Gene Therapy AN NM Biology 1233

By: Angelica Nino

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Gene Therapy AN NM Biology 1233 - Video

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What are bone marrow and hematopoietic stem cells?

Bone marrow is the soft, sponge-like material found inside bones. It contains immature cells known as hematopoietic or blood-forming stem cells. (Hematopoietic stem cells are different from embryonic stem cells. Embryonic stem cells can develop into every type of cell in the body.) Hematopoietic stem cells divide to form more blood-forming stem cells, or they mature into one of three types of blood cells: white blood cells, which fight infection; red blood cells, which carry oxygen; and platelets, which help the blood to clot. Most hematopoietic stem cells are found in the bone marrow, but some cells, called peripheral blood stem cells (PBSCs), are found in the bloodstream. Blood in the umbilical cord also contains hematopoietic stem cells. Cells from any of these sources can be used in transplants.

What are bone marrow transplantation and peripheral blood stem cell transplantation?

Bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) are procedures that restore stem cells that have been destroyed by high doses of chemotherapy and/or radiation therapy. There are three types of transplants:

Why are BMT and PBSCT used in cancer treatment?

One reason BMT and PBSCT are used in cancer treatment is to make it possible for patients to receive very high doses of chemotherapy and/or radiation therapy. To understand more about why BMT and PBSCT are used, it is helpful to understand how chemotherapy and radiation therapy work.

Chemotherapy and radiation therapy generally affect cells that divide rapidly. They are used to treat cancer because cancer cells divide more often than most healthy cells. However, because bone marrow cells also divide frequently, high-dose treatments can severely damage or destroy the patients bone marrow. Without healthy bone marrow, the patient is no longer able to make the blood cells needed to carry oxygen, fight infection, and prevent bleeding. BMT and PBSCT replace stem cells destroyed by treatment. The healthy, transplanted stem cells can restore the bone marrows ability to produce the blood cells the patient needs.

In some types of leukemia, the graft-versus-tumor (GVT) effect that occurs after allogeneic BMT and PBSCT is crucial to the effectiveness of the treatment. GVT occurs when white blood cells from the donor (the graft) identify the cancer cells that remain in the patients body after the chemotherapy and/or radiation therapy (the tumor) as foreign and attack them. (A potential complication of allogeneic transplants called graft-versus-host disease is discussed in Questions 5 and 14.)

What types of cancer are treated with BMT and PBSCT?

BMT and PBSCT are most commonly used in the treatment of leukemia and lymphoma. They are most effective when the leukemia or lymphoma is in remission (the signs and symptoms of cancer have disappeared). BMT and PBSCT are also used to treat other cancers such as neuroblastoma (cancer that arises in immature nerve cells and affects mostly infants and children) and multiple myeloma. Researchers are evaluating BMT and PBSCT in clinical trials (research studies) for the treatment of various types of cancer.

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Bone Marrow Transplantation and Peripheral Blood Stem Cell ...

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Two men in landmark heart stem cell study tell their stories.

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Jim Dearing of Louisville, Ky., one of the first men in the world to receive heart stem cells, might have helped start a medical revolution that could lead to a cure for heart failure.

Three years after getting the experimental stem cell procedure, following two heart attacks and heart failure, Dearings heart is working normally.

2012 WebMD, LLC. All rights reserved.

The difference is clear and dramatic -- and it's lasting, according to findings now being made public for the first time.

Dearing first showed "completely normal heart function" on an echocardiogram done in 2011, says Roberto Bolli, MD, who is leading the stem cell trial at the University of Louisville. Those results have not been published before.

That was still true in July 2012, when Dearing again showed normal heart function on another echocardiogram.

Based on those tests, Bolli says, "Anyone who looks at his heart now would not imagine that this patient was in heart failure, that he had a heart attack, that he was in the hospital, that he had surgery, and everything else."

It's not just Dearing who has benefited. His friend, Mike Jones, who had even more severe heart damage, also got the stem cell procedure in 2009. Since then, scarred regions of his heart have shrunk. His heart now appears leaner and stronger than it was before.

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Stem Cell Research: Heart Stem Cells May Help Heal Hearts ...

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Dec 16, 2014 Dermal fibroblasts are directly reprogrammed to pigmented melanocytes by three transcription factors (SOX10, MITF and PAX3). Credit: Ruifeng Yang, Perelman School of Medicine, University of Pennsylvania

As the main component of connective tissue in the body, fibroblasts are the most common type of cell. Taking advantage of that ready availability, scientists from the Perelman School of Medicine at the University of Pennsylvania, the Wistar Institute, Boston University School of Medicine, and New Jersey Institute of Technology have discovered a way to repurpose fibroblasts into functional melanocytes, the body's pigment-producing cells. The technique has immediate and important implications for developing new cell-based treatments for skin diseases such as vitiligo, as well as new screening strategies for melanoma. The work was published this week in Nature Communications.

The new technique cuts out a cellular middleman. Study senior author Xiaowei "George" Xu, MD, PhD, an associate professor of Pathology and Laboratory Medicine, explains, "Through direct reprogramming, we do not have to go through the pluripotent stem cell stage, but directly convert fibroblasts to melanocytes. So these cells do not have tumorigenicity."

Changing a cell from one type to another is hardly unusual. Nature does it all the time, most notably as cells divide and differentiate themselves into various types as an organism grows from an embryo into a fully-functional being. With stem cell therapies, medicine is learning how to tap into such cell specialization for new clinical treatments. But controlling and directing the process is challenging. It is difficult to identify the specific transcription factors needed to create a desired cell type. Also, the necessary process of first changing a cell into an induced pluripotent stem cell (iPSC) capable of differentiation, and then into the desired type, can inadvertently create tumors.

Xu and his colleagues began by conducting an extensive literature search to identify 10 specific cell transcription factors important for melanocyte development. They then performed a transcription factor screening assay and found three transcription factors out of those 10 that are required for melanocytes: SOX10, MITF, and PAX3, a combination dubbed SMP3.

"We did a huge amount of work," says Xu. "We eliminated all the combinations of the other transcription factors and found that these three are essential."

The researchers first tested the SMP3 combination in mouse embryonic fibroblasts, which then quickly displayed melanocytic markers. Their next step used a human-derived SMP3 combination in human fetal dermal cells, and again melanocytes (human-induced melanocytes, or hiMels) rapidly appeared. Further testing confirmed that these hiMels indeed functioned as normal melanocytes, not only in cell culture but also in whole animals, using a hair-patch assay, in which the hiMels generated melanin pigment. The hiMels proved to be functionally identical in every respect to normal melanocytes.

Xu and his colleagues anticipate using their new technique in the treatment of a wide variety of skin diseases, particularly those such as vitiligo for which cell-based therapies are the best and most efficient approach.

The method could also provide a new way to study melanoma. By generating melanocytes from the fibroblasts of melanoma patients, Xu explains, "we can screen not only to find why these patients easily develop melanoma, but possibly use their cells to screen for small compounds that can prevent melanoma from happening."

Perhaps most significantly, say the researchers, is the far greater number of fibroblasts available in the body for reprogramming compared to tissue-specific adult stem cells, which makes this new technique well-suited for other cell-based treatments.

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New technology directly reprograms skin fibroblasts for a new role

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17:52 16 December 2014

Oliver Pritchard

Vince Cable said the facility will put the UK at the cutting-edge of cell therapy research.

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Stevenage will be leading the UKs fight to find cures for diseases like cancer when a 55 million state-of-the-art cell therapy centre is built.

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Business developer Cell Therapy Catapult revealed plans to build the plant at the Stevenage Bioscience Catalyst campus today after saying the town ticked all the firms criteria.

The investment should create up to 150 jobs at the Gunnels Wood Road site and will generate 1.2 billion of revenue by 2020 80 per cent via export.

