ASH honors Scott Armstrong, M.D., Ph.D., with 2014 William Dameshek Prize

PUBLIC RELEASE DATE:

22-Jul-2014

Contact: Amanda Szabo aszabo@hematology.org 202-552-4914 American Society of Hematology

(WASHINGTON, July 22, 2014)The American Society of Hematology will present the 2014 William Dameshek Prize to Scott Armstrong, MD, PhD, of Memorial Sloan Kettering Cancer Center for his exceptional work in leukemia research and cancer stem cell biology.

This prize, named after the late William Dameshek, MD, a renowned hematologist, past president of ASH, and the first editor of the Society's journal Blood, recognizes an individual who has made a recent, outstanding contribution to the field of hematology. Dr. Armstrong will accept his award at 9:30 a.m. on Tuesday, December 9, during the 56th ASH Annual Meeting and Exposition in San Francisco.

Dr. Armstrong is the Director of the Leukemia Center at Memorial Sloan Kettering Cancer Center (MSK), where he also serves as Vice Chair for Basic and Translational Research in Pediatrics and as a full member of the MSK Cancer Biology and Genetics Program. His research focuses on the biology and epigenetics of a class of leukemias initiated by mixed lineage leukemia (MLL) gene translocations. Throughout his career, Dr. Armstrong has sought to uncover unique insights into the origin and properties of cancer stem cells, the signaling pathways sustaining cancer cell self-renewal, and the epigenetic mechanisms dependent on MLL-fusion oncogenes.

In 2002 Dr. Armstrong published a seminal paper in Nature Genetics demonstrating that MLLs exhibited a unique expression signature. In subsequent papers published in Cancer Cell in 2003 and Blood in 2004, Dr. Armstrong described how the FMS-like tyrosine kinase-3 (FLT3) is highly expressed and often mutated in MLLs. Dr. Armstrong's findings, in conjunction with the work of others, have led to clinical trials of FLT3 in various forms of leukemia. Over the past several years, Dr. Armstrong has extended his elegant study of MLL-rearranged leukemic stem cells in several publications, including Nature, Science, Cancer Cell, and Blood, all while taking advantage of rapidly developing technologies in the fields of genomics, epigenetics, and stem cell biology in a quest to yield new therapies for leukemia.

Dr. Armstrong began his medical career in 1996 after earning his MD and PhD from the University of Texas Southwestern, where he trained with Nobel Laureates Joseph Goldstein, MD, and Michael Brown, MD. After completing a residency in pediatrics at Boston Children's Hospital and a clinical fellowship at Dana-Farber Cancer Institute and Boston Children's Hospital, Dr. Armstrong held a postdoctoral fellowship in the laboratory of the late Stanley Korsmeyer, MD, at Dana-Farber Cancer Institute, where he studied the molecular basis of infant leukemias instigated by MLL gene translocations. Following his postdoctoral training, Dr. Armstrong served as an attending and principal investigator in the Dana-Farber Cancer Institute pediatric hematology/oncology program, launching an independent laboratory to study the molecular genetics and therapeutics of leukemia and particularly MLL-rearranged disease, where he remained until he was recruited to MSK in 2012.

In addition to his membership to ASH, Dr. Armstrong is a member of the Society of Pediatric Research, the American Society of Pediatric Hematology/Oncology, the Society for Hematology and Stem Cells, and the American Society for Clinical Investigation. His recent awards include the American Pediatric Society and Society for Pediatric Research E. Mead Johnson Award for Research in Pediatrics, the Memorial Sloan Kettering Cancer Center Paul Marks Prize for Cancer Research, and the International Society of Experimental Hematology McCulloch and Till Award. Earlier this year, Dr. Armstrong was awarded the Frank A. Oski Memorial Award from the American Society of Pediatric Hematology/Oncology and was elected to the Association of American Physicians.

"ASH is pleased to honor Dr. Armstrong for his pioneering research in the fields of genomics and stem cell biology that is helping to fuel new therapies for patients diagnosed with devastating leukemias," said ASH President Linda J. Burns, MD, of the University of Minnesota. "His leadership and landmark discoveries in the fields of cancer stem cells and leukemia will undoubtedly leave a lasting imprint on contemporary cancer research."

