Stem Cell Clinic

Novel Molecule Reduces the Aggressiveness of Pediatric Cancer – Technology Networks

In Brazil, scientists affiliated with the Human Genome and Stem Cell Research Center (HUG-CELL) at the University of So Paulo (USP) have identified a molecule capable of reducing the aggressiveness of embryonal central nervous system tumors. These are malignant tumors that start in fetal cells in the brain and mainly affect children up to four years old.

The results arepublishedin the journalMolecular Oncology.HUG-CELLis one of the Research, Innovation and Dissemination Centers (RIDCs) supported by So Paulo Research Foundation - FAPESP. Its principal investigator isMayana Zatz, Professor of Human and Medical Genetics at USP's Institute of Biosciences (IB).

The approach proposed by the group can be classified as a type of microRNA-based therapy. A microRNA is a small RNA molecule that does not encode protein but plays a regulatory role in the genome. In this study, researchers used a synthetic version of an inhibitor of microRNA-367 (miR-367) with anti-tumor activity.

"We demonstrated in an animal model of a central nervous system tumor that treatment with a microRNA inhibitor attenuates properties of tumor stem cells and prolongs survival," saidOswaldo Keith Okamoto, a professor at IB-USP and the principal investigator for the study.

Okamoto explained that embryonal central nervous system tumors such as medulloblastomas and atypical teratoid/rhabdoid tumors (AT/RTs) tend to contain cells with characteristics similar to those of stem cells, which boosts their tumorigenic potential and capacity to invade tissue while also making them more resistant to cell death.

These tumors are caused by genetic or epigenetic aberrations in stem cells and neural progenitors when the nervous system is being formed during embryonic development. The neural stem cells that undergo these alterations later give rise to tumor cells. They form aggressive, fast-growing tumors that may appear shortly after birth, in later childhood or in adolescence.

In a previous study, the group tested an approach that used the Zika virus to destroy tumor stem cells (read more atagencia.fapesp.br/27677).

Expression and inhibition

A more recent study was led byCarolini Kaid, a postdoctoral researcher at IB-USP with a scholarship fromFAPESP.

Previous research has already shown that OCT4A, one of the genes that encode pluripotency factors, is overexpressed in aggressive medulloblastomas and that this overexpression is associated with an unfavorable prognosis. During hermaster's research, Kaid detected the expression of miR-367, a gene that promotes stem-like traits in tumor cells, in parallel with overexpression of OCT4A (read more atagencia.fapesp.br/21959).

The researchers then tested a specific synthetic inhibitor of miR-367 containing minor chemical alterations that make it more stable in cells. A patent application has been filed for the invention.

After inducing the formation of central nervous system tumors in mice using three different strains of tumor cells, the researchers injected the miR-367 inhibitor into the brain's right lateral ventricle, a pathway to the cerebrospinal fluid that surrounds the brain and spinal cord. From there, the miR-367 inhibitor was able to access the tumor cells.

Tumor size was reduced considerably, and survival improved in all groups of mice. The results confirmed what had previously been observed in cell cultures.

In this model, the researchers noted that when the synthetic molecule interacted with miR-367 in tumor cells, it prevented this microRNA from affecting the levels of proteins it normally regulates, such as ITGAV and SUZ12.

The latter is known to be involved in silencing pluripotency-related genes in embryonic stem cells.

While the role of ITGAV in embryonal central nervous system tumors is not fully understood, ITGAV is known to participate in the renewal of both normal and tumor stem cells.

"When miR-367 is inhibited in cancer cells, it stops regulating several proteins. This molecular alteration eventually affects the properties of these cells, resulting in an attenuation of the tumor's aggressiveness. This is what makes the strategy interesting," Kaid said.

The researchers believe that in humans, the synthetic molecule alone may be capable of at least containing the development of these tumors and improving survival. Even so, they are testing combinations of the molecule with drugs currently used to treat the tumors. They want to find out whether the approaches could be combined using lower doses of chemotherapy drugs.

