Cardiac stem cells from heart disease patients may be harmful – Medical Xpress

June 15, 2017

Patients with severe and end-stage heart failure have few treatment options available to them apart from transplants and "miraculous" stem cell therapy. But a new Tel Aviv University study finds that stem cell therapy may, in fact, harm heart disease patients.

The research, led by Prof. Jonathan Leor of TAU's Sackler Faculty of Medicine and Sheba Medical Center and conducted by TAU's Dr. Nili Naftali-Shani, explores the current practice of using cells from the host patient to repair tissueand contends that this can prove deleterious or toxic for patients. The study was recently published in the journal Circulation.

"We found that, contrary to popular belief, tissue stem cells derived from sick hearts do not contribute to heart healing after injury," said Prof. Leor. "Furthermore, we found that these cells are affected by the inflammatory environment and develop inflammatory properties. The affected stem cells may even exacerbate damage to the already diseased heart muscle."

Tissue or adult stem cells"blank" cells that can act as a repair kit for the body by replacing damaged tissueencourage the regeneration of blood vessel cells and new heart muscle tissue. Faced with a worse survival rate than many cancers, many heart failure patients have turned to stem cell therapy as a last resort.

"But our findings suggest that stem cells, like any drug, can have adverse effects," said Prof. Leor. "We concluded that stem cells used in cardiac therapy should be drawn from healthy donors or be better genetically engineered for the patient."

Hope for improved cardiac stem cell therapy

In addition, the researchers also discovered the molecular pathway involved in the negative interaction between stem cells and the immune system as they isolated stem cells in mouse models of heart disease. After exploring the molecular pathway in mice, the researchers focused on cardiac stem cells in patients with heart disease.

The results could help improve the use of autologous stem cellsthose drawn from the patients themselvesin cardiac therapy, Prof. Leor said.

"We showed that the deletion of the gene responsible for this pathway can restore the original therapeutic function of the cells," said Prof. Leor. "Our findings determine the potential negative effects of inflammation on stem cell function as they're currently used. The use of autologous stem cells from patients with heart disease should be modified. Only stem cells from healthy donors or genetically engineered cells should be used in treating cardiac conditions."

The researchers are currently testing a gene editing technique (CRISPER) to inhibit the gene responsible for the negative inflammatory properties of the cardiac stem cells of heart disease patients. "We hope our engineered stem cells will be resistant to the negative effects of the immune system," said Prof. Leor.

Explore further: Adult stem cell types' heart repair potential probed

More information: Nili Naftali-Shani et al, Left Ventricular Dysfunction Switches Mesenchymal Stromal Cells Toward an Inflammatory Phenotype and Impairs Their Reparative Properties Via Toll-Like Receptor-4Clinical Perspective, Circulation (2017). DOI: 10.1161/CIRCULATIONAHA.116.023527

Journal reference: Circulation

Provided by: Tel Aviv University

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Cardiac stem cells from heart disease patients may be harmful - Medical Xpress

Newly identified method of gene regulation challenges accepted science – Stanford Medical Center Report

The work builds upon a previous study from Barnas laboratory that was published June 1 in Cell. The lead author of that study was postdoctoral scholar Deniz Simsek, PhD. It showed that ribosomes also differ in the types of proteins they accumulate on their outer shells. It also identified more than 400 ribosome-associated proteins, called RAPs, and showed that they can affect ribosomal function.

Every biology student learns the basics of how the genetic code is used to govern cellular life. In broad strokes, the DNA in the nucleus carries the building instructions for about 20,000 genes. Genes are chosen for expression by proteins that land on the DNA and transcribe the DNA sequence into short pieces of mobile, or messenger, RNA that can leave the nucleus. Once in the cells cytoplasm, the RNA binds to ribosomes to be translated into strings of amino acids known as proteins.

Every living cell has up to 10 million ribosomes floating in its cellular soup. These tiny engines are themselves complex structures that contain up to 80 individual core proteins and four RNA molecules. Each ribosome has two main subunits: one that binds to and reads the RNA molecule to be translated, and another that assembles the protein based on the RNA blueprint. As shown for the first time in the Cell study, ribosomes also collect associated proteins called RAPs that decorate their outer shell like Christmas tree ornaments.

Until recently, ribosomes have been thought to take an important but backstage role in the cell, just taking in and blindly translating the genetic code, said Barna. But in the past couple of years there have been some intriguing hints of a more complex scenario. Some human genetic diseases caused by mutations in ribosomal proteins affect only specific organs or tissues, for example. This has been very perplexing. We wanted to revisit the textbook notion that all ribosomes are the same.

In 2011, members of Barnas lab showed that one core ribosomal protein called RPL38/eL38 is necessary for the appropriate patterning of the mammalian body plan during development; mice with a mutation in this protein developed skeletal defects such as extra ribs, facial clefts and abnormally short, malformed tails.

Shi and Fujii used a quantitative proteomics technology called selected reaction monitoring to precisely calculate the quantities, or stoichiometry, of each of several ribosomal proteins isolated from ribosomes within mouse embryonic stem cells. Their calculations showed that not all the ribosomal proteins were always present in the same amount. In other words, the ribosomes differed from one another in their compositions.

We realized for the first time that, in terms of the exact stoichiometry of these proteins, there are significant differences among individual ribosomes, said Barna. But what does this mean when it comes to thinking about fundamental aspects of a cell, how it functions?

To find out, the researchers tagged the different ribosomal proteins and used them to isolate RNA molecules in the act of being translated by the ribosome. The results were unlike what they could have ever imagined.

We found that, if you compare two populations of ribosomes, they exhibit a preference for translating certain types of genes, said Shi. One prefers to translate genes associated with cell metabolism; another is more likely to be translating genes that make proteins necessary for embryonic development. We found entire biological pathways represented by the translational preferences of specific ribosomes. Its like the ribosomes have some kind of ingrained knowledge as to what genes they prefer to translate into proteins.

The findings dovetail with those of the Cell paper. That paper showed that there is more to ribosomes than the 80 core proteins, said Simsek. We identified hundreds of RAPs as components of the cell cycle, energy metabolism, and cell signaling. We believe these RAPs may allow the ribosomes to participate more dynamically in these intricate cellular functions.

Barna and her team have taken a big step toward understanding how ribosomes control protein synthesis by looking at unperturbed stem cells form mammals, said Jamie Cate, PhD, professor of molecular and cell biology and of chemistry at the University of California-Berkeley. They found built-in regulators of translation for a subset of important mRNAs and are sure to find more in other cells. Cate was not involved in the research.

The fact that ribosomes can differ among their core protein components as well as among their associated proteins, the RAPs, and that these differences can significantly affect ribosomal function, highlights a way that a cell could transform its protein landscape by simply modifying ribosomes so that they prefer to translate one type of gene say, those involved in metabolism over others. This possibility would free the cell from having to micromanage the expression levels of hundreds or thousands of genes involved in individual pathways. In this scenario, many more messenger RNAs could be available than get translated into proteins, simply based on what the majority of ribosomes prefer, and this preference could be tuned by a change in expression of just a few ribosomal proteins.

Barna and her colleagues are now planning to test whether the prevalence of certain types of ribosomes shift during major cellular changes, such as when a cell enters the cell cycle after resting, or when a stem cell begins to differentiate into a more specialized type of cell. Theyd also like to learn more about how the ribosomes are able to discriminate between classes of genes.

