Immunology Research

Anderson, Pennsylvania, United States

Immunology Research

Anderson, Pennsylvania, United States

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CrowdReviews.com Partnered with Madridge Conferences to Announce International Conference on Immunology and Immunotechnology Immunology-2017 features highly enlightening and interactive sessions to encourage the exchange of ideas across a wide range of disciplines in the field of immunology. Immunology-2017 mainly showcases comprehensive approaches in immunology study and research. The field of Immunology is growing rapidly and its development is making tremendous impacts in medical sciences. Immunology-2017 invites the contributions related to immunology research. You can submit your work in these broad themes. Conference mainly focuses on: Clinical and cellular immunology Tumour and cancer immunology Neuro immunology Parasitology Autoimmunity and Therapathies Mucosal immunology Reproductive Immunology Immunobiology Infection & Inflammatory Disease Rheumatology Haematopoiesis Transplantation Immunology Virology Immunodermatology Molecular and Structural Immunology Veterinary Immunology and Immunopathology Allergology and Immunology All the abstracts should be submitted through Immunology-2017 Speakers: · Nadir Kadri, Karolinska Institute, Sweden · Pawel Gajdanowicz, Wroclaw Medical University, Poland · Joel Babdor, Stanford University School of Medicine, USA · Kwan Chow, Washington University, USA · Abdallah Badou, Cadi Ayyad University, Morocco Immunology-2017 Organizing Committee: · Carmen Fernández , Stockholm University, Sweden · Carl Borrebaeck, Lund University, Sweden · SY Seong, Seoul National University College of Medicine, South Korea · Shi, Guo-Ping, Brigham and Women's Hospital, USA · Gideon Berke, Weizmann Institute of Science, Isreal · Eyad Elkord, United Arab Emirates University, United ArabEmirates · Noah Isakov, Ben Gurion University of the Negev, Isreal · Joel Pomerantz, The Johns Hopkins University School of Medicine, USA · NanShan Chang, Institute of Molecular Medicine, Taiwan · Hisaya Akiba, Juntendo University School of Medicine, Japan · Ricardo Luiz Dantas Machado, Evandro Chagas Institute, Brazil Immunology-2017 is organizing an outstanding Scientific Exhibition/Program and anticipates the world’s leading specialists involved in Immunology Research. They welcome Sponsorship and Exhibitions from the Companies and Organizations who wish to showcase their products at this exciting event. Register for the conference and book your slots at: Contact person: Sumanjani immunology@madridge.com immunology@madridge.net Naples, FL, May 09, 2017 --( PR.com )-- International Conference Immunology and Immunotechnology is going to be held during November 1-3, 2017 in Barcelona, Spain.Immunology-2017 features highly enlightening and interactive sessions to encourage the exchange of ideas across a wide range of disciplines in the field of immunology. Immunology-2017 mainly showcases comprehensive approaches in immunology study and research. The field of Immunology is growing rapidly and its development is making tremendous impacts in medical sciences.Immunology-2017 invites the contributions related to immunology research. You can submit your work in these broad themes.Conference mainly focuses on:Clinical and cellular immunologyTumour and cancer immunologyNeuro immunologyParasitologyAutoimmunity and TherapathiesMucosal immunologyReproductive ImmunologyImmunobiologyInfection & Inflammatory DiseaseRheumatologyHaematopoiesisTransplantation ImmunologyVirologyImmunodermatologyMolecular and Structural ImmunologyVeterinary Immunology and ImmunopathologyAllergology and ImmunologyAll the abstracts should be submitted through online abstract submission or can be mailed at immunology@madridge.com Immunology-2017 Speakers:· Nadir Kadri, Karolinska Institute, Sweden· Pawel Gajdanowicz, Wroclaw Medical University, Poland· Joel Babdor, Stanford University School of Medicine, USA· Kwan Chow, Washington University, USA· Abdallah Badou, Cadi Ayyad University, MoroccoImmunology-2017 Organizing Committee:· Carmen Fernández , Stockholm University, Sweden· Carl Borrebaeck, Lund University, Sweden· SY Seong, Seoul National University College of Medicine, South Korea· Shi, Guo-Ping, Brigham and Women's Hospital, USA· Gideon Berke, Weizmann Institute of Science, Isreal· Eyad Elkord, United Arab Emirates University, United ArabEmirates· Noah Isakov, Ben Gurion University of the Negev, Isreal· Joel Pomerantz, The Johns Hopkins University School of Medicine, USA· NanShan Chang, Institute of Molecular Medicine, Taiwan· Hisaya Akiba, Juntendo University School of Medicine, Japan· Ricardo Luiz Dantas Machado, Evandro Chagas Institute, BrazilImmunology-2017 is organizing an outstanding Scientific Exhibition/Program and anticipates the world’s leading specialists involved in Immunology Research. They welcome Sponsorship and Exhibitions from the Companies and Organizations who wish to showcase their products at this exciting event.Register for the conference and book your slots at: http://immunology.madridge.com/register.php Contact person:Sumanjani