Before clinical trials can be performed, however, pharmacology and toxicity studies will be necessary, as will pharmacokinetic testing to show how the molecule is metabolized and how long it stays in the organism (its half-life).

When embryonal central nervous system tumors are conventionally treated with surgery, chemotherapy and/or radiotherapy, morbidity and mortality rates for these patients are high. These tumors correspond to 10% of all central nervous system cancer cases in children.

Even patients who survive longer than most may suffer from permanent treatment-related sequelae that impair their quality of life, such as problems with development, cognition, locomotion and speech.

Reference: Kaid et al. 2019.miR367 as a therapeutic target in stemlike cells from embryonal central nervous system tumors. Molecular Oncology. DOI: https://doi.org/10.1002/1878-0261.12562.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Novel Molecule Reduces the Aggressiveness of Pediatric Cancer - Technology Networks

At the American Academy of Stem Cell Physicians Live Congress 2019, FDA Safety Panel Says No to the Bad Actors – PRNewswire

MIAMI, Nov. 7, 2019 /PRNewswire/ -- The American Academy of Stem Cell Physicians (AASCP) was joined by the alliance leader Janet Marchibroda in hosting a safety standards panel on Nov. 2 at the AASCP Live Congress 2019. The panel which was moderated by Janet Marchibroda, the president of The Alliance for cell therapy now, and included attendance via Skypeby Dr. Peter Marks, director of the Center for Biologics and Evaluation and Research was well-received by physicians from around the world.

The panel discussed safety precautions and considered guidelines for the safety of patients, calling out the bad actors in the field. They noted that current safety guidelines are antiquated and need revision to meet the demands of new cutting-edge medicine such as stem cells, which is a growing field in medical biologics.

Dr. A.J. Farshchian, a spokesperson forthe AASCP, was honored with the 2019 Visionary Award for his pioneering work with the AASCP and the stem cell industry. He said, "There's been too much talk but no action. We need to change that to ensure the safety of the patients who receive care. AASCP will gladly point out the bad actors to the FDA, are we telling on each other? Yes. Are we breaking the Code? No, we are just preserving what's left of this industry."

Later he added, "Many physicians and scientists are starting to believe that some of the regulations regarding stem cells which have been written many years ago have not kept up with the rapidly advancing science. These regulations must be revisited because they are all pass."

At the AASCP Live Congress, board certifications were also provided. To receive the board certification, physicians must meet stringent qualifications, including attending weekly meetings and pass a written and oral exam. The AASCP congratulates those who were recognized, including Dr. Rene Blaha, Dr. Warren Bleiweiss, Dr. Paula Marchionda and Dr. Kalpana Patel, all of whom received diplomat status; and Dr. Max Citrin, who received associate diplomat status.

The American Academy and its board also granted the title of associate professor and all rights therein to Dr. Richard Hull and Dr. Leonid Macheret. Dr. Richard Hull, who also earned tenure with the AASCP, said of the conference, "It is a great pleasure teaching this group of physicians. I love to teach and these physicians are so eager to learn."

To learn more about the AASCP, their educational initiatives and certification, visit AASCP.net.

About AASCP

The American Academy of Stem Cell Physicians (AASCP) is an organization created to advance research and the development of therapeutics in regenerative medicine, including diagnosis, treatment, and prevention of disease related to or occurring within the human body. The AASCP aims to serve as an educational resource for physicians, scientists, and the public. To learn more, visit AASCP.net

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At the American Academy of Stem Cell Physicians Live Congress 2019, FDA Safety Panel Says No to the Bad Actors - PRNewswire

2019s Allen Distinguished Investigators will focus on the mysteries of our cells – Yahoo Tech

The Paul G. Allen Frontiers Group, a division of Seattles Allen Institute, is making a total of $7.5 million in awards to its latest class of five biomedical researchers.

The themes for this years Allen Distinguished Investigators focus on stem cell therapies and single-cell interactions in their native environments.

