Category Archives: Cell Medicine

June 8, 2017 by Geri Clark The camera-based imaging platform Scott Blanchard and his team developed to track how individual proteins, called G protein-coupled receptors (GPCRs), respond to their environments. Credit: Dr. Daniel Terry/Weill Cornell Medicine

New imaging methods that allow researchers to track the individual protein molecules on the surface of cells have been developed by Weill Cornell Medicine investigators. The results offer unprecedented insight into how cells sense and respond to their environments.

G protein-coupled receptors (GPCRs) are proteins that reside within the cellular membrane and relay signals into the cell to regulate fundamental aspects of human physiology. The signals received through GPCRs include everything from light, which activates the proteins in cells that enable vision, to chemicals such as neurotransmitters that regulate mood, to signals that trigger pain. Nearly half of all clinically used drugs work by targeting distinct GPCRs.

"These proteins are critical to every aspect of human physiology," said co-senior study author Scott Blanchard, professor of physiology and biophysics at Weill Cornell Medicine. "We need to know how GPCRs recognize all of these signals, how they process the signals and how they transmit the information into the cell to invoke a specific action. Only in doing so will we be able to develop new generations of drugs that more accurately target these proteins and thus can help without causing collateral damage."

In a paper published June 7 in Nature, Blanchard and colleagues at Weill Cornell Medicine, Stanford and Columbia Universities describe an important advance in this direction, achieved with the use of an imaging technique called single-molecule Fluorescence Energy Transfer (smFRET) that allowed the researchers to watch individual GPCR molecules as they responded to molecules of adrenaline, a hormone that controls functions including heartbeat, breathing and dilation of blood vessels.

"We knew already that the GPCR molecule physically changes upon binding adrenaline and that this process enables it to bind intracellular proteins," Blanchard said. "What we didn't know much about is how this activation process actually happens. And that's the critical missing information that has limited our understanding of drug efficacy."

To enable them to view this process, Blanchard's team developed new reporter molecules called fluorophores that emit fluorescent light and can be attached to the GPCR to inform on its motions when adrenaline binds. The Blanchard lab also developed a new microscope that can follow these light messages with greater accuracy. The researchers then watched and recorded the movements, using complex computation to learn how the protein responds to its interactions with adrenaline and with another protein in the cell, called heterotrimeric G protein, which senses the response and lets the cell know that the GPCR has been activated by adrenaline.

The result is a high-resolution, high-speed film that reveals the details of the molecular relationships that transmit the adrenaline signal through the GPCR into the cell. This revealed to the research team for the first time a series of reversible steps in the process by which an activated GPCR interacts with its intracellular G protein that have never been seen before. This allowed them to conclude their paper by describing why "Quantitative single-molecule imaging investigations will be crucial in . delineating distinct ligand-dependent GPCR signaling pathways."

"These are important insights that wouldn't be possible without the imaging techniques that increase our understanding of how these molecular machines actually work and how signals are conveyed from the outside to the inside of the cell," said Blanchard, who is on related patents, including a patent licensed to Lumidyne for one of the fluorophores used in the study. Blanchard is a co-founder with equity in Lumidyne, a company that focuses on fluorescence technologies. "Being able to see the inner workings of the GPCRs has enormous implications for drug discovery for everything from pain management to heart disease and cancer. The clinical implications of this technology can reach very far."

Explore further: Cholesterol may help proteins pair up to transmit signals across cell membranes

More information: G. Glenn Gregorio et al. Single-molecule analysis of ligand efficacy in 2ARG-protein activation, Nature (2017). DOI: 10.1038/nature22354

Journal reference: Nature

Provided by: Cornell University

Cholesterol may act as a selective glue that binds proteins into paired structures that enable human cells to respond to outside signals, according to a new study in PLOS Computational Biology.

Researchers at the University of Michigan, Stanford University and biotech company ConfometRx have captured the first cryo-electron microscopy snapshots of a key cellular receptor in action.

Researchers from Charit Universittsmedizin Berlin have been studying two proteins that play a vital role in many bodily processes. The aim of the research was to establish how G-protein-coupled receptors (GPCRs) and ...

