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  • richardmitnick 1:25 pm on February 8, 2017 Permalink | Reply
    Tags: Pluripotent stem cells, Stem Cell Research, , UCLA researchers turn stem cells into somites the precursors to skeletal muscle cartilage and bone   

    From UCLA: “UCLA researchers turn stem cells into somites, precursors to skeletal muscle, cartilage and bone” 

    UCLA bloc


    February 07, 2017
    Sarah C.P. Williams

    The new protocol turned 90 percent of human pluripotent stem cells into somite cells in just four days; those somite cells then generated (left to right) cartilage, bone and muscle cells. UCLA Broad Stem Cell Research Center/Cell Reports


    Adding just the right mixture of signaling molecules — proteins involved in development — to human stem cells can coax them to resemble somites, which are groups of cells that give rise to skeletal muscles, bones, and cartilage in developing embryos. The somites-in-a-dish then have the potential to generate these cell types in the lab, according to new research led by senior author April Pyle at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.


    Pluripotent stem cells, by definition, can become any type of cell in the body, but researchers have struggled to guide them to produce certain tissues, including muscle. In developing human embryos, muscle cells — as well as the bone and cartilage of vertebrae and ribs, among other cell types — arise from small clusters of cells called somites.

    Researchers have studied how somites develop in animals and identified the molecules that seem to be an important part of that process in animals. But when scientists have tried to use those molecules to coax human stem cells to generate somites, the protocols have been inefficient.


    The scientists isolated the minuscule developing human somites and measured expression levels of different genes both before and after the somites were fully formed. For each gene that changed levels during the process, the researchers tested whether adding molecules to boost or suppress the function of that gene in human pluripotent stem cells helped push the cells to become somite-like. They found that the optimal mixture of molecules in humans was different than what had been tried in animals. Using the new combination, they could turn 90 percent of human stem cells into somite cells in just four days.

    The scientists followed the cells over the next four weeks and determined that they were indeed able to generate cells including skeletal muscle, bone and cartilage that normally develop from somites.


    The new protocol to create somite-like cells from human pluripotent stem cells opens the door to researchers who want to make muscle, bone and cartilage cells in the lab. Pyle’s group plans to study how to use muscle cells generated from the new somites to treat Duchenne muscular dystrophy, a severe form of muscle degeneration that currently does not have a cure.


    Pyle is a UCLA associate professor of microbiology, immunology and molecular genetics. The first author of the study is Haibin Xi; co-authors are Wakana Fujiwara, Karen Gonzalez and Majib Jan of UCLA; Katja Schenke-Layland and Simone Liebscher of Germany’s Eberhard Karls University Tübingen; and Ben Van Handel of CarthroniX Inc., a California-based biopharmaceutical company.


    The study was published in the journal Cell Reports.

    See the full article here .

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    UC LA Campus

    For nearly 100 years, UCLA has been a pioneer, persevering through impossibility, turning the futile into the attainable.

    We doubt the critics, reject the status quo and see opportunity in dissatisfaction. Our campus, faculty and students are driven by optimism. It is not naïve; it is essential. And it has fueled every accomplishment, allowing us to redefine what’s possible, time after time.

    This can-do perspective has brought us 12 Nobel Prizes, 12 Rhodes Scholarships, more NCAA titles than any university and more Olympic medals than most nations. Our faculty and alumni helped create the Internet and pioneered reverse osmosis. And more than 100 companies have been created based on technology developed at UCLA.

  • richardmitnick 1:33 pm on December 8, 2016 Permalink | Reply
    Tags: , , , Stem Cell Research   

    From Harvard: “Colorful clones track stem cells” 

    Harvard University

    Harvard University

    November 23, 2016 {Just found this in social media.]
    Hannah Robbins, HSCI Communications


    Harvard Stem Cell Institute (HSCI) researchers have used a colorful cell-labeling technique to track the development of the blood system and trace the lineage of adult blood cells traveling through the vast networks of veins, arteries, and capillaries back to their parent stem cells in the marrow.

    Developed at Harvard’s Center for Brain Science, the technique involves coding multiple colors of fluorescent protein into a cell’s DNA. As genes recombine inside the cell, the cell elaborates a color unique to its genetic code. For blood stem cells, that color becomes a genetic signature passed down to daughter cells; purple stem cells, for example, will only make purple blood cells.

    Two independent research teams, one led by David Scadden, HSCI co-director and Gerald and Darlene Jordan Professor of Medicine at Harvard University, and the other by his colleague Leonard Zon, HSCI Executive Committee member and director of the Stem Cell Program at Boston Children’s Hospital, adapted the color-based labeling to the blood system to better understand how blood stem cells behave.

    In a study recently published in Cell, a research team led by Scadden found that in mice individual blood stem cells had a specific and restricted blood production repertoire.

    “We used to think of stem cells as the mother cell that gives rise to all these other cells in the system on an as-needed basis,” said Vionnie Yu, first author of the study and, at the time of the research, a postdoctoral fellow in Scadden’s lab. But their results suggest that stem cells have a scripted set of responses and cannot make just any blood cell type.

    When transplanted into a new environment, each cell not only consistently made the same mature blood cell types but also the same number of those cells. Additionally, clones responded similarly to inflammatory and chemotoxic stress, suggesting the cells had a hardwired memory dictating their behavior. They found that this memory was written into the stem cell epigenome.

    Blood stem cells, said Scadden, may be more like chess pieces with a fixed way they can behave within the system.

    “When you are young and have a full chess set you can mount a vigorous and multilayered defense to an attack on your system,” Scadden said, “but if you lose chess pieces with age or you don’t receive a full suite of players during a bone marrow transplant, the pieces you have left could determine your ability to protect yourself.”

    In addition to looking at blood stem cells in adult mice, color tagging also allows researchers to explore the blood system as a zebrafish embryo develops.

    “We’ve been working with David Scadden for years as part of the HSCI. Initially, we presented our work at a joint lab meeting and realized we could study stem cell clones with this multicolor system,” said Zon, who is also a professor in Harvard’s Stem Cell and Regenerative Biology department. “We shared ideas and results, and even wrote a grant together on the topic. It is wonderful that studying clonal dynamics in two different animals could provide such complementary information.”