The field of stem cell biology has the potential to change how we treat diseases by helping precision medicine, and theres so much we still dont understand about the interplay between cells in living tissues or organs, Kathy Richmond, director of the Frontiers Group, said today in a news release.

Our 2019 Allen Distinguished Investigators are pushing their fields in these two areas, through new technology development, probing pivotal interactions in the body that cause health to fail, and generating creative new stem cell models that will improve our understanding of different human diseases, she said.

The late Microsoft co-founder Paul Allen gave the Allen Distinguished Investigator program its start in 2010 as a way to support significant early-stage research thats less likely to receive grants from traditional sources. This years selections bring the roster to a total of 74 researchers, including 13 from the University of Washington.

Each of the investigators will receive $1.5 million in support for their projects over three years. Heres a rundown on the Class of 2019:

The 2019 Allen Distinguished Investigators include Samantha Morris of Washington University in St. Louis, Joshua Rabinowitz of Princeton University, Clive Svendsen of Cedars-Sinai Medical Center, Savas Tay of the University of Chicago and James Wells of Cincinnati Childrens Hospital Medical Center. (Allen Institute Photos)

Samantha Morris of Washington University in St. Louis aims to create a blueprint of cell identity that will enable researchers to improve the way they generate different kinds of cells from human stem cells.

Joshua Rabinowitz of Princeton University will lead a team developing new technologies to study metabolites, the molecules that result from our bodies conversion of food into energy, as well as metabolic activity in single cells from mouse and human tissue.

Clive Svendsen of Cedars-Sinai Medical Center will use stem cells to model how interactions between the gut microbiome and the brain might influence neuron death in patients with Parkinsons disease.

Savas Tay and his colleagues at the University of Chicago are looking into the roots of Crohns disease by combining the study of gene expression with single-cell measurements of proteins and protein complexes, using samples of healthy and diseased gut tissue.

James Wells and his colleagues of Cincinnati Childrens Hospital Medical Center will use stem cells to study maladies that affect enteroendocrine cells, which sense nutrients from the food we eat and then control how those nutrients are processed in the intestines.

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2019s Allen Distinguished Investigators will focus on the mysteries of our cells - Yahoo Tech

MD Anderson Partners with Takeda to Develop CAR Natural Killer-Cell Therapy – Cancer Network

The University of Texas MD Anderson Cancer Center and Takeda Pharmaceutical Company Limited have entered an exclusive license agreement and research agreement to develop and market chimeric antigen receptor-directed natural killer (CAR NK)-cell therapies.

Under the agreement, Takeda will receive access to MD Andersons treatment platform in order to develop and commercialize the CAR NK-cell therapies for up to 4 programs, according to the announcement made Tuesday.

With their expertise in hematologic malignancies and commitment to developing next-generation cell therapies, Takeda is the ideal collaborator to help our team advance CAR NK-cell therapies to patients in need of treatments, said Katy Rezvani, MD, PhD, a professor of stem cell transplantation and cellular therapy at MD Anderson.

The therapy has a similar strategy to the much-touted CAR T-cell therapy, which shows major promise in many cancers, by collecting certain white blood cells of patients, arming them with targeted surface receptors to battle the subjects particular cancer, and then infusing them back into the patients blood.

However, chemotherapy may leave some patients without sufficient autologous T cells in their blood for treatment with CAR T-cell therapy, while others may not have the time that is required for a laboratory to generate enough T cells, according to the researchers.

CAR NK-cell therapy, developed at MD Anderson, uses natural killer cells from cord blood. The team has said that it allows production of a therapy that doesnt have to be tailored for each and every patientand also obviates the possibility of graft-versus host disease, which is a danger with some T-cell varieties.

The MD Anderson team used a retrovirus to introduce new genes into the NK cells: CD19 is added to increase the CAR NK specificity for B-cell malignancies; interleukin 15 (IL15) is added to prolong the present of the cells in the body; and a CASP9-based suicide gene as a kind of safety measure, which can be activated to trigger apoptosis by small-molecule dimerizers if there is toxicity after infusion.

