New Research Breakthroughs at UHN
Missing Gene an Early Cancer Alert
A team of OCI/PMH scientists stunned the cancer research world in June with their announcement that a protein discovered in yeast is a powerful tumour suppressor.
Drs. Razq Hakem, Rama Khokha (OCI/PMH) and postdoctoral fellows Peter McPherson and Bénédicte Lemmers showed that a loss of one or both copies of the Mus81 gene led to the development of lymphomas and other cancers in mice.
“This finding was surprising because everyone had thought that this protein was required for the processing of DNA structures called “Holiday Junctions” that occur during DNA repair. Our work disproves this theory, and reveals an important function for Mus81 as a tumour suppressor,” explains Dr. Hakem.
The next step is to determine whether cancer patients have a mutated form of the protein. “If this is shown to be true in humans, we will have a way of screening for people at risk.”
Science. 2004 Jun 18;304(5678):1822-26.
[PubMed abstract]
Institute: OCI/PMH
Divisions: Cell & Molecular Biology and Experimental Therapeutics
Priority Platform: Genes, Proteins & People
Molecular Complexes Control Brain Function
The cells of our nervous system communicate with each other by sending messages via chemicals called neurotransmitters. The release of these chemicals though, requires several steps and involves several proteins, and new research by Dr. Elise Stanley (TWRI/TWH) and postdoctoral fellows Qi Li and Anthony Lau reveals that this process is far more complicated than once thought.
Using state-of-the-art imaging technology, the research team found that the many proteins involved in releasing these chemicals—once thought to be separate from each other—are actually part of a single complex.
“Our research shows that the point of transmitter release contains highly evolved, miniscule molecular machines designed to transfer information between nerve cells under very tight control,” says Dr. Stanley.
J Neurosci. 2004. Apr 21;24(16):4070-81.
[PubMed abstract]
Institute: TWRI/TWH
Division: Cell & Molecular Biology
Priority Platform: Genes, Proteins & People
Dietary Supplement Lifts Heavy Hearts
New research by Drs. Peter Backx, Michael Sole, Peter Liu (TGRI/TGH), and graduate student Gavin Oudit points to a new therapy for treating cardiovascular disease that results from excess absorption of iron by the body.
The team supplemented the diets of mice suffering from this condition, called “iron overload”, with taurine, one of the most abundant amino acids in the body. This new treatment reduced death and improved heart function in the mice. Explains Dr. Sole, “We are excited about the potential to use taurine as a treatment in humans. Since taurine is a natural, nontoxic substance found in many foods, we hope that it will prove to be a very effective and nontoxic treatment in humans.”
Circulation. 2004 Apr 20;109(15):1877-85.
[PubMed abstract]
Institute: TGRI/TGH
Divisions: Cell & Molecular Biology, Genomic Medicine, Experimental Therapeutics
Time's Up: Clock Proteins Offer Clues for Insomnia and Jet Lag Cures
Our internal clock is crucial for controlling the timing of rhythmic functions such as sleeping, waking, and digestion, and research from the lab of Dr. Emil Pai (OCI/PMH) offers new insight into how the proteins that make up this circadian clock may interact with one another.
Dr. Pai together with graduate students Robert Garces and Ning Wu as well as technician Wanda Gillon used advanced structural biology techniques to elucidate the structure and interactions of the clock proteins in cyanobacteria—the simplest organisms known to have an internal clock.
“Our results suggest how mutated clock proteins disrupt the timing of rhythmic functions at the molecular level,” says Dr. Pai. “This represents the first step in our quest to understand how our own, much more complicated system of clock proteins might function—information that will be key to the future development of treatments for disorders such as insomnia, jet lag, and even some forms of heart disease.”
EMBO J. 2004 Apr 21;23(8):1688-98.
[PubMed abstract]
Institute: OCI/PMH
Division: Structural & Molecular Biology
Priority Platform: Genes, Proteins & People
Surprising New Stroke Culprit Fingered
A recent study by scientists at TWRI/TWH reveals that a new link between proteins involved in cell death and stroke—NMDA receptors—and a protein called PTEN—most commonly known for its role in cancer protection—may lead to a new stroke treatment.
