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Tag Archives: Ottawa Hospital Research Insitute

Friday Science Review: January 21, 2011

How to Build a Retina — Hope for the Three Blind Mice

Ottawa Hospital Research Institute ♦ Review Published in Stem Cells, Jan. 14, 2011

There have been waves of progress in the stem cell world and regenerative medicine is a field that continues to amaze. In a recently published review, Dr. Valerie Wallace underlines the anatomy and developmental sequence of the retina and provides insight into the biological pathways that can be exploited to re-create retinal cells in the lab. The retina is a light-sensitive tissue found at the back of the eye that contains specialized photoreceptor cells known as cones and rods. After light passes through the lens into the eye it travels through a jelly-like substance in the middle to reach the retina. The retina then converts these photons of energy to a signal that the brain can register as an image. The key to producing functional retinal cells is in exploiting the signaling pathways and chemical cues that lead to their natural formation in the body. In 2009 a paper published in Cell Stem Cell provided evidence that human embryonic stem cell-derived photoreceptors could integrate into the retina and partially repair vision loss in blind mice. This was a pivotal study demonstrating that cell types derived in vitro can potentially be used to rescue vision. There are hopes that similar techniques will be able to treat patients suffering from a variety of retinal diseases, including glaucoma, retinitis pigmentosa, age-related macular degeneration, and diabetic neuropathy. However, as is the case with all prospective transplantation therapies, producing pure, safe, and functional populations of relevant cell types in the lab will be a difficult hurdle to jump — but certainly not one that is impossible to jump. Protocols for the derivation and identification of photoreceptor cells are currently being honed and as we continue to learn more about the developmental pathways that contribute to their formation, these cell populations will move closer to being implemented in the clinic.

Genomic Signature Cracks the Case

Pacific Biological Station ♦ Published in Science, Jan. 14, 2011

In a nice bit of detective work researchers at the Pacific Biological Station in Nanaimo, BC, have figured out the probable cause of the precipitous decline in Canada’s stock of wild salmon. Historically, as many as 8 million sockeye salmon return annually from the Pacific Ocean to spawn in the Fraser River basin. However over the past two decades these numbers have dropped rapidly as salmon die en route to their destination. In 2009 the returns to the river were less than the replacement rate, a finding that spurred a judicial inquiry into the matter. Investigators were able to correlate physiological profiles with failed migration and reproduction by taking non-lethal biopsies of gill tissue from salmon caught in the ocean and tracking salmon with radio transmitters. The gene expression profiles of fish that were successful in making the journey back to the Fraser were then compared with those that perished en route. Researchers found several genes that were associated with survivorship and noted that 60% of fish contained a gene expression signature that was predictive of in-river fate when they were greater than 200km from the mouth of the river. Several genes in the mortality-related signature had known linkages to viral activity, consistent with the finding that fish with this signature also exhibited an up-regulation in inflammatory and apoptotic processes. Researchers attribute the increased mortality of sockeye salmon to viral infection, being exacerbated by the physiological demands placed on salmon as they return from a salt water environment to a fresh water environment and begin their long journey upstream.

The Genome, The Proteome, How About the Tyrosine Phosphatome?

McGill University ♦ Review Published in Nature Reviews Cancer, Jan. 2011

We’re in the era of “-omics” and as we continue to explore the microscopic world within us we find more and more families to apply the suffix to. Protein tyrosine phosphatases (PTPs) play an important role in the regulation of numerable biological processes that are intertwined in the development of cancer. Dr. Sofi Julien and her colleagues at the Goodman Cancer Research Centre and Department of Biochemistry at McGill University have prepared an impressive review on the “human cancer tyrosine phosphatome”. The work focuses on the genetic and epigenetic alterations that may lead to loss or gain in function of PTPs that are involved in cancer formation, and provides figures illustrating such things as the location of PTP genes on chromosomes, the location of mutations in PTPs, and proposed mechanisms of both oncogenic and tumour suppressor functions. Interestingly, PTPs have modes of action that can both cause and prevent cancers depending on the cellular context. PTPs exert their effects by removing phosphate groups from target proteins, and depending on the type of protein that becomes dephosphorylated, the resulting signaling cascade can promote or suppress tumour formation. PTPs counter the effects of protein tyrosine kinases (PTKs) which add phosphate groups to target proteins as opposed to removing them. The activity of PTPs and PTKs exist in a sort of equilibrium within the body and shifts in this balance can have detrimental effects. Generally speaking members of the kinase family are considered to be oncogenic because overzealous phosphorylation activity, particularly activation of growth receptors on the extremity of cells, can lead to rapid and uncontrolled cell proliferation. Since the late 1980s, when the first true phosphatase was discovered, more than 100 have been identified by scientists. PTPs have the potential to be used as prognostic indicators for different cancer types. Investigators are also hoping that PTPs may prove to be effective drug targets for cancers where PTP hyperactivity is known to contribute to formation and onset of disease. PTP inhibitors, including natural compounds, small molecules, silencing RNAs, and anti-sense molecules are all under development. The only advanced clinical trial of an anti-PTP therapeutic is ISIS’s 113715 which targets PTPN1. The antisense molecule successfully made its way through a phase II clinical trial for diabetes. PTPN1 has been identified as an oncoprotein in a mouse model of breast cancer suggesting that it may also have utility in an oncology setting.


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