The Cross-Border Biotech Blog

Biotechnology, Health and Business in Canada, the United States and Worldwide

Tag Archives: T cells

Friday Science Review: April 9, 2010

New fixes for diabetes, HIV, and nerve damage…

Nano-Vaccine Cures Diabetes: To prevent the immune system from attacking pancreatic cells in Type 1 diabetes, a nanotechnology based “vaccine” was used successfully to stop the disease in mice.  The strategy involves nanoparticles that are coated with diabetes specific peptides and bound to MHC molecules. When injected into the body, they stimulate regulatory T cells – the “friendly” T cells that prevent the “bad” T cells from destroying the insulin producing beta cells in the pancreas.  The advantage of this method is that it is specific to the ‘diabetes T cells’ and there are no negative effects on the rest of the immune system.  Other autoimmune diseases may also benefit from a nanoparticle vaccine approach.  Dr. Pere Santamaria’s team at the University of Calgary describes their work in the online edition of Immunity and has licensed this innovative technology to Parvus Therapeutics, Inc., a U of C spin-off company.

Allowing Neural Regeneration: The p75NTR receptor is important for the development of the nervous system during childhood.  A new research study published in Nature Neuroscience describes an inhibitory effect of p75 neurotrophin receptors (p75NTR) in the adult nervous system.  Not only does it prevent adult nerve cells from regenerating, it actively destroys axons as necessary if any aberrant connections try to form.  This monitoring system is likely skewed in neurological diseases or disorders.  Thus, further molecular information surrounding p75NTR in the nervous system can lead to developing strategies to facilitate nerve regeneration to occur or prevent degenerative disorders.  Dr. Freda Miller and her team conducted the research at The Hospital for Sick Children in Toronto.

HIV’s Secret Weapon Revealed: The discovery of how the viral protein called Vpu facilitates HIV-1 proliferation in a host may present opportunities to block this pathway with a small molecule inhibitor.  Vpu binds to and blocks Tetherin, a natural antiviral protein on the cell surface that can sense and capture the virus and prevent production and further transmission of HIV-1.  HIV-1 has evolved with Vpu as its weapon to impede Tetherin from reaching the cell surface where it acts to tether viruses.  Now it is time for scientists to outsmart the virus and find a method to block Vpu.  Dr. Éric A. Cohen directed his team at the Institut de Recherches Cliniques de Montréal and reports the study in this week’s PLoS Pathogens journal.

Cell-Cell Krazy Glue: The integrity of cell-cell contacts is important for the maintenance of the epithelial cell layer and aberrations may contribute to disease progression such as in cancer metastasis.   Two proteins involved in this cell-cell adhesion are p120 catenin and E-cadherin.  Dr. Mitsuhiko Ikura at the Ontario Cancer Institute performed NMR structural studies to provide a detailed map and understanding of the protein-protein interaction between catenin and cadherin.  The detailed study, published in the journal Cell, describe both dynamic and static interactions that contribute to the stability of the adhesion interaction between cells.

Bring out the Bazooka: Following the article above on the epithelial cell layer, this study examines a protein called Bazooka (Par3 in mammalian cells) in fruit flies.  It is expressed on epithelial cells and acts a protein interaction hub to regulate the integrity of the epithelial structure.  Using a series of gene mutants, gene mapping and bioinformatics techniques, researchers identified up to 17 genes that associate with Bazooka to regulate epithelial structure, many of these are novel interactions with Bazooka.  Further study is necessary to determine how they work together and how this translates to human tissues.  The list of genes is available in the article online in PLoS One journal and was reported by lead researcher Dr. Tony Harris at the University of Toronto.