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ASH honors Scott Armstrong, M.D., Ph.D., with 2014 William Dameshek Prize

USC, UCLA and UCSF put their heads together to find cures for craniofacial defects

PUBLIC RELEASE DATE:

17-Jul-2014

Contact: Cristy Lytal lytal@med.usc.edu 323-442-2172 University of Southern California - Health Sciences

One in every 2,000 babies is born with a skull that can't grow normally. Various sections of these babies' skulls are fused together at joints called sutures, constricting the developing brain and disrupting vision, sleep, eating and IQ. For these young patients, risky skull-expanding surgeries become an almost annual event.

Now, three leading universities for stem cell research the University of Southern California (USC); the University of California, Los Angeles (UCLA); and the University of California, San Francisco (UCSF) have joined forces to find better solutions for these and other patients with craniofacial defects.

All three institutions have leading stem cell research centers established with support from Eli and Edythe Broad, and all three are home to top scientists and clinicians in the field of craniofacial biology.

"The value of this collaboration is bringing together a bunch of interested scientists from three major institutions in California around really important problems," said Andy McMahon, director of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC. "It's really going to take a group of scientists across these different places with different expertise to be able to make progress towards helping these patients."

Mark Urata a plastic and reconstructive surgeon at USC, Children's Hospital Los Angeles and Cedars-Sinai Medical Center underscores the need to invent less painful, dangerous and disruptive treatments for babies with fused skulls. "The operation we perform is state-of-the-art," he explained. "We're doing this better than most people in the country, and yet it's not good enough."

Yang Chai the George and MaryLou Boone Professor, director of the Center for Craniofacial Molecular Biology (CCMB) and associate dean of Research at the Ostrow School of Dentistry of USC sees tremendous value in teaming up with clinicians such as Urata. "Really, our faces are our identities, and the first thing you see when you look at someone is his or her face," said Chai. "And when someone has a craniofacial malformation, it really presents a significant challenge to that individual. By working closely with the clinicians, researchers can do more for these kids."

The group has already convened for two day-long faculty retreats, which have attracted funding from USC's CCMB, the UCSF Program in Craniofacial and Mesenchymal Biology, and the UCLA Clinical and Translational Science Institute. Participants included: McMahon, Urata, Chai, Ruchi Bajpai, Gage Crump, Scott Fraser, Robert Maxson, Amy Merrill, Janet Oldak, Pedro Sanchez, Michael Paine, Songtao Shi, Malcolm Snead, Stephen Yen and Jian Xu from USC; Jeffery Bush, Lindsey Criswell, Ophir Klein, Sarah Knox, Margaret Langham, Ralph Marcucio, Sneha Oberoi, Jason Pomerantz, Richard Schneider and Nathan Young from UCSF; and Daniel Cohn, Katrina Dipple, Deborah Krakow, Justine Lee and Kristen Yee from UCLA.

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USC, UCLA and UCSF put their heads together to find cures for craniofacial defects

International Stem Cell Corporation Should Win EU Patent Case

The European Union Court of Justice will likely agree that stem cells can be patented, setting a new precedent for scientists to use this controversial method for research and development.

This is an extremely important case with industry-wide consequences, Dr. Simon Craw, of the International Stem Cell Corporation, the American biotech company at the center of the case.

The California-based firm applied for two patents on the technology it uses to produce stem cells but was rejected. European Union laws dictate that embryos cannot be patented on ethical grounds, because they can develop into humans.

Technically, embryos are eggs that have been fertilized with human sperm. But ISC Corp. uses chemicals to activate the cells instead, which are then called parthenotes.

EU Advocate General Pedro Cruz Villaln wrote in a Thursday opinion that since these cells cannot possibly develop into humans, they arent subject to the ethical laws that apply to human beings.

Its a great day for scientific rationale with the Judge correctly recognizing the difference between human parthenogenesis and fertilization, Craw said.

Three years ago, the EU court ruled against patents on discoveries that involve the stem cells, saying the use of human cells in this was immoral.

But it all started in 2004 when Greenpeace challenged a patent filed by a German stem cell researcher, which described a method to turn stem cells into nerve cells.

Greenpeace said the work was contrary to public order because the embryos were destroyed, according to a report in the Guardian from the time.

A group of 13 scientists wrote in the journal Nature that year to express profound concern over the recommended ban, which represents a blow to years of effort to derive medical applications from embryonic stem cells.

