On May 22nd, Krembil Senior Scientist Dr. Karen Davis became the President-Elect of the Canadian Pain Society (CPS).
CPS is a society of scientists and health professionals who have a vested interest in pain research and management. The society supports the treatment of pain as a basic human right and is currently advocating for a Canadian National Pain Strategy.
Dr. Davis will serve as President-Elect for two years, after which she will serve as the President for the subsequent two years. In her new role, she is hoping to draw more attention to pain research, care and education.
At UHN, Dr. Davis’ research program is focused on deciphering the central mechanisms underlying pain, and the influence of attention and brain plasticity under normal conditions and in patients with neurologic or psychiatric disorders.
Congratulations Dr. Davis!
Every year, Krembil researchers make discoveries that provide new insight into the mechanisms that underpin arthritis, as well as diseases of the brain and eyes. Converting these discoveries into novel therapeutics and diagnostics—through a process known as knowledge translation—is a daunting and challenging task.
To support researchers in this pursuit, the Krembil Research Institute has established a new facility: the Centre for Medicinal Chemistry and Drug Discovery (CMCDD). This facility is led by Dr. Mark A. Reed, a medicinal chemist with extensive experience in drug discovery and development in industry.
Once the facility is fully operational, Dr. Reed envisions that it will offer a variety of services to promote knowledge translation. It will work closely with researchers to assess the ‘translatability’ of their research and provide them with a roadmap of experiments that need to be completed to pique the interest of potential investors. The facility will employ medicinal chemists who will build compounds needed to validate new drug targets—an essential step in the drug discovery process. It will also assist researchers in securing funds to support preclinical and clinical studies.
Since his recruitment in August 2017, Dr. Reed has made significant progress in building CMCDD and nurturing relationships with researchers—its primary clientele. He has been advising several researchers and helping them prepare translational research grants, including some submitted to LAB150, a new initiative created by MaRS Innovation and the company Evotec to accelerate drug development. Two of the grants were selected to progress to the final stage of the competition.
The CMCDD is located on the 5th floor of the Krembil Discovery Tower where it has access to all of the equipment and resources needed for the Centre’s medicinal chemistry activities. Within the next two years, Dr. Reed plans to populate this space with up to five medicinal chemists to support drug discovery efforts.
“By providing key capabilities that facilitate knowledge translation, CMCDD will help UHN bridge the gap between scientific discovery and improved patient outcomes,” said Dr. Reed.
Krembil’s annual Research Day was held on May 23rd and was attended by approximately 200 researchers, trainees and staff, as well as Dr. Bradly Wouters, UHN’s EVP of Science and Research.
Since the event’s creation in 2000, Research Day has been and continues to be devoted to showcasing the hard work of Krembil graduate students and postdoctoral fellows. The 2018 edition gave 78 trainees the opportunity to share their research with their colleagues through a variety of formats including oral presentations, posters and three-minute elevator pitches. At the end of the day, those who did the best job presenting their work were rewarded with an honorary certificate and a cash prize. Krembil trainees were also instrumental in making Research Day happen: they played a leading role in organizing the day, designing the front cover of the Research Day booklet and hosting the keynote speaker.
This year’s invited speaker was Dr. Samer Hattar, Chief and Senior Investigator of the Section of Light and Circardian Rhythms (SLCR) at the National Institute of Mental Health. Dr. Hattar is most well-known for his research characterizing a light-sensing cell in the eye known as intrinsically photosensitive retinal ganglion cell (ipRGC). His keynote address at Krembil Research Day focused on his latest work showing how light can influence mood and learning through ipRGCs and specific brain regions.
Dr. Donald Weaver, Director of the Krembil Research Institute, thanks all of the individuals who made this year’s Research Day a success, including the Trainee Affairs Committee and its Chair, Dr. Mary Pat McAndrews; the Krembil Administration team; the presentation judges; and the Nadler Family, whose generous donation funded the presentation prizes.