    In a study published Monday in Nature Cell Biology, the researcher team led by Zon used the color-tagging system to find the origin and number of stem cells that contribute to lifelong blood production.

    About 24 to 30 hours after fertilization, dozens of stem cells budded off from the dorsal side of the aorta. Only 20 made it to a secondary site before heading to the kidney marrow, the zebrafish equivalent to human and mouse bone marrow.

    After transplanting the multicolored marrow into fish that had received sublethal doses of radiation, the researchers found that some blood stem cell lineages supplied a greater proportion of blood than they had before and that certain lineages could survive harsher conditions than others.

    Knowing which cells are responsible for blood production could have implications for understanding the development of blood cancers, explained Jonathan Henninger, a graduate student in Zon’s lab at Boston Children’s Hospital and first author in the study.

    For example, one cell could develop a mutation that gives it a competitive edge, allowing it to take over the blood system.

    “If that cell starts behaving badly, it could lead to blood disorders, such as myeloid dysplasia and leukemia,” Henninger said.

    Researchers know these disorders come from a single stem cell or a downstream progenitor cell, said Henninger, but right now they are looking at populations of stem cells in bulk. “To be able to identify that single cell that went awry could help us better understand these diseases.”

    See the full article here .

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    Harvard University campus

    Harvard is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s best known landmark.

    Harvard University has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

  • richardmitnick 9:48 am on December 5, 2016 Permalink | Reply
    Tags: , , Breakthrough Prizes, , Roeland Nusse, , Stem Cell Research,   

    From Stanford: “Roeland Nusse wins $3 million Breakthrough Prize” 

    Stanford University Name
    Stanford University

    Krista Conger

    Roeland Nusse was awarded the 2017 Breakthrough Prize in life sciences for his contributions to the understanding a signaling molecule called Wnt. Norbert von der Groeben

    The developmental biologist was honored for helping to decode how Wnt signaling proteins affect embryonic development, cancer and the activity of tissue-specific adult stem cells that repair damage after injury or disease.

    Roeland Nusse, PhD, the Virginia and Daniel K. Ludwig Professor in Cancer Research and a Howard Hughes Medical Institute investigator, was honored this evenng with a 2017 Breakthrough Prize in life sciences.

    Nusse was awarded the $3 million prize for his contributions to the understanding of how a signaling molecule called Wnt affects normal development, cancer and the functions of adult stem cells in many tissues throughout the body.

    “This is a complete surprise,” said Nusse, who is professor and chair of developmental biology. “My gratitude goes out to many people — my past and present postdoctoral scholars and graduate students and my former mentors have all contributed to the success of my research. The research and collaborative environment at Stanford and the long-term support from the Howard Hughes Medical Institute have also been fantastic. I see this award as a great honor for the entire community.”

    The Breakthrough Prizes, initiated in 2013, honor paradigm-shifting research and discovery in the fields of life sciences, fundamental physics and mathematics. In total, about $25 million was awarded at this year’s ceremony, a black-tie, red-carpet affair at the NASA Ames Research Center in Mountain View. The event was hosted by actor Morgan Freeman. The Grammy Award-winning pop star Alicia Keys provided entertainment.

    “Roel’s pioneering work has provided deep insights into an essential molecular signaling pathway that controls normal embryonic development and adult tissue repair, and that contributes to cancer when it is not properly regulated. His work has served as a model for many others in our field and accelerated further studies of these critical processes,” said Stanford President Marc Tessier-Lavigne, PhD. “We are grateful that the Breakthrough Prize recognizes the work of scientific leaders who are inspiring others to pursue discovery that is truly transformative, benefiting all of humanity.”

    Nusse’s interest in Wnt began in the 1980s as a postdoctoral scholar in the laboratory of Harold Varmus, MD, who was then on the faculty of UC-San Francisco. In 1982, Nusse discovered the Wnt1 gene, which was abnormally activated in a mouse model of breast cancer. He subsequently discovered that members of the Wnt family of proteins also play critical roles in embryonic development, cell differentiation and tissue regeneration.

    “Roel has devoted his career to identifying one of the major signaling molecules in embryonic development, and clarifying its role in cancer development and in tissue regeneration,” said Lloyd Minor, MD, dean of the School of Medicine. “The importance of Wnt signaling in these processes cannot be overestimated. His work has been the foundation of much of modern developmental biology, and we are very proud of his contributions.”

    Nusse’s more recent work has focused on understanding how Wnt family members control the function of adult stem cells in response to injury or disease. In 1996, he identified the cell-surface receptor to which Wnt proteins bind to control cells’ functions, and in 2002 he was the first to purify Wnt proteins — an essential step to understanding how they work at a molecular level.

    “My work has shifted significantly over the years due to the influence of my Stanford colleagues, although it has always been focused on Wnt,” said Nusse. “When I arrived at Stanford, I was studying the involvement of the Wnt proteins in mouse development and cancer. I then switched to fruit flies, and then to the study of adult stem cells. Stanford has supported me during this evolution of my research career.”

    Nusse’s lab is currently devoted to understanding how Wnt signaling affects the function of adult stem cells in the liver to help the organ heal after injury, as well as what role Wnt signaling might play in the development of liver cancer.

    “The Breakthrough Prizes are a sign of the times,” said Nusse. “Together with the recently announced Chan Zuckerberg Initiative, they show how the wealth of Silicon Valley is now making an impact not just in the field of computer science, but also in biomedical fields. This is very exciting.”

    Nusse is a member of the Ludwig Center for Cancer Stem Cell Research and Medicine at Stanford, of the Stanford Cancer Institute and of the Stanford Institute for Stem Cell Biology and Regenerative Medicine. He was awarded the Peter Debye Prize from the University of Maastricht in 2000. He is a member of the U.S. National Academy of Sciences, the European Molecular Biology Organization and the Royal Dutch Academy of Sciences. He is also a fellow of the American Academy of Arts and Sciences.

    In all, seven $3 million Breakthrough Prizes — five in the life sciences, one in fundamental physics and one in mathematics — were awarded to 12 recipients. In addition, a special Breakthrough Prize in fundamental physics was awarded to the more than one thousand researchers who proved the existence of gravitational waves in February of 2016.