(Phys.org)A research team at Weill Cornell Medical College has solved the 3D crystal structure of a member protein in one of the most important classes of human proteinsthe G protein-coupled receptors (GPCRs). These ...

For the first time, scientists from the Florida campus of The Scripps Research Institute (TSRI) have created detailed "fingerprints" of a class of surface receptors that have proven highly useful for drug development.

G protein-coupled receptors (GPCRs) are the largest class of cell surface receptors in our cells, involved in signal transmission across the cell membrane. One of the biggest questions is how a signal recognized at the extracellular ...

(Phys.org)One of the greatest challenges in generating energy from renewable sources is finding a way to store the continuously fluctuating energy being produced. Batteries, supercapacitors, and most other energy-storage ...

New imaging methods that allow researchers to track the individual protein molecules on the surface of cells have been developed by Weill Cornell Medicine investigators. The results offer unprecedented insight into how cells ...

Scientists and engineers from the University of Bath have developed biodegradable cellulose microbeads from a sustainable source that could potentially replace harmful plastic ones that contribute to ocean pollution.

Calcium carbonate, or CaCO3, comprises more than 4% of the earth's crust. Its most common natural forms are chalk, limestone, and marble, produced by the sedimentation of the shells of small fossilized snails, shellfish, ...

Using the principles behind the formation of sandcastles from wet sand, North Carolina State University researchers have achieved 3-D printing of flexible and porous silicone rubber structures through a new technique that ...

A team of chemists in Canada has developed a way to process metals without using toxic solvents and reagents.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

The rest is here:
Imaging technique shows molecular machinery at work - Phys.Org

There is a great deal of interest and research in the field of regenerative medicine, especially as it relates to sports performance and the treatment of sports injuries. The future of regenerative sports medicine is bright and its usage and indications are bound to expand.

The term regenerative medicine and the use of "biologics" broadly refer to natural products that are harvested and used to supplement healing. In orthopedic sports medicine, the use of biologics entails the use of growth factors, cells or tissue.

Researchers have performed throughout 500 clinical trials evaluating mesenchymal stem cells and there have been more than 180 trials evaluating platelet rich plasma, which is a testimony to the level of interest in biologics and the hope of treating or modulating various disease processes. Unfortunately, the scientific approach to studying these therapies and interventions has been quite disordered, with little standardization of the biologic preparation being studied. This lack of standardization has made it difficult to compare study outcomes and validate conclusions of disparate studies.

The use of biologics is highly regulated by the Food and Drug Administration, and currently the FDA does not allow orthopedists in the U.S. to harvest mesenchymal stem cells from bone and expand these cells in culture for injection into an arthritic knee, for example.

There are several types of stem cells: embryonic, which are omnipotent and can give rise to an entire organism, and adult stem cells, which are multipotent and can differentiate into certain types of cells. The use of embryonic stem cells is highly regulated, there is ethical considerations, and there is some risk of tumor growth. For these reasons, adult stem cells are currently used in orthopedic sports medicine treatments.

Defining stem cells

Stem cells have four defining qualities: they can reproduce; they can differentiate into a number of different cell types; they can mobilize and they can turn on or off other cells in their local environment. Mesenchymal stem cells can be obtained from bone, fat, synovial tissue and periosteum.

There are several types of stem cells: embryonic, which are omnipotent and can give rise to an entire organism, and adult stem cells, which are multipotent and can differentiate into certain types of cells. The use of embryonic stem cells is highly regulated, there is ethical considerations, and there is some risk of tumor growth. For these reasons, adult stem cells are currently used in orthopedic sports medicine treatments.

As for current orthopedic applications, platelet rich plasma injections have been shown to be more effective than hyaluronate injections for the treatment of mild to moderate arthritis in younger and middle aged patients. Unfortunately, insurance companies still consider platelet rich plasma injections experimental and therefore do not cover them.

There have been numerous studies assessing whether there is a benefit to injecting platelet rich plasma at the time of rotator cuff repair and most studies to date have not shown a functional benefit or better healing rates. There are even fewer studies looking at injecting BMA at the time of rotator cuff repair and again no benefit has been demonstrated to date.