Although the findings of the two papers introduce a new concept of genetic regulation within the cell, they make a kind of sense, the researchers said.

About 60 percent of a cells energy is spent making and maintaining ribosomes, said Barna. The idea that they play no role in the regulation of genetic expression is, in retrospect, a bit silly.

Other Stanford co-authors are graduate students Kyle Kovary and Naomi Genuth; postdoctoral scholar Hannes Rost, PhD; and Mary Teruel, PhD, assistant professor of chemical and systems biology.

The research was supported by the New York Stem Cell Foundation, the Alfred P. Sloan Foundation, the Mallinckrodt Foundation, a Pew Scholars Award and the National Institutes of Health (a Directors New Innovator Award and grants R21HD086730, R01DK101743, R01DK106241 and P50GM107615).

Stanfords departments of Developmental Biology and of Genetics also supported the work.

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Newly identified method of gene regulation challenges accepted science - Stanford Medical Center Report

Induced Cell Turnover: A proposed modality for in situ tissue regeneration & repair – Medical Xpress

June 15, 2017 Credit: Biogerontology Research Foundation, Feinberg School of Medicine & Swammerdam Institute for Life Sciences

Thursday, July 15, 2017, London, UK: Scientists at the Biogerontology Research Foundation, Feinberg School of Medicine at Northwestern University and Swammerdam Institute of Life Sciences at the University of Amsterdam have published a paper on a proposed method of in situ tissue regeneration called Induced Cell Turnover (ICT) in the journal Human Gene Therapy. The proposed therapeutic modality would aim to coordinate the targeted ablation of endogenous cells with the administration of minimally-differentiated, hPSC-derived cells in a gradual and multi-phasic manner so as to extrinsically mediate the turnover and replacement of whole tissues and organs with stem-cell derived cells.

"One of the major hurdles limiting traditional cell therapies is low levels of engraftment and retention, which is caused in part by cells only being able to engraft at locations of existing cell loss, and by the fact that many of those vacancies have already become occupied by ECM and fibroblasts (i.e. scar tissue) by the time the cells are administered, long after the actual occurrence of cell loss. The crux underlying ICT is to coordinate endogenous cell ablation (i.e. induced apoptosis) with replacement cell administration so as to manually vacate niches for new cells to engraft, coordinating these two events in space and time so as to minimize the ability for sites of cell loss to become occupied by ECM and fibroblasts. This would be done in a gradual and multi-phasic manner so as to avoid acute tissue failure resulting from the transient absence of too many cells at any one time. While the notion of endogenous cell clearance prior to replacement cell administration has become routine for bone marrow transplants, it isn't really on the horizon of researchers and clinicians working with solid tissues, and this is something we'd like to change." said Franco Cortese, Deputy Director and Trustee of the Biogerontology Research Foundation, and lead author on the paper.

Cell-type and tissue-specific rates of induced turnover could be achieved using cell-type specific pro-apoptotic small molecule cocktails, peptide mimetics, and/or tissue-tropic AAV-delivered suicide genes driven by cell-type specific promoters. Because these sites of ablation would still be "fresh" when replacement cells are administered, the presumption is that the patterns of ablation will make administered cells more likely to engraft where they should, in freshly vacated niches where the signals promoting cell migration and engraftment are still active. By varying the dose of cell-type targeted ablative agents, cell type and tissue-specific rates of induced turnover could be achieved, allowing for the rate and spatial distribution of turnover to be tuned to the size of the tissue in order to avoid ablating too many cells at once and inadvertently inducing acute tissue failure.

"Cell therapies are limited by low levels of engraftment, and in principal their ability to improve clinical outcomes is limited by the fact that they can only engraft at locations of existing cell loss. Conversely, therapeutic tissue and organ engineering requires surgery, is more likely to introduce biochemical and mechanical abnormalities to tissue ultrastructure through the decellularization process, and is fundamentally incapable of replacing distributed tissues and structures with a high degree of interconnectivity to other tissues in the body. The aim of ICT is to form a bridge between these two main pillars to regenerative medicine, extending the efficacy of cell therapies beyond a patch for existing cell loss and accomplishing the aim of tissue and organ engineering (i.e. the replacement and regeneration of whole tissues and organs) while potentially remaining free of some of their present limitations." said Giovanni Santostasi, co-author on the paper and a researcher at the Feinberg School of Medicine, Northwestern University.

While future iterations of the therapy could use patient-derived cells, such as ESCs derived via somatic cell nuclear transfer (SCNT) or iPSCs derived from nuclear reprogramming, shorter-term applications would likely use existing stem cell lines immunologically matched to the patient via HLA matching. The authors contend that the cloning of adult organisms with normal lifespans from adult somatic cells testifies to the fact that adult cells can be rejuvenated and used to produce a sufficient quantity of daughter cells to replace the sum of cells constituting adult organisms, and that serial cloning experiments (in which this process is done iteratively, using an adult cell of each subsequent generation to derive the next) attests to this fact even more strongly.

"ICT could theoretically enable the controlled turnover and rejuvenation of aged tissues. The technique is particularly applicable to tissues that are not amenable to growth ex vivo and implantation (as with solid organs)such as the vascular, lymphatic, and nervous systems. The method relies upon targeted ablation of old, damaged and/or senescent cells, coupled with a titrated replacement with patient-derived semi-differentiated stem and progenitor cells. By gradually replacing the old cells with new cells, entire tissues can be replaced in situ. The body naturally turns over tissues, but not all tissues and perhaps not optimally. I am reminded of the quote attributed to Heraclitus: 'No man ever steps in the same river twice, for it's not the same river and he's not the same man.'" said Sebastian Aguiar, a coauthor on the paper and researcher at the Swammerdam Institute of Life Sciences, University of Amsterdam.

"Reversing aging in humans will require a multi-step approach at multiple levels of the organismal organization. In situ targeted ablation of the senescent cells and regeneration will be an important component of comprehensive anti-aging therapies." said Alex Zhavoronkov, Chief Science Officer of the Biogerontology Research Foundation.

The researchers originally proposed ICT in 2016 in the context of biomedical gerontology as a possible means of preventing and/or negating age-related phenotypic deviation for the purposes of healthspan extension, and in this new paper they refine the methodological underpinnings of the approach, take a closer look at potential complications and strategies for their deterrence, and analyze ICT in the context of regenerative medicine as an intervention for a broader range of conditions based on disease or dysfunction at the cellular and intercellular level, with potential utilities absent from traditional cell therapies and tissue/organ engineering, the two main pillars of regenerative medicine. The intervention is still very much conceptual, and any potential utilities over other therapeutic modalities within regenerative medicine would need to be verified via preclinical studies, but their hope is to stimulate further research at this interface between geroscience and regenerative medicine.

More information: Francesco Albert Bosco Cortese et al, Induced Cell Turnover: A novel therapeutic modality for in situ tissue regeneration, Human Gene Therapy (2017). DOI: 10.1089/hum.2016.167

Journal reference: Human Gene Therapy

Provided by: Biogerontology Research Foundation

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Induced Cell Turnover: A proposed modality for in situ tissue regeneration & repair - Medical Xpress

Pierre Coulombe, Ph.D. to lead UM Department of Cell & Developmental Biology – University of Michigan Health System News (press release)

ANN ARBOR, MI One of the oldest departments at the University of Michigan is about to get a new leader. The U-M Board of Regents today approved the appointment of Pierre A. Coulombe, Ph.D., to lead the Department of Cell and Developmental Biology in the Medical School.