    Probing for dark matter

    Peter Graham. No image credit

    In addition, three $100,000 New Horizons in Physics Prizes were awarded at the ceremony. Peter Graham, PhD, an assistant professor of physics at Stanford, shared one of them with Asimina Arvanitaki of the Perimeter Institute in Ontario, Canada, and Surjeet Rajendran of the University of California-Berkeley, for “pioneering a wide range of new experimental probes of fundamental physics.”

    Graham earned a PhD at Stanford and completed postdoctoral studies at the Stanford Institute for Theoretical Physics before joining the Stanford faculty in 2010. In 2014, he received an Early Career Award from the Department of Energy.

    Graham has developed new experiments to detect particles known as dark matter, which physicists have reason to believe exist but haven’t yet been able to detect. Physicists have theorized about what dark matter might be, and based on that work have designed experiments to detect those theorized particles. However, those experiments would miss one possible variant of what dark matter might be, known as an axion.

    “It was a scary scenario that this might be what dark matter is and our current experiments wouldn’t detect it,” Graham said.

    Graham designed new experimental approaches that would detect axions if they turn out to be what make up dark matter. “This prize is a huge honor,” Graham said. “It’s great to get recognition from the community for this new direction; it will really help this emerging field.”

    Three $100,000 New Horizons in Mathematics prizes were also awarded at the Breakthrough Prize ceremony.

    In addition, two teenagers — one from Peru and one from Singapore — each won the 2017 Breakthrough Junior Challenge. They will each receive $400,000 in educational prizes.

    The Breakthrough Prizes are funded by grants from the Brin Wojcicki Foundation, established by Google founder Sergey Brin and 23andMe founder Anne Wojcicki; Mark Zuckerberg’s fund at the Silicon Valley Community Foundation; Alibaba founder Jack Ma’s foundation; and DST Global founder Yuri Milner’s foundation. Recipients are chosen by committees comprised of prior prizewinners.

    Amy Adams, director for science communications at the Stanford News Service, contributed to this article.

    See the full article here .

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  • richardmitnick 10:51 am on July 29, 2016 Permalink | Reply
    Tags: , Stem Cell Research,   

    From UCLA: “Metabolic molecule speeds up process by which stem cells differentiate” 

    UCLA bloc


    July 28, 2016
    Sarah C.P. Williams

    Neural cells produced from human pluripotent stem cells in the presence of a metabolite called alpha-ketoglutarate. UCLA Broad Stem Cell Research Center.

    Researchers at the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research have discovered that a metabolic molecule called alpha-ketoglutarate helps pluripotent stem cells mature early in the process of becoming adult organs and tissues. The findings, published online today in the journal Cell Metabolism, could be valuable for scientists working toward stem cell–based therapies for a wide range of diseases.

    Pluripotent stem cells have the ability to create any specialized cell in the body, such as skin, bone, blood or nervous system cells — a process called differentiation. Because of that ability, scientists are studying pluripotent stem cells to determine whether they can generate healthy tissues that could be used to treat people with conditions ranging from Alzheimer’s disease to blindness.

    But to coax pluripotent stem cells into any desired cell type, scientists have to find the right conditions and mixture of molecules to add to the stem cells to promote differentiation.

    “One of the biggest challenges in our field has been to use pluripotent stem cells to efficiently create specialized cells that can carry out specific functions in the body,” said Dr. Michael Teitell, the study’s senior author and a member of the Broad Stem Cell Research Center. “Our findings may help overcome that challenge and let scientists more easily create cells to treat disease.”

    As they differentiate into specialized cells, pluripotent stem cells undergo a shift in their metabolism, and they begin converting sugars to energy more efficiently. Teitell and his colleagues wondered whether molecules involved in metabolism, or metabolites, might be more than just byproducts of this shift, and might actually help the stem cells differentiate.

    To find out, they added a metabolite called alpha-ketoglutarate to a mixture of molecules that normally turns human pluripotent stem cells into nervous system cells. Within the first four days of the experiment, 5 percent to 40 percent more cells differentiated into neural cells than usual. The researchers saw similar results when they added alpha-ketoglutarate to other cocktails of molecules that are used to produce other cell types. The alpha-ketoglutarate, they found, sped up the process of differentiation.

    “On its own, alpha-ketoglutarate probably wouldn’t promote differentiation, but when you add it to other factors that propel the creation of specialized cells, it seems to accelerate this process,” said Tara TeSlaa, first author of the new study and a graduate student in Teitell’s lab.

    Since alpha-ketoglutarate is known to change how genes are regulated by removing methyl chemical groups from the DNA in a cell, Teitell and TeSlaa suspected that the molecule was helping cells turn off genes related to pluripotency and turn on genes related to more efficient differentiation.

    To test that theory, they added another chemical, succinate, to the stem cell mixtures. Succinate blocks the same DNA demethylation chemical reaction that alpha-ketoglutarate promotes. Indeed, the addition of succinate caused the stem cells to differentiate slower and less efficiently, which provided further evidence that alpha-ketoglutarate works by acting on genes.

    “Until very recently, metabolites have been overlooked as a way to help pluripotent stem cells differentiate,” said Teitell, professor of pathology and laboratory medicine at the UCLA David Geffen School of Medicine. “This work helps to change that view.”

    Teitell and TeSlaa think that others in the field will build upon their study by testing whether alpha-ketoglutarate improves a variety of stem cell differentiation processes. They are planning follow-up studies to find out exactly which genes alpha-ketoglutarate regulates and how it can promote differentiation in some situations.

    The research was supported by grants from the California Institute for Regenerative Medicine (RB1-01397 and RT3-07678) and the National Institutes of Health (GM073981, P01GM081621, CA156674, CA90571, GM114188, and CA185189), as well as a Ruth L. Kirschstein National Research Service Award (GM007185), Discovery/NantWorks Biotechnology Awards (Bio07-10663 and 178517), an American Cancer Society Research Scholar Award (RSG-12-257-01-TBE), and by the UCLA Broad Stem Cell Research Center–Rose Hills Foundation Training Award.

    See the full article here .

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    UC LA Campus

    For nearly 100 years, UCLA has been a pioneer, persevering through impossibility, turning the futile into the attainable.