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International Stem Cell Corporation Should Win EU Patent Case

Can heart damage be fixed?

STORY HIGHLIGHTS

(CNN) -- In medical school, Gerald Karpman was taught that when it comes to matters of the heart, what's done is done.

"If you survived the heart attack, you survived at the level that you were going to be," he recalls. "Whatever damage was done was permanent."

That thinking has prevailed until very recently, when studies involving a handful of patients showed an infusion of stem cells might help rebuild healthy hearts in heart attack survivors.

On March 7, Karpman joined that perilous club. A dermatologist in Camarillo, California, and a former marathon runner, the 66-year-old had a rigorous routine: eight to 10 miles of walking each day and a meticulous, meatless diet.

But that morning, sitting at his home computer, a pain kicked in.

"Within about 30 seconds, I was in extreme discomfort," recalls Karpman, who says it was worse than the kidney stones he once suffered. "I couldn't sit still. I mean even driving the car (to the hospital), I couldn't put a seat belt on; I'm just moving around, just trying to think of something else."

Karpman made it to Los Robles Hospital and Medical Center in Thousand Oaks, where doctors used stents to reopen an artery in his heart and save his life.

As he lay recovering, he took in some grim news: Nearly 20% of his heart muscle was dead, starved of oxygen. Dead heart tissue leaves a scar, interrupting the coordinated muscle action that makes the heart such an efficient pump.

A standard measure of the heart's pumping ability is the ejection fraction, the percentage of blood in the left ventricle that is pumped out with each heartbeat. A healthy ejection fraction is between 55 and 70, according to the American Heart Association. Karpman's was 30.

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Can heart damage be fixed?

Heart attack damage may be reversible

STORY HIGHLIGHTS

For more, watch "Sanjay Gupta | M.D." on Saturday at 4:30 p.m. and Sunday at 7:30 a.m. ET.

(CNN) -- In medical school, Gerald Karpman was taught that when it comes to matters of the heart, what's done is done.

"If you survived the heart attack, you survived at the level that you were going to be," he recalls. "Whatever damage was done was permanent."

That thinking has prevailed until very recently, when studies involving a handful of patients showed an infusion of stem cells might help rebuild healthy hearts in heart attack survivors.

On March 7, Karpman joined that perilous club. A dermatologist in Camarillo, California, and a former marathon runner, the 66-year-old had a rigorous routine: eight to 10 miles of walking each day and a meticulous, meatless diet.

But that morning, sitting at his home computer, a pain kicked in.

"Within about 30 seconds, I was in extreme discomfort," recalls Karpman, who says it was worse than the kidney stones he once suffered. "I couldn't sit still. I mean even driving the car (to the hospital), I couldn't put a seat belt on; I'm just moving around, just trying to think of something else."

Karpman made it to Los Robles Hospital and Medical Center in Thousand Oaks, where doctors used stents to reopen an artery in his heart and save his life.

As he lay recovering, he took in some grim news: Nearly 20% of his heart muscle was dead, starved of oxygen. Dead heart tissue leaves a scar, interrupting the coordinated muscle action that makes the heart such an efficient pump.

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Heart attack damage may be reversible

Patient-specific stem cells and personalized gene therapy

PUBLIC RELEASE DATE:

10-Jul-2014

Contact: Lucky Tran lt2549@cumc.columbia.edu 212-305-3689 Columbia University Medical Center

NEW YORK, NY (July 10, 2014) Columbia University Medical Center (CUMC) researchers have created a way to develop personalized gene therapies for patients with retinitis pigmentosa (RP), a leading cause of vision loss. The approach, the first of its kind, takes advantage of induced pluripotent stem (iPS) cell technology to transform skin cells into retinal cells, which are then used as a patient-specific model for disease study and preclinical testing.

Using this approach, researchers led by Stephen H. Tsang, MD, PhD, showed that a form of RP caused by mutations to the gene MFRP (membrane frizzled-related protein) disrupts the protein that gives retinal cells their structural integrity. They also showed that the effects of these mutations can be reversed with gene therapy. The approach could potentially be used to create personalized therapies for other forms of RP, as well as other genetic diseases. The paper was published recently in the online edition of Molecular Therapy, the official journal of the American Society for Gene & Cell Therapy.