Experimental model could be instrumental in testing novel therapies for diseases that now lack treatments WASHINGTON - An off-the-shelf dietary supplement available for pennies per dose demonstrated the ability to reverse cellular damage linked to specific genetic mutations in transgenic fruit flies, an experimental model of genetic mutation-induced renal cell injury that features striking similarities to humans, a Children's National Health System research team reports April 20 in Journal of the American Society of Nephrology. "Transgenic Drosophila that carry mutations in this critical pathway are a clinically relevant model to shed light on the genetic mutations that underlie severe kidney disease in humans, and they could be instrumental for testing novel therapies for rare diseases, such as focal segmental glomerulosclerosis (FSGS), that currently lack treatment options," says Zhe Han, Ph.D., principal investigator and associate professor in the Center for Cancer & Immunology Research at Children's National and senior study author. Nephrotic syndrome (NS) is a cluster of symptoms that signal kidney damage, including excess protein in the urine, low protein levels in blood, swelling and elevated cholesterol. The version of NS that is resistant to steroids is a major cause of end stage renal disease. Of more than 40 genes that cause genetic kidney disease, the research team concentrated on mutations in genes involved in the biosynthesis of Coenzyme Q10 (CoQ10), an important antioxidant that protects the cell against damage from reactive oxygen. "This represents a benchmark for precision medicine," Han adds. "Our gene-replacement approach silenced the fly homolog in the tissue of interest - here, the kidney cells - and provided a human gene to supply the silenced function. When we use a human gene carrying a mutation from a patient for this assay, we can discover precisely how a specific mutation - in many cases only a single amino acid change - might lead to severe disease. We can then use this personalized fly model, carrying a patient-derived mutation, to perform drug testing and screening to find and test potential treatments. This is how I envision using the fruit fly to facilitate precision medicine." Drosophila pericardial nephrocytes perform renal cell functions including filtering of hemolymph (the fly's version of blood), recycling of low molecular weight proteins and sequestration of filtered toxins. Nephrocytes closely resemble, in structure and function, the podocytes of the human kidney. The research team tailor-made a Drosophila model to perform the first systematic in vivo study to assess the roles of CoQ10 pathway genes in renal cell health and kidney function. One by one, they silenced the function of all CoQ genes in nephrocytes. As any individual gene's function was silenced, fruit flies died prematurely. But silencing three specific genes in the pathway associated with NS in humans - Coq2, Coq6 and Coq8 - resulted in abnormal localization of slit diaphragm structures, the most important of the kidney's three filtration layers; collapse of membrane channel networks surrounding the cell; and increased numbers of abnormal mitochondria with deformed inner membrane structure. The flies also experienced a nearly three-fold increase in levels of reactive oxygen, which the study authors say is a sufficient degree of oxidative stress to cause cellular injury and to impair function - especially to the mitochondrial inner membrane. Cells rely on properly functioning mitochondria, the cell's powerhouse, to convert energy from food into a useful form. Impaired mitochondrial structure is linked to pathogenic kidney disease. The research team was able to "rescue" phenotypes caused by silencing the fly CoQ2 gene by providing nephrocytes with a normal human CoQ2 gene, as well as by providing flies with Q10, a readily available dietary supplement. Conversely, a mutant human CoQ2 gene from an patient with FSGS failed to rescue, providing evidence in support of that particular CoQ2 gene mutation causing the FSGS. The finding also indicated that the patient could benefit from Q10 supplementation. Video: Using the Drosophila model to learn more about disease in humans Paper: A Personalized Model of COQ2 Nephropathy Rescued by the Wild-Type COQ2 Allele or Dietary Coenzyme Q10 Supplementation