In announcing the agreement, MD Anderson and Takeda emphasized that the off-the-shelf CAR NK treatment could be administered at outpatient locations.

So far, the treatment has proven safe: An ongoing phase I/2a clinical study in patients with relapsed and refractory B-cell malignancies showed that the CD19 CAR NK-therapy has not been associated with the severe cytokine release syndrome or neurotoxicity observed with existing CAR-T therapies.

Takeda said they plan to initiate a pivotal study of the CD19 CAR NK-cell therapy in 2021.

MD Anderson receives an upfront payment that was unspecified by the parties as part of the deal, as well as tiered royalties on eventual net sales, according to the statement.

Rezvani said the goal is to make therapies that get to patients and ultimately change lives.

Our vision is to improve upon existing treatments by developing armored CAR NKs that could be administered off-the-shelf in an outpatient settingenabling more patients to be treated effectively, quickly, and with minimal toxicities, said Rezvani.

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MD Anderson Partners with Takeda to Develop CAR Natural Killer-Cell Therapy - Cancer Network

First UK patient treated with tissue engineered product for rare eye disease – Hospital Healthcare Europe

Limbal cell stem cell deficiency (LSCD) is a rare condition that can lead to blindness, and affects just 3.3 out of 100,000 people in the EU.

Chiesi UK has announced that the first NHS funded patient with LSCD caused by chemical eye burns has been treated with its stem-cell based therapy, Holoclar, the first advanced therapy medicinal product containing stem cells to be approved in the EU.

In 2017, the National Institute for Health and Care Excellence (NICE) recommended Holoclar as an option for adults with moderate-to-severe LSCD after eye burns, if it is only used to treat one eye and in those who have already had a conjunctival limbal autograft (or there is not enough tissue for a conjunctival limbal autograft or it is contraindicated).

The therapy is a tissue engineered product which consists of cells taken from the patients healthy limbus (at the edge of the cornea) during a biopsy. The cells obtained during the biopsy are then transported to the manufacturing facility at Holostem Terapie Avanzate in Italy, where they are prepared and grown in a unique culture to create a new layer of healthy tissue. After at least 50 days, this layer of healthy tissue is delivered back to the treating hospital and implanted by a surgeon into the damaged eye helping it to heal and repair the damaged corneal surface. In case of a partial bilateral problem, the healthy cells are taken from a spared portion of a patients less damaged eye.

Professor Francisco Figueiredo, Consultant Ophthalmologist at the Newcastle upon Tyne Hospitals NHS Foundation Trust and Professor of Ophthalmology at Newcastle University who treated the first NHS funded patient following NICE approval, said, In Newcastle we are a leading centre with an international reputation in autologous limbal stem cell transplantation, and our significant scientific research and clinical experience in limbal stem cell deficiency has led to us having proudly performed the first Holoclar treatment on an NHS patient. This operation was the first of a series that may benefit a number of blind patients over the next few years, not only from Newcastle but from across the whole of the UK, helping to restore their sight and comfort.

Chiesis UK Managing Director, Tom Delahoyde commented, We are delighted that the first patient outside of a clinical trial has received this innovative and breakthrough medicine. This first NHS treatment marks a major milestone for those people with LSCD due to physical or chemical burns and we look forward to many more eligible patients benefiting from such a ground-breaking therapy. Chiesi would like to thank NHS England and the approved Trusts for their support on setting up this new service in the NHS over the last two years and reaching this milestone today.

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First UK patient treated with tissue engineered product for rare eye disease - Hospital Healthcare Europe

Spaceflight alters heart cells but they quickly recover back on Earth – New Scientist News

By Ruby Prosser Scully

Joseph Wu lab, Stanford University School of Medicine

Human heart cells are altered by spaceflight but return mostly to normal when back on Earth. The findings could help scientists understand why astronauts hearts change and how to prevent it.