Friday Science Review: March 12, 2010

Good viruses, bad viruses, biomarkers and protein structures in this week’s research highlights…

Biomarker for Hodgkin’s Lymphoma Subset: Using a high-throughput genomic approach to associate gene expression profile with treatment outcomes for Hodgkin lymphoma, researchers identified an overexpression of genes typically expressed by macrophages in samples from patients who had experienced a relapse after treatment.  This was confirmed histologically by looking at stained tissue samples and tallying the number of macrophages – high numbers of macrophages are associated with treatment resistance in Hodgkin lymphoma.  About 25% of patients fall into this category where a biomarker test could shuttle them into a more aggressive or experimental treatment option and may prevent them from being exposed to the side effects of primary treatments that are likely to fail.  The study, led by B.C. Cancer Agency researcher Dr. Randy Gascoyne, is reported in The New England Journal of Medicine with an editorial that is touting this as the “breakthrough we have been looking for.”

Immune System Boost for HIV Patients:  A very important molecular discovery may give a boost to restoring immune function in HIV infected patients.  Renowned HIV scientist, Dr. Rafick-Pierre Sékaly, and his cross-border research teams at the Université de Montréal and Vaccine and Gene Therapy Institute of Florida identified that the protein PD-1 is up-regulated by the release of bacterial products from the gut.  Another factor, IL-10, is subsequently increased and together this is what shuts down the CD4+ T-cell immune system in HIV patients.  Therefore, the scientists suggest that new immunotherapies should aim to block PD-1 and IL-10 to help restore the debilitated immune system in HIV infected patients.  The research article appears in this week’s Nature Medicine.

Not All Viruses are Bad: The ubiquitous reovirus has oncolytic actions against different types of cancer when used as a therapeutic approach.  Now, prostate cancer may be added to the growing list of cancers, which includes ovarian, breast, pancreatic and gliomas, that may be treated with a reovirus based strategy.  In fact, the Calgary-based Oncolytics Biotech Inc. technology platform and pipeline are based on the reovirus and contributed to the prostate study.  In the prostate cancer clinical study, a viral concoction was injected into prostate cancer nodules and three weeks later, the prostates were resected.  There was evidence of cancer cell death and overall, the procedure was deemed safe with only mild side effects experienced by the patients.  The success of this pilot study should draw interest to expand the clinical trial novel treatment for prostate cancer.  Dr. Donald Morris led the research and medical team at the University of Calgary and reports the study in Cancer Research.

Having Fun with Names: This study provides more molecular and structural details than you probably need to know but I want to point out the cool protein domain name: Really Interesting New Gene or RING domain.  It is an important component of a group of proteins that regulate the potent oncogene called eIF4E (eukaryotic translation initiation factor).  The details of the Université de Montréal study are described in the Proceedings of the National Academy of Sciences.

Pump It Up: Another structural study that I want to point out because of its importance: the V-ATPase.  This is a membrane proton pump that controls the acidity of the cellular environment and can play critical roles for the cell in promoting a diseased state.  SickKids Research Instiute scientist, Dr. John Rubinstein explains “In some types of cancer, the pumps are “hijacked” to acidify the external environment of tumours, allowing the cancer to invade surrounding tissues and spread throughout the body.  The cells that take up bone minerals also use V-ATPases to dissolve bone, a process that must be limited in treating osteoporosis.”  More details on the study are found here in the Proceedings of the National Academy of Sciences.

Paradoxical Signalling Interaction: The phosphatidylinositol 3-kinase (PI3K) signaling pathway is a well studied signaling module and its aberrant activity is implicated in a number of diseases including cancer.  It is also the target of a handful of therapeutic drugs currently under study or in trials.  However, the new study led by Dr. Deborah Anderson at the Saskatchewan Cancer Agency throws a new twist into the pathway.  Their data identifies a paradoxical interaction between the p85 regulatory subunit of PI3K and the PTEN phosphatase enzyme since these two enzymes have opposing actions.  This is certainly food for thought for researchers in this field to rethink their signalling models.  A recent news article headlines this study as the “on switch” for cancer cell growth but it is really a much more complicated puzzle than that.  The data is presented in the early edition of the Proceedings of the National Academy of Sciences.