News Article | June 29, 2017
Site: www.eurekalert.org

Beijing, 16 June, 2017: The new journal Cardiovascular Innovations and Applications (CVIA) has just published the second issue of Volume 2, with a Special China Focus Issue. The CVIA China Focus Issue has been Guest Edited by Professor Changsheng Ma, Capital Medical University and National Center for Cardiovascular Clinical Research, Beijing, China and brings together contributions from leading cardiologists in the United States and China together with several commentaries by C. Richard Conti, the Editor-in-Chief of CVIA. In his introductory editorial, Professor Changsheng Ma writes: "Cardiovascular diseases (CVD) have become the main cause of death and a critical public health burden in contemporary China. I was invited by Dr. Richard Conti, editor in chief of the journal to be the guest editor of this issue focusing on CVD in China. It is my privilege to work with the leading cardiologists and research scientists in the field to delineate the outline of CVD in China, including epidemiology, prevention, rehabilitation, clinical management et al. This issue not only elaborates the major clinical issues but also highlights future perspectives in cardiovascular disease of China." Papers in this issue are: Dayi Hu Dyslipidemia and Management of Atherosclerotic Cardiovascular Diseases in China: New Evidence and New Guidelines Yuhua Liao and Yiyi Wang Cardiovascular Immunology Research in Wuhan Union Hospital: Over the Past 25 years Xinli Li and Iokfai Cheang The Usage of Heart Failure Biomarkers in China Jingwei Zhang and Meilin Liu Antithrombotic Therapy: Focus on the Elderly C. Richard Conti Some Thoughts About Warfarin and NOACS Linjuan Guo, Ying Ding, Fuwei Liu, Wengen Zhu, and Xinghua Jiang Role of Second-Generation Drug-Eluting Stents and Bypass Grafting in Coronary Artery Disease: A Systematic Review and Meta-analysis Yafei Cui, Dong Zhao, Jiayi Sun, Miao Wang, Yinglong Liu, and Jing Liu Hospitalization for Congenital Heart Disease in Beijing: Patient Characteristics and Temporal Trends Xinqiang Han and Jianming Li Catheter Ablation of Atrial Fibrillation: Where Are We? Abigail Afolabi, Sining Hu, Chao Wang, Yinchun Zhu, Irina Mustafina, Lin Lin, Gonghui Zheng, Chunyang Zhe, Haibo Jia, Jingbo Hou, and Bo Yu Role of Optical Coherence Tomography in Diagnosis and Treatment of Patients with Acute Coronary Syndromes Xiong-Fei Pan, Ruiwei Meng, Na Liu, and An Pan Depression, Anxiety, and Cardiovascular Disease in Chinese: a Review for a Bigger Picture Rongjing Ding, Jianchao Li, Limin Gao, Liang Zhu, Wenli Xie, Xiaorong Wang, Qin Tang, Huili Wang, and Dayi Hu The Effect of Home-Based Cardiac Rehabilitation on Functional Capacity, Behavior, and Risk Factors in Patients with Acute Coronary Syndrome in China Wenbo He, Zhibing Lu, and Hong Jiang Clinical Utility of Amlodipine/Valsartan Fixed-Dose Combination in the Management of Hypertension in Chinese Patients Ji-Guang Wang, Yi Chen, Qi-Fang Huang, Yan Li, and Ben Freedman Rationale and Design of the Randomized Controlled Trial of Intensive Versus Usual ECG Screening for Atrial Fibrillation in Elderly Chinese by an Automated ECG System in Community Health Centers in Shanghai (AF-CATCH) Jing Ping Sun, Xing Sheng Yang, and Shaochun Wang The Role of Echocardiography in Hypertrophic Cardiomyopathyv C. Richard Conti Hypertrophic "Obstructive" Cardiomyopathy: Role of Systolic Anterior Motion of the Mitral Valve Xing Sheng Yang, Jing Ping Sun, and Bryan Yan Clinical Syndromes Associated with Cardiovascular Diseases: A Review C. Richard Conti Great Wall International Congress of Cardiology (GWICC) and Relationship to the American College of Cardiology (ACC) and the New Journal, CVIA CVIA is available on the IngentaConnect platform and at http://cvia-journal. . Submissions may be made using ScholarOne Manuscripts. There are no author submission or article processing fees.