Business secretary Vince Cable said: This therapy is at the very cutting edge of medical research, and is using our own cells in the fight against life-threatening diseases including cancer.

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Stevenage to be at cutting-edge of fight for medical cures after 55 million cell therapy centre plans announced

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Q2115 Yun,J., Sonabend,A.M., Ulasov,I.V., Kim,D.H., Rozhkova,E.A., Novosad,V., Dashnaw,S., Brown,T., Canoll,P., Bruce,J.N., Lesniak,M.S. A novel adenoviral vector labeled with superparamagnetic iron oxide nanoparticles for real-time tracking of viral delivery.JOURNAL OF CLINICAL NEUROSCIENCE 2012; 19(-6-):875-880. >>> Rhodamine-dextran; protein, Ad5-green flourescent; Rat; 2ML1; 96 hours; Animal info (male, Harlan Sprague Dawley, adult); MRI; gene therapy.

Q1884 Jang,E., Albadawi,H., Watkins,M.T., Edelman,E.R., Baker,A.B. Syndecan-4 proteoliposomes enhance fibroblast growth factor-2 (FGF-2)-induced proliferation, migration, and neovascularization of ischemic muscle.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2012; 109(-5-):1679-1684. >>> Fibroblast growth factor-2; syndecan-4, proteoliposome; SC; Rat; 1004; 7-16 days; Controls received mp w/ PBS; animal info (Sprague Dawley); wound clips used; ischemia.

Q1062 Fang,M.R., Wang,J., Huang,J.Y., Ling,S.C., Rudd,J.A., Hu,Z.Y., Yew,D.T., Han,S. The Neuroprotective Effects of Reg-2 Following Spinal Cord Transection Injury.Anatomical Record-Advances in Integrative Anatomy and Evolutionary Biology 2011; 294(-1-):24-45. >>> Regeneration gene protein 2; ciliary neurotrophic factor; Saline; CSF/CNS (intrathecal, subarachnoid space); Rat; 2001D; 2001; 7 days; 24 hours; Controls received mp w/ vehicle; animal info (adult, female, 200-250 g, Sprague Dawley); functionality of mp verified by residual volume; spinal cord injury.

Q0609 Chen,Q.M., Butler,D., Querbes,W., Pandey,R.K., Ge,P., Maier,M.A., Zhang,L.G., Rajeev,K.G., Nechev,L., Kotelianski,V., Manoharan,M., Sah,D.W.Y. Lipophilic siRNAs mediate efficient gene silencing in oligodendrocytes with direct CNS delivery.JOURNAL OF CONTROLLED RELEASE 2010; 144(-2-):227-232. >>> RNA, small interfering; cholesterol-conjugate siRNA; PBS; CSF/CNS (corpus callosum); Rat; 2ML1; 7 days; Controls received mp w/ vehicle; gene therapy; animal info (Male Sprague-Dawley); tissue perfusion (parenchyma); Agents are CNPase siRNA, Cholesterol-CNPas siRNA, Cholesterol-Luciferase siRNA.

P9637 Mookerjee,I., Hewitson,T.D., Halls,M.L., Summers,R.J., Mathai,M.L., Bathgate,R.A.D., Tregear,G.W., Samuel,C.S. Relaxin inhibits renal myofibroblast differentiation via RXFP1, the nitric oxide pathway, and Smad2.FASEB Journal 2009; 23(-4-):1219-1229. >>> Relaxin, recomb. human gene-2; Mice; 1007D; 7 days; Animal info (male, Rlx wt, KO).

P9511 Uchibori,R., Okada,T., Ito,T., Urabe,M., Mizukami,H., Kume,A., Ozawa,K. Retroviral vector-producing mesenchymal stem cells for targeted suicide cancer gene therapy.JOURNAL OF GENE MEDICINE 2009; 11(-5-):373-381. >>> Ganciclovir; IP; Mice (nude); 28 days; Controls received mp w/ PBS; animal info (6 wks old, male, Balb/c, nu/nu); gene therapy.

P9121 Qiang,Y.W., Shaughnessy,JD Jr, Yaccoby,S. Wnt3a signaling within bone inhibits multiple myeloma bone disease and tumor growth.Blood 2008; 112(-2-):374-382. >>> Gene, Wnt3a, recomb.; Bone; Mice (SCID); 1004; 4 weeks; Controls received mp w/ PBS; animal info (Myelomatous SCID-hu); tissue perfusion (myelomatous bone); Wnt3a is a human gene; ALZET pump was "directly connected to the open side of the implanted bone, allowing continual exposure of the myelomatous bone to rWnt3a".

P8865 Kobayashi,M., Okada,T., Murakami,T., Ozawa,K., Kobayashi,E., Morita,T. Tissue-targeted in vivo gene transfer coupled with histone deacetylase inhibitor depsipeptide (FK228) enhances adenoviral infection in rat renal cancer allograft model systems.UROLOGY 2007; 70(-6-):1230-1236. >>> Ganciclovir; IP; Rat; 7 days; Gene therapy; animal info (male, ACI, 6-8 wks old).

P8852 Wang,H.Y., Ghosh,A., Baigude,H., Yang,C.S., Qiu,L.H., Xia,X.G., Zhou,H.X., Rana,T.M., Xu,Z.S. Therapeutic gene silencing delivered by a chemically modified small interfering RNA against mutant SOD1 slows amyotrophic lateral sclerosis progression.Journal of Biological Chemistry 2008; 283(-23-):15845-15852. >>> RNA, small interfering, modified; RNA, small interfering; PBS; CSF/CNS (intrathecal, subarachnoid space); Mice (transgenic); 1007D; 2004; 7, 28 days; 72 hours; Controls received mp w/ vehicle; functionality of mp verified by residual volume; dose-response (Fig. 3); no stress (see pg. 15846, 15849); stability verified by 28 days in vivo (see Fig. 2); half-life (p. 15846) "short"; gene therapy; brain tissue distribution; animal info (SOD1G93A Tg); neurodegenerative (ALS); mp + catheter positioning confirmed; Target (SOD1); "when infused at disease onset at the therapeutic dose for 4 weeks, this siRNA slows disease progression without detectable adverse effects." The catheter was implanted between the L5 and L6 vertebra and connected to a primed Alzet osmotic pump with the PE50 tube. The catheter was stitched to the surface muscle, and the Alzet osmotic pumps were placed under the skin on the back of the mouse..

P8528 Neal,Z.C., Sondel,P.M., Bates,M.K., Gillies,S.D., Herweijer,H. Flt3-L gene therapy enhances immunocytokine-mediated antitumor effects and induces long-term memory.CANCER IMMUNOLOGY IMMUNOTHERAPY 2007; 56(-11-):1765-1774. >>> Interleukin-2, recomb. human; SC; Mice; 2001; 4 days; Controls received mp w/ no treatment; cancer (neuroblastoma); peptides; animal info (female, A/J, ICR, 6-8 weeks old); gene therapy.

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References on the Use of ALZET Osmotic Pumps in Gene Therapy

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PUBLIC RELEASE DATE:

16-Dec-2014

Contact: Simon Shears simon.shears@cancer.org.uk Cancer Research UK @CR_UK

Cancer Research UK scientists have shown that loss of a gene called PTEN triggers some cases of an aggressive form of ovarian cancer, called high-grade serous ovarian cancer, according to a study published in Genome Biology today (Wednesday)*.

In a revolutionary approach the researchers from the Cancer Research UK Cambridge Institute made the discovery by combining images from cancer samples with genetic data. They proved conclusively that loss of PTEN was commonly found only in the cancerous cells and not the 'normal' cells that help make up the tumour mass.