Coulombe will become chair on August 1, and lead one of the nine basic science departments of Michigan Medicine, U-Ms academic medical center. The departments researchers study how structure governs function in cells and tissues throughout the body, and how complex arrays of signals are integrated to foster the proper development of tissues and organs. They also study stem cells, including embryonic stem cells, and train undergraduate, graduate and medical students in cell biology.

The department traces its roots back to 1854, soon after the founding of the Medical School, when it was known as the Department of Anatomy.

Coulombe comes to Michigan from Johns Hopkins University, where he chaired the Department of Biochemistry and Molecular Biology in the Bloomberg School of Public Health for nine years, and held the E.V. McCollum professorship as well as several joint appointments in the School of Medicine. At Hopkins, Coulombe was noted for at recruiting and nurturing junior faculty members to success, and developing robust training programs for graduate students and post-doctoral fellows. He was also instrumental in addressing the departments infrastructure needs.

To me, cell and developmental biology are critically important endeavors as one seeks to translate the wealth of knowledge acquired in biochemistry and molecular biology, along with the power of imaging techniques, into a better understanding of how organs and tissues form, and operate, under normal and disease conditions, he says. This knowledge is also important for developing novel therapies for human disease. U-M already is a formidable institution, and otherwise is making a substantial investment into biomedical research. Therefore, I am absolutely thrilled about the opportunity to lead Cell & Developmental Biology, and team up with my new colleagues in the department and at U-M, to fulfill this potential.

In addition to his appointment in Cell & Developmental Biology, Coulombe will have a joint appointment in the U-M Department of Dermatology. His research focuses on understanding how keratin proteins and the nanoscale filaments they form foster an optimal architecture and function in skin and related epithelia, and how disruption of these processes result in diseases ranging from inherited conditions to cancer.

A native of Montral, Qubec, Coulombe earned his undergraduate degree from the Universit du Qubec Montral and his Ph.D. in Pharmacology from Universit de Montral. He completed his postdoctoral fellowship in the Department of Molecular Genetics and Cell Biology & Howard Hughes Medical Institute at the University of Chicago before joining Johns Hopkins School of Medicine in 1992. He is the author of more than 140 peer-reviewed publications and one book, holds one patent, and has received multiple awards in recognition of his research and teaching endeavors.

For more about the U-M Department of Cell and Developmental Biology, visit https://medicine.umich.edu/dept/cell-developmental-biology.

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Pierre Coulombe, Ph.D. to lead UM Department of Cell & Developmental Biology - University of Michigan Health System News (press release)

Banks targets embryonic stem cell research funding – Fort Wayne Journal Gazette

Rep. Jim Banks, R-3rd, introduced legislation Thursday that would prevent the use of federal funds for stem cell research involving human embryos.

Banks' bill would direct the U.S. Department of Health and Human Services to give priority to medical research with the greatest potential for near-term clinical benefit in human patients and that does not use stem cells from destroyed, discarded or created embryos.

Scientists say embryonic stem cells show potential for transforming into other cells that might repair tissue damaged by disease or injury. Human embryonic stem cells used in research come from donated, unused fertilized eggs developed for in vitro fertilization procedures.

Adult blood stem cells are used to treat leukemia, and adult neural stem cells have been tested for brain disorders and spinal cord injuries.

This bipartisan bill prioritizes stem cell research that has a real impact on patients suffering right now while ensuring that research is conducted ethically without destroying human embryos, Banks, a freshman lawmaker from Columbia City, said in a statement.

Rep. Dan Lipinski, D-Ill., co-sponsored Banks' bill, which is called the Patients First Act of 2017.

The Dickey-Wicker Amendment of 1996 prohibited HHS from funding research using created or destroyed human embryos. But a federal court ruled in 2011 that Dickey-Wicker was ambiguous and did not ban research using stem cells from in vitro fertilization.

The Alliance for Regenerative Medicine, a coalition of medical companies, research institutions and patient advocacy groups that support embryonic stem cell research, had little to say Thursday about Banks' legislation.

As an organization representing the broader global regenerative medicine sector, our position is that we are in favor of government funds supporting the best science in an effort to speed safe and efficacious products to patients in need, Lyndsey Scull, senior communications director for ARM, said in an email.

Scull said ARM would monitor Banks' bill in the legislative process.

Banks' proposal states it would promote the derivation of pluripotent stem cell lines without the creation of human embryos for research purposes and without the destruction or discarding of, or risk of injury to, a human embryo.

The National Institutes of Health defines pluripotent stem cells as those that can give rise to any type of cell in the body except those needed to support and develop a fetus in the womb. They come from embryos and fetal tissue, although induced pluripotent stem cells are genetically reprogrammed cells taken from adult tissues.

In May, Banks led a letter signed by 40 other Republican House members that asked President Donald Trump to replace Dr. Francis Collins as the director of the NIH because of Collins' support for human embryonic stem cell research. Trump announced last week that he is retaining Collins, a geneticist nominated for NIH chief by President Barack Obama and confirmed by unanimous consent by the Senate in 2009.

The NIH is an HHS agency.

bfancisco@jg.net

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Banks targets embryonic stem cell research funding - Fort Wayne Journal Gazette

Pro-Life Congressional Bill Urges NIH to Stop Killing Human Beings in Embryonic Stem Cell Research – LifeNews.com

Republican Congressman Jim Banks (IN-03) today joined with Democratic Congressman Dan Lipinski (IL-03) to introduce a bipartisan bill to direct the Department of Health and Human Services (HHS) and the National Institutes of Health (NIH) to prioritize life-affirming stem cell research with near-term benefits for human patients and to refrain from creating or destroying human embryos in the process.

This bipartisan bill prioritizes stem cell research that has a real impact on patients suffering right now while ensuring that research is conducted ethically with destroying human embryos, said Banks. HHS and NIH both perform important life-saving research and promoting research that protects life has support on both sides of the aisle.

If enacted, the Banks legislation would direct HHS to prioritize stem cell research that has the greatest potential for near-term benefit in human patients. The bill also prohibits such research from creating or destroying human embryonic stem cells in the process.

Follow LifeNews.com on Instagram for pro-life pictures.

The bill would direct the HHS Secretary, in consultation with the Director of the NIH, to publish final guidelines to ensure all future research prioritizes the potential for near-term clinical benefit in human patients while refraining from creating or destroying human embryos in the process. Additionally, the bill would require the HHS Secretary to submit a report each fiscal year outlining the number of stem cell research proposals that were peer reviewed, a summary of all related proposals that were not funded and a subsequent explanation for why they failed to receive funding.

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Pro-Life Congressional Bill Urges NIH to Stop Killing Human Beings in Embryonic Stem Cell Research - LifeNews.com

Stem cell scientist joins crowded field to unseat Rohrabacher – The Hill

Stem cell researcher Hans Keirstead is the latest Democrat to jump into the race to unseat longtime Rep. Dana Rohrabacher (R) in one of Californias top swing seats.

Keirstead announced his bid on Thursday, touting a career in medicine and saying he can bring a new outlook to Congress.