    We doubt the critics, reject the status quo and see opportunity in dissatisfaction. Our campus, faculty and students are driven by optimism. It is not naïve; it is essential. And it has fueled every accomplishment, allowing us to redefine what’s possible, time after time.

    This can-do perspective has brought us 12 Nobel Prizes, 12 Rhodes Scholarships, more NCAA titles than any university and more Olympic medals than most nations. Our faculty and alumni helped create the Internet and pioneered reverse osmosis. And more than 100 companies have been created based on technology developed at UCLA.

  • richardmitnick 8:47 am on July 25, 2016 Permalink | Reply
    Tags: , , , Stem Cell Research   

    From Hopkins: “Johns Hopkins biologists find protein that bolsters growth of damaged muscle tissue” 

    Johns Hopkins
    Johns Hopkins University

    Jul 19, 2016
    Arthur Hirsch

    Johns Hopkins University biologists have found that a protein that plays a key role in the lives of stem cells can bolster the growth of damaged muscle tissue, a step that could potentially contribute to treatments for muscle degeneration caused by old age and diseases such as muscular dystrophy.

    The results, published online by the journal Nature Medicine, show that a particular type of protein called integrin is present on the stem cell surface and used by stem cells to interact with, or “sense,” their surroundings. How stem cells sense their surroundings, also known as the stem cell “niche,” affects how they live and last for regeneration. The presence of the protein β1-integrin was shown to help promote the transformation of those undifferentiated stem cells into muscle after the tissue has degraded and improve regenerated muscle fiber growth as much as 50 percent.

    While the presence of β1-integrin in adult stem cells is apparent, “its role in these cells has not been examined,” especially its influence on the biochemical signals promoting stem cell growth, wrote the three authors—Chen-Ming Fan, an adjunct biology professor at Johns Hopkins; Michelle Rozo, who completed her doctorate in biology at Hopkins this year; and doctoral student Liangji Li.

    The experiment shows that β1-integrin—one of 28 types of integrin—maintains a link between the stem cell and its environment, and interacts biochemically with a growth factor called fibroblast growth factor (FGF) to promote stem cell growth and restoration after muscle tissue injury. Aged stem cells do not respond to FGF, and the results also show that β1-integrin restores aged stem cell’s ability to respond to FGF to grow and improve muscle regeneration.

    By tracking an array of proteins inside the stem cells, the researchers tested the effects of removing β1-integrin from the stem cell. This is based on the understanding that the activities of stem cells—undifferentiated cells that can become specialized—are dependent on their environment and supported by the proteins found there.

    “If we take out β1-integrin, all these other [proteins] are gone,” Fan, the study’s senior author and a staff member at the Carnegie Institution for Science in Washington and Baltimore, said in an interview.

    Why that is the case is not clear, but the experiment showed that without β1-integrin, stem cells could not sustain growth after muscle tissue injury.

    By examining β1-integrin molecules and the array of proteins that they used to track stem cell activity in aged muscles, the authors found that all of these proteins looked like they had been removed from aged stem cells. They injected an antibody to boost β1-integrin function into aged muscles to test whether this treatment would enhance muscle regeneration. Measurements of muscle fiber growth with and without boosting the function of β1-integrin showed that the protein led to as much as 50-percent more regeneration in cases of injury in aged mice.

    When the same β1-integrin function-boosting strategy was applied to mice with muscular dystrophy, the muscle was able to increase strength by about 35 percent.

    Fan said the team’s research will next try to determine what is happening inside the stem cells as they react with their immediate environment, as a step to understanding more about the interaction of the two. That, in turn, could help refine the application of integrin as a therapy for muscular dystrophy and other diseases, and for age-related muscle degeneration.

    “We provide here a proof-of-principle study that may be broadly applicable to muscle diseases that involve [stem cell] niche dysfunction,” the authors wrote. “But further refinement is needed for this method to become a viable treatment.”

    See the full article here .

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    The Johns Hopkins University opened in 1876, with the inauguration of its first president, Daniel Coit Gilman. “What are we aiming at?” Gilman asked in his installation address. “The encouragement of research … and the advancement of individual scholars, who by their excellence will advance the sciences they pursue, and the society where they dwell.”

    The mission laid out by Gilman remains the university’s mission today, summed up in a simple but powerful restatement of Gilman’s own words: “Knowledge for the world.”

    What Gilman created was a research university, dedicated to advancing both students’ knowledge and the state of human knowledge through research and scholarship. Gilman believed that teaching and research are interdependent, that success in one depends on success in the other. A modern university, he believed, must do both well. The realization of Gilman’s philosophy at Johns Hopkins, and at other institutions that later attracted Johns Hopkins-trained scholars, revolutionized higher education in America, leading to the research university system as it exists today.

  • richardmitnick 8:08 am on July 18, 2016 Permalink | Reply
    Tags: , , Stem Cell Research   

    From Stanford: “Researchers coax human stem cells to rapidly generate bone, heart muscle” 

    Stanford University Name
    Stanford University

    July 14 2016
    Krista Conger
    Tel 650-725-5371

    A new study shows that combining positive and negative signals can quickly and efficiently steer stem cells down complex developmental pathways to become specialized tissues that could be used in the clinic.

    Researchers at the Stanford University School of Medicine have mapped out the sets of biological and chemical signals necessary to quickly and efficiently direct human embryonic stem cells to become pure populations of any of 12 cell types, including bone, heart muscle and cartilage.

    The ability to make pure populations of these cells within days rather than the weeks or months previously required is a key step toward clinically useful regenerative medicine — potentially allowing researchers to generate new beating heart cells to repair damage after a heart attack or to create cartilage or bone to reinvigorate creaky joints or heal from trauma.

    The study also highlights key, but short-lived, patterns of gene expression that occur during human embryo segmentation and confirms that human development appears to rely on processes that are evolutionarily conserved among many animals. These insights may also lead to a better understanding of how congenital defects occur.

    “Regenerative medicine relies on the ability to turn pluripotent human stem cells into specialized tissue stem cells that can engraft and function in patients,” said Irving Weissman, MD, the director of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine, and also of its Ludwig Cancer Center. “It took us years to be able to isolate blood-forming and brain-forming stem cells. Here we used our knowledge of the developmental biology of many other animal models to provide the positive and negative signaling factors to guide the developmental choices of these tissue and organ stem cells. Within five to nine days we can generate virtually all the pure cell populations that we need.”

