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Archive - Aug 30, 2017

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Rare Genetic Variant in CX3CR1 Gene for Microglia Receptor May Contribute to Risk of Schizophrenia and Autism

Huntington's disease, cystic fibrosis, and muscular dystrophy are each diseases that can be traced to a single mutation. Diagnosis in asymptomatic patient for these diseases is relatively easy – if you have the mutation, then you are at risk. Complex diseases, on the other hand, do not have a clear mutational footprint. A new multi-institutional study by Japanese researchers shows a potential rare gene mutation that could act as a predictor for two neurodevelopmental disorders, schizophrenia and autism. "Aberrant synapse formation is important in the pathogenesis of schizophrenia and autism," says Osaka University Professor Toshihide Yamashita, one of the authors of the study. "Microglia contribute to the structure and function of synapse connectivities." Microglia are the only cells in the brain that express the receptor CX3CR1. Mutations in this receptor are known to affect synapse connectivity and cause abnormal social behavior in mice. Such mutations have also been associated with neuroinflammatory diseases such as multiple sclerosis, but no study has shown a role in neurodevelopment disorders. Working with this hypothesis, the researchers conducted a statistical analysis of the CX3CR1 gene in over 7,000 schizophrenia and autism patients and healthy subjects, finding one mutant candidate, a single amino acid switch from alanine to threonine, as a candidate marker for prediction. "Rare variants alter gene function, but occur at low frequency in a population. They are of high interest for the study of complex diseases that have no clear mutational cause," said Dr. Yamashita, who added the alanine-to-threonine substitution was a rare variant. The structure of CX3CR1 includes a domain known as Helix 8, which is important for initiating a signaling cascade. Computer models showed that one amino acid change is enough to compromise the signaling.

University of Buffalo Pharmacy Professor Awarded $1.5 Million to Silence Exosome-Mediated Chatter Among Cancer Cells

With the support of a new $1.58 million grant from the National Institutes of Health (NIH), University at Buffalo researchers aim to develop a targeted treatment to prevent communication between cancer cells. By developing biomaterials that target exosomes – lipid vesicles secreted by many cells that act as a courier between them – the researchers will deliver anti-cancer drugs to alter the pathogenic messages being delivered. Exosomes, once thought of as the cell’s garbage disposal, have the ability to transport genetic information, allowing them to reprogram cells and alter their function. When secreted by a cancer cell into the circulatory system, exosomes may carry genetic material that enhances the spread of cancer to surrounding tissue and other parts of the body. “Reprograming these exosomes may disarm the dangerous package that they carry, potentially preventing tumor growth and spread to distant sites or organs,” says Juliane Nguyen (photo), PharmD, PhD, Principal Investigator and Assistant Professor in the Department of Pharmaceutical Sciences in the School of Pharmacy and Pharmaceutical Sciences. The announcement was made in a UB press release dated August 28, 2017 and authored by Marcene Robinson. “This will lay the foundation for the development of novel drug carriers for treating diseases in which exosomes are pathological. More specifically, these new carriers have the potential to prevent metastasis in cancer patients.” Currently, there are no therapeutic strategies capable of disrupting the pathogenic communication facilitated by exosomes. The four-year grant is provided through the NIH’s National Institute of Biomedical Imaging and Bioengineering.

Some Women with History of Pre-Eclampsia Have Significantly Lower Risk for Breast Cancer

Researchers have demonstrated that women with a history of pre-eclampsia, a pregnancy complication characterized by high blood pressure, have as much as a 90% decrease in breast cancer risk if they carry a specific common gene variant. Further studies are now underway to determine the mechanism of this protection in an effort to develop new breast cancer prevention strategies for all women. The study was published online on August 18, 2017 in Cancer Causes & Control. The open-access article is titled "Functional IGF1R Variant Predicts Breast Cancer Risk in Women with Preeclampsia in California Teachers Study.” The research, directed by lead author Mark Powell, MD, MPH, and Buck Institute Professor Christopher Benz, MD, was carried out in the large California Teachers Study. Women with pre-eclampsia were found to have a 74% lower risk of the most common type of breast cancer (hormone receptor positive) if they carried two T alleles of a variant of the insulin-like growth factor receptor gene when compared to women carrying no T alleles. This decrease in risk increased to 90% if the pregnancy with preeclampsia occurred before the age of 30. "We are thrilled to work with researchers from our Scientific Advisory Board on this exciting project with the potential for developing a new approach to prevention. This very much fits with our goal of reducing the risk of breast cancer," said Rose Barlow, Executive Director of Zero Breast Cancer, which administered the study with funding from the Avon Foundation for Women. "This research could contribute to understanding the key impact of pregnancy on breast cancer risk, and may help explain why some women are protected while others are not," said Dr. Powell, who is a visiting scientist at the Buck Institute and is Director of the Breast Cancer Prevention Project. Dr.