Congratulations to everyone who presented their work!
A complete list of presentation awardees can be viewed here.
View a video of the Krembil Research Day here.
Each year, UHN’s Technology Development and Commercialization Office (UHN-TDC) awards and celebrates a UHN Inventor who illustrates noteworthy excellence through inventiveness in research, critical contributions and commercial successes to impact patient lives and their quality of life.
Driven by the overarching goal of freeing patients from the recurrent toll of degenerative and chronic diseases, Drs. Keller and Laflamme have been pioneering and studying cell-based therapeutic approaches since the 1990s and the early 2000s, respectively, long before the field of cell-based therapy and regenerative medicine was formally recognized.
“Their bold achievements in pluripotent stem cell therapy have the potential to go beyond symptomatic treatment to discovering new therapies that promise to cure many chronic degenerative diseases,” said Dr. Brad Wouters, UHN Executive Vice President, Science and Research, in announcing the award at yesterday’s Annual General Meeting in the Auditorium at the MaRS Discovery District.
Regenerative medicine harnesses the power of undifferentiated cells to repair, regenerate or replace damaged or dysfunctional cells, tissues and organs.
“The burden of chronic diseases is gigantic,” says Dr. Laflamme. “And, we generally treat patients at the margin, treat symptoms only, and don’t address the fundamental degeneration of tissues and organs over time.”
But pointing to the potential of regenerative medicine, Dr. Laflamme adds: “Rather than a pill you have to take for the rest of your life to keep things from getting worse or to improve symptoms, you actually get at the root cause [and cure] the disease.”
Dr. Keller adds, that “the range of diseases that one can treat is only left to our imagination. It can be heart, liver, blood cell diseases, diabetes… and our worst neurodegenerative diseases, such as Parkinson’s disease.”
As director of the McEwen Centre for Regenerative Medicine, which was founded by the generous support of Rob and Cheryl McEwen, and a Senior Scientist at Princess Margaret Cancer Centre at UHN, Dr. Keller’s enabling research demonstrated that stem cells can be differentiated in vitro to become functional, beating atrial, ventricular and pacemaker heart cells.
Dr. Laflamme holds the Robert R. McEwen Chair in Cardiac Regenerative Medicine at UHN and is a Principal Investigator at the McEwen Centre for Regenerative Medicine, as well as, Senior Scientist at the Toronto General Hospital Research Institute at UHN. Dr. Laflamme’s laboratory is focused on developing stem cell-based therapies to restore damaged hearts in heart failure patients.
As Senior Scientist at Princess Margaret Cancer Centre, Dr. Keller’s enabling research demonstrated that unspecified embryonic stem cells can be differentiated in vitro to become functional, beating atrial, ventricular and pacemaker heart cells.
Dr. Laflamme's lab at the Toronto General Hospital Research Institute is focused on developing novel cell based therapies to restore damaged hearts in heart failure patients. In heart failure models, he has shown that differentiated stem cells can regenerate and repair damaged heart muscle.
By joining forces, Drs. Keller and Laflamme have made outstanding advances and demonstrated in preclinical heart failure disease models that, in the words of Dr. Laflamme, “pluripotent stem cells can be preferentially induced,” given the right set of biological signals “to become treatment useful cell types to regenerate and replace atrial, ventricular and pacemaker heart muscle cells,” which make up the intricate machinery of a normally functioning heart.
When asked why it has taken so long for this therapeutic approach to be applied to patient care, Drs. Keller and Laflamme point to the complexity inherent in large-scale manufacturing of suitable, specialized stem cells—billions of cells are often needed—for use in human patients to address the safety concerns, immune rejection and efficacy of this treatment approach.
In 2016, however, overcoming these challenges became manageable. Due to the dedicated relationships within the Toronto biocluster, key players including Bayer AG, a global biopharmaceutical company, and Versant Ventures, a prominent venture capital firm, launched BlueRock Therapeutics in Toronto with a US$225 million series A investment and licensed UHN’s enabling technology portfolio discovered by Drs. Keller and Laflamme.