News Article | July 26, 2017
Site: www.biosciencetechnology.com

In preclinical studies, tumors that consitutively expressed the protein indoleamine 2,3-dioxygenase (IDO1) responded to the cyclooxygenase-2 (COX-2) inhibitor celecoxib (Celebrex) and had improved infiltration of certain subsets of T cells, making them more likely to respond to anti-PD1 therapies, according to data published in Cancer Immunology Research, a journal of the American Association for Cancer Research. “A key challenge in cancer immunotherapy is to understand why some patients respond to immunotherapy but many others do not,” said Benoit J. Van den Eynde, MD, PhD, professor at Ludwig Institute for Cancer Research at de Duve Institute and Université catholique de Louvain in Brussels, Belgium. “If we understand why, we can then select and treat only those patients who will benefit from the treatment, but most importantly, we can devise strategies to make immunotherapy work in those who are not currently responding.” Many tumors use IDO1 as a shield to protect themselves from immune attack, explained Van den Eynde. Some of them start building and raising their shields when they are being attacked by T cells, which is called adaptive resistance. In such tumors, IDO1 expression is associated with inflammation and T-cell infiltration. However, some tumors produce IDO1 constitutively (continuously) and have their shields ready and raised before any immune attack. Such tumors are fully protected and can prevent T-cell attack by disabling the T cells right away. “This is what we call intrinsic resistance and may explain why some tumors are ‘cold,’ meaning, not infiltrated by T cells,” Van den Eynde said. “We wanted to understand the molecular mechanisms that make some tumors express IDO1 constitutively,” he added. Using two human melanoma cell lines, Van den Eynde and colleagues first demonstrated that COX-2 and its product, prostaglandin E2 (PGE2), caused the constitutive expression of IDO1 by utilizing the MAPK, PKC, and PI3K cell-signaling pathways. These results held true in other human tumor cell lines as well, including lung, ovarian, and head and neck cancer cell lines. “These data provide evidence that COX-2 drives tumor-induced immunosuppression through constitutive expression of IDO1,” Van den Eynde noted. Next, they showed that immunodeficient mice reconstituted with human lymphocytes and bearing human ovarian tumor xenografts with constitutive IDO1 expression responded to celecoxib as well as the IDO1 inhibitor, epacadostat. “The outcomes we observed with COX-2 inhibitors and IDO1 inhibitors were identical, which came as a surprise,” Van den Eynde said. “It is always very useful to have two compounds acting on the same pathway with two different modes of action: In case tumors start resisting one compound, they may still be sensitive to the other.” By mining the transcriptomics data of 1,041 different human tumor cell lines from the Broad Institute, the researchers found a correlation between IDO1 expression and activation of the COX-2/PGE2 axis in several cancer types, including stomach, pancreatic, liver, and lung cancers, and sarcoma. “Our studies provide a clear rationale to test, in the clinics, combinations of anti-PD1 immunotherapy and COX-2 inhibitors,” Van den Eynde said. “This should be straightforward given the fact that both anti-PD1 and COX-2 inhibitors are already approved for clinical use in different contexts.” Initial analysis by the team indicated that about 10 to 50 percent of human tumors express IDO1 constitutively, depending on tumor type. This study was funded by Ludwig Institute for Cancer Research, Walloon Excellence in Life Sciences and Biotechnology (WELBIO, Belgium), FNRS-Télévie (Belgium), Foundation Against Cancer (Belgium), de Duve Institute and Université catholique de Louvain. Van den Eynde has ownership interest in iTeos Therapeutics, a biotechnology company developing IDO1 inhibitors.