"The use of patient-specific cell lines for testing the efficacy of gene therapy to precisely correct a patient's genetic deficiency provides yet another tool for advancing the field of personalized medicine," said Dr. Tsang, the Laszlo Z. Bito Associate Professor of Ophthalmology and associate professor of pathology and cell biology.

While RP can begin during infancy, the first symptoms typically emerge in early adulthood, starting with night blindness. As the disease progresses, affected individuals lose peripheral vision. In later stages, RP destroys photoreceptors in the macula, which is responsible for fine central vision. RP is estimated to affect at least 75,000 people in the United States and 1.5 million worldwide.

More than 60 different genes have been linked to RP, making it difficult to develop models to study the disease. Animal models, though useful, have significant limitations because of interspecies differences. Researchers also use human retinal cells from eye banks to study RP. As these cells reflect the end stage of the disease process, however, they reveal little about how the disease develops. There are no human tissue culture models of RP, as it would dangerous to harvest retinal cells from patients. Finally, human embryonic stem cells could be useful in RP research, but they are fraught with ethical, legal, and technical issues.

The use of iPS technology offers a way around these limitations and concerns. Researchers can induce the patient's own skin cells to revert to a more basic, embryonic stem celllike state. Such cells are "pluripotent," meaning that they can be transformed into specialized cells of various types.

In the current study, the CUMC team used iPS technology to transform skin cells taken from two RP patientseach with a different MFRP mutationinto retinal cells, creating patient-specific models for studying the disease and testing potential therapies.

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Patient-specific stem cells and personalized gene therapy

Stem Cell Research Center – University of Pittsburgh

At the University of Pittsburgh / Children's Hospital of Pittsburgh of UPMC Stem Cell Research Center (SCRC), scientists and physicians are working around the clock to expand the possibilities of tissue engineering by unlocking the potential of gene therapy and adult stem cell research and transferring research findings into the development of effective treatments for damaged or diseased tissues. Medicine has moved from treating the pain of injuries to treating their cause and the SCRC has taken the initiative to lead this movement in the area of cellular therapeutics.

Led by Dr. Johnny Huard, the faculty and staff of the SCRC are using cutting edge technology in cellular techniques, observation, and analyzation to seek out the answers to the cellular therapies of tomorrow. Muscular injuries, including muscular dystrophy, bone fractures, nervous system conduction pathways, cardiac repair, and vascular blockages are all being targeted by the Center as areas of keen interest in medicine. Each member of the center along with their projects and individual skills are focused on the translation of their research from the Center's laboratories into your clinic.

The SCRC is a fully collaborative center spanning many disciplines throughout the University of Pittsburgh Medical Center (UPMC) and the Children's Hospital of Pittsburgh of UPMC. Many of the Center's collaborative colleagues reside in the focus groups within its laboratories.

The Departments of Orthopaedics, Cardiothroacic Surgery, and Rehabilitation along with the Pittsburgh Cancer Institute and the McGowan Center for Regenerative Medicine, among others, each share in the SCRC's goals for the future of cellular regenerative medicine.

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Stem Cell Research Center - University of Pittsburgh

Stem cell program – KU Medical Center

A primary and high-priority area of interest in the CVRI involves investigation of adult stem cell biology and therapy. A growing body of evidence supports the notion that transplantation of adult stem/progenitor cells can induce cardiac repair and improve left ventricular function and structure after myocardial infarction. The stem cell program in the CVRI conducts research to identify the optimal cell for this purpose and to enhance the outcomes via modification of cells before transplantation.

The major goals of the stem cell program are:

Relevant projects:

Mesenchymal stem cell therapy for infarct repair: Mesenchymal stem cells represent a rare population of primitive cells that reside in the bone marrow and participate in organ repair following injury. Injection of these cells after myocardial infarction can repair the heart and improve left ventricular function. These studies are broadly directed at improving the outcomes of MSC therapy for cardiac repair.

Wnt11 signaling in stem cell-induced cardiac repair: Wnt11 is a member of the 'wingless' family of glycoproteins that participate in various biological processes, including cellular proliferation, differentiation, and migration during development. The goal of this project is to delineate the role of Wnt11 signaling in differentiation of adult bone marrow cells and in cardiac repair.

Pretreatment of stem cells for greater cardiac differentiation: Our laboratory has extensive experience with the induction of cellular differentiation using various defined media. The primary goal of this project is to identify biological agents that will direct differentiation of adult stem/progenitors in cardiac lineages.