BlueRock is also using Toronto-based industry-leading state-of-the-art cell manufacturing platforms to produce unlimited quantities of specialized stem cells and is targeting areas with great unmet clinical need—neurodegenerative and cardiac diseases—the very areas in which Drs. Keller and Laflamme are renowned worldwide.
As founding scientists and investigators in BlueRock, Drs. Keller and Laflamme are championing to position not only BlueRock, which represents Canada’s largest biotechnology investment of its type, but also UHN as a leading research hospital, to impact the lives of millions of patients in Canada and the world over.
“It is this outstanding scientific teamwork and the bold strategy to develop a cure for heart disease via commercialization that has won them the award,” Dr. Wouters said.
Welcome to the latest issue of Research Spotlight.
This newsletter highlights top research advancements across UHN and from over 450 researchers appointed at five research institutes. As Canada’s largest research hospital, UHN is a national and international source for discovery, education and patient care.
Stories in this month’s issue:
● PUTTING SAFETY AT RISK: New research suggests that concerns about rapid approval of anticancer drugs may be warranted.
● THE RIGHT PRESCRIPTION FOR EXERCISE: Combining aerobic and resistance training found to significantly enhance stroke recovery.
● THE BODY’S TRASH DISPOSAL SYSTEM: Body’s system for removing dead cells could be new therapeutic target for lupus and cancer.
● LIVING WITH HALF A HEART: New insights provided for adults living with hypoplastic left heart syndrome.
The best defence is a good offence. This adage, often applied to sports or military strategies, suggests that attacking one’s opponent offers the greatest protection. Researchers and clinicians are taking this approach to fight cancer—developing powerful new therapies that seek out and kill cancer cells.
One such approach is immune therapy: it works by boosting the number and activity of tumour-infiltrating lymphocytes (TILs), immune cells that go on the offensive by migrating into tumours to target and destroy them. Although this strategy holds promise, challenges remain because certain tumours have developed defence mechanisms that block TIL activity.
These tumours, however, are no match for Dr. Pamela Ohashi. She is a pioneer in figuring out how the immune system interacts with cancer in order to develop new immune therapies.
In an article published in the prestigious journal Nature Medicine, Dr. Ohashi and her research team, including Dr. Sarah Crome, revealed that an internal battle may be going on: they found that certain ovarian tumours contain other immune cells, called regulatory innate lymphoid cells (ILCregs), that block the activity of cancer-fighting TILs. The ILCregs did this in two ways: they reduced the ability of TILs to grow and multiply, and altered the ability of the TILs to attack cancer cells.
The team also found that the tumours from some patients contained ILCregs, while those from others did not, suggesting that some tumours may be able to attract or promote growth of ILCregs.
Immune therapies work by helping the immune system to target and kill cancer."
“By looking at tumour biology from this different perspective, we have a better understanding of the barriers that prevent a strong immune response,” explains Dr. Ohashi. “Our research reveals a promising new strategy to develop combined therapies that simultaneously target ILCregs while promoting TIL growth and function—delivering a stronger ‘one-two punch’ against the disease.”
Building on these findings, her team is now developing a test to identify ILCregs in patients, which may help predict whether the patient will respond to immune therapy. Dr. Ohashi says, “This knowledge would help doctors and patients make more informed medical decisions, personalize cancer treatment and ultimately improve the effectiveness of immune therapies.”
The Michener Institute of Education at UHN is offering a two-week, hands-on workshop on genome editing techniques and applications.
The course is an opportunity for researchers, trainees and staff to develop skills using CRISPR/Cas technology. It will also be useful for beginners to work on developing protocols in collaboration with experienced research technicians.
The course comprises in-person lectures and laboratory time, as well as online course material. Spaces are limited, so register early.
Details and Registration