    Weissman and Lay Teng Ang, of the Genome Institute of Singapore, are the senior authors of the study, published July 7 in Cell. Graduate student Kyle Loh and research assistant Angela Chen, both at Stanford, share lead authorship of the study.

    Unraveling the mysteries

    Embryonic stem cells are pluripotent, meaning they can become any type of cell in the body. They do so by responding to a variety of time- and location-specific cues within the developing embryo that direct them to become specific cell types. Researchers have learned a lot about how this process is controlled in animals, including fish, mice and frogs.

    In contrast to many other animals, human embryonic development is a mysterious process, particularly in the first weeks after conception. This is because cultivating a human embryo for longer than 14 days is banned by many countries and scientific societies. But we do know that, like other animals, the human embryo in its earliest stages consists of three main components known as germ layers: the ectoderm, the endoderm and the mesoderm.

    Each of these germ layers is responsible for generating certain cell types as the embryo develops. The mesoderm, for example, gives rise to key cell types, including cardiac and skeletal muscle, connective tissue, bone, blood vessels, blood cells, cartilage and portions of the kidneys and skin.

    “The ability to generate pure populations of these cell types is very important for any kind of clinically important regenerative medicine,” said Loh, “as well as to develop a basic road map of human embryonic development. Previously, making these cell types took weeks to months, primarily because it wasn’t possible to accurately control cell fate. As a result, researchers would end up with a hodgepodge of cell types.”

    Loh and Chen wanted to know what signals drive the formation of each of the mesodermally derived cell types. To do so, they started with a human embryonic stem cell line, which they chemically nudged to become cells that form what’s known as the primitive streak on the hollow ball of cells of the early embryo. They then experimented with varying combinations of well-known signaling molecules, including WNT, BMP and Hedgehog, as a way to coax these cells to become ever-more-specialized precursor cells.

    A yes-and-no strategy

    They learned that often the cells progressed down the developmental path through a series of consecutive choices between two possible options. Think about the carnival game in which a disc is dropped down a slanted, peg-studded board to land in one of several cups at the bottom. The eventual destination is determined by whether the disc goes to the left or right of each consecutive peg.

    The quickest, most efficient way to micromanage the cells’ developmental decisions was to apply a simultaneous combination of factors that both encouraged the differentiation into one lineage while also actively blocking the cells from a different fate — a kind of “yes” and “no” strategy.

    For example, cells in the primitive streak can become either endoderm or one of two types of mesoderm. Inhibiting the activity of a signaling molecule called TGF beta drives the cells to a mesodermal fate. Adding a signaling molecule called WNT, while also blocking the activity of another molecule known as BMP, promotes differentiation into one kind of mesoderm; conversely, adding BMP while blocking WNT drives the cells to instead become the other type of mesoderm.

    “We learned during this process that it is equally important to understand how unwanted cell types develop and find a way to block that process while encouraging the developmental path we do want,” said Loh.

    By carefully guiding the cells’ choices at each fork in the road, Loh and Chen were able to generate bone cell precursors that formed human bone when transplanted into laboratory mice and beating heart muscle cells, as well as 10 other mesodermal-derived cell lineages.

    At each developmental stage, the researchers conducted single-cell RNA sequencing to identify unique gene expression patterns and assess the purity of individual cell populations. By looking at the gene expression profile in single cells, the researchers were able to identify previously unknown transient states that typified the progression from precursor to more-specialized cells.

    Segmentation in embryo development

    In particular they observed for the first time a transient pulse of gene expression that precedes the segmentation of the human embryo into discrete parts that will become the head, trunk and limbs of the body. The process mirrors what is known to occur in other animals, and confirms that the segmentation process in human development has been evolutionarily conserved.

    “The segmentation of the embryo is a fundamental step in human development,” said Loh. “Now we can see that, evolutionarily, it’s a very conserved process.” Understanding when and how segmentation and other key developmental steps occur could provide important clues as to how congenital birth defects arise when these steps go awry.

    The ability to quickly generate purified populations of specialized precursor cells has opened new doors to further study.

    “Next, we’d like to show that these different human progenitor cells can regenerate their respective tissues and perhaps even ameliorate disease in animal models,” said Loh.

    Stanford co-authors of the study are data analyst Pang Wei Koh; former undergraduate student Tianda Deng; instructor Rahul Sinha, PhD; graduate students Jonathan Tsai, Amira Barkal, Kimberle Shen and Benson George; research assistant Rachel Morganti; postdoctoral scholar Nathaniel Fernhoff, PhD; assistant professor of pathology Gerlinde Wernig, MD; former graduate student Zhenghao Chen; professor of pathology and of pediatrics Hannes Vogel, MD; assistant professor of genetics and of computer science Anshul Kundaje, PhD; professor of developmental biology William Talbot, PhD; and professor of developmental biology Philip Beachy, PhD.

    The study was supported by the California Institute for Regenerative Medicine, the National Institutes of Health (grants HL125040, GM007365, HL119553, HL071546, HL100405, NS069375, RR029338 and OD018220), the Howard Hughes Medical Institute, anonymous donors, the Agency for Science, Technology and Research in Singapore, the Siebel Stem Cell Institute, the Fannie and John Hertz Foundation, the National Science Foundation, the Davidson Institute for Talent Development, the Paul and Daisy Soros Fellowship for New Americans and the Alfred Sloan Foundation.

    Stanford’s Departments of Pathology and of Developmental Biology also supported the work.

    See the full article here .

