robbert Dijkgraaf: “The Usefulness of Useless Knowledge” | Talks at Google


Alzheimer’s patients treated with focused ultrasound

Thursday, 4 May, 2017

Have a watch of the three video clips and read of the CTV News report, “Alzheimer’s patients treated with ultrasound to open the blood-brain barrier

Canadian researchers have taken a key first step that could potentially lead to a whole new way of treating Alzheimer’s disease.

The researchers from Sunnybrook Health Sciences Centre and University of Toronto are using focused ultrasound to safely open the blood-brain barrier in patients with Alzheimer’s disease, with the hopes this will help clear the brain of toxic plaque.

It’s an “out of the box” approach using patients like Karen Hellerman. The 62-year-old from Chatham, Ont. was diagnosed with early stage dementia.

Hellerman is losing her short-term memory and her ability to process complex tasks.
“Sometimes I can get it out, and sometimes I can’t and that disturbs me. “ Hellerman told CTV News. Her husband Neil knows there are no drug treatments to effectively slow or stop the disease.

“As her dementia gets worse, her physical state will get worse…it’s not a good thing. And she’s young, she’s gonna miss part of her life,” said Neil.

She is patient No. 3 in a group of six people with early Alzheimer’s disease, participating in the first study of its kind.

One of the biggest challenges in treating brain disease is getting drug therapies past the blood-brain barrier, which is like a protective “wrap” that surrounds even the tiniest blood vessels in the brain and acts as a “gate” to protect the brain from toxins and proteins that could enter through the bloodstream.

CTV News, “A group of Toronto doctors are trying to break new ground in the treatment of Alzheimer’s disease. Avis Favaro has exclusive video.


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