Both national and local Democrats are excited about Keirsteads entry into the race to challenge Rohrabacher, who has become a top target ahead of the 2018 midterms. Keirstead is the CEO at AiVita Biomedical in Irvine, Calif., and his biography says hes an internationally known stem cell scientist who has led therapy development for late stage cancers and other diseases.

Democrats are targeting several GOP-held seats in California. Hopes are especially high for Rohrabachers Orange County-based seat, since Hillary ClintonHillary Rodham ClintonTrump supporter who lost tight Va. gov primary weighs Senate run Stem cell scientist joins crowded field to unseat Rohrabacher Single-payer healthcare is far more expensive than advocates claim MORE carried the district by less than 2 points in 2016.

Im running for Congress because I believe that innovative thinking and a people-first attitude matter to the constituents of this district. If given the opportunity to represent our community in Congress, Ill bring a new perspective of problem solving and accountability.

At least four other Democrats are already running to challenge Rohrabacher, who has served in Congress for nearly 30 years. Some of those Democratic contenders include business owner Laura Oatman and businessman Henry Rouda, who are both former registered Republicans.

Rohrabacher has never had a serious Democratic challenge. While hes had a well-known pro-Russia stance for years, his views have been thrown into the spotlight amid the investigations into Russian meddling in the 2016 presidential election.

The New York Times reported last month that the FBI warned Rohrabacher in 2012 that Russian spies wanted to recruit him.

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Stem cell scientist joins crowded field to unseat Rohrabacher - The Hill

Molecular Genetics – Cell and Gene Therapy Conferences

Sessions/Tracks

Track 1:Molecular Biology

Molecular biologyis the study of molecular underpinnings of the processes ofreplication,transcription,translation, and cell function. Molecular biology concerns themolecularbasis ofbiologicalactivity between thebiomoleculesin various systems of acell,gene sequencingand this includes the interactions between theDNA,RNAand proteinsand theirbiosynthesis. Inmolecular biologythe researchers use specific techniques native to molecular biology, increasingly combine these techniques and ideas from thegeneticsandbiochemistry.

RelatedMolecular Biology Conferences| Genetics Conferences|Gene Therapy Conferences|Biotechnology Conferences| Immune Cell Therapy Conferences

2nd World Congress onHuman Genetics&Genetic Disorders, November 02-03, 2017 Toronto, Canada; 9th International Conference onGenomicsandPharmacogenomics, June 15-16, 2017 London, Uk; 6th International Conference and Exhibition onCellandGene Therapy, Mar 27-28, 2017 Madrid, Spain; Gordon Research Conference,Viruses&Cells, 14 - 19 May 2017, Lucca, Italy;Human Genome Meeting(HGM 2017), February 5-7 2017, Barcelona, Spain; Embl Conference:Mammalian GeneticsAndGenomics:From Molecular Mechanisms To Translational Applications, Heidelberg, Germany, October 24, 2017;GeneticandPhysiological Impacts of Transposable Elements, October 10, 2017, Heidelberg, Germany.

American Society for Cell Biology;The Society for Molecular Biology & Evolution;American Society for Biochemistry and Molecular Biology;The Nigerian Society of Biochemistry and Molecular Biology;Molecular Biology Association Search Form - CGAP.

Track 2:Gene Therapy and Genetic Engineering

Thegenetic engineeringis also called asgenetic modification. It is the direct manipulation of an organism'sofgenomeby usingbiotechnology. It is a set of technologies used to change the genetic makeup of the cell and including the transfer of genes across species boundaries to produce improved novelorganisms. Genesmay be removed, or "knocked out", using anuclease.Gene is targetinga different technique that useshomologousrecombinationto change anendogenous gene, and this can be used to delete a gene, removeexons, add a gene, or to introducegenetic mutations. There is an dna replacement therapy, Genetic engineering does not normally include traditional animal and plant breeding, gene sequencing, in vitro fertilization, induction of polyploidy,mutagenesisand cell fusion techniques that do not use recombinant nucleic acids or a genetically modified organism in the process,diseases treated with gene therapywas initially meant to introduce genes straight into human cells, focusing on diseases caused by single-gene defects, such as cystic fibrosis, hemophilia, muscular dystrophy and sickle cell anemia

RelatedMolecular Biology Conferences| Genetics Conferences|Gene Therapy Conferences|Biotechnology Conferences| Immune Cell Therapy Conferences

8thWorld Congress onMolecular Pathology, June 26-27, 2017 San Diego, USA; 11thInternational Conference onSurgical Pathology& Practice, March 27-28, 2017, MADRID, SPAIN; 13th EuropeanPathologyCongress, Aug 02-03, 2017, MILAN, ITALY; 28th Annual Meeting, Austrian Society ForHuman GeneticsAnd The Swiss Society OfMedical GeneticsCombined Meeting 2017 march 29, 2017 - March 31, 2017, bochum , Germany.

Association for Clinical Genetic Science;Genetics Society of America | GSA;Association of Genetic Technologists;Molecular Genetics - Human Genetics Society of Australasia;Genetic Engineering - Ecological Farming Association.

Track 3:Cell & Gene Therapy

Cell therapy is also calledcellular therapyorCyto therapy, in which cellular material is injected into patient this generally means intact, living cells. The first category iscell therapyin mainstream medicine. This is the subject of intense research and the basis of potential therapeutic benefit. Such research can be controversial when it involves human embryonic material. The second category is in alternative medicine, and perpetuates the practice of injecting animal materials in an attempt to cure disease.Gene therapyis the therapeutic delivery of nucleic acid polymers into a patient's cells as a drug to treat disease. Gene therapy is a way to fix agenetic problemat its source. The polymers are either translated into proteins, interfere with targetgene expression, or possibly correct genetic mutations. The most common form uses DNA that encodes a functional,therapeutic gene to replace a mutated gene. The polymer molecule is packaged within a "vector", which carries the molecule inside cells. Vectors used in gene therapy, the vector incorporates genes intochromosomes. The expressed nucleases then knock out and replace genes in the chromosome. The Center forCell and Gene Therapyconducts research into numerous diseases, including but not limited to PediatricCancer, HIV gliomaandCardiovascular disease.

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2nd World Congress onHuman Genetics&Genetic Disorders, November 02-03, 2017 Toronto, 27 Canada ; 7th International Conference onPlant Genomics, July 03-05, 2017, Bangkok, Thailand ; American Society ofGeneandCell Therapy(ASGCT) 20th Annual Meeting, 10 - 13 May 2017, Washington, DC;Genomic Medicine for Clinicians(course), January 25-27, 2017, Hinxton , Cambridge, UK; Embo Conference:ChromatinandEpigenetics, Heidelberg, Germany, May 3, 2017; 14th International Symposium on Variants in theGenomeSantiago de Compostela, Galicia, Spain, June 5 - 8, 2017;

Genetics and Molecular Medicine - American Medical Association;Genetics Society of America / Gsa;British Society for Genetic Medicine;British Society for Gene and Cell Therapy; Australasian Gene Therapy Society.

Track 4:Cell Cancer Immunotherapy

Immunologydeals with the biological and biochemical basis for the body's defense against germs such as bacteria, virus and mycosis (fungal infections) as well as foreign agents such asbiological toxinsand environmental pollutants, and failures and malfunctions of these defense mechanisms. Cancer immunotherapy is the use of the immune system to treat cancer. Immunotherapies can be categorized as active, passive or hybrid (active and passive). Antibodies are proteins produced by the immune system that bind to a target antigen on the cell surface. The immune system normally uses them to fight pathogens. A type of biological therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection, and other diseases. Some types of immunotherapy only target certain cells of the immune system. Others affect the immune system in a general way. Types of immunotherapy include cytokines, vaccines, bacillus Calmette-Guerin (BCG), and some monoclonal antibodies.