NEW YORK--(BUSINESS WIRE)--Cytovia, the oncology subsidiary of Immune Pharmaceuticals Inc. (NASDAQ:IMNP) ("Immune"), a clinical stage biopharmaceutical company, today announced the publication of results showing favorable effects of its lead immunotherapeutic compound Ceplene® (histamine dihydrochloride) in cancer. The results of the new article confirm and extend previous findings showing that treatment of mice with Ceplene® efficiently reduces the formation of lung melanoma metastases. Using genetically modified mice, the authors also show that the beneficial effect of treatment with Ceplene® in reducing metastasis was likely explained by its inhibitory effect on NOX2, which is an enzyme expressed by myeloid blood cells. In the article, the investigators additionally report that combination immunotherapy with Ceplene® and interleukin-15 (IL-15) reduced melanoma metastasis by over 70%, an incremental effect over Ceplene alone or IL-15 alone. The article was published in Cancer Immunology Research and is found on this link: https://www.ncbi.nlm.nih.gov/pubmed/28760732 “Cytovia has recently filed a patent aiming to protect the use of Ceplene® and other inhibitors of NOX2 in reducing or preventing cancer metastasis,” said Dr. Daniel Teper, CEO of Cytovia. He added: “The reduction of metastasis obtained by the combination of Ceplene® and IL-15 is suggestive of a novel combinatorial immunotherapy that merits further study.” Ceplene® (histamine dihydrochloride) is an immunostimulant that is approved for use in >30 countries in Europe for the maintenance of first remission in patients with acute myeloid leukemia (AML). Ceplene® is administered in conjunction with low-dose IL-2 for enhanced anti-tumor immunity. Specifically, Ceplene® acts by countering NOX2-mediated immunosuppression and thus improves activation of anti-tumor lymphocytes such as T cells and NK cells. When administered together with the T cell/NK cell activator IL-2, Ceplene® promotes immune-mediated killing of cancer cells, thus providing a strong pharmacological rationale for this combination immunotherapy. Aspects on the effects of Ceplene® on anti-tumor immunity have been reported in >50 scientific articles. In an international Phase III clinical study in 320 AML patients, the combination of Ceplene® and low-dose IL-2 has been shown to prevent relapse of leukemia while maintaining good quality of life during treatment. A recent Phase IV study in 84 AML patients demonstrated efficient activation of anti-tumor immunity during treatment with Ceplene®/IL-2 and also identified tools that may prognosticate the clinical benefit of the treatment. During 2015-17, detailed results of the Phase IV study were presented in several medical journals including Leukemia, a leading journal in hematology. Following the recent acquisition from Mylan, Cytovia holds worldwide rights for Ceplene®. Immune Pharmaceuticals Inc. (NASDAQ: IMNP) is dedicated to alleviating the burden of patients suffering from autoimmune diseases by developing novel immunotherapeutic agents. Immune's lead product candidate, bertilimumab, is in Phase 2 clinical development for bullous pemphigoid, an orphan autoimmune dermatological condition, and for ulcerative colitis. Other potential relevant indications for bertilimumab include atopic dermatitis, Crohn's disease, severe asthma and Non-Alcoholic Steato-Hepatitis (NASH). Also, Immune’s pipeline includes topical nano-formulated cyclosporine-A for the treatment of psoriasis and atopic dermatitis and AmiKet™ and AmiKet™ Nano™ for the treatment of neuropathic pain. Immune's oncology subsidiary, Cytovia, plans to develop and commercialize Ceplene for maintenance remission in AML in combination with IL-2. Additional oncology pipeline products include Azixa® and crolibulin, which are clinical stage vascular disrupting agents, and bispecific antibodies and NanomAbs™, which are novel technology platforms. For more information, please visit Immune's website at www.immunepharma.com, the content of which is not a part of this press release. This news release, and any oral statements made with respect to the information contained in this news release, may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. You are urged to consider statements that include the words "may," "will," "would," "could," "should," "believes," "estimates," "projects," "potential," "expects," "plans," "anticipates," "intends," "continues," "forecast," "designed," "goal" or the negative of those words or other comparable words to be uncertain and forward-looking. Such forward-looking statements include statements that express plans, anticipation, intent, contingency, goals, targets, future development and are otherwise not statements of historical fact. Forward-looking statements include, among others, statements regarding the Company's ability to reduce expenses, capitalize on strategic alternatives, develop its assets, and generate value for shareholders. These statements are based on our current expectations and are subject to risks and uncertainties that could cause actual results or developments to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. There can be no assurance that the Company will ever successfully complete its anticipated corporate restructuring, or that the Company will be able to reduce expenses, capitalize on strategic alternatives, develop its assets, and generate value for shareholders. Factors that may cause actual results or developments to differ materially include, but are not limited to: the risks associated with the adequacy of our existing cash resources and our ability to continue as a going concern; the risks associated with our ability to continue to meet our obligations under our existing debt agreements; the risk that ongoing or future clinical trials will not be successful; the risk that our compounds under development will not receive regulatory approval or achieve significant commercial success; the risk that we will not be able to find a partner to help conduct future trials or commercialize our product candidates on attractive terms, on a timely basis or at all; the risk that our product candidates that appear promising in early research and clinical trials do not demonstrate safety and/or efficacy in larger-scale or later-stage clinical trials; the risk that we will not obtain approval to market any of our product candidates; the risks associated with dependence upon key personnel; the risks associated with reliance on collaborative partners and others for further clinical trials, development, manufacturing and commercialization of our product candidates; the cost, delays and uncertainties associated with our scientific research, product development, clinical trials and regulatory approval process; our history of operating losses since our inception; the highly competitive nature of our business; risks associated with litigation; and risks associated with our ability to protect our intellectual property. These factors and other material risks are more fully discussed in our periodic reports, including our reports on Forms 8-K, 10-Q and 10-K and our other filings with the U.S. Securities and Exchange Commission. You are urged to carefully review and consider the disclosures found in our filings, which are available at www.sec.gov or at www.immunepharma.com. You are cautioned not to place undue reliance on any forward-looking statements, any of which could turn out to be wrong due to inaccurate assumptions, unknown risks or uncertainties or other risk factors. We expressly disclaim any obligation to publicly update any forward-looking statements contained herein (including those relating to the corporate reorganization and exploration of strategic alternatives), whether as a result of new information, future events or otherwise, except as required by law.