Previous studies of astronauts have found that spaceflight reduces both heart rate and blood pressure and increases the amount of blood pumped by the heart. But most research on how this happens has been done either on animals or on whole human tissues or organs.

To gain further insights, Alexa Wnorowski at Stanford University in California and her colleagues performed experiments using human heart cells.

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First, they took blood from three people with no history of heart disease. They then reprogrammed some of the blood cells into stem cells that were then coaxed to form heart muscle cells.

Half of the heart muscle cells were put on a SpaceX spacecraft travelling to the International Space Station for a resupply mission. The other half were kept on Earth for comparison.

After five and a half weeks, the cells in orbit were returned to the ground and the scientists examined the effects of microgravity on them.

Read more: What happened when one twin went to space and the other stayed home?

The team found differences in the way that 3000 genes were expressed in these cells. The most notable changes were to genes responsible for metabolism and the functioning of mitochondria, which are the energy powerhouses of cells.

Around 1000 of these genes were still different after 10 days back on Earth, which is equivalent to roughly 4 to 5 per cent of all known human genes. But most of the genes responsible for the changes to the cells mitochondria and metabolism had returned to normal.

It isnt clear from this study what effects the changes might have on astronauts. A previous study looked at two people who were twins: one went to space for a year and the other remained on Earth. It found changes to genes associated with cell mitochondria and metabolism in blood cells in the twin who had been to space. These werent seen in the other twin.

This raises the possibility that spaceflight has similar effects on multiple cell types, including heart and blood cells, says Wnorowski. But its also not quite enough data to draw that large of a conclusion, she says.

The team plans to send 3D tissue structures with multiple different cells types on an upcoming trip to the International Space Station to see how they are affected.

Journal reference: Stem Cell Reports, DOI: 10.1016/j.stemcr.2019.10.006

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Spaceflight alters heart cells but they quickly recover back on Earth - New Scientist News

Researchers Find Link Between Eye Disease And Degeneration Of The Brain – BioSpace

[2][2] https://www.sciencedirect.com/science/article/pii/S0092867417311315?via%3Dihub

Notes to Editor:

The research findings described in this media release can be found in the scientific journal JAMA, under the title, Association of genetic variants with primary open angle glaucoma among individuals with African ancestry by The Genetics of Glaucoma in people of African Descent (GGLAD) consortium.

The authors of the paper are:

Michael A Hauser, PhD1,2,3+; R Rand Allingham, MD2,3+; Tin Aung, MD, PhD3,4+; Carly J Van Der Heide, MD5+; Kent D Taylor, PhD6,7+; Jerome I Rotter, MD6+; Shih-Hsiu J Wang, MD, PhD 8+; Pieter WM Bonnemaijer, MD9,10+; Susan E Williams, MD11+; Sadiq M Abdullahi, MD12; Khaled K Abu-Amero, PhD13; Michael G. Anderson, MD5; Stephen Akafo MD14; Mahmoud B Alhassan MD12; Ifeoma Asimadu, MD15; Radha Ayyagari, PhD16; Saydou Bakayoko, MD17,18; Prisca Biangoup Nyamsi, MD19; Donald W Bowden, PhD20; William C Bromley, MD21; Donald L Budenz, MD22; Trevor R Carmichael, MD, PhD11; Pratap Challa, MD2; Yii-Der Ida Chen, PhD6,7, Chimdi M Chuka-Okosa, MD23; Jessica N Cooke Bailey, PhD24,25; Vital Paulino Costa, MD26; Dianne A Cruz, MS27; Harvey DuBiner, MD28; John F Ervin, BA29; Robert M Feldman, MD30; Miles Flamme-Wiese, BSE5; Douglas E Gaasterland, MD31; Sarah J Garnai, BS32; Christopher A Girkin, MD33; Nouhoum Guirou, MD17,18; Xiuqing Guo, PhD6; Jonathan L Haines, PhD24,25; Christopher J Hammond, MD34; Leon Herndon, MD2; Thomas J Hoffmann, PhD35,36; Christine M Hulette, MD8; Abba Hydara, MD37; Robert P Igo, Jr, PhD24; Eric Jorgenson, PhD38; Joyce Kabwe, MD39; Ngoy Janvier Kilangalanga, MD39; Nkiru Kizor-Akaraiwe, MD 15,40; Rachel W Kuchtey, MD, PhD41; Hasnaa Lamari, MD42; Zheng Li, MD, PhD43, Jeffrey M Liebmann, MD44; Yutao Liu, PhD45,46,47; Ruth JF Loos, PhD48,49; Monica B Melo, PhD50; Sayoko E Moroi, MD, PhD32; Joseph M Msosa, MD51; Robert F Mullins, PhD5; Girish Nadkarni, MD48,52; Abdoulaye Napo, MD17,18; Maggie C Y Ng, PhD20; Hugo Freire Nunes, PhD50; Ebenezer Obeng-Nyarkoh, MA21; Anthony Okeke, MD53; Suhanya Okeke, MD15,40; Olusegun Olaniyi, MD12; Olusola Olawoye, MD54; Mariana Borges Oliveira, MD50; Louise R Pasquale, MD55,56; Rodolfo A. Perez-Grossmann, MD57; Margaret A Pericak-Vance, PhD58; Xue Qin, PhD59; Michele Ramsay, PhD60; Serge Resnikoff, MD, PhD61,62; Julia E Richards, PhD32,63; Rui Barroso Schimiti, MD64; Kar Seng Sim, MS43; William E Sponsel, MD65,66; Paulo Vinicius Svidnicki, PhD50; Alberta AHJ Thiadens; MD, PhD9; Nkechinyere J Uche, MD23,40; Cornelia M van Duijn, PhD9; Jos Paulo Cabral de Vasconcellos, MD, PhD 26; Janey L Wiggs, MD, PhD 67,68; Linda M Zangwill, PhD16; Neil Risch, PhD35,36,38+; Dan Milea, MD, PhD3+,; Adeyinka Ashaye, MD54+,; Caroline CW Klaver, MD, PhD 9,69+,; Robert N Weinreb, MD16+,; Allison E Ashley Koch, PhD1+,; John H Fingert, MD, PhD 5+,; & Chiea Chuen Khor, MD, PhD 3,43+