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9thAnnual Meeting onImmunologyandImmunologist, July 03-05, 2017 Kuala Lumpur, Malaysia; 8th MolecularImmunology&ImmunogeneticsCongress, March 20-21, 2017 Rome, Italy; 8th EuropeanImmunologyConference, June 29-July 01, 2017 Madrid, Spain; July 03-05, 2017; B Cells and T Follicular Helper Cells Controlling Long-Lived Immunity (D2), April 2017, 2327, Whistler, British Columbia, Canada; Mononuclear Phagocytes in Health,Immune Defense and Disease, 304 May, Austin, Texas, USA;Modeling Viral Infections and ImmunityMAY 2017, 14, Estes Park, Colorado, USA; IntegratingMetabolism and Immunity(E4)292 June, Dublin, Ireland.

The American Association of Immunologists;Clinical Immunology Society ; Indian Immunology Society;IUIS - International Union of Immunological Societies;American Society for Histocompatibility and Immunogenetics.

Track 5:Clinical Genetics

Clinical geneticsis the practice of clinical medicine with particular attention tothe hereditary disorders. Referrals are made togenetics clinicsfor the variety of reasons, includingbirth defects,developmental delay,autism,epilepsy, and many others. In the United States, physicians who practice clinical genetics are accredited by theAmerican Board of Medical Genetics and Genomics(ABMGG).In order to become a board-certified practitioner of a Clinical Genetics, a physician must complete minimum of 24 months of his training in a program accredited by the ABMGG. Individual seeking acceptance intoclinical geneticstraining programs and should hold an M.D. or D.O. degree (or their equivalent)and he/she have completed a minimum of 24 months of their training in ACGME-accredited residency program internal medicine, pediatrics and gynecology or other medical specialty.

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Belgian Society OfHuman GeneticsMeeting 2017 february 17, 2017, Belgium; American College Of Medical Genetics 2017 AnnualClinical GeneticsMeeting march 21-25 2017, phoenix , United States; German Society Of Human Genetics 28th Annual Meeting, Austrian Society ForHuman GeneticsAnd The Swiss Society OfMedical GeneticsCombined Meeting 2017 march 29, 2017 - March 31, 2017, bochum , Germany; Spanish Society OfHuman GeneticsCongress 2017april 25, 2017 - April 28, 2017 madrid , Spain;

Clinical Genetics Associates;Clinical Genetics Society(CGS);The genetic associate;International Conference on Clinical and Medical Genetics;Association for Clinical Genetic Science;The American Society of Human Genetics.

Track 6:Pharmacogenetics

Pharmacogeneticsis the study of inherited genetic differences in drug metabolic pathways which can affect individual responses towards the drugs, both in their terms of therapeutic effect as well as adverse effects. In oncology, Pharmacogenetics historically is the study ofgerm line mutations(e.g., single-nucleotide polymorphisms affecting genes coding forliver enzymesresponsible for drug deposition and pharmacokinetics), whereaspharmacogenomicsrefers tosomatic mutationsin tumoral DNA leading to alteration in drug response.

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Spanish Society OfHuman GeneticsCongress 2017april 25, 2017 - April 28, 2017, madrid , Spain; 8th World Congress onPharmacology, August 07-09, 2017 Paris, France; World Congress onBio therapeutics, May 22-23, 2017, Mexico City, Mexico; 8th World Congress OnPharmacologyAndToxicology, July 24-26, 2017, Melbourne, Australia; German Society Of Human Genetics 28th Annual Meeting, Austrian Society ForHuman GeneticsAnd The Swiss Society OfMedical GeneticsCombined Meeting 2017march 29, 2017 - March 31, 2017 bochum , Germany.

Pharmacogenomics - American Medical Association;Associate Principal Scientist Clinical Pharmacogenetics;European Society of Pharmacogenomics and Personalised Therapy;Genome-wide association studies in pharmacogenomics.

Track 7:Molecular Genetic Pathology

Molecular genetic pathologyis an emerging discipline withinthe pathologywhich is focused in the study and diagnosis of disease through examination of molecules within the organs, tissues or body fluids. A key consideration is more accurate diagnosis is possible when the diagnosis is based on both morphologic changes in tissuestraditional anatomic pathologyand onmolecular testing. Molecular Genetic Pathology is commonly used in diagnosis of cancer and infectious diseases. Integration of "molecular pathology" and "epidemiology" led tointerdisciplinaryfield, termed "molecular pathological epidemiology" (MPE),which representsintegrative molecular biologicand population health science.

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8th World Congress OnMolecular Pathology, June 26-27, 2017 San Diego, USA; 11th International Conference OnSurgical Pathology& Practice, March 27-28, 2017, Madrid, Spain; 13th EuropeanPathologyCongress, Aug 02-03, 2017, Milan, Italy; Embl Conference:Mammalian GeneticsAndGenomics, Heidelberg, Germany, October 24, 2017; Embo|Embl Symposium: TheMobile Genome: Genetic And Physiological Impacts Of Transposable Elements, Heidelberg, Germany, October 10, 2017.

Clinical Pathology Associates Molecular Pathology; Association mapping Wikipedia;Association for Molecular Pathology(AMP);Molecular Pathology - Association of Clinical Pathologists;SELECTBIO - Molecular Pathology Association of India.

Track 8:Gene Mapping

Genomemappingis to place a collection of molecular markers onto their respective positions ongenome.Molecular markerscome in all forms. Genes can be viewed as one special type of genetic markers in construction ofgenome maps, and the map is mapped the same way as any other markers. The quality ofgenetic mapsis largely dependent upon the two factors, the number of genetic markers on the map and the size of themapping population. The two factors are interlinked, and as larger mapping population could increase the "resolution" of the maps and prevent the map being "saturated". Researchers begin a genetic map by collecting samples of blood or tissue from family members that carry a prominent disease or trait and family members that don't. Scientists then isolate DNA from the samples and closely examine it, looking for unique patterns in the DNA of the family members who do carry the disease that the DNA of those who don't carry the disease don't have. These unique molecular patterns in the DNA are referred to as polymorphisms, or markers.

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3rd WorldBio Summit&Expo, Abu Dhabi, UAE, June 19-21, 2017; 9th International Conference onGenomicsandPharmacogenomicsJune 15-16, 2017 London, Uk; Keystone Symposium: Mononuclear Phagocytes in Health,Immune DefenseandDisease, 304 May 2017, Austin, Texas, USA;Molecular Neurodegeneration(course) Hinxton, Cambridge, UK, January 9-14, 2017;

Association for Clinical Genetic Science;Genome-wide association study Wikipedia;Gene mapping by linkage and association analysis NCBI;Gene mapping by linkage and association analysis | Springer Link.