PTEN acts as a brake in healthy cells, preventing a chain of events from occurring that triggers cells to rapidly divide and make new copies. Loss of this gene removes this brake - a genetic mistake that is already known to trigger the development of many cancer types.

The discovery could pave the way for new treatments that are able to block cell signals switched on in tumours with low levels of PTEN.

Study author, Dr Filipe Correia Martins**, at the Cancer Research UK Cambridge Institute, said: "Very little is known about the genetic faults behind this form of aggressive ovarian cancer. But our important study conclusively proves that PTEN is a key player in this disease. The next step is to develop our approach to be able to rapidly identify tumours with low levels of PTEN, so that doctors can pick the best treatments."

The study looked at images and genetic data from The Cancer Genome Atlas - a collection of samples from hundreds of different cancer types cataloguing all the genetic changes. The team analysed levels of PTEN in around 500 ovarian tumour samples. The images helped researchers to home in on PTEN levels in the cancer cells while ignoring the other cells in the samples.

Around 7,000 women are diagnosed with ovarian cancer each year in the UK and 35 per cent will survive for at least 10 years.

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Combining images and genetic data proves gene loss behind aggressive ovarian cancers

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PUBLIC RELEASE DATE:

16-Dec-2014

Contact: Sue McGreevey smcgreevey@partners.org 617-724-2764 Massachusetts General Hospital @MassGeneralNews

Massachusetts General Hospital (MGH) investigators have developed a method of detecting, across the entire genome of human cells, unwanted DNA breaks induced by use of the popular gene-editing tools called CRISPR-Cas RNA-guided nucleases (RGNs). Members of the same team that first described these off-target effects in human cells describe their new platform, called Genome-wide Unbiased Indentification of DSBs Evaluated by Sequencing (GUIDE-seq), in a report being published online in Nature Biotechnology.

"GUIDE-seq is the first genome-wide method of sensitively detecting off-target DNA breaks induced by CRISPR-Cas nucleases that does not start with the assumption that these off-target sites resemble the targeted sites," says J. Keith Joung, MD, PhD, associate chief for Research in the MGH Department of Pathology and senior author of the report. "This capability, which did not exist before, is critically important for the evaluation of any clinical use of CRISPR-Cas RGNs."

Used to cut through a double strand of DNA in order to introduce genetic changes, CRISPR-Cas RGNs combine a bacterial gene-cutting enzyme called Cas9 with a short RNA segment that matches and binds to the target DNA sequence. In a 2013 Nature Biotechnology paper, Joung and his colleagues reported finding that CRISPR-Cas RGNs could also induce double-strand breaks (DSBs) at sites with significant differences from the target site, including mismatches of as many as five nucleotides. Since such off-target mutations could potentially lead to adverse effects, including cancer, the ability to identify and eventually minimize unwanted DSBs would be essential to the safe clinical use of these RGNs, the authors note.

The method they developed involves use of short, double-stranded oligonucleotides that are taken up by DSBs in a cell's DNA, acting as markers of off-target breaks caused by the use of CRISPR-Cas. Those tags allow the identification and subsequent sequencing of those genomic regions, pinpointing the location of off-target mutations. Experiments with GUIDE-seq showed it was sensitive enough to detect off-target sites at which CRISPR RGNs induced unwanted mutations of a gene that occur with a frequency of as little as 0.1 percent in a population of cells. These experiments also revealed that, since many such mutations took place at sites quite dissimilar from the targeted site, no easy rules would predict the number or location of off-target DSBs.

Two existing tools designed to predict off-target mutations by analysis of the target sequence were much less effective than GUIDE-seq in predicting confirmed off-target sites and also misidentified sites that did not prove to have been cut by the enzyme. Comparing GUIDE-seq with a tool called ChIP-seq - which identifies sites where proteins bind to a DNA strand - confirmed that ChIP-seq does not provide a robust method for identifying CRISPR-Cas-induced DSBs.

GUIDE-seq was also able to identify breakpoint hotspots in control cell lines that were not induced to express the CRISPR RGNs. "Various papers have described fragile genomic sites in human cells before," Joung notes, "but this method may be the first to identify these sites without the addition of drugs that enhance the occurrence of such breaks. We also were surprised to find those breaks occurred largely at different sites in the two cell lines used in this study. The ability to capture these RGN-independent breaks suggests that GUIDE-seq could be a useful tool for studying and monitoring DNA repair in living cells."

In addition, GUIDE-seq was able to verify that an MGH-developed approach for improving the accuracy of CRISPR-Cas by shortening the guiding RNA segment reduced the number of DSBs throughout the genome. Joung also expects that GUIDE-seq will be useful in identifying off-target breaks induced by other gene-editing tools. Along with pursuing that possibility, he notes the importance of investigating the incidence and detection of off-target mutations in human cells not altered to create cell lines - a process that transforms them into immortalized cancer cells. Understanding the range and number of off-target mutations in untransformed cells will give a better picture of how CRISPR-Cas RGNs and other tools would function in clinical applications.

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New method identifies genome-wide off-target cleavage sites of CRISPR-Cas nucleases

Recommendation and review posted by Bethany Smith

PUBLIC RELEASE DATE:

16-Dec-2014

Contact: Kathryn Ryan kryan@liebertpub.com 914-740-2100 Mary Ann Liebert, Inc./Genetic Engineering News @LiebertOnline

New Rochelle, NY, December 16, 2014-Consuming caffeinated or sugary drinks can affect the body's metabolism, causing changes in heart and respiratory rate and weight gain. The results of a new study exploring whether individuals respond differently to caffeinated drinks that do or do not contain sugar and to sugar alone are published in Journal of Caffeine Research: The International Multidisciplinary Journal of Caffeine Science, a peer-reviewed publication from Mary Ann Liebert, Inc., publishers. The article is available free on the Journal of Caffeine Research website at http://online.liebertpub.com/doi/full/10.1089/jcr.2014.0023 until January 16, 2015.

The article entitled "Caffeine With and Without Sugar: Individual Differences in Physiological Responses During Rest", by Elaine Rush, PhD and coauthors, Auckland University of Technology (Auckland, New Zealand), describes a study in which heart rate and carbon dioxide production (as a measure of respiration) were measured 30 minutes before and after individuals consumed a defined quantity of sugar, caffeine, or sugar and caffeine. Responses to the different treatments varied widely among individuals.

"Given the caveat that sugar itself affects brain reward just as caffeine does, and this effect will in itself cause variations, this is still an essential paper for the scientist and the lay person to read," says Patricia A. Broderick, PhD, Editor-in-Chief of Journal of Caffeine Research, Medical Professor in Physiology, Pharmacology & Neuroscience, The Sophie Davis School of Biomedical Education, The City College of New York, The City University of New York, and Adjunct Professor in Neurology, New York University Langone Medical Center and Comprehensive Epilepsy Center.

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About the Journal

Journal of Caffeine Research: The International Multidisciplinary Journal of Caffeine Science is a quarterly journal published in print and online. The Journal covers the effects of caffeine on a wide range of diseases and conditions, including mood disorders, neurological disorders, cognitive performance, cardiovascular disease, and sports performance. Journal of Caffeine Research explores all aspects of caffeine science including the biochemistry of caffeine; its actions on the human body; benefits, dangers, and contraindications; and caffeine addiction and withdrawal, across all stages of the human life span from prenatal exposure to end-of-life. Tables of content and a sample issue may be viewed on the Journal of Caffeine Research website at http://www.liebertpub.com/jcr.

About the Publisher

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Do caffeine's effects differ with or without sugar?

Recommendation and review posted by Bethany Smith

PUBLIC RELEASE DATE:

16-Dec-2014

Contact: Kathryn Ryan kryan@liebertpub.com 914-740-2100 Mary Ann Liebert, Inc./Genetic Engineering News @LiebertOnline

New Rochelle, NY, December 16, 2014--Veterans of the U.S. armed forces who have received a diagnosis consistent with transgender status are more likely to have serious suicidal thoughts and plans and to attempt suicide. A new study shows that this group has a higher risk of suicide death than the general population of veterans, as described in an article in LGBT Health, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the LGBT Health website until January 16, 2015.