However, there have been some animal studies in which stem cells have been further manipulated and utilized (which the FDA does not currently allow in humans) that have shown some improved bone tendon healing. As for meniscal repair, the results of animal studies have been mixed. Some studies have shown that BMA loaded onto a scaffold can even regrow meniscal like repair tissue, but others have not demonstrated a difference in healing in animal models.

Dr. Richard Cunningham, M.D. is a board-certified, fellowship-trained orthopedic surgeon and knee and shoulder specialist with Vail-Summit Orthopaedics. For more information, visit http://vailknee.com.

Read more:
Ask a Vail Sports Doc: The future of regenerative sports medicine - Vail Daily News

Visit the News Hub

Trehalose triggers cellular housekeeping in artery-clogging plaque

A new study shows that a type of natural sugar called trehalose triggers an important cellular housekeeping process in immune cells that helps treat atherosclerotic plaque. The image shows a cross section of a mouse aorta, the main artery in the body, with a large plaque. Straight red lines toward the upper left are the wall of the aorta. Yellow areas are where housekeeping cells called macrophages are incinerating cellular waste.

Researchers have long sought ways to harness the bodys immune system to treat disease, especially cancer. Now, scientists have found that the immune system may be triggered to treat atherosclerosis and possibly other metabolic conditions, including fatty liver disease and type 2 diabetes.

Studying mice, researchers at Washington University School of Medicine in St. Louis have shown that a natural sugar called trehalose revs up the immune systems cellular housekeeping abilities. These souped-up housecleaners then are able to reduce atherosclerotic plaque that has built up inside arteries. Such plaques are a hallmark of cardiovascular disease and lead to an increased risk of heart attack.

The study is published June 7 in Nature Communications.

We are interested in enhancing the ability of these immune cells, called macrophages, to degrade cellular garbage making them super-macrophages, said senior author Babak Razani, MD, PhD, an assistant professor of medicine.

Macrophages are immune cells responsible for cleaning up many types of cellular waste, including misshapen proteins, excess fat droplets and dysfunctional organelles specialized structures within cells.

In atherosclerosis, macrophages try to fix damage to the artery by cleaning up the area, but they get overwhelmed by the inflammatory nature of the plaques, Razani explained. Their housekeeping process gets gummed up. So their friends rush in to try to clean up the bigger mess and also become part of the problem. A soup starts building up dying cells, more lipids. The plaque grows and grows.

In the study, Razani and his colleagues showed that mice prone to atherosclerosis had reduced plaque in their arteries after being injected with trehalose. The sizes of the plaques measured in the aortic root were variable, but on average, the plaques measured 0.35 square millimeters in control mice compared with 0.25 square millimeters in the mice receiving trehalose, which translated into a roughly 30 percent decrease in plaque size. The difference was statistically significant, according to the study.

The effect disappeared when the mice were given trehalose orally or when they were injected with other types of sugar, even those with similar structures.

Found in plants and insects, trehalose is a natural sugar that consists of two glucose molecules bound together. It is approved by the Food and Drug Administration for human consumption and often is used as an ingredient in pharmaceuticals. Past work by many research groups has shown trehalose triggers an important cellular process called autophagy, or self-eating. But just how it boosts autophagy has been unknown.

In this study, Razani and his colleagues show that trehalose operates by activating a molecule called TFEB. Activated TFEB goes into the nucleus of macrophages and binds to DNA. That binding turns on specific genes, setting off a chain of events that results in the assembly of additional housekeeping machinery more of the organelles that function as garbage collectors and incinerators.

Trehalose is not just enhancing the housekeeping machinery thats already there, Razani said. Its triggering the cell to make new machinery. This results in more autophagy the cell starts a degradation fest. Is this the only way that trehalose works to enhance autophagy by macrophages? We cant say that for sure were still testing that. But is it a predominant process? Yes.

The researchers are continuing to study trehalose as a potential therapy for atherosclerosis, especially since it is not only safe for human consumption but is also a mild sweetener. One obstacle the scientists would like to overcome, however, is the need for injections. Trehalose likely loses its effectiveness when taken orally because of an enzyme in the digestive tract that breaks trehalose into its constituent glucose molecules. Razani said the research team is looking for ways to block that enzyme so that trehalose retains its structure, and presumably its function, when taken by mouth.