Investigators, trainees, and associates:

Last modified: Apr 01, 2014

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Stem cell program - KU Medical Center

New stem cell research retracted

Almost five months after publication, Nature retracted two papers regarding new stem cell research. This retraction came after various errors were spotted, both in the papers presented and the attempted recreations of the experiments described. The research, which claimed that embryonic stem cells could be created by exposing normal skin cells to stress, appeared to be a medical breakthrough at the time of publication.

The lead author was found guilty of misconduct, while her employer was threatened numerous times with dismantlement, reports Scientific American. It appeared that parts of the methods were plagiarized from previous studies in the stem cell field, and the supposed 'different' cells and embryos described in the study were actually the same.

It was only after recreation of the described methods failed that the errors were brought forth and scrutinized by various outside sources, including one of the co-authors. The Riken Center for Developmental Biology in Japan began in-depth investigations into the studies in February 2014, and categorized some of the major errors that skewed the written results as misconduct, reports Uncover California.

Nature released a statement regarding the publication, saying, "The episode has further highlighted flaws in Natures procedures and in the procedures of institutions that publish with us."

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New stem cell research retracted

Stem cell type resists chemotherapy drug

A new study shows that adipose-derived human stem cells, which can become vital tissues such as bone, may be highly resistant to the common chemotherapy drug methotrexate (MTX). The preliminary finding from lab testing may prove significant because MTX causes bone tissue damage in many patients.

MTX is used to treat cancers including acute lymphoblastic leukemia, the most common form of childhood cancer. A major side effect of the therapy, however, is a loss of bone mineral density. Other bone building stem cells, such as bone marrow derived stem cells, have not withstood MTX doses well.

"Kids undergo chemotherapy at such an important time when they should be growing, but instead they are introduced to this very harsh environment where bone cells are damaged with these drugs," said Olivia Beane, a Brown University graduate student in the Center for Biomedical Engineering and lead author of the study. "That leads to major long-term side effects including osteoporosis and bone defects. If we found a stem cell that was resistant to the chemotherapeutic agent and could promote bone growth by becoming bone itself, then maybe they wouldn't have these issues."

Stem cell survivors

Originally Beane was doing much more basic research. She was looking for chemicals that could help purify adipose-derived stem cells (ASCs) from mixed cell cultures to encourage their proliferation. Among other things, she she tried chemotherapy drugs, figuring that maybe the ASCs would withstand a drug that other cells could not. The idea that this could help cancer patients did not come until later.

In the study published online in the journal Experimental Cell Research, Beane exposed pure human ASC cultures, "stromal vascular fraction" (SVF) tissue samples (which include several cell types including ASCs), and cultures of human fibroblast cells, to medically relevant concentrations of chemotherapy drugs for 24 hours. Then she measured how those cell populations fared over the next 10 days. She also measured the ability of MTX-exposed ASCs, both alone and in SVF, to proliferate and turn into other tissues.

Beane worked with co-authors fellow center member Eric Darling, the Manning Assistant Professor in the Department of Molecular Pharmacology, Physiology and Biotechnology, and research assistant Vera Fonseca.

They observed that three chemotherapy drugs -- cytarabine, etoposide, and vincristine -- decimated all three groups of cells, but in contrast to the fibroblast controls, the ASCs withstood a variety of doses of MTX exceptionally well (they resisted vincristine somewhat, too). MTX had little or no effect on ASC viability, cell division, senescence, or their ability to become bone, fat, or cartilage tissue when induced to do so.

The SVF tissue samples also withstood MTX doses well. That turns out to be significant, Darling said, because that's the kind of tissue that would actually be clinically useful if an ASC-based therapy were ever developed for cancer patients. Hypothetically, fresh SVF could be harvested from the fat of a donor, as it was for the study, and injected into bone tissue, delivering ASCs to the site.

To understand why the ASCs resist MTX, the researchers conducted further tests. MTX shuts down DNA biosynthesis by binding the protein dihydrofolate reductase so that it is unavailable to assist in that essential task. The testing showed that ASCs ramped up dihydrofolate reductase levels upon exposure to the drug, meaning they produced enough to overcome a clinically relevant dose of MTX.

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Stem cell type resists chemotherapy drug