Based on data gathered from the VA National Patient Care Database from 2000-2009, John Blosnich, PhD, MPH and coauthors from VA Pittsburgh Healthcare System and University of Pittsburgh (PA), University of Rochester (NY), VA Central Office (Washington, DC), East Tennessee State University (Johnson City, TN), and VISN2 Center of Excellence for Suicide Prevention (Canandaigua, NY), determined that while the suicide death rate among veterans with transgender-related diagnoses was higher than for veterans in general, it was similar to the suicide death rate for veterans with serious mental illness such as depression or schizophrenia.

The authors report their findings in the article "Mortality among Veterans with Transgender-Related Diagnoses in the Veterans Health Administration, FY2000-2009."

"Although this study suggests comparably elevated rates of suicide among veterans with transgender-related ICD-9-CM diagnoses and veterans with any psychiatric diagnosis, suicides among transgender veterans occurred at a younger age, resulting in greater potential years of life lost," says LGBT Health Editor-in-Chief William Byne, MD, PhD, James J. Peters VA Medical Center, Bronx, NY and Icahn School of Medicine at Mount Sinai, New York, NY. "VA has a multifaceted strategy to reduce suicide among veterans. Its commitment in 2011, and reaffirmed in 2013, to provide respectful transgender-specific healthcare as well staff training in transgender cultural awareness and sensitivity may also address the high suicide rate among transgender veterans."

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About the Journal

Spanning a broad array of disciplines, LGBT Health, published quarterly online with Open Access options and in print, brings together the LGBT research, health care, and advocacy communities to address current challenges and improve the health, well-being, and clinical outcomes of LGBT persons. The Journal publishes original research, review articles, clinical reports, case studies, legal and policy perspectives, and much more. Complete tables of content and a sample issue may be viewed on the LGBT Health website.

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Are transgender veterans at greater risk of suicide?

Recommendation and review posted by Bethany Smith

Gang Bao will bring a host of new expertise to Rice Universitys part in the fight against cancer and many other diseases when he joins the faculty March 1.

The highly regarded Robert A. Milton Chair in Biomedical Engineering at Georgia Institute of Technology and Emory University is the latest recruit to move to Houston with $6 million in funding from the Cancer Prevention and Research Institute of Texas (CPRIT).

Bao and his colleagues, nine of whom will join him at Rice, cover a wide range of research linked primarily by their interest in the genetic roots of disease and the promise of nanotechnology and biomolecular approaches to treat them.

Among their ongoing projects, lab members are working on targeted genome modification using engineered nucleases, the development of magnetic nanoparticles for use as contrast agents and for ablation of tumors and the application of fluorescent molecular beacons for specific RNA detection in living cells.

Dr. Bao has an outstanding track record of center leadership in developing and applying nanomedicine for disease diagnosis and treatment, and is a fantastic addition to the Rice effort in translational nanomedicine, said Michael Deem, chair of the Department of Bioengineering and the John W. Cox Professor of Biochemical and Genetic Engineering.

His work in the mid-2000s involved groundbreaking contributions to the molecular imaging field, and he has turned to nanomedicine and nanomaterials-based interventions, for example, with special contributions to the isolation of specific cell types from differentiating human pluripotent stem cells. Most recently, Dr. Bao has made major contributions to the use of the CRISPR/Cas9 system for genome editing, Deem said.

The opportunity to work at Rices BioScience Research Collaborative, with its close connections and proximity to the Texas Medical Center, made the offer too good to resist, said Bao, who will be the Foyt Family Professor in the Department of Bioengineering and the CPRIT Senior Scholar in Cancer Research at Rice.

One thing I really like is that this building is right in the Texas Medical Center, very close to (the University of Texas) MD Anderson (Cancer Center), Texas Childrens (Hospital) and Baylor (College of Medicine), he said. For cancer research, this will make it much easier for me to work with colleagues at MD Anderson, a few blocks away, or at Baylor.

Another attraction, really, is that the undergraduate programs at Rice are super strong. I always want to attract undergraduates to my lab to do research, he said.

Along with his lab, Bao brings his Nanomedicine Center for Nucleoprotein Machines to Rice. The National Institutes of Health-funded center is developing gene correction techniques to address an estimated 6,000 single-gene disorders. Their first target is sickle cell disease, caused by a single mutation in the beta-globin gene. The mutation causes the body to make sticky, crescent-shaped red blood cells that contain abnormal hemoglobin and can block blood flow in limbs and organs.

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Gang Bao combines genetic, nano and imaging techniques to fight disease

Recommendation and review posted by Bethany Smith

In an interesting move, Pfizer ( PFE ) has struck a deal with Spark Therapeutics to establish a gene therapy platform. King's College Professor Michael Linden, who is an expert in gene therapy research, will lead the effort. Under the agreement, Pfizer will make an upfront payment of $20 million to Spark Therapeutics and $260 million in additional milestone-based payments. In return, Pfizer will handle late stage clinical trials, approval and commercialization of the product. Spark is currently investigating the efficacy of gene therapy forhemophilia B, and its program will enter early phase trials next year. Gene therapy has been under scientific research for over 2 decades, but viable therapies have yet to gain commercial acceptance due to safety and delivery-related issues. However, Pfizer's move and some other recent developments in the industry suggest that the therapy may be coming off age. There is another implication of this move. Even if successful, Pfizer is still a long way away from a commercialized gene-derived therapy. It is thus just a single step in its program to reverse its revenue decline in coming years. Other actions are possible, or even likely, including an outright acquisition of a substantially larger company, considering that most deals announced thus far are focused on early stage compounds.

Our price estimate for Pfizer stands at $35 , implying a premium of about 20% to the market price.

See Full Analysis For Pfizer

Establishing a gene therapy platform is a welcome move, and points towards Pfizer's willingness to innovate and take risks. Gene therapy involves treating a disease through modification of defective or absent gene. Such modification can include replacing, altering or supplementing existing genetic material. The approach offers the potential to treat rare hereditary diseases and open new doors in curing cancer. Although it is too early to estimate the revenue potential of this industry, a successful launch can pave way for big pharmaceutical firms to revive their declining businesses provided they jump on the bandwagon at the right time. Although Spark's gene therapy platform initially will focus on treatment of hemophilia B, there exists the potential for developing similar therapies for the treatment of cancer. This is where Pfizer is showing special interest. Its oncology drug sales jumped 16% globally in Q3 2014, sustaining the growth rate observed in the second quarter and representing a growth acceleration compared to the first quarter. For the first nine months, the segment's revenue growth stood at roughly 13%. The figure is the highest among the company's primary business segments, with vaccine sales racing past that of oncology drugs only in the third quarter. We expect the company to continue to push for deals and possibly, acquisitions, that can strengthen its oncology pipeline.

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Pfizer Moving Into Gene Therapy Is A Welcome Move

Recommendation and review posted by Bethany Smith

PHILADELPHIA As the main component of connective tissue in the body, fibroblasts are the most common type of cell. Taking advantage of that ready availability, scientists from the Perelman School of Medicine at the University of Pennsylvania, the Wistar Institute, Boston University School of Medicine, and New Jersey Institute of Technology have discovered a way to repurpose fibroblasts into functional melanocytes, the body's pigment-producing cells. The technique has immediate and important implications for developing new cell-based treatments for skin diseases such as vitiligo, as well as new screening strategies for melanoma. The work was published this week in Nature Communications.

