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The following research breakthroughs are only a selection of the achievements made by UHN Researchers this year. For more research stories see Net Results and Net Results EXPRESS.
January
Drs. Tak Mak and Pam Ohashi (Amgen/OCI/PMH and OCI/PMH, respectively) showed that mice lacking bcl10 lack a functioning immune system and specifically, that immune cells isolated from these mice do not respond to antigen receptor activation, the common signal for immune response. They further showed that, in these mutant cells, the ability to activate the transcription factor NFkB is lost.
These findings indicate that the bcl10 molecule is a missing link between antigen receptor signaling and NFkB activation and lymphocyte proliferation. They further point to the possibility that, in lymphoma, bcl10 may not be disrupted, as previously thought, but instead may be upregulated.
If this is the case, effective new lymphoma treatments which inhibit bcl10 function may be in the offing.
(PubMed abstract)
February
Scientists in the Division of Genomic Medicine at TGRI/TGH led by Dr. York Pei identify a mechanism responsible for increased severity of autosomal dominant polycystic kidney disease, a hereditary disease that affects 1/1000 births.
Most of the cases of this disease are caused by inheritance of a mutation in one of two genes. However, in screening 48 members of a family in which 28 had the disease, scientists found two people who possessed both mutations, an inheritance never before observed. These two individuals also had a more severe form of the disease—providing for the fist time in vivo evidence that these gene products interact in the same pathway that leads to cyst development in this kidney disease.
(PubMed abstract)
March
Cataracts are the leading cause of blindness in most countries. Dr. Elise Heon and a team from the UHN Vision Science Research Program (TWRI/TWH) recently studied a relatively rare form of cataract inheritance in a large family. They located a novel gene site on chromosome 9—a finding that may shed light on the formation of age-related cataracts.
(PubMed abstract)
March
Researchers in the UHN Women's Health Program, led by Dr. Donna Stewart (TGRI/TGH), surveyed 378 breast cancer survivors to determine their views on what caused their cancer. Forty-two percent pointed to stress; 26%, to genetics; 25%, to environment; and 24%, to hormones.
When asked what prevented their cancer from recurring, 60% credited a positive attitude and 50%, a good diet. Other protective effects reported included healthy lifestyle (40%), exercise (30%), stress reduction (28%), prayer (26%) and complementary therapies (11%). Luck and the anticancer drug tamoxifen were tied at 4% each.
(PubMed abstract)
April
Osteonecrosis is a destructive bone disease that can lead to damage of joints. It is often associated with the autoimmune disease lupus.
Drs. Dafna Gladman and Murray Urowitz, Directors of the UHN Centre for Prognosis Studies in the Rheumatic Diseases (part of the UHN Arthritis and Autoimmunity Research Centre) recently studied the factors which predispose a lupus patient to getting osteonecrosis.
They found that use of glucocorticosteroids (a common and powerful treatment for autoimmune diseases), arthritis and cytotoxic medications are all risk factors for developing osteonecrosis.
(PubMed abstract)
June
What happens when the left temporal lobe—a region known to be important to processing the meanings of words—is affected by epilepsy? TWRI/TWH scientists Drs. Mary Pat McAndrews and David Mikulis investigated this problem using the technique of functional MRI, in which brain activity is scanned as subjects perform mental tasks.
They looked at two types of language processing—phonological processing which takes place primarily in the frontal lobe and semantic processing which involves both frontal and temporal lobes.
Surprisingly, patients with a seizure focus in the left temporal lobe showed normal amounts of activity in the affected region but greater activity than normal in the left frontal and right temporal areas for both types of processing.
These results suggest that in left temporal lobe epilepsy, as in dyslexia, language processing may be reorganized in the brain.
(PubMed abstract)
June
Leukemias are often associated with a type of genetic mutation called a translocation: bits of chromosomes are literally exchanged with each other as leukemia develops, disrupting normal cell growth.
A team led by OCI/PMH scientist Dr. Jeremy Squire showed that these translocations can also be associated with deletions—loss of genetic material in the region of these exchanges—with dire consequences for patients.
In patients with chronic myelogenous leukemia, those with deletions had a shorter survival time and a higher relapse rate following bone marrow transplant.
In the future, it will become routine for diagnostic labs to test for deletions as well as translocations in people with leukemia.
(PubMed abstract)
June
Cells contain complex sugar-containing structures on their surfaces which are involved in many cell functions. In cancer, changes in the number and distribution of these structures can indicate a higher probability of metastasis and poor prognosis.
The Golgi alpha-mannosidase II is an enzyme which produces these structures, and scientist Dr. David Rose (OCI/PMH) recently determined the structure of this molecule and its complex with the inhibitor swainsonine, as well as with a substrate-like molecule.
Knowledge of this structure will help researchers develop stronger, more specific anti-cancer drugs. (PubMed abstract)
August
Lung tissue is delicate, and the process of preserving lungs prior to transplant can extract a toll, particularly in terms of the function of organ after transplant.
A team led by TGRI/TGH scientist and thoracic surgeon Dr. Shaf Keshavjee are investigating new ways of protecting this delicate tissue from damage during and immediately after transplant.
Their strategy involves using gene therapy to introduce genes which have a protective effect on the tissue. Specifically, they showed that introducing Il-10, a cytokine, into donor lungs was successful in enhancing the function of the organ after transplant.
"Our eventual hope is to bring this therapy to the clinical setting to use in humans," says Dr. Keshavjee, "to improve the outcomes of transplantation in our patients."
(PubMed abstract)
August
Another cancer secret is revealed by scientists at OCI/PMH when they demonstrate an important connection between PTEN and p53, two genes commonly mutated in human cancers.
A team led by Drs. Tak Mak and Sam Benchimol showed that p53 can actually control expression of PTEN, and that PTEN, in turn, is required for nomal functioning of p53 in cancer suppression. This finding may shed light on the genesis of cancer in humans.
(PubMed abstract)
September
In the future, cell therapy may offer the best hope for ailing hearts. Survival of transplanted cells, however, is dependent on their ability to obtain a blood supply.
In a paper published in Sept 2001, TGRI/TGH Drs. Terrence Yau, Ren-Ke Li, Donald Mickle and Richard Weisel showed a successful way of ensuring this. Transfecting cells with a growth factor gene (VEGF) prior to transplant increased growth of blood vessels in the area of the transplant by an amazing 70%.
(PubMed abstract)
December
Today's advanced instrumentation provides tools to study the structure of a molecule and even to "tweak" this structure to optimize function.
OCI/PMH scientist Dr. Mitsu Ikura and colleagues have used NMR data to rationally design a new version of a molecule which is used to measure ion concentration in the cell. They were able to study similar molecules and so tweak the molecular design significantly. The new molecule has improved measurement sensitivity and is now being used by scientists all over the world. (PubMed abstract)
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