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    Leland and Jane Stanford founded the University to “promote the public welfare by exercising an influence on behalf of humanity and civilization.” Stanford opened its doors in 1891, and more than a century later, it remains dedicated to finding solutions to the great challenges of the day and to preparing our students for leadership in today’s complex world. Stanford, is an American private research university located in Stanford, California on an 8,180-acre (3,310 ha) campus near Palo Alto. Since 1952, more than 54 Stanford faculty, staff, and alumni have won the Nobel Prize, including 19 current faculty members

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  • richardmitnick 6:04 am on July 13, 2016 Permalink | Reply
    Tags: , Breakthrough in scaling up life-changing stem cell production, Stem Cell Research,   

    From U Nottingham: “Breakthrough in scaling up life-changing stem cell production” 


    University of Nottingham

    13 Jul 2016
    Emma Rayner

    Human embryonic stem cell line HUES1 grown in the new conditions E8+Inter-alpha-inhibitor and imaged for stem cell marker Oct4 (green) and cell-cell attachment molecule E-cadherin (red) with nuclear counter-staining (blue). Credit: Dr. Sara Pijuan-Galito and Dr. Cathy Merry, Wolfson Centre for Stem Cells, Tissue Engineering & Modelling and Centre for Biomolecular Sciences, The University of Nottingham

    Scientists have discovered a new method of creating human stem cells which could solve the big problem of the large-scale production needed to fully realise the potential of these remarkable cells for understanding and treating disease.

    The discovery has been made by a team of scientists at The University of Nottingham, Uppsala University and GE Healthcare in Sweden.

    Human pluripotent stem cells are undifferentiated cells which have the unique potential to develop into all the different types of cells in the body. With applications in disease modelling, drug screening, regenerative medicine and tissue engineering, there is already an enormous demand for these cells, which will only grow as their use in the clinic and by the pharmaceutical industry increases.

    The production of stem cells at the scale required for optimal application in modern healthcare is currently not feasible because available culture methods are either too expensive, or reliant on substances that would not be safe for clinical use in humans.

    In this new piece of research, published on Wednesday 13th July 2016 in Nature Communications, a team combining researchers from The University of Nottingham’s Wolfson Centre for Stem Cells, Tissue Engineering and Modelling, Uppsala University and GE Healthcare has identified an improved method for human stem cell culture that could lead to quicker and cheaper large scale industrial production.

    The work was started at Uppsala University in Sweden, and the first author, Dr Sara Pijuan-Galitó, is now continuing her work as a Swedish Research Council Research Fellow at Nottingham. Sara said: “By using a protein derived from human blood called Inter-alpha inhibitor, we have grown human pluripotent stem cells in a minimal medium without the need for costly and time-consuming biological substrates. Inter-alpha inhibitor is found in human blood at high concentrations, and is currently a by-product of standard drug purification schemes.

    “The protein can make stem cells attach on unmodified tissue culture plastic, and improve survival of the stem cells in harsh conditions. It is the first stem cell culture method that does not require a pre-treated biological substrate for attachment, and therefore, is more cost and time-efficient and paves the way for easier and cheaper large-scale production.”

    Lead supervisor Dr Cecilia Annerén, who has a joint position at Uppsala University and at GE Healthcare in Uppsala, said: “As coating is a time-consuming step and adds cost to human stem cell culture, this new method has the potential to save time and money in large-scale and high-throughput cultures, and be highly valuable for both basic research and commercial applications.”

    Co-author on the paper Dr Cathy Merry added: “We now intend to combine Inter-alpha inhibitor protein with our innovative hydrogel technology to improve on current methods to control cell differentiation and apply it to disease modelling. This will help research into many diseases but our focus is on understanding rare conditions like Multiple Osteochondroma (an inherited disease associated with painful lumps developing on bones) at the cellular level. Our aim is to replicate the 3 dimensional environment that cells experience in the body so that our lab-bench biology is more accurate in modelling diseases.”

    Dr Sara Pijuan-Galitó has also been awarded the prestigious Sir Henry Wellcome Postdoctoral Fellowship. This will enable her to combine Inter-alpha inhibitor with improved synthetic polymers in collaboration with other regenerative medicine pioneers at the University, Professor Morgan Alexander and Professor Chris Denning. This team plans to further improve on current human stem cell culture, designing an economical and safe method that can be easily translated to large-scale production and can deliver the billions of cells necessary to start taking cellular therapeutics to the individual patients.

    See the full article here .

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    “The University of Nottingham shares many of the characteristics of the world’s great universities. However, we are distinct not only in our key strengths but in how our many strengths combine: we are financially secure, campus based and comprehensive; we are research-led and recruit top students and staff from around the world; we are committed to internationalising all our core activities so our students can have a valuable and enjoyable experience that prepares them well for the rest of their intellectual, professional and personal lives.”

  • richardmitnick 11:35 am on July 3, 2016 Permalink | Reply
    Tags: , Stem Cell Research,   

    From Weimann: “Straight to the Gut” 

    Weizmann Institute of Science logo

    Weizmann Institute of Science

    16.06.2016 [This just made it to social media.]
    No writer credit found

    Stem cells must get oriented before taking on new properties

    (l-r) Julian Nicenboim, Lihee Asaf, Dr. Karina Yaniv and Dr. Gideon Hen explain how lymph stem cells get their signals straight. No image credit

    Understanding what makes these adult stem cells tick is a difficult undertaking: They can be hard to find, and each type may respond to several different signals and operate by different sets of rules. So when Yaniv and her group in the Weizmann Institute of Science’s Biological Regulation Department discovered, a year ago, that the body has a special store of stem cells that differentiate into lymphatic vessels, they were able to solve a 100-year old disagreement about the origins of the lymph system. But their findings also enabled them to grow lymph cells in lab cultures for the first time.

    This advance led to a new study, recently reported in Development, which sheds new light on what else these “special” stem cells can do, and how they do it. Yaniv, postdoctoral fellow Gideon Hen and research student Julian Nicenboim focused on the cells called endothelial cells that build blood vessel walls. “The endothelial cells in the blood vessels of the brain are very different from those found in the liver or kidneys. What tells these cells to adopt the characteristics of one or the other?”

    The researchers added fluorescent markers to the developing blood vessels of zebrafish embryos; these markers can switch their color from green to red under ultraviolet light. This enabled the team to trace the differentiation of living cells under the microscope over the course of several days.

    The group followed the fate of the previously identified stem cells, finding that they also give rise to the vasculature of the digestive system. In contrast to the cells that differentiate into adult lymph cells, those bound for the liver, intestinal or pancreatic blood vessels have a special set of signals − proteins in two families known as BMP and VEGF − to guide them on their way. The scientists discovered that these proteins are expressed for only a short period of time, and they first enable the cells to exit their protected “niche.” Only once these cells are pointed toward the proper organ can they begin to take on the properties required for the particular blood vessel of their final destination.