Track 9:ComputationalGenomics

Computational genomics refers to the use of computational and statistical analysis to decipherbiologyfromgenome sequencesand related data, including DNA and RNA sequence as well as other "post-genomic" data. This computational genomics is also known asComputational Genetics. These, in combination with computational and statistical approaches to understanding the function of the genes and statistical association analysis, this field is also often referred to as Computational and Statistical Genetics/genomics. As such, computational genomics may be regarded as a subset of bioinformatics and computational biology, but with a focus on using whole genomes rather than individual genes to understand the principles of how the DNA of a species controls its biology at the molecular level and beyond. With the current abundance of massive biological datasets, computational studies have become one of the most important means to biological discovery.The field is defined and includes foundations in thecomputer sciences,applied mathematics, animation, biochemistry, chemistry, biophysics,molecular genetics,neuroscienceandvisualization. Computational biology is different from biological computation, which is a subfield of computer engineering using bioengineering and biology to build computers, but is similar tobioinformatics.

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Modeling Viral Infections and Immunity,10. MAY 2017, 14, Estes Park, Colorado, USA;Integrating Metabolism and Immunity(E4)292 June, Dublin, Ireland; EMBL Conference:Mammalian GeneticsandGenomics, Heidelberg, Germany, October 24, 2017; EMBO|EMBL Symposium: The Mobile Genome:GeneticandPhysiological Impacts of Transposable Elements, Heidelberg, Germany, October 10, 2017;

American Association of Bio analysts - Molecular/Genetic Testing;ISCB - International Society for Computational Biology;International Society for Computational Biology Wikipedia;Bioinformatics societies OMICtools;Towards an Australian Bioinformatics Society.

Track 10:Molecular Biotechnology

Molecular Biotechnologyis the use of living systems and organisms to develop or to make products, or "any technological application that uses the biological systems, living organisms or derivatives, to make or modify products or processes for specific use. Molecular biotechnology results from the convergence of many areas of research, such as molecular biology, microbiology, biochemistry, immunology, genetics and cell biology. It is an exciting field fueled by the ability to transfer genetic information between organisms with the goal of understanding important biological processes or creating a useful product. The completion of the human genome project has opened a myriad of opportunities to create new medicines and treatments, as well as approaches to improve existing medicines. Molecular biotechnology is a rapidly changing and dynamic field. As the pace of advances accelerates, its influence will increase. The importance and impact of molecular biotechnology is being felt across the nation. Depending on the tools and applications, it often overlaps with the related fields of bioengineering,biomedical engineering, bio manufacturing andmolecular engineering.Biotechnologyalso writes on the pure biological sciences animalcell culture, biochemistry,cell biology, embryology, genetics, microbiology, andmolecular biology.

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8th EuropeanImmunologyConference, June 29-July 01, 2017 Madrid, Spain; World Congress onBio therapeutics, May 22-23, 2017, Mexico City, Mexico;Human Genome Meeting(HGM 2017), February 5-7 2017, Barcelona, Spain;Integrating MetabolismandImmunity (E4), 292 June, Dublin, Ireland.

Biotech Associations - Stanford University;Indian Society of Genetics, Biotechnology Research & Development;Genetics and Molecular Medicine - American Medical Association;Genetics Society of America | GSA, British Society for Genetic Medicine;Heritability in the Era of Molecular Genetics - Association for Psychological science.

Track 11:Genetic Transformation

Genetic Transformationis the genetic alteration of cell resulting from the direct uptake and incorporation ofexogenous genetic materialfrom its surroundings through thecell membrane. Transformation is one of three processes for horizontal gene transfer, in which exogenous genetic material passes from bacterium to another, the other two being conjugation transfer of genetic material between two bacterial cells in direct contact andTransductioninjection offoreign DNAby a bacteriophage virus into thehost bacterium. And about 80 species of bacteria were known to be capable of transformation, in 2014, about evenly divided betweenGram-positiveandGram-negative Transformation" may also be used to describe the insertion of new genetic material into non-bacterial cells, including animal and plant cells.

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13th EuropeanPathologyCongress, Milan, Italy; Embl Conference:Mammalian GeneticsAndGenomics, Heidelberg, Germany, October 24, 2017; Embo|Embl Symposium: TheMobile Genome: Genetic And Physiological Impacts Of Transposable Elements, Heidelberg, Germany, October 10, 2017; 2nd World Congress onHuman Genetics&Genetic Disorders, November 02-03, 2017 Toronto, Canada; 9th International Conference onGenomicsandPharmacogenomics, June 15-16, 2017 London, Uk;

American Society of Gene & Cell Therapy: ASGCT;Gene Therapy Societies and Patient Organizations - Gene Therapy Net;European Society of Gene and Cell Therapy (ESGCT);British Society for Gene and Cell Therapy;Gene Therapy - American Medical Association.

Track 12:Genetic Screening

Genetic screenis an experimental technique used to identify and select the individuals who possess a phenotype of interest inmutagenized population. A genetic screen is a type ofphenotypic screen. Genetic screen can provide important information on gene function as well as the molecular events that underlie a biological process or pathway. While thegenome projectshave identified an extensive inventory of genes in many different organisms, genetic screens can provide valuable insight as to how thosegenes function.

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13th EuropeanPathologyCongress, Aug 02-03, 2017, Milan, Italy; 2nd World Congress onHuman Genetics&Genetic Disorders, November 02-03, 2017 Toronto, 27 Canada; 7th International Conference onPlant Genomics, July 03-05, 2017, Bangkok, Thailand; Embl Conference:Mammalian GeneticsAndGenomics, Heidelberg, Germany, October 24, 2017; Embo|Embl Symposium: TheMobile Genome: Genetic And Physiological Impacts Of Transposable Elements, Heidelberg, Germany, October 10, 2017, 10 - 13 May 2017, American Society ofGeneandCell Therapy(ASGCT) 20th Annual Meeting, Washington, DC;

Association for Clinical Genetic Science; Association for Molecular Pathology (AMP);Mapping heritability and molecular genetic associations with cortical;Genetics and Molecular Medicine - American Medical Association.

Track 13:Regulation of Gene Expression

Regulation of Gene expressionincludes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA), and is informally termed gene regulation. Sophisticated programs of gene expression are widely observed in biology, Virtually any step of gene expression can be modulated, fromtranscriptional initiation,RNA processing, and post-translational modificationof a protein. Often, one gene regulator controls another in a gene regulatory network. Any step of gene expression may be modulated, from theDNA-RNA transcriptionstep to post-translational modification of a protein.

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7th International Conference onPlant Genomics, July 03-05, 2017, Bangkok, Thailand; EMBO|EMBL Symposium: The Mobile Genome:GeneticandPhysiological Impacts of Transposable Elements, Heidelberg, Germany, October 10, 2017; 10. MAY 2017, 14, Estes Park, Colorado, USA,Modeling Viral Infections and Immunity; 292 June, Dublin, Ireland,Integrating Metabolism and Immunity(E4); MAY 2017, 14, Estes Park, Colorado, USA,Modeling Viral InfectionsandImmunity; 8th EuropeanImmunologyConference, June 29-July 01, 2017 Madrid, Spain; 9th International Conference onGenomicsandPharmacogenomics, June 15-16, 2017 London, Uk;

Gene Therapy Societies and Patient Organizations - Gene Therapy Net;European Society of Gene and Cell Therapy (ESGCT);British Society for Gene and Cell Therapy;Gene Therapy - American Medical Association

Track 14: Cancer Gene Therapy

Cancer is an abnormal growth of cells the proximate cause of which is an imbalance in cell proliferation and death breaking-through the normal physiological checks and balances system and the ultimate cause of which are one or more of a variety of gene alterations. These alterations can be structural, e.g., mutations, insertions, deletions, amplifications, fusions and translocations, or functional (heritable changes without changes in nucleotide sequence). No single genomic change is found in all cancers and multiple changes (heterogeneity) are commonly found in each cancer generally independent of histology. In healthy adults, the immune system may recognize and kill the cancer cells or allow non-detrimental host-cancer equilibrium; unfortunately, cancer cells can sometimes escape the immune system resulting in expansion and spread of these cancer cells leading to serious life threatening disease. Approaches to cancer gene therapy include three main strategies: the insertion of a normal gene into cancer cells to replace a mutated (or otherwise altered) gene, genetic modification to silence a mutated gene, and genetic approaches to directly kill the cancer cells. Pathway C represents immunotherapy using altered immune cells. Another unique immunotherapy strategy facilitated by gene therapy is to directly alter the patient's immune system in order to sensitize it to the cancer cells. One approach uses mononuclear circulating blood cells or bone marrow gathered from the patient.