Using an animal model, Drs. Qi Wan, Jim Eubanks, and Michael Fehlings found that low levels of PTEN reduced the number of functioning NMDA receptors in the brain, suggesting a role for PTEN in controlling neuronal function.
“Not only did PTEN attenuate the function of NMDA receptors and reduce their expression,” says Dr. Wan, “but it also activated another signaling protein, resulting in reduced neuronal death after stroke. This suggests that low levels of PTEN offer two ways of protecting against neuronal damage in stroke.”
J Neurosci. 2004 Apr 21;24(16):4052-60.
[PubMed abstract]
Institute: TWRI/TWH
Division: Cell & Molecular Biology
New Risk Factor for Heart Disease Revealed
When most people think about heart disease risk factors, they immediately think of cholesterol. However, mounting evidence—including that recently reported by Drs. Subodh Verma, Donald Mickle and Richard Weisel (TGRI/TGH)—suggests that what we really should worry about is our levels of C-reactive protein (CRP).
CRP is released in response to inflammation, such as that associated with heart disease. The TGRI/TGH team sought to determine how CRP affects the specialized cells that enable the growth of new blood vessels following ischemia, a condition characterized by lack of oxygen in heart muscle.
Says Dr. Verma, “When the heart lacks oxygen, the body responds by launching a process that grows more blood vessels in the heart. However, our research showed that high levels of CRP directly inhibit the survival and function of cells critical for vessel growth. CRP thus represents an important link between inflammation and heart disease.”
Circulation. 2004 May 4;109(17):2058-67.
[PubMed abstract]
Institute: TGRI/TGH
Division: Experimental Therapeutics
Chromosome Tips Important for Cancer
Telomeres are important for chromosome replication during cell division, but each time a cell divides, they get shorter, until the cell dies. It is thought that this process evolved to protect us from cancer: however, the precise role that short telomeres may contribute to cancer risk by fostering genetic instability is as yet unknown. 
Using mice genetically engineered to possess only a limited ability to maintain telomeres, Dr. Lea Harrington (AMDI/OCI/PMH) and her colleagues Natalie Erdmann and Yie Liu have studied how these short telomeres are maintained.
“The results suggest that low levels of a protein called telomerase reverse transcriptase (TERT) plays a key role in protecting cells from genetic instability even when telomeres are short,” says Dr. Harrington. “This has important implications with respect to human cancer and aging, and these mice make useful models for studies aimed at understanding the significance of low levels of telomerase activity.”
Proc Natl Acad Sci USA. 2004 Apr 20;101(16):6080-5.
[PubMed abstract]
Institute: AMDI/OCI/PMH
Division: Cell & Molecular Biology
Priority Platform: Genes, Proteins & People
Kidney Malfunction Increases Burden in Heart Failure
Kidneys are underappreciated organs. Though their jobs may seem humble, their role in controlling blood volume and salt and water retention is key for maintaining proper function of many organs, including the heart.
Now TGRI/TGH’s Dr. John Parker has shown for the first time that people suffering from chronic heart failure have malfunctioning blood pressure sensors in their kidneys. Says Dr. Parker, “If the kidneys can’t respond to control signals, they can’t get rid of extra liquid in the body. This places an extra burden on the heart to pump all this volume—and in heart failure the heart is already struggling to function.”
Circulation. 2004 Jun 15;109(23):2862-5.
[PubMed abstract]
Institute: TGRI/TGH
Division: Clinical Investigation & Human Physiology
Breaking News from UHN Research
TWRI Director Elected to Royal Society
UHN Research extends its congratulations to Dr. Peter St George-Hyslop, newly elected Fellow of the Royal Society of London. Recognized for his research on Alzheimer disease, Dr. St George-Hyslop joins an illustrious group of 1240 scientists from the commonwealth. The honour of this membership is accorded to only 44 citizens annually.