News Article | February 21, 2017
Site: globenewswire.com

HOUSTON, Feb. 21, 2017 (GLOBE NEWSWIRE) -- Bio-Path Holdings, Inc., (NASDAQ:BPTH), a biotechnology company leveraging its proprietary DNAbilize™ liposomal delivery and antisense technology to develop a portfolio of targeted nucleic acid cancer drugs, today announced the appointment of D. Craig Hooper, Ph.D., to its Scientific Advisory Board (SAB). “It is with great pleasure we welcome Dr. Hooper to our SAB. His extensive experience in the neuroimmunology field will be extremely valuable to Bio-Path as we seek to advance our liposomal RNAi antisense platform to deliver a safe and systemic brain cancer immunotherapy,” said Peter Nielsen, President and Chief Executive Officer of Bio-Path. “Bio-Path is developing a truly innovative platform that has the potential to transform antisense drug delivery,” commented Dr. Hooper. “I’m honored to join Bio-Path’s SAB and look forward to working with my esteemed colleagues to help advance DNAbilize™ and offer meaningful new immunotherapy treatments to patients.” D. Craig Hooper, Ph.D., is a Professor of Cancer Biology and Neurological Surgery at Thomas Jefferson University. Dr. Hooper has published over 140 papers in peer-reviewed journals and serves on the editorial boards of the Journal of Immunology Research, Scientific Reports and the Journal of Immunology. In 2016 he was inducted into the National Academy of Inventors (NAI). Dr. Hooper received his Ph.D. in Immunology and B.Sc. in Physiology from McGill University. He completed his post-doctoral research fellowship at the University of Bristol. Bio-Path is a biotechnology company focused on developing therapeutic products utilizing DNAbilize™, its proprietary liposomal delivery and antisense technology, to systemically distribute nucleic acid drugs throughout the human body with a simple intravenous transfusion. Bio-Path’s lead product candidate, prexigebersen (BP1001, liposomal Grb2 antisense), is in a Phase II study for blood cancers and in preclinical studies for solid tumors. Bio-Path’s second drug candidate, also a liposomal antisense drug, is ready for the clinic where it will be evaluated in lymphoma and solid tumors. For more information, please visit the Company's website at http://www.biopathholdings.com.