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8th EuropeanImmunologyConference, June 29-July 01, 2017 Madrid, Spain; World Congress onBio therapeutics, May 22-23, 2017, Mexico City, Mexico;Human Genome Meeting(HGM 2017), February 5-7 2017, Barcelona, Spain;Integrating MetabolismandImmunity (E4), 292 June, Dublin, Ireland.

Biotech Associations - Stanford University;Indian Society of Genetics, Biotechnology Research & Development;Genetics and Molecular Medicine - American Medical Association;Genetics Society of America | GSA, British Society for Genetic Medicine;Heritability in the Era of Molecular Genetics - Association for Psychological science.

Track 15:Genetic Transplantation

Transplantation genetics is the field of biology and medicine relating to the genes that govern the acceptance or rejection of a transplant. The most important genes deciding the fate of a transplanted cell, tissue, or organ belong to what is termed the MHC (the major histocompatibility complex). Genetic Transplantation is the moving of an organ from one body to another or from a donor site to another location on the person's own body, to replace the recipient's damaged or absent organ. Organs and/or tissues that aretransplantedwithin the same person's body are calledauto grafts. Transplants that are recently performed between two subjects of the same species are calledallografts. Allografts can either be from a living or cadaveric source Organs that can be transplanted are the heart, kidneys, liver, lungs, pancreas, intestine, and thymus. The kidneys are the most commonlytransplanted organs, followed by the liver and then the heart. The main function of the MHC antigens is peptide presentation to the immune system to help distinguish self from non-self. These antigens are called HLA (human leukocyte antigens). They consists of three regions: class I (HLA-A,B,Cw), class II (HLA-DR,DQ,DP) and class III (no HLA genes)

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8th World Congress onPharmacology, August 07-09, 2017 Paris, France; International Conference onClinicalandMolecular Genetics, Las Vegas, USA, April 24-26, 2017; Aug 02-03, 2017, 13th EuropeanPathologyCongress, Milan, Italy; Embl Conference:Mammalian GeneticsAndGenomics, Heidelberg, Germany, October 24, 2017; 7th International Conference onPlant Genomics, July 03-05, 2017, Bangkok, Thailand.

American society of Transplantation;American Society of Transplant Surgeons: ASTS; Patient associations. Donation and transplantation;American Society of Gene & Cell Therapy ASGCT;Gene Therapy Societies and Patient Organizations - Gene Therapy Net.

Track 16:Cytogenetics

Cytogeneticsis a branch ofgeneticsthat is concerned withstudy of the structure and function of the cell, especially thechromosomes. It includes routine analysis of G-banded chromosomes, othercytogenetic banding techniques, as well as molecular Cytogenetics such as fluorescent in suitable hybridization FISH and comparativegenomic hybridization.

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9thAnnual Meeting onImmunologyandImmunologist, July 03-05, 2017 Kuala Lumpur, Malaysia; 8th MolecularImmunology&ImmunogeneticsCongress, March 20-21, 2017 Rome, Italy; 8th EuropeanImmunologyConference, June 29-July 01, 2017 Madrid, Spain; July 03-05, 2017; B Cells and T Follicular Helper Cells Controlling Long-Lived Immunity (D2), April 2017, 2327, Whistler, British Columbia, Canada.

European Cytogeneticists Association;Association of Genetic Technologists;Association for Clinical Genetic Science;Cytogenetics - Human Genetics Society of Australasia;European Cytogeneticists Association

Molecular Biology 2016

Molecular Biology 2016 Report

2ndWorld Bio Summit & Molecular Biology Expowas organized during October 10-12, 2016 at Dubai, UAE. The conference was marked with the attendance ofEditorial Board Members of supporting journals, Scientists, young and brilliant researchers, business delegates and talented student communities representing more than 25 countries, who made this conference fruitful and productive.

This conference was based on the theme Recent advances in Bio Science which included the following scientific tracks:

Molecular Biology

Microbiology

Analytical Molecular Biology

Bioinformatics

Biochemistry and Molecular Biology

Molecular Biology and Biotechnology

Cancer Molecular Biology

Computational Biology

Molecular Biology of the Cell

Molecular biology of the cardiovascular system

Molecular Biology in Cellular Pathology

Molecular Biology of Diabetes

Molecular Biology and Genetic Engineering

Enzymology and Molecular Biology

Molecular Biology of the Gene

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Molecular Genetics - Cell and Gene Therapy Conferences

For experimental cancer therapy, a struggle to ensure supply keeps up with demand – Science Magazine

The year-old Novartis-Penn Center for Advanced Cellular Therapeutics in Philadelphia supplies cancer fighting T cells to multiple hospitals, visible out the window.

CANNONDESIGN

By Jennifer Couzin-FrankelJun. 13, 2017 , 3:15 PM

A transformative cancer therapy based on modified immune cells has lured doctors, companies, and patients alike, but many are hitting a frustrating roadblock: generating enough of these chimeric antigen receptor (CAR)-T cells to meet surging demand. The situation is fluid, with shortages cropping up in some places and easing in others. Doctors, meanwhile, are grappling with how best to distribute the experimental therapy among very sick patients in clinical trials.

How do I allocate the resource in a way thats fairest to everybody and that treats the most patients and potentially saves the most lives? asks Stephan Grupp, a pediatric oncologist at the Childrens Hospital of Philadelphia (CHOP) in Pennsylvania. Grupp has offered CAR-T therapy to more than 150 children with late-stage acute lymphoblastic leukemia (ALL)and worries that because of supply limitations, he cant help more.

CAR-T cell therapy took the cancer world by storm in the summer of 2010. It involves removing a patients immune cells, genetically modifying them to fight their particular cancer, then transfusing them back. The approach is riskysome have even died from itbut for blood cancers in particular, its been remarkable, saving patients at the 11th hour and keeping some in remission for years.

For patients, getting the most anticipated new treatments is never easy. Clinical trials are tightly controlled and not everyone is eligible. But for this personalized approach, the difficulties are multiplied. From the beginning, CAR-T cells were tough to produce. Unlike a drug, each batch is designed for a specific patient. Production involves genetic engineering and working with live cells, and it is still mostly done by hand, by highly trained technicians. Preparing cells for a single patient can take weeks and cost tens of thousands of dollars.