    Blood vessels of a zebrafish embryo (red). The nuclei of the endothelial cells in these vessels are labeled in yellow, allowing researchers to track cell migration during development. The arrow indicates migration of cells arising from a blood vessel. Such cells arise from a pool of stem cells, and will give rise to blood vessels of the intestine, liver and the pancreas. No image credit.

    Yaniv says that these findings may shed light on another mystery: Where do cancerous or otherwise pathological blood cells come from? Such cells have supercharged capacities for differentiation and migration, leading to the suspicion that the “special” stem cells could be the source. Yaniv and her group are presently conducting research on adult zebrafish, tracking the new stem cell population in hopes of gaining deeper insight into their functions and malfunctions in the adult system.

    Dr. Karina Yaniv’s research is supported by the Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics; the Adelis Foundation; and the estate of Georges Lustgarten. Dr. Yaniv is the incumbent of the Louis and Ida Rich Career Development Chair.

    See the full article here .

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    Weizmann Institute Campus

    The Weizmann Institute of Science is one of the world’s leading multidisciplinary research institutions. Hundreds of scientists, laboratory technicians and research students working on its lushly landscaped campus embark daily on fascinating journeys into the unknown, seeking to improve our understanding of nature and our place within it.

    Guiding these scientists is the spirit of inquiry so characteristic of the human race. It is this spirit that propelled humans upward along the evolutionary ladder, helping them reach their utmost heights. It prompted humankind to pursue agriculture, learn to build lodgings, invent writing, harness electricity to power emerging technologies, observe distant galaxies, design drugs to combat various diseases, develop new materials and decipher the genetic code embedded in all the plants and animals on Earth.

    The quest to maintain this increasing momentum compels Weizmann Institute scientists to seek out places that have not yet been reached by the human mind. What awaits us in these places? No one has the answer to this question. But one thing is certain – the journey fired by curiosity will lead onward to a better future.

  • richardmitnick 8:35 am on May 19, 2016 Permalink | Reply
    Tags: , Stem cell advance could be key step toward treating deadly blood diseases, Stem Cell Research,   

    From UCLA: “Stem cell advance could be key step toward treating deadly blood diseases” 

    UCLA bloc


    May 17, 2016
    Mirabai Vogt-James

    Vincenzo Calvanese, Dr. Hanna Mikkola and Diana Dou are working toward being able to create hematopoietic stem cells in the lab so that they are a perfect match for transplant recipients. UCLA Broad Stem Cell Research Center

    Scientists at the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research have made several discoveries that are critically important to understanding how blood stem cells are created and maintained — both in the body and in the laboratory.

    The findings may lead to the creation of a new source of life-saving blood-forming stem cells, which could help people with a wide range of blood diseases by reducing many of the risks of bone marrow transplants. Thousands of people each year in the U.S. alone are diagnosed with diseases that could be treated with the procedure.

    The study*, led by senior author Dr. Hanna Mikkola and first co-authors Vincenzo Calvanese and Diana Dou, was published in the journal Nature Cell Biology.

    Blood-forming stem cells, or hematopoietic stem cells, are found in the bone marrow and can create any type of blood cell. The researchers pinpointed the function of a cluster of specialized genes that play a key role in creating and preserving hematopoietic stem cells and identified the process by which those genes are activated during human development and in the laboratory.

    For decades, doctors have used bone marrow transplants to treat people with diseases of the blood or immune system. One complicating factor has always been that certain proteins in the donor’s and recipient’s cells must match so that the donor’s immune system doesn’t reject the transplant. But finding a perfect match can be difficult, and the process is risky for both donors and recipients.

    The UCLA research could provide a way to create patient-specific hematopoietic stem cells, which would reduce some of the challenges associated with bone marrow transplants.

    “Our work focuses on finding a way to generate a supply of these life-saving hematopoietic stem cells in the lab so that they are a perfect match to the patient in need of a transplant,” said Mikkola, a professor of molecular, cell and developmental biology in the UCLA College and a member of the UCLA Jonsson Comprehensive Cancer Center. “One big challenge is that when we try to create hematopoietic stem cells from pluripotent stem cells in the lab, they don’t acquire the same abilities of the real hematopoietic stem cells found in the body.”

    Access mp4 video here .

    Pluripotent stem cells are capable of becoming any cell type in the human body. However, some tissue-specific stem cells, such as hematopoietic stem cells, have been difficult to derive from pluripotent stem cells, creating a fundamental challenge associated with the creation of stem cell-based medical treatments.

    Mikkola and the research team first tried to create hematopoietic stem cells in the lab from pluripotent stem cells. When they compared the lab-created cells to the hematopoietic stem cells found in the body, they found that an important cluster of genes, called HOXA genes, weren’t activated in the lab-created cells. They also showed that HOXA genes help hematopoietic stem cells maintain their stem cell attributes, such as the ability to generate more copies of themselves, which is a defining characteristic of any kind of stem cell.

    “Without the ability to self-renew, hematopoietic stem cells cannot be used for transplantation therapies,” said Calvanese, an assistant project scientist in Mikkola’s lab. “Our findings show that the activation of HOXA genes can be used as a marker for hematopoietic stem cells that have acquired the capacity to renew themselves.”

    Access mp4 video here .

    The researchers’ next challenge was to pinpoint the naturally occurring process that activates HOXA genes, so they could try to replicate the process in the lab. They found that mimicking the effects of retinoic acid, a compound derived from vitamin A, acts like a switch that turns on the HOXA genes during the development of hematopoietic stem cells.

    “Inducing retinoic acid activity at a very specific time in cell development makes our lab-created cells more similar to the real hematopoietic stem cells found in the body,” said Dou, a graduate student in Mikkola’s lab. “This is an important step forward as we work to develop hematopoietic stem cells for transplantation therapies for life-threatening blood diseases.”

    The researchers’ next step will be to refine the process they’ve developed in order to produce lab-created hematopoietic stem cells that have — and maintain — all of the functions of human hematopoietic stem cells.