News Article | February 10, 2017
Site: www.biosciencetechnology.com

Specific genetic errors that trigger congenital heart disease (CHD) in humans can be reproduced reliably in Drosophila melanogaster - the common fruit fly - an initial step toward personalized therapies for patients in the future. "Studying CHD in fruit flies provides a fast and simple first step in understanding the roles that individual genes play in disease progression," says Zhe Han, Ph.D., a principal investigator and associate professor in the Center for Cancer & Immunology Research at Children's National Health System and senior author of the paper published Jan. 20, 2017 in eLife. "Our research team is the first to describe a high-throughput in vivo validation system to screen candidate disease genes identified from patients. This approach has the potential to facilitate development of precision medicine approaches for CHD and other diseases associated with genetic factors," Han says. Some 134 genes have been implicated in causing CHD, a birth defect that affects 8 in 1,000 newborns, according to the National Institutes of Health. The research team led by Han used high-throughput techniques to alter the activity of dozens of genes in flies' hearts simultaneously in order to validate genes that cause heart disease. "Our team was able to characterize the effect of these specific genetic alterations on heart development, structure and activity," Han adds. "The development of the human heart is a complicated process in which a number of different cell types need to mature and differentiate to create all of the structures in this essential organ. The precise timing of those cellular activities is critical to normal heart development, with disruptions in the structure of proteins called histones linked to later heart problems.". Of 134 genes studied by the research team, 70 caused heart defects in fruit flies, and several of the altered genes are involved in modifying the structure of histones. Quantitative analyses of multiple cardiac phenotypes demonstrated essential structural, functional and developmental roles for these genes, including a subgroup encoding histone H3K4 modifying proteins. The scientists then corroborated their work by reliably reproducing in flies the effect of specific genetic errors identified in humans with CHD. "This may allow researchers to replicate individual cases of CHD, study them closely in the laboratory and fashion treatments personalized to that patient specifically," he adds. "Precise gene-editing techniques could be used to tailor-make flies that express a patient's specific genetic mutation. Treating CHD at the level of DNA offers the potential of interrupting the current cycle of passing along genetic mutations to each successive generation."


News Article | February 22, 2017
Site: www.eurekalert.org

Two drugs used to treat asthma and allergies may offer a way to prevent a form of pneumonia that can kill up to 40 percent of people who contract it, researchers at the University of Virginia School of Medicine have found. Influenza pneumonia results when a flu infection spreads to alveolar air sacs deep within the lungs. Normally, a flu infection does not progress that far into the lower respiratory tract, but when it does, the results can be deadly. "If infection is severe enough, and the immune response is potent enough, you get injury to these cells and are no longer able to get sufficient oxygen exchange," explained UVA researcher Thomas J. Braciale, MD, PhD. "As a result of the infection of the cells, you can develop lethal pneumonia and die." But early administration of the two asthma drugs, Accolate and Singulair, could prevent the infection of the alveolar cells deep in the lower respiratory tract, Braciale's research suggests. "The excitement of this is the possibility of someone coming to see the physician with influenza that looks a little more severe than usual and treating them with the drugs Singulair or Accolate and preventing them from getting severe pneumonia," he said. "The fatality rate from influenza pneumonia can be pretty high, even with all modern techniques to support these patients. Up to 40 percent. So it's a very serious problem when it occurs." Unlike bacterial pneumonia, influenza pneumonia is caused by a virus. That makes it very difficult to treat - and makes the possibility of prevention all the more tantalizing. "When we look at pandemic strains of influenza that have high mortality rates, one of the best adaptations of those pandemic viruses is their ability to infect these alveolar epithelial cells," explained researcher Amber Cardani, PhD. "It's one of the hallmarks for certain strains that cause the lethality in these pandemics." Once influenza spreads deep into the lungs, the body's own immune response can prove harmful, resulting in severe damage to the alveolar air sacs. "It's an important observation the field is coming to," Cardani said. "We really need to limit the infection of these lower respiratory airways." The researchers determined that the alveolar epithelial cells are typically protected from influenza infection by immune cells called alveolar macrophages. In some instances, however, the flu virus can prevent the macrophages from carrying out their protective function, allowing the epithelial cells to become vulnerable to infection. "It's not as though they lack alveolar macrophages, it's just that their alveolar macrophages don't work right when they get exposed to the flu," Braciale said. "And those are the types of patients, who potentially would eventually go to the intensive care unit, that we think could be treated early in infection with Accolate or Singulair to prevent infection of these epithelial cells and prevent lethal infection." For their next steps, the researchers are consulting with colleagues to determine if patients being treated with Accolate and Singulair are less likely to develop influenza pneumonia during flu outbreaks. "This was a totally unexpected observation," Braciale said. "When I told multiple colleagues who are infectious disease or pulmonary physicians, they were absolutely flabbergasted." The findings have been published by the scientific journal PLOS Pathogens. It was written by Cardani, Adam Boulton, Taeg S. Kim and Braciale. Braciale and Cardani are both part of UVA's Department of Microbiology, Immunology and Cancer Biology and UVA's Beirne B. Carter Center for Immunology Research. Braciale's primary appointment is with the Department of Pathology. The work was supported by the National Institutes of Health, grant R01AI015608-35, and the NIH's National Institute of General Medical Sciences, grants T32 GM007055 and T32 GM007055.