The new technique cuts out a cellular middleman. Study senior author Xiaowei George Xu, MD, PhD, an associate professor of Pathology and Laboratory Medicine, explains, "Through direct reprogramming, we do not have to go through the pluripotent stem cell stage, but directly convert fibroblasts to melanocytes. So these cells do not have tumorigenicity."

Changing a cell from one type to another is hardly unusual. Nature does it all the time, most notably as cells divide and differentiate themselves into various types as an organism grows from an embryo into a fully-functional being. With stem cell therapies, medicine is learning how to tap into such cell specialization for new clinical treatments. But controlling and directing the process is challenging. It is difficult to identify the specific transcription factors needed to create a desired cell type. Also, the necessary process of first changing a cell into an induced pluripotent stem cell (iPSC) capable of differentiation, and then into the desired type, can inadvertently create tumors.

Xu and his colleagues began by conducting an extensive literature search to identify 10 specific cell transcription factors important for melanocyte development. They then performed a transcription factor screening assay and found three transcription factors out of those 10 that are required for melanocytes: SOX10, MITF, and PAX3, a combination dubbed SMP3.

"We did a huge amount of work," says Xu. "We eliminated all the combinations of the other transcription factors and found that these three are essential."

The researchers first tested the SMP3 combination in mouse embryonic fibroblasts, which then quickly displayed melanocytic markers. Their next step used a human-derived SMP3 combination in human fetal dermal cells, and again melanocytes (human-induced melanocytes, or hiMels) rapidly appeared. Further testing confirmed that these hiMels indeed functioned as normal melanocytes, not only in cell culture but also in whole animals, using a hair-patch assay, in which the hiMels generated melanin pigment. The hiMels proved to be functionally identical in every respect to normal melanocytes.

Xu and his colleagues anticipate using their new technique in the treatment of a wide variety of skin diseases, particularly those such as vitiligo for which cell-based therapies are the best and most efficient approach.

The method could also provide a new way to study melanoma. By generating melanocytes from the fibroblasts of melanoma patients, Xu explains, "we can screen not only to find why these patients easily develop melanoma, but possibly use their cells to screen for small compounds that can prevent melanoma from happening."

Perhaps most significantly, say the researchers, is the far greater number of fibroblasts available in the body for reprogramming compared to tissue-specific adult stem cells, which makes this new technique well-suited for other cell-based treatments.

The research was supported by the National Institutes of Health (R01-AR054593, P30-AR057217)

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Cutting Out the Cellular Middleman: New Technology Directly Reprograms Skin Fibroblasts For a New Role

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Consider the relationship between an air traffic controller and a pilot. The pilot gets the passengers to their destination, but the air traffic controller decides when the plane can take off and when it must wait. The same relationship plays out at the cellular level in animals, including humans. A region of an animal's genome -- the controller -- directs when a particular gene -- the pilot -- can perform its prescribed function.

A new study by cell and systems biologists at the University of Toronto (U of T) investigating stem cells in mice shows, for the first time, an instance of such a relationship between the Sox2 gene which is critical for early development, and a region elsewhere on the genome that effectively regulates its activity. The discovery could mean a significant advance in the emerging field of human regenerative medicine, as the Sox2 gene is essential for maintaining embryonic stem cells that can develop into any cell type of a mature animal.

"We studied how the Sox2 gene is turned on in mice, and found the region of the genome that is needed to turn the gene on in embryonic stem cells," said Professor Jennifer Mitchell of U of T's Department of Cell and Systems Biology, lead invesigator of a study published in the December 15 issue of Genes & Development.

"Like the gene itself, this region of the genome enables these stem cells to maintain their ability to become any type of cell, a property known as pluripotency. We named the region of the genome that we discovered the Sox2 control region, or SCR," said Mitchell.

Since the sequencing of the human genome was completed in 2003, researchers have been trying to figure out which parts of the genome made some people more likely to develop certain diseases. They have found that the answers are more often in the regions of the human genome that turn genes on and off.

"If we want to understand how genes are turned on and off, we need to know where the sequences that perform this function are located in the genome," said Mitchell. "The parts of the human genome linked to complex diseases such as heart disease, cancer and neurological disorders can often be far away from the genes they regulate, so it can be dificult to figure out which gene is being affected and ultimately causing the disease."

It was previously thought that regions much closer to the Sox2 gene were the ones that turned it on in embryonic stem cells. Mitchell and her colleagues eliminated this possibility when they deleted these nearby regions in the genome of mice and found there was no impact on the gene's ability to be turned on in embryonic stem cells.

"We then focused on the region we've since named the SCR as my work had shown that it can contact the Sox2 gene from its location 100,000 base pairs away," said study lead author Harry Zhou, a former graduate student in Mitchell's lab, now a student at U of T's Faculty of Medicine. "To contact the gene, the DNA makes a loop that brings the SCR close to the gene itself only in embryonic stem cells. Once we had a good idea that this region could be acting on the Sox2 gene, we removed the region from the genome and monitored the effect on Sox2."

The researchers discovered that this region is required to both turn Sox2 on, and for the embryonic stem cells to maintain their characteristic appearance and ability to differentiate into all the cell types of the adult organism.

"Just as deletion of the Sox2 gene causes the very early embryo to die, it is likely that an abnormality in the regulatory region would also cause early embryonic death before any of the organs have even formed," said Mitchell. "It is possible that the formation of the loop needed to make contact with the Sox2 gene is an important final step in the process by which researchers practicing regenerative medicine can generate pluripotent cells from adult cells."

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Cell biologists discover on-off switch for key stem cell gene

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Regular physical activity may correct the brain's metabolism to stave off dementia

THINKSTOCK

If you carried a gene that doubled your likelihood of getting Alzheimer's disease, would you want to know? What if there was a simple lifestyle change that virtually abolished that elevated risk? People with a gene known as APOE e4 have a higher risk of cognitive impairment and dementia in old age. Even before behavioral symptoms appear, their brains show reduced metabolism, altered activity and more deterioration than those without the high-risk gene. Yet accumulating research is showing that carrying this gene is not necessarily a sentence for memory loss and confusionif you know how to work it to your advantage with exercise.

Scientists have long known that exercise can help stave off cognitive decline. Over the past decade evidence has mounted suggesting that this benefit is even greater for those at higher genetic risk for Alzheimer's. For example, two studies by a team in Finland and Sweden found that exercising at least twice a week in midlife lowers one's chance of getting dementia more than 20 years later, and this protective effect is stronger in people with the APOE e4 gene. Several others reported that frequent exerciseat least three times a week in some studies; up to more than an hour a day in otherscan slow cognitive decline only in those carrying the high-risk gene. Furthermore, for those who carry the gene, being sedentary is associated with increased brain accumulation of the toxic protein beta-amyloid, a hallmark of Alzheimer's.

More recent studies, including a 2012 paper published in Alzheimer's & Dementia and a 2011 paper in NeuroImage, found that high-risk individuals who exercise have greater brain activity and glucose uptake during a memory task compared with their less active counterparts or with those at low genetic risk.

This link to metabolism may help explain why exercise protects APOE e4 carriers. According to a theory proposed in May by anthropologist David Raichlen and psychologist Gene Alexander, both at the University of Arizona, the answer lies in our evolutionary past. Two million years ago, when our ancestors were much more physically activefor example, perhaps running long distances to hunt preyonly the high-risk gene variant existed, they argue. The gene allowed for better metabolism during intense activity, and its downside, faster cognitive decline, was counteracted by our ancestors' active way of life. As humans adopted more sedentary habits, other variants of the gene appeared, and in modern times we are now seeing the negative effect of the high-risk gene more often than its benefit.

Although these studies suggest that exercise is exceptionally protective for those at highest risk, some findings buck the trend. One large-scale study reported that high levels of leisure-time activity reduced risk of dementia five years later but only in those who did not carry the high-risk APOE e4 gene. These inconsistencies suggest the interaction may be complex, although most of the evidence still indicates that an active lifestyle has great value.