Friday Science Review: February 26, 2010

A few medical research applications this week…

Personalized Medicine – for Lung Cancer: To develop a personalized medicine approach to treating non-small cell lung cancer (NSCLC), researchers generated a xenograft model where they implant human tumour tissue into the renal capsule of a host mouse.  As the tumour establishes itself, the mouse then becomes the platform for testing various chemotherapy regimes (cisplatin+vinorelbine; cisplatin+docetaxel; cisplatin+gemcitabine) to determine which one or combination therapy is the most effective against each of the different tumours.  They compared the results of the treatments in mice to retrospective patient outcomes and found significant correlation to consider the xenograft model a success.  Although it takes about 6-8 weeks for the results, they believe that it is quick enough to gain an insightful preliminary assessment of the potential therapeutic outcome.  Dr. Yuzhuo Wang led his team at the BC Cancer Agency and reports their work in Clinical Cancer Research.

HIV-1 Molecular Manipulations: HIV-1 infected patients exhibit a loss of CD4+ T cells, which are essential players in the defense against viral infections.  A new study reveals how the HIV-1 protein, Vpr, activates the Natural Killer (NK) cells by inducing the expression of stress-related proteins at the cell surface of CD4+ T cells.  The NK cells recognize the stress signals on CD4+ T cells and attacks and destroy these cells, leaving the patient with severely reduced CD4+ T cells.  Researchers also noticed that the continuous activation of NK cells eventually desensitizes them and they eventually lose their ability to perform their normal duties in attacking infected cells.  The molecular mechanisms of Vpr discovered in this study should help in future research leading to new therapeutic strategies.  Dr. Éric Cohen and his team at the Institut de recherches cliniques de Montréal describe their research in last week’s issue of Blood.

Protecting Your Heart: The blood pressure cuff you see in every doctor’s office can be used to limit the severity of heart attacks by triggering a molecular response in the body that protects the heart during an attack.  It is called remote ischemic preconditioning where the blood pressure cuff is used to intermittently cut off blood flow to the arm during an attack.  This triggers an innate response warning message throughout the body to release molecules to protect itself from the lack of blood flow.  In this particular study, the size of the heart attacks were reduced by 30-50% compared to control groups.  It is one of the most effective treatments and is relatively simple to administer.  Dr. Andrew Redington at The Hospital for Sick Children led the international study and is published in the The Lancet.

Friday Science Review: November 20, 2009

Intestinal disease genomics and how hedgehogs cause arthritis…

Genetic Clues to ‘Belly Aches’ in Children: The largest genomic investigation into early onset inflammatory bowel disease (IBD) including Crohn’s disease and ulcerative colitis involved the efforts of an international research team.  In total, genetic information from 3,400 children with IBD and 12,000 healthy children were compared.  This study resulted in the identification of five genetic regions associated with susceptibility to pediatric and adolescent IBD.  The team is now taking a closer look at these regions to try to identify the specific proteins that may explain why or how the disease develops.  Another question that they would like to address is why some individuals develop IBD early whereas others develop it later in life.  Two Toronto researchers, Dr. Anne Griffiths (Sickkids) and Dr. Mark Silverberg (Mount Sinai Hospital), contributed their expertise to the study, which appears in this week’s issue of Nature Genetics.

Colon Cancer Susceptibility Genes: In another intestinal disease research project, scientists noticed that different strains of mice exhibited different levels of resistance or susceptibility to colon cancer induced by a chemical carcinogen.  Using genetic studies, the determining factor was mapped to a specific region in chromosome 3 that they designated as colon cancer susceptibility locus 3 (Ccs3).  Within this region are about 94 known genes and they have identified a subset that are expressed at high levels in the colon.  What is also interesting is that Ccs3 in mice is homologous to regions in human chromosome 1 and 4, which also contain genes known to be associated with inflammatory bowel disease and colorectal cancer.  This mouse model will be a very useful tool for future studies on the pathogenesis of colon cancer.  Dr. Philippe Gros led the research team at McGill University and published the study in the journal Oncogene.