1Department of Medicine, Duke University, Durham, NC, 2Department of Ophthalmology, Duke University, Durham, NC, 3Singapore Eye Research Institute, Singapore, 4Singapore National Eye Center, Singapore and Duke-NUS Medical School, Singapore, 5Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, 6The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 7Department of Pediatrics, Harbor-University of California, Los Angeles Medical Center, Torrance, CA, 8Department of Pathology, Duke University, Durham, NC, 9Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands, 10Rotterdam Eye Hospital, Rotterdam, The Netherlands, 11Division of Ophthalmology, Department of Neurosciences, University of the Witwatersrand, Johannesburg, South Africa, 12National Eye Centre, Kaduna, Nigeria, 13Department of Ophthalmology, College of Medicine, King Saud University, Riyadh 11411, Saudi Arabia, 14Unit of Ophthalmology, Department of Surgery, University of Ghana Medical School, Accra, Ghana, 15Department of Ophthalmology, ESUT Teaching Hospital Parklane, Enugu, Nigeria, 16Department of Ophthalmology, Hamilton Glaucoma Center, Shiley Eye Institute, University of California, San Diego, La Jolla, CA, 17Institut d'Ophtalmologie Tropicale de l'Afrique, Bamako, Mali, 18Universit des sciences des techniques et des technologies de Bamako, Bamako, Mali, 19Service spcialis d'ophtalmologie, Hpital Militaire de Rgion No1 de Yaound, Yaound, Cameroun, 20Department of Biochemistry, Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, 21Center for Human Genetics, Bar Harbor, ME, 22Department of Ophthalmology, University of North Carolina, Chapel Hill, NC, 23University of Nigeria Teaching Hospital, Ituku Ozalla, Enugu, Nigeria, 24Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, 25Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, 26Department of Ophthalmology, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil, 27Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, 28Clayton Eye Care Center Management, Inc., Marrow, GA, 29Kathleen Price Bryan Brain Bank and Biorepository, Department of Neurology, Duke University, Durham, NC, 30Ruiz Department of Ophthalmology & Visual Science, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 31The Emmes Corporation, Rockville, MD, 32Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, 33Department of Ophthalmology and Visual Sciences, University of Alabama Birmingham, Birmingham, AL, 34Section of Academic Ophthalmology, School of Life Course Sciences, FoLSM, King's College London, London, United Kingdom, 35Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, 36Institute for Human Genetics, University of California San Francisco, San Francisco, CA, 37Sheikh Zayed Regional Eye Care Centre, Kanifing, The Gambia, 38Kaiser Permanente Northern California (KPNC), Division of Research, Oakland, CA, 39Department of Ophthalmology, Saint Joseph Hospital, Kinshasa, Limete, Democratic Republic of the Congo, 40The Eye Specialists Hospital, Enugu, Nigeria, 41Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, TN, 42Clinique Spcialise en Ophtalmologie Mohammedia, Mohammedia, Morocco, 43Genome Institute of Singapore, Singapore, 44Bernard and Shirlee Brown Glaucoma Research Laboratory, Harkness Eye Institute, Columbia University Medical Center, New York, NY, 45Cellular Biology and Anatomy, Augusta University, Augusta, GA, 46James & Jean Culver Vision Discovery Institute, Augusta University, Augusta, GA, 47Center for Biotechnology & Genomic Medicine, Augusta University, Augusta, GA, 48The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 49The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 50Center for Molecular Biology and Genetic Engineering, University of Campinas, Campinas, Brazil, 51Lions Sight-First Eye Hospital, Kamuzu Central Hospital, Lilongwe, Malawi, 52Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 53Nigerian Navy Reference Hospital, Ojo, Lagos, Nigeria, 54Department of Ophthalmology, University of Ibadan, Ibadan, Nigeria, 55Icahn School of Medicine at Mount Sinai, Department of Ophthalmology, New York, NY, 56Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, 57Instituto de Glaucoma y Catarata, Lima, Peru, 58John P Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, 59Duke Molecular Physiology Institute, Duke University, Durham, NC, 60Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa, 61Brien Holden Vision Institute, Sydney, Australia, 62School of Optometry and Vision Science, University of New South Wales, Sydney, Australia, 63Department of Epidemiology, University of Michigan, Ann Arbor, MI, 64Hoftalon Hospital, Londrina, Brazil, 65San Antonio Eye Health, San Antonio, TX, 66Eyes of Africa, Child Legacy International (CLI) Hospital, Msundwe, Malawi, 67Harvard University Medical School, 68Massachusetts Eye and Ear Hospital, Boston, MA, 69Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands

+ Drs. Hauser, Allingham, Aung, Van Der Heide, Taylor, Rotter, Wang, Bonnemaijer, Williams, Risch, Milea, Ashaye, Klaver, Weinreb, Ashley Koch, Fingert, and Khor contributed to the work equally.

Author contributions: Drs Hauser (mike.hauser@duke.edu) and Khor (khorcc@gis.a-star.edu.sg) had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis

For media queries and clarifications, please contact:

Lyn LaiOfficer, Office of Corporate CommunicationsGenome Institute of Singapore, A*STARTel: +65 6808 8258Email: laiy@gis.a-star.edu.sg

Ravi ChandranCorporate CommunicationsSingapore National Eye CentreTel: +65 8121 8569Email: ravi.chandran@snec.com.sg

About A*STARs Genome Institute of Singapore (GIS)

The Genome Institute of Singapore (GIS) is an institute of the Agency for Science, Technology and Research (A*STAR). It has a global vision that seeks to use genomic sciences to achieve extraordinary improvements in human health and public prosperity. Established in 2000 as a centre for genomic discovery, the GIS will pursue the integration of technology, genetics and biology towards academic, economic and societal impact.