Exercise is important for healthy aging, regardless of genetics, but Raichlen emphasizes that for individuals that are APOE e4 carriers, studies certainly underline the importance of maintaining physical activity across the life span. And with further research, he suggests, a better understanding of the evolutionary origins of genotype-lifestyle interactions will help identify populations that may particularly benefit from behavioral changes.

This article was originally published with the title "Exercise Counteracts Genetic Risk for Alzheimer's."

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Exercise Counteracts Genetic Risk for Alzheimer's

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We would not expect a baby to join a team or participate in social situations that require sophisticated communication. Yet, most developmental biologists have assumed that young cells, only recently born from stem cells and known as "progenitors," are already competent at inter-communication with other cells.

New research from Carnegie's Allan Spradling and postdoctoral fellow Ming-Chia Lee shows that infant cells have to go through a developmental process that involves specific genes before they can take part in the group interactions that underlie normal cellular development and keep our tissues functioning smoothly. The existence of a childhood state where cells cannot communicate fully has potentially important implications for our understanding of how gene activity on chromosomes changes both during normal development and in cancerous cells. The work is published in Genes and Development.

The way that the molecules that package a cell's chromosomes are organized in order to control gene activity is known as the cell's "epigenetic state." The epigenetic state is fundamental to understanding Spradling and Lee's findings. To developmental biologists, changes in this epigenetic state ultimately explain how the cell's properties are altered during tissue maturation.

"In short, acquired epigenetic changes in a developing cell are reminiscent of the learned changes the brain undergoes during childhood," Spradling explained. "Just as it remains difficult to map exactly what happens in a child's brain as it learns, it is still very difficult to accurately measure epigenetic changes during cellular development. Not enough cells can usually be obtained that are at precisely the same stage for scientists to map specific molecules at specific chromosomal locations."

Lee and Spradling took advantage of the unsurpassed genetic tools available in the fruit fly to overcome these obstacles and provide new insight into the epigenetics of cellular development.

Using a variety of tools and techniques, they focused on cells in the fruit fly ovary and were able identify a specific gene called lsd1 that is needed for ovarian follicle progenitor cells to mature at their normal rate. The researchers found that the amount of the protein that is encoded by this gene, Lsd1, which is present in follicle progenitors decreases as the cells approach differentiation. What's more, the onset of differentiation could be shifted by changing the levels of Lsd1 protein that are present. They deduced that differentiation ensues when Lsd1 levels fall below a critical threshold, and that this likely corresponds to when genes can be stably expressed.

"The timing of differentiation is very important for normal development," Lee said. "Differentiation onset determines how many times progenitors divide, and even small perturbations in Lsd1 levels changed the number of follicle cells that were ultimately produced, which reduced ovarian function."

Previously, it was thought that the follicle cell progenitors started to differentiate based on an external signal they received from another kind of ovarian cells known as germ cells. Lee and Spradling found that while this germ cell signal was essential, it was already being regularly sent even before the progenitors responded. Instead, it was the Lsd1-mediated change in their epigenetic state that timed when progenitor cells started to respond to the signal and begun differentiating. Once they become competent, however, differentiating follicle cells communicate extensively with their neighbors, and continued to do so throughout their lives.

As is frequently the case in basic biological research, the molecules and mechanisms studied here are found in most multicellular animals and hence the researchers conclusions are likely to apply broadly throughout the animal kingdom, including in humans.

In addition, to the importance of this research for understanding how animal chromosomes change during normal development, it may also help clarify alterations in the epigenetic state that take place in some cancers. A minority of cells in such cancers begin to express high levels of Lsd1 and to behave like undifferentiated progenitors.

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Baby cells learn to communicate using the lsd1 gene

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PUBLIC RELEASE DATE:

15-Dec-2014

Contact: Kathryn Ryan kryan@liebertpub.com 914-740-2100 Mary Ann Liebert, Inc./Genetic Engineering News @LiebertOnline

New Rochelle, NY, December 15, 2014-Adiponectin, a collagen-like protein secreted by fat cells, derives from the ADIPOQ gene. Variations in this gene may increase risk for type 2 diabetes, cardiovascular disease, and various cancers. A new study that links specific variations in the ADIPOQ gene to either higher or lower colorectal cancer risk is published in Genetic Testing and Molecular Biomarkers, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available on the Genetic Testing and Molecular Biomarkers website until January 11, 2014.

Xin Guo, First Affiliated Hospital of Harbin Medical University, China, and Jiaqi Liu, Liuping You, Gang Li, Yuenan Huang, and Yunlong Li, Second Affiliated Hospital of Harbin Medical University, explored the relationship between two polymorphisms in the adiponectin gene and the risk of colorectal cancer in the article "Association Between Adiponectin Polymorphisms and the Risk of Colorectal Cancer." They also showed that these genetic variations may interact with environmental factors, such as red meat intake, to affect cancer risk.

"This paper suggests that adiponectin gene sequence may have significant prognostic value for colorectal cancer," says Kenneth I. Berns, MD, PhD, Editor-in-Chief of Genetic Testing and Molecular Biomarkers, and Director of the University of Florida's Genetics Institute, College of Medicine, Gainesville, FL.

###

About the Journal

Genetic Testing and Molecular Biomarkers is an authoritative peer-reviewed journal published monthly online with Open Access options and in print that reports on all aspects of genetic testing, including molecular and biochemical based tests and varied clinical situations; ethical, legal, social, and economic aspects of genetic testing; and issues concerning effective genetic counseling. Genetic Testing and Molecular Biomarkers is the official journal of Genetic Alliance. Complete tables of content and a free sample issue may be viewed on the Genetic Testing and Molecular Biomarkers website.

About the Publisher

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New colorectal cancer risk factor identified

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Alnylam Pharmaceuticals, Inc. ( ALNY ) announced its pipeline growth strategy for the development and commercialization of RNAi therapeutics across three strategic therapeutic areas (STArs) - genetic medicines, cardio-metabolic disease and hepatic infectious disease.

Alnylam's genetic medicine STAr consists of a broad pipeline of RNAi therapeutics including patisiran (phase III - APOLLO) and revusiran (phase III - ENDEAVOUR), being developed for the treatment of transthyretin-mediated amyloidosis. Additionally, the company reported positive initial data from a phase I study on ALN-AT3 last week.

The company is advancing ALN-AT3 for the treatment of hemophilia and rare bleeding disorders. Further, the company plans to initiate a phase I/II study on ALN-CC5 for paroxysmal nocturnal hemoglobinuria.

Meanwhile, Alnylam intends to commercialize its genetic medicine products in the U.S. and EU, while Genzyme, a Sanofi ( SNY ) company, will develop and commercialize in the rest of the world.

In its cardio-metabolic disease STAr, Alnylam recently initiated a phase I study on ALN-PCSsc (RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia) with initial data expected in mid-2015. Alnylam has an agreement with The Medicines Company ( MDCO ) for ALN-PCSsc. Alnylam is also advancing other candidates including ALN-AC3 (hypertriglyceridemia), ALN-ANG (hypertriglyceridemia and mixed hyperlipidemia) and ALN-AGT (hypertensive disorders of pregnancy including preeclampsia) among others.

Finally, Alnylam's hepatic infectious disease STAr includes ALN-HBV for the treatment of hepatitis B viral infection. The company intends to file an investigational new drug (IND) application or an IND equivalent in late 2015.

Alnylam is looking for partnerships for programs in its cardio-metabolic disease and hepatic infectious disease STArs. At the same time it intends to retain significant product commercialization rights in the U.S. and EU.