Hedgehogs are Key to Osteoarthritis: An unexpected discovery may hold the key to solving painful osteoarthritic disease.  Elevated expression or activity of a group of proteins called Hedgehog resulted in the development of osteoarthritis in mice.  In simple terms, the balance of this signalling pathway in chondrocyte cells determines whether they go on to make cartilage or bone.  In the animal model of osteoarthritis, Hedgehog levels are high and there is less cartilage being produced from the chrondrocytes.  Obviously, Hedgehog becomes an immediate pharmacologic target for the treatment or prevention of osteoarthritis.  You may find it strange that this study on a disease primarily affecting adults is from The Hospital for Sick Children but it just shows that research is full of surprises and you never know where it may take you!  Dr. Benjamin Alman and his research team reported their study in the online edition of Nature Medicine.

Pathway Signalling Antibody Production: A key signalling pathway required for the efficient production of antibodies was identified recently and verified using knockout mice.  A receptor on T cells called ICOS (Inducible Costimulator) is required for their conversion into a specialized type of T cell called Tfh cells (follicular B helper T cells).  As the name implies, their role is to help B cells make the right antibodies to the target.  Dr. Woong-Kyung Suh’s team at Institut de recherches cliniques de Montréal discovered that ICOS activates an enzyme called phosphoinositide 3-kinase (PI3K), which eventually leads to the release of factors that trigger the formation of Tfh cells.  With this knowledge, researchers may find ways to tweak the system to suppress (in autoimmune disease) or enhance (in infectious disease) antibody production as required.  The study is reported in the Proceedings of the National Academy of Sciences.

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Friday Science Review: July 31, 2009

My first post… a two week round-up.

New direction for treating obesity:  A study headed by Dr. Hans-Michael Dosch’s group at The Hostpital for Sick Children in Toronto demonstrated that killer T cells in visceral fat are activated to destroy fat cells and control insulin resistance.  With increasing weight gain, however, the killer T cells become overwhelmed as fat cells grow and inflammatory T cells move in.  Although these studies were performed in mice, it appears that humans also have a similar system in place.  The good news is that treatment with an anti-CD3 drug can give the immune system a boost and help reduce inflammatory T cells.  Even better news is that this drug is already in clinical use to protect against organ rejection, which means clinical trials to combat obesity may start as early as next year.  The article was published on-line this week in Nature Medicine.

Cool headed Toucan.  After decades of speculation over the purpose of the toucan’s over-sized beak – from sexual ornament to feeding purposes – researchers at Brock University in Ontario, in collaboration with scientists in Brazil, published an article in Science showing that the toucan’s beak acts as a highly efficient cooling unit.  They have the greatest beak-to-body size ratio and use this large surface area as a heat exchanger (akin to elephants’ ears) to regulate body temperature by modifying blood flow.  If only we had a ‘heat wave’ problem this summer…

Setback in Huntington’s Disease research.  A decade long study concluding with disappointing results was reported in PNAS this week.  Researchers at Laval University and University of South Florida analyzed the brains of HD patients who had undergone neural transplantations about ten years ago as a potential treatment.  Although there were mild clinical benefits, the grafts were short-lived and also had undergone disease-like degeneration.

Barcoding Nemo. As part of the International Barcode of Life Project to identify all plants and animals based on signature DNA sequences, spear-headed by Paul Herbert at the University of Guelph, the ornamental fish was added to the list.  Accurate identification of ornamental fish is important for establishing regulations, conservation practices and tracking origins.  The DNA barcode reference for these fish is based on the cytochrome c oxidase subunit I (COI) gene where 98% of the fish have distinct barcode clusters.  The article was published in PLoS One last week.

Funny etiology: two curious New York high schoolers initiated the project and recruited the Guelph lab, sparking headlines last summer when they discovered that some sushi restaurants were mislabeling cheaper fish as more expensive types.

Other DNA barcoding projects include other fish, butterflies, and birds.  To find out more, visit the Canadian Centre for DNA Barcoding or the International Barcode of Life Project (iBOL).


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