The key research areas at the GIS include Human Genetics, Infectious Diseases, Cancer Therapeutics and Stratified Oncology, Stem Cell and Regenerative Biology, Cancer Stem Cell Biology, Computational and Systems Biology, and Translational Research.

The genomics infrastructure at the GIS is utilised to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact.

For more information about GIS, please visit http://www.a-star.edu.sg/gis.

About the Agency for Science, Technology and Research (A*STAR)

The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector agency that spearheads economic oriented research to advance scientific discovery and develop innovative technology. Through open innovation, we collaborate with our partners in both the public and private sectors to benefit society.

As a Science and Technology Organisation, A*STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and enhances lives by contributing to societal benefits such as improving outcomes in healthcare, urban living, and sustainability.

We play a key role in nurturing and developing a diversity of talent and leaders in our Agency and research entities, the wider research community and industry. A*STARs R&D activities span biomedical sciences and physical sciences and engineering, with research entities primarily located in Biopolis and Fusionopolis. For ongoing news, visit http://www.a-star.edu.sg/.

About Singapore Eye Research Institute (SERI)

Established in 1997, SERI is Singapores national research institute for ophthalmic and vision research. SERIs mission is to conduct high impact eye research with the aim to prevent blindness, low vision and major eye diseases common to Singaporeans and Asians. SERI has grown from a founding team of five in 1997 to a faculty of 220, encompassing clinician scientists, scientists, research fellows, PhD students and support staff. This makes SERI one of the largest research institutes in Singapore and the largest eye research institute in Asia-Pacific. In addition, SERI has over 250 adjunct faculties from various eye departments, biomedical institutes and tertiary centres in Singapore.

SERI has amassed an impressive array of more than 3,585 scientific papers as of July 2019, and has secured more than $314 million in external peer-reviewed competitive grants. To date, SERIs faculty has been awarded more than 568 national and international prizes and filed more than 130 patents. Serving as the research institute of the Singapore National Eye Centre and affiliated to the Duke-NUS Medical School, National University of Singapore, SERI undertakes vision research in collaboration with local clinical ophthalmic centres and biomedical research institutions, as well as major eye centres and research institutes throughout the world. Today, SERI is recognized as a pioneering centre for high quality eye research in Asia, with breakthrough discoveries that has translated to significant paradigm shift in eye care delivery. For more information, visit http://www.seri.com.sg

About Singapore National Eye Centre (SNEC)

Singapore National Eye Centre was incorporated in 1989 and commenced operations in 1990. It is the designated national centre within the public sector healthcare network, and spearheads and coordinates the provision of specialised ophthalmological services with emphasis on quality education and research. Since its opening in 1990, SNEC has achieved rapid growth and currently manages an annual workload of 400,000 outpatient visits and 40,000 major eye surgeries and lasers.

Ten subspecialties in Cataract and Comprehensive Ophthalmology, Corneal and External Eye Disease, Glaucoma, Neuro-Ophthalmology, Oculoplastics, Pediatric Ophthalmology and Strabismus, Refractive Surgery, Ocular Inflammation and Immunology, Medical Retina and Surgical Retina have been established to provide a full range of eye treatments from comprehensive to tertiary levels for the entire spectrum of eye conditions.

SNEC was accorded the Excellence for Singapore Award in 2003 for achieving excellence in the area of Ophthalmology, thrusting Singapore into international prominence. In 2006, SNEC received the first Minister for Health Award for public health. Clinician scientists from Singapore National Eye Centre and Singapore Eye Research Institute were awarded the prestigious President's Science and Technology Award in 2009, 2010 and 2014 for their outstanding contributions in translational, clinical and epidemiological research in cornea, retina and glaucoma. Visit us at http://www.snec.com.sg.

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Researchers Find Link Between Eye Disease And Degeneration Of The Brain - BioSpace