    The research was supported by grants from the California Institute for Regenerative Medicine, the National Institutes of Health (RO1 DK100959, P01 GM081621, PO1 HL073104 and HL086345), the National Science Foundation Graduate Research Fellowship Program, the Leukemia and Lymphoma Society, and the UCLA Broad Stem Cell Research Center and its training programs, which are supported in part by the Shaffer Family Foundation and the Rose Hills Foundation.

    *Science paper:
    Medial HOXA genes demarcate haematopoietic stem cell fate during human development

    See the full article here .

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    UC LA Campus

    For nearly 100 years, UCLA has been a pioneer, persevering through impossibility, turning the futile into the attainable.

    We doubt the critics, reject the status quo and see opportunity in dissatisfaction. Our campus, faculty and students are driven by optimism. It is not naïve; it is essential. And it has fueled every accomplishment, allowing us to redefine what’s possible, time after time.

    This can-do perspective has brought us 12 Nobel Prizes, 12 Rhodes Scholarships, more NCAA titles than any university and more Olympic medals than most nations. Our faculty and alumni helped create the Internet and pioneered reverse osmosis. And more than 100 companies have been created based on technology developed at UCLA.

  • richardmitnick 9:44 am on March 28, 2016 Permalink | Reply
    Tags: , Stem Cell Research,   

    From U Washington: “Stem cell research gets undergrads out of classroom” 

    U Washington

    University of Washington

    McKenna Princing

    Deepkiran Singh, a UW junior in biochemistry, demonstrates pipetting, a lab technique to measure or transfer liquids.

    UW undergraduate Randy Lu grasps a pair of tweezers in each hand. His fingers making imperceptible movements as he dissects the tiny abdomen of a fruit fly. The tweezers and Lu’s hands look garishly large next to the insect, which is a mere speck in a glass dish. Lu has to look through a microscope in order to see it in detail.

    Leaning over Lu’s shoulders is his mentor and fellow undergraduate Debra Del Castillo, who guides him as he learns how to master the light touch necessary to complete such delicate work. Lu is not the first student Del Castillo has mentored: As program coordinator for an undergraduate research project that brings students into the lab of UW biochemistry professor, Hannele Ruohola-Baker at UW Medicine’s Institute for Stem Cell and Regenerative Medicine Research. Del Castillo has overseen the work of dozens of students for the past two years.

    The students contribute to an ongoing study examining a protective signal daughter cells send back to their stem cells in the germ line of fruit flies. The signal seems to help the stem cells survive even when they are targeted with chemotherapy or radiation. Researchers believe this phenomenon could explain why some cancers are so difficult to eradicate.

    To combat this, researchers are screening nearly 1,600 different molecules to see if any prevent the daughter cells from sending that signal. Molecules that do this could be turned into a drug that would prevent tumors from regenerating.

    The screen is an intensive process composed of multiple steps—a perfect opportunity, Del Castillo feels, to teach undergraduates how real-world science often works.

    Debra Del Castillo looks through a confocal microscope to check undergraduate Randy Lu’s progress dissecting flies. McKenna Princing

    “Most undergraduate programs have labs where the experiments are highly optimized, where you know what the results are going to be,” she said.

    Ruohola-Baker testified to the explorative nature of the work students partake in.

    “You are the first one in the world to find the answer for your question when you come in the morning to develop that film, study those stem cells in the confocal microscope or analyze their level of RNA after the drug treatment,” she said. “Your job is to go to the edge of human knowledge and push beyond.”

    The step-by-step process looks like this: Students feed one of the small molecules in question to a days-old fruit fly, then sacrifice the insect, isolate the affected cells and put them through a lengthy immunohistochemistry protocol. Next come dissection and analysis to determine whether or not the molecule interfered with the protective signal. Students are usually trained for three to four months before they are allowed to complete the process on their own and analyze results.

    “I have to work with them a lot to get the confidence to make that call, because they’re young and they’ve never done this before, and they’re afraid they’ve done it wrong,” Del Castillo said.

    She, too, had to develop confidence when she first joined the project. Currently a post-baccalaureate studying biochemistry, she took a winding path to get where she is now: A degree and then a job in engineering, followed by many years of caregiving, first for her children and then for her aunt, who was diagnosed with Huntington’s disease.

    “It all ended at once; I went from caregiving to nothing, so I thought I’d go back to school,” she said. “In high school, I had wanted to be a doctor or medical researcher, but because I came from a family where all these strange things happened—my mother died at 27, my grandmother got schizophrenia at age 50—I didn’t feel like I had the support to go for it when I was young.”

    She eventually found out that Huntington’s runs in the family. She was tested and does not carry the gene. That knowledge spurred her to pursue medical research. She wants to do studies that might lead to new ways to protect other people from disease. At North Seattle College she fell in love with cellular biology and organic chemistry. There she participated in her first research project, an experience that ultimately inspired her to bring undergraduates into the lab at UW.

    Currently, 14 undergraduates are involved in the study; each works up to 25 hours a week. One student, biochemistry junior Deepkiran Singh, wants to become a gynecological surgeon and feels contributing to research helps her prepare for that goal.

    “Working with your hands, being precise, is really important,” she said. “Before, I was shaky; I had to learn. And it’s good to have lab experience when you go into medicine. I have more of a sense of freedom here [than in a classroom].”

    Del Castillo believes the work will have lasting effects on students.

    “Young people spend so much time in school, but this really prepares them for real-world jobs,” she said. “To see the principles of science and biochemistry at work is so profound: It sets the stage for them to have a realistic understanding of what it takes to get valid, reproducible results and to do good science.”

    See the full article here .

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    The University of Washington is one of the world’s preeminent public universities. Our impact on individuals, on our region, and on the world is profound — whether we are launching young people into a boundless future or confronting the grand challenges of our time through undaunted research and scholarship. Ranked number 10 in the world in Shanghai Jiao Tong University rankings and educating more than 54,000 students annually, our students and faculty work together to turn ideas into impact and in the process transform lives and our world. For more about our impact on the world, every day.

    So what defines us — the students, faculty and community members at the University of Washington? Above all, it’s our belief in possibility and our unshakable optimism. It’s a connection to others, both near and far. It’s a hunger that pushes us to tackle challenges and pursue progress. It’s the conviction that together we can create a world of good. Join us on the journey.

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