Alnylam expects to provide additional guidance on pipeline programs in its three STArs in Jan 2015. We expect investor focus to remain on Alnylam's pipeline.

Alnylam currently carries a Zacks Rank #2 (Buy). A better-ranked stock in the health care sector is Amgen Inc. ( AMGN ) carrying a Zacks Rank #1 (Strong Buy).

ALNYLAM PHARMA (ALNY): Free Stock Analysis Report

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Alnylam Provides Pipeline Update, Growth Strategy - Analyst Blog

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By Bryan Grossman

Thanks to modern technology, genetic counselors in Colorado Springs now can meet with patients in Durango by two-way live audio/video conferencing. Patients in Durango who seek genetic counseling can schedule appointments with Penrose Cancer Center genetic counselors and meet with them virtually. Penrose is in partnership with Mercy Regional Medical Center.

Appointments physically take place at Mercy Family Medicines Three Springs and Horse Gulch locations in Durango, where a medical assistant sits down with the patient in the clinic room, initiates the video counseling session and introduces the patient. In Colorado Springs, a Penrose Cancer Center genetic counselor logs on simultaneously and meets with the patient as if it were an in-person appointment.

Prior to the start of this program, patients at MRMC didnt have access to local genetic counseling services, saidElena Strait, certified genetic counselor. This telemedicine program allows us to meet a need in a way that makes sense for MRMC patients. They are thrilled to receive this service without leaving home, and Durango medical providers appreciate having us as a resource for their patients.

Genetic counseling services include recording a detailed family history and using family history information to estimate the risk of developing cancer, estimate the risk of an inherited cancer, review the pros and cons of genetic testing and help patients decide if testing is appropriate, coordinate genetic testing, consider ways to screen for and prevent cancer based on risks and explore implications with family members

Genetic counseling is a program that Penrose Cancer Centers parent company, Centura Health, is excited to grow, according to a news release sent by Penrose. The goal is ultimately to involve genetic counselors at other hospitals in the network to reach additional outlying communities throughout Colorado and western Kansas. Centura isalso servicing other rural affiliate hospitals with telemedicine services for pulmonology, outpatient gastrointestinal clinic needs and tumor board consultations.

What is Telemedicine?

Formally defined, it is the use of medical information exchanged from one site to another via electronic communications to improve a patients clinical health status. It includes a growing variety of applications and services using two-way video, email, wireless tools and other forms of telecommunications.

Beginning40years ago with demonstrations of hospitals extending care to patients in remote areas, the use of telemedicine has spread rapidly and is now becoming integrated into the ongoing operations of hospitals, specialty departments, home health agencies, private physician offices as well as consumers homes and workplaces.

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Penrose offers genetic counseling via telemedicine

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ANN ARBOR (PRWEB) December 15, 2014

Gene therapy pioneer and longtime Veterans Affairs researcher Dr. David Fink received the 2014 Paul B. Magnuson Award from VA in a ceremony at the VA Ann Arbor Healthcare System on Dec. 15, 2014.

Dr. Fink is a staff neurologist and an investigator with the Geriatric Research, Education and Clinical Center at the Ann Arbor VA. He is also the Robert Brear Professor and Chair of Neurology at the University of Michigan. He has been with VA since 1982.

A Harvard Medical School graduate, Fink has pioneered methods to introduce genes into the body to treat chronic pain and other nervous-system diseases. His team led the first human clinical trial of gene therapy for pain. The phase 1 trial, published in the Annals of Internal Medicine in 2011, involved 10 cancer patients with severe pain who had failed to respond even to high doses of morphine or other pain drugs. Finks group gave them skin injections of an inactive form of the herpes simplex virus as a means to deliver a gene known as PENK. The gene helps the body produce an opioid-like molecule called proenkephalin.

The gene treatment, based on years of research, is safe in humans and led to pain reduction. A larger phase 2 clinical trial of the approach is now being planned.

Besides cancer pain, Finks work focuses on Veterans and others with nerve-related conditions such as spinal cord injury and diabetic neuropathy. The team is developing non-replicating viral vectors, similar to the one used in the 2011 human trial, to ferry genes into the nervous system that code for the production of the bodys own pain relievers. A related approach, now being funded by VA, is to use the vectors to bring about the continuous release of proteins that protect nerve cells from dying. This could help prevent neuropathy and the sharp chronic pain it entails.

Dr. Finks work holds tremendous potential for treating Veterans with chronic neurological disease, said Robert McDivitt, an Army Veteran and director of the VA Ann Arbor Healthcare System.

Fink was presented the award by Dr. Carolyn Clancy, VAs Interim Undersecretary for Health. Also attending the ceremony was Dr. Patricia Dorn, director of VA Rehabilitation Research and Development, which each year presents the Magnuson Award as the highest honor for VA rehabilitation investigators.

The award is named for Paul B. Magnuson, a bone and joint surgeon who was a key figure in the expansion of the VA research program after World War II. He was known for his dedication to finding new treatments and devices to help Veterans cope with their disabilities, and, as he put it, to restoring each patient to his family, his job, and his life. Established in 1998, the Magnuson Award consists of a plaque, a one-time award of $5,000, and $50,000 per year for up to three years to supplement ongoing peer-reviewed research.

About the VA Ann Arbor Healthcare System Since 1953, VA Ann Arbor Healthcare System which includes the VA Ann Arbor Medical Center, the VA Toledo Community Based Outpatient Clinic [CBOC], the VA Flint CBOC, and the VA Jackson CBOC, as well as the VA Center for Clinical Management Research, an HSR&D Center of Innovation, has provided state-of-the-art healthcare services to the men and women who have proudly served our nation. More than 65,000 Veterans living in a 15-county area of Michigan and Northwest Ohio utilized VAAAHS in fiscal year 2014. The Ann Arbor Medical Center also serves as a referral center for specialty care.

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VAs Magnuson Award to Gene Therapy Pioneer in Ann Arbor

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Scientists at Indiana University and colleagues at Stanford and the University of Texas have demonstrated a technique for "editing" the genome in sperm-producing adult stem cells, a result with powerful potential for basic research and for gene therapy.

The researchers completed a "proof of concept" experiment in which they created a break in the DNA strands of a mutant gene in mouse cells, then repaired the DNA through a process called homologous recombination, replacing flawed segments with correct ones.

The study involved spermatogonial stem cells, which are the foundation for the production of sperm and are the only adult stem cells that contribute genetic information to the next generation. Repairing flaws in the cells could thus prevent mutations from being passed to future generations.

"We showed a way to introduce genetic material into spermatogonial stem cells that was greatly improved from what had been previously demonstrated," said Christina Dann, associate scientist in the Department of Chemistry at IU Bloomington and a co-author of the study. "This technique corrects the mutation, theoretically leaving no other mark on the genome."

The paper, "Genome Editing in Mouse Spermatogonial Stem/Progenitor Cells Using Engineered Nucleases," was published in the online science journal PLOS-ONE.

The lead author, Danielle Fanslow, carried out the research as an IU research associate and is now a doctoral student at Northwestern University. Additional co-authors are from the Stanford School of Medicine and the University of Texas Southwestern Medical Center.

A challenge to the research was the fact that spermatogonial stem cells, like many types of adult stem cells, are notoriously difficult to isolate, culture and work with. It took years of intensive effort by multiple laboratories before conditions were created a decade ago to maintain and propagate the cells.

For the IU research, a primary hurdle was to find a way to make specific, targeted modifications to the mutant mouse gene without the risk of disease caused by random introduction of genetic material. The researchers used specially designed enzymes, called zinc finger nucleases and transcription activator-like effector nucleases, to create a double strand break in the DNA and bring about the repair of the gene.

Stem cells that had been modified in the lab were then transplanted into the testes of sterile mice. The transplanted cells grew or colonized within the mouse testes, indicating the stem cells were viable. However, attempts to breed the mice were not successful.