The demand took off when doctors began reporting impressive results in leukemia and, later, lymphoma, with response rates ranging from 40% to 50% in lymphoma to more than 90% in some leukemias. More researchers joined the fray, keen to test CAR-T therapy in patients with other cancers. Companies joined in, too, anticipating a burgeoning market. Dozens of trials are underway, and two CAR-T cell products, for childhood and young adult ALL and aggressive B-cell lymphoma, may be approved later this year by the U.S. Food and Drug Administration (FDA).

The promise of this stuff outpaced the typical approach to development, Grupp says. With about 50 scientists and technicians working furiously to produce cell therapies for trials throughout the University of Pennsylvania (UPenn), CHOP can treat about five children each month. That number rules my life, says Grupp, who receives two or three calls a week about yet another child whose parents hope to secure the therapy. He engages in a delicate dance, trying to keep some children stable while treating the sickest, before theyre too sick to benefit. So far, he believes, he has reached everyone referred from within the United States in time.

At the National Cancer Institute in Bethesda, Maryland, hematologist James Kochenderfers waiting list is driven by the two or three CAR-T cell products a month hes able to secure from the agencys facility. Thats not enough to accommodate all the adults eligible for the seven CAR-T trials hes running in blood cancers. He usually enrolls on a first-come, first-served basis.

Demand for the therapy is also spurring competition for the researchers and technicians who create the cells. Everyone is losing [people] to everyone else, says immunologist Bruce Levine of UPenn, who directs the cell production facility. He guards against the poaching of his staff by companies that can pay a higher salary, in part by stressing a connection with patients at the hospitals he can see out his window. We have patients come over on a regular basis who received cells made in UPenns facility. No company can offer that.

One center that says its keeping up with demand is Baylor College of Medicine in Houston, Texas, in part because of a stroke of luck. We kind of overbuilt, opening a vast facility in 2010, says Adrian Gee, who runs it. Seattle Childrens Hospital in Washington recently broke ground on a building that in a few years will triple or quadruple its cell therapy capacity, now about 10 batches of CAR-T cells a month.

Another way to generate cells for more patients is to shorten the time it takes to make them. Right now the time from vein to vein ranges from about 2 to 4 weeks, depending partly on the technique. Scientists are experimenting with more efficient approaches. Rebecca Gardner, a pediatric oncologist at Seattle Childrens, says the hospital is shifting to one that shaves a week or two off its 3- to 4-week time frame.

Ultimately, the supply problem can be solved with money, says Ronald Levy, a lymphoma specialist at Stanford University in Palo Alto, California. And no one has more money to funnel into CAR-T therapy than the companies. Novartis, for example, spent $43 million on a manufacturing facility in Morris Plains, New Jersey, and last week it released results from a lymphoma trial in which cells were frozen and flown to and from patients in 10 countries.

But some researchers wonder whether the companies will be ready to accommodate the surge in demand expected if FDA approves the first CAR-T therapies. The strain on supplies would increase if doctors want to offer CAR-T therapy to patients off-label, to those who fall outside the approved indication but might still benefit. Unlike a traditional drug, every order needs to be placed through the companiesand its not clear whether they and FDA will support off-label use. If Novartiss product is approved for leukemia patients up to 28 years old, say, and you have a 28.1-year-old, does that mean you cant treat them? asks David Maloney, an oncologist and immunotherapist at the Fred Hutchinson Cancer Research Center in Seattle. I dont know whats going to happen.

For now, scientists are pondering how to best allocate the therapy. At Seattle Childrens, pediatrician and bioethicist Douglas Diekema was drafted by colleagues to offer ethical guidance on what to do if the hospital cant make enough CAR-T cells for everyone in planned trials in brain and other solid tumors, as well as more leukemia trials. A year from now well probably have six to seven trials, up from three today, Gardner says.

Last month, Diekema and his colleagues published a paper online in the Journal of Medical Ethics describing a triage plan for selecting volunteers for CAR-T trials. They argued that, when possible, doctors should focus on the likelihood and magnitude of benefit, treating the sickest patients first. In a second paper still under review, the team will discuss how to allocate CAR-T therapy across clinical trials. There, the ethical calculus is different, including whether the disease affects many people versus just a few.

I did get a 10 p.m. phone call recently, saying we may need to implement the patient allocation strategy, Diekema says. But the hospital, in the end, managed to get the cells to everyone. We dodged it this time, Diekema says. Now, like many others, hes waiting for the next crunch.

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For experimental cancer therapy, a struggle to ensure supply keeps up with demand - Science Magazine

Lab-created antibody could hold the secret to making stem cell therapy safer – Phys.Org

June 15, 2017 Researchers from the A*STAR Bioprocessing Technology Institute involved in the study. Credit: A*STAR Bioprocessing Technology Institute

Stem cells have paved the way for a new era in regenerative medicine, but their use is fraught with risk. Now, A*STAR scientists have developed an antibody that could make stem cell therapy safer.

Human pluripotent stem cells that can differentiate in a petri dish to become any cell needed to repair tissues and organs, hold great promise. Since the first human embryonic stem cells were isolated in 1998, scientists have edged closer to developing 'cell therapy' for humans. In early 2017, a Japanese man became the first patient to receive a retina transplant made of reprogrammed pluripotent stem cells to treat macular degeneration.

These potential rewards come with great risk. Differentiating stem cells into other cell types is an imperfect process, and any stem cells that remain in a culture of transplanted cells can form dangerous by-products, including tumors, such as teratomas.

"If stem cells become a cell therapy product there will be the question of safety," Andre Choo, from the A*STAR Bioprocessing Technology Institute, explains.

Choo and his team are working to make stem cell treatments safer by creating antibodies that 'clean up' the pluripotent stem cells which fail to differentiate.

In 2016, the researchers used a whole-cell immunization strategy to generate different antibodies by injecting mice with viable embryonic stem cells. They then isolated the antibodies and tested their ability to search and destroy pluripotent stem cells in a culture dish.

One antibody, tagged 'A1', was discovered which destroyed pluripotent stem cells in minutes but left other cells unharmed.

Choo's team then focused on how the antibody destroyed its target. The scientists discovered that A1 docks to sugar molecules that are only present on the surface of embryonic stem cells, setting off a signaling cascade that ruptures the stem cell.

"That was quite exciting because it now gives us a view of the mechanism that is responsible for the cell-killing effect," says Choo.

Understanding this mechanism could allow Choo's team to combine the A1 antibody with other treatments to clean stem cells from a mixture of differentiated cells even more effectively.

The finding could also pinpoint how best to target antibodies against sugar molecules on other unwanted cells, including cancer cells.

"We hope that in the near future regenerative medicine will have a place in the clinic," says Choo, who wants this antibody to be part of that process.

The A*STAR-affiliated researchers contributing to this research are from the Bioprocessing Technology Institute. For more information about the team's research, please visit the Stem Cell 1 group webpage.

Explore further: New tools to study the origin of embryonic stem cells

More information: Ji Yun Zheng et al. Excess reactive oxygen species production mediates monoclonal antibody-induced human embryonic stem cell death via oncosis, Cell Death and Differentiation (2017). DOI: 10.1038/cdd.2016.164

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Stem cells have paved the way for a new era in regenerative medicine, but their use is fraught with risk. Now, A*STAR scientists have developed an antibody that could make stem cell therapy safer.

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Lab-created antibody could hold the secret to making stem cell therapy safer - Phys.Org