DRI Utilizes Funding to Launch Lindsey Inserra-Hughes Immune Tolerance Seminar Series to Advance Immunology Research for Type 1 Diabetes


News Article | November 18, 2016
Site: www.eurekalert.org

WASHINGTON, DC - A Children's National Health System research team has uncovered a novel process by which the gene APOL1 contributes to renal disease, according to a paper published November 18 in the Journal of the American Society of Nephrology. Mutated versions of the APOL1 gene render people of African descent at heightened risk of developing chronic kidney disease. Employing powerful genetic approaches, Children's National researchers were able to mimic APOL1 renal cell pathology in the fruit fly Drosophila melanogaster. This opens the door to pinpointing other proteins that interact with APOL1, a vital first step toward identifying medicines to treat renal diseases that currently have no drug therapy. "This is one of the hottest research topics in the kidney field. We are the first group to generate this result in fruit flies," says Zhe Han, PhD, a senior Drosophila specialist and associate professor in the Center for Cancer & Immunology Research at Children's. Han, senior author of the paper, will present the study results this week during Kidney Week 2016, the American Society of Nephrology's annual gathering in Chicago that is expected to draw more than 13,000 kidney professionals from around the world. The advantages of Drosophila for biomedical research include its rapid generation time and an unparalleled wealth of sophisticated genetic tools to probe deeply into fundamental biological processes underlying human diseases. People of African descent frequently inherit a mutant version of the APOL1 gene that affords protection from African sleeping sickness, but is associated with a 17- to 30-fold greater chance of developing certain types of kidney disease. That risk is even higher for individuals infected with the human immunodeficiency virus (HIV). Drosophila renal cells, called nephrocytes, accurately mimic pathological features of human kidney cells during APOL1-associated renal disease. "Nephrocytes share striking structural and functional similarities with mammalian podocytes and renal proximal tubule cells, and therefore provide us a simple model system for kidney diseases," says Han, who has studied the fruit fly for 20 years and established the fly nephrocyte as a glomerular kidney disease model in 2013 with two research papers in the Journal of the American Society of Nephrology. In this most recent study, Han's team cloned a mutated APOL1 gene from podocyte cells cultured from a patient with HIV-associated nephropathy. They created transgenic flies making human APOL1 in nephrocytes and observed that initially the transgene caused increased cellular functional activity. As flies aged, however, APOL1 led to reduced cellular function, increased cell size, abnormal vesicle acidification, and accelerated cell death. "The main functions of nephrocytes are to filter proteins and remove toxins from the fly's blood, to reabsorb protein components, and to sequester harmful toxins. It was surprising to see that these cells first became more active and temporarily functioned at higher levels," says Han. "The cells got bigger and stronger but, ultimately, could not sustain that enhancement. After swelling to almost twice their normal size, the cells died. Hypertrophy is the way that the human heart responds to stress overload. We think kidney cells may use the same coping mechanism." The Children's research team is a multidisciplinary group with members from the Center for Cancer & Immunology Research, the Center for Genetic Medicine Research, and the Division of Nephrology.The team also characterized fly phenotypes associated with APOL1 expression that will facilitate the design and execution of powerful Drosophila genetic screening approaches to identify proteins that interact with APOL1 and contribute to disease mechanisms. Such proteins represent potential therapeutic targets. Currently, transplantation is the only option for patients with kidney disease linked to APOL1. "This is only the beginning," Han says. "Now, we have an ideal pre-clinical model. We plan to start testing off-the-shelf therapeutic compounds, for example different kinase inhibitors, to determine whether they block any of the steps leading to renal cell disease."

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