"Whether the failure to produce sperm was a result of abnormalities in the transplanted cells or the recipient testes was unclear," the researchers write.

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'Genome editing' could correct genetic mutations for future generations

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A tour around the Cell Therapy Catapult facility
Take a tour around the finished laboratory and office space at Cell Therapy Catapult, completed in March 2014. In this exclusive video, we talk to the Cell Therapy Catapult CEO, Keith Thompson,...

By: ISGplc

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A tour around the Cell Therapy Catapult facility - Video

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Living Cell Technologies Limited today announced that the final patient has been successfully implanted in its Phase I/IIa clinical trial of regenerative cell therapy NTCELL for Parkinsons disease. The operation took place at Auckland City Hospital last week.

The Phase I/IIa clinical trial, led by Dr Barry Snow, is an open-label investigation of the safety and clinical effects of NTCELL in patients who no longer respond to current therapy. Dr Snow MBChB, FRACP, FRCPC, leads the Auckland Movement Disorders Clinic at the Auckland District Health Board and is an internationally recognised clinician and researcher in Parkinsons disease.

LCT anticipates presenting the results of the 26-week trial at the 19th International Congress of Parkinsons Disease and Movement Disorders in San Diego in June 2015.

Dr Ken Taylor, chief executive, notes that the success of the implant procedure means that LCTs clinical programme remains on track.

"The treatment phase of the trial has been completed on schedule. We believe NTCELL has the potential to be the first disease-modifying treatment for patients who are failing the current conventional treatment for Parkinsons disease," said Dr Taylor.

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Patient implants in Parkinsons trial completed

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MITTEILUNG UEBERMITTELT VON BUSINESS WIRE. FUER DEN INHALT IST ALLEIN DAS BERICHTENDE UNTERNEHMEN VERANTWORTLICH.

PARIS --(BUSINESS WIRE)-- 13.10.2014 --

Stem cells hold great promise for treating a variety of human diseases and injuries. Basic and translational stem cell research is among the most competitive fields in the life sciences. We have co-organized the first Bridging Biomedical Worlds conference of our new series of international scientific meetings: Turning Obstacles into Opportunities for Stem Cell Therapy.

The goal of this conference is to promote progress in the translation of basic stem cell research into stem cell therapies. To do this, presentations will highlight diverse areas of on-going stem cell biology research. In addition, panelists will discuss obstacles to translation and the associated risks and ethical controversies. These panels will provide a means to accelerate communication and cooperation among researchers, bioengineers, clinicians and industry scientists, and will explore ways to implement international policies, regulations and guidelines to ensure the development of safe and effective stem cell therapies worldwide. Participants will hear about the latest basic and translational stem cell research from more than 20 distinguished speakers from China, Japan, Europe and theUnited States.

This conference held in Beijing, China, October 13-15, 2014 is co-organized by the Fondation IPSEN, AAAS/Science and AAAS/Science Translational Medicine, in association withFred Gage (Salk Institute for Biological Studies) and Qi Zhou (Institute of Zoology, Chinese Academy of Sciences).

About AAAS/Science The American Association for the Advancement of Science (AAAS) is the worlds largest general scientific society and publisher of the journal Science (www.sciencemag.org) as well as Science Translational Medicine (www.sciencetranslationalmedicine.org) and Science Signaling (www.sciencesignaling.org). AAAS was founded in 1848, and includes some 261 affiliated societies and academies of science, serving 10 million individuals.Sciencehas the largest paid circulation of any peer-reviewed general science journal in the world, with an estimated total readership of 1 million. The non-profit AAAS (www.aaas.org) is open to all and fulfills its mission to advance science and serve society not only by publishing the very best scientific research but also through initiatives in science policy, international programs and science education. http://www.sciencemag.org

About AAAS/Science Translational Medicine Science Translational Medicine, launched in October 2009, is the newest journal published by AAAS/Science. The goal of Science Translational Medicineis to promote human health by providing a forum for communicating the latest biomedical research findings from basic, translational, and clinical researchers from all established and emerging disciplines relevant to medicine. Despite 50 years of advances in our fundamental understanding of human biology and the emergence of powerful new technologies, the translation of this knowledge into effective new treatments and health measures has been slow. This paradox illustrates the daunting complexity of the challenges faced by translational researchers as they apply the basic discoveries and experimental approaches of modern science to the alleviation of human suffering. A major goal ofScience Translational Medicineis to publish papers that identify and fill the scientific knowledge gaps at the junction of basic research and medical application in order to accelerate the translation of scientific knowledge into new methods for preventing, diagnosing and treating human disease. http://www.sciencetranslationalmedicine.org

About the Institute of Zoology, Chinese Academy of Sciences Institute of Zoology (IOZ), Chinese Academy of Sciences (CAS), is one of the leading research institutions in China. The institute consists of 76 professors (including 2 members of Chinese Academy of Sciences), 3 state key research laboratories and 1 zoological museum. The major research areas of IOZ include animal sciences, cell membrane biology, stem cells and reproduction. The stem cell research teams of IOZ include over 10 PIs, and they mainly focus on questions related to the establishment of pluripotent stem cell lines, neural stem cell induction and regeneration, mechanism studies of pluripotency and differentiation regulation of embryonic stem cells, animal model establishment and functional studies, etc. The major achievements in the field of stem cell research made by IOZ faculties include: obtained the first healthy animal (Xiaoxiao the mouse) using induced pluripotent stem cells (iPSCs) via tetraploid complementation method, identified molecular markers for the evaluation of pluripotency levels of stem cells and the related regulatory mechanisms, achieved cell fate conversion across different germ layers, established various types of human and mouse embryonic stem cell lines, as well as the Beijing Stem Cell Bank, etc. These achievements has once been selected as one of the TIMES Top 10 Medical Breakthroughs in 2009, and twice been selected as Top 10 Breakthroughs in Science and Technology in China. The Beijing Stem Cell Bank now functions as a resource for stem cell and regenerative medicine studies, providing various types of embryonic stem cell lines, adult stem cell lines and somatic cell lines for many research groups. IOZ also hosts modern animal model research centers for pigs and monkeys, which have generated a few valuable animal models for disease mechanism studies and pharmaceutical researches. http://www.english.ioz.cas.cn

About the Fondation Ipsen Established in 1983 under the aegis of the Fondation de France, the mission of the Fondation Ipsen is to contribute to the development and dissemination of scientific knowledge. The long-standing action of the Fondation Ipsen aims at fostering the interaction between researchers and clinical practitioners, which is essential due to the extreme specialization of these professions. The ambition of the Fondation Ipsen is to initiate a reflection about the major scientific issues of the forthcoming years. It has developed an important international network of scientific experts who meet regularly at meetings known as Colloques Mdecine et Recherche, dedicated to five main themes: Alzheimer's disease, neurosciences, longevity, endocrinology and cancer science. Moreover the Fondation Ipsen has started since 2007 several meetings in partnership with the Salk Institute, the Karolinska Institutet, the Massachusetts General Hospital, the Days of Molecular Medicine Global Foundation as well as with the science journals Nature, Cell and Science. The Fondation Ipsen has published over one hundred books and has awarded more than 250 prizes and research grants. http://www.fondation-ipsen.org

Fondation Ipsen For further information, please contact: Isabelle de Segonzac, Image Sept E-mail : isegonzac@image7.fr Tel. : +33 (0)1 53 70 74 70

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BUSINESS WIRE: The 1st Meeting of the Series Bridging Biomedical Worlds: Turning Obstacles into Opportunities for ...

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Genetic Engineering Training Part 1
Part 1 of the tutorial for the approaches required to complete the recombinant DNA assignment.

By: Chris Schramek

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Genetic Engineering Training Part 1 - Video

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