This work was supported by grants from the National Institutes of Health (NIH), grant numbers K08 HL098559 and R01 HL125838; the Washington University Diabetic Cardiovascular Disease Center and Diabetes Research Center, grant number P30 DK020579; The Foundation for Barnes-Jewish Hospital; and the Wylie Scholar Award from the Vascular Cures Foundation.

Sergin I, Evans TD, Zhang X, Bhattacharya S, Stokes CJ, Song E, Ali S, Dehestani B, Holloway KB, Micevych PS, Javaheri A, Crowley JR, Ballabio A, Schilling JD, Epelman S, Weihl CC, Diwan A, Fan D, Zayed MA, Razani B. Exploiting macrophage autophagy-lysosomal biogenesis as a therapy for atherosclerosis. Nature Communications. June 7, 2017.

Washington University School of Medicines 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked seventh in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

Here is the original post:
Type of sugar may treat atherosclerosis, mouse study shows - Washington University School of Medicine in St. Louis

Dr. Franck Mauvais-Jarvis is a leading voice in the debate to bring sex parity to pre-clinical research. Photo by Paula Burch-Celentano.

Over the last decade, many drugs that have been pulled from the market due to toxicity were withdrawn because they affected women more than men. It turns out, the studies that brought the drugs to market were designed using only male cells and animal models, a common flaw a Tulane endocrinologist is working to help correct. We really need to study both sexes, says Dr. Franck Mauvais-Jarvis, a leading voice in the debate to bring sex parity to pre-clinical research. The focus on a single sex threatens to limit the impact of research findings as results may be relevant to only half of the population. Mauvais-Jarvis, a professor of endocrinology at Tulane University School of Medicine, is the lead author of a newly published article in the journal Cell Metabolism to help scientists who study obesity, diabetes or other metabolic diseases better account for inherent sex differences in research. While the National Institutes of Health recently mandated researchers consider sex as a biological variable by including both sexes in pre-clinical research, there is little guidance in designing studies to fully consider sex differences in underlying biological mechanisms. The article outlines the causes of sex differences in research models and the methods for investigators to account for these factors. Mauvais-Jarvis goal is to help investigators better understand that sex differences are not simply a superficial aspect of research that only account for different sets of hormones. He maintains that male and female are two different biological systems. Sex differences are at the core of the mechanism for biological traits and disease, Mauvais-Jarvis says. We believe that the incorporation of appropriately designed studies on sex differences in metabolism and other fields will accelerate discovery and enhance our ability to treat disease. This is the fundamental basis of precision medicine. The article is co-authored by Drs. Arthur Arnold and Karen Reue, two experts in the genetics of sex differences at the University of California, Los Angeles.

Read the original:
Does the sex of a cell matter in research? - News from Tulane

June 6, 2017 In this image of a human breast tumor, a cluster of malignant cells that have become resistant to chemotherapy are shown in red. Credit: NCI

Researchers at University of California San Diego School of Medicine report that cancer cells appear to communicate to other cancer cells, activating an internal mechanism that boosts resistance to common chemotherapies and promotes tumor survival.

The findings are published online in the June 6 issue of Science Signaling.

Six years ago, Maurizio Zanetti, MD, professor in the Department of Medicine at UC San Diego School of Medicine and a tumor immunologist at Moores Cancer Center at UC San Diego Health, published a paper in PNAS suggesting that cancer cells exploit an internal mechanism used by stressed mammalian cells, called the unfolded protein response (UPR), to communicate with immune cells, notably cells derived from the bone marrow, imparting them with pro-tumorigenic characteristics.

The UPR is activated in response to unfolded or misfolded proteins accumulating in the endoplasmic reticulum (ER)an organelle that carries out several metabolic functions in the cells and the site where proteins are built, folded and sent for secretion. The UPR can often decide cell death or survival.

In their new paper, Zanetti and colleagues say cancer cells appear to take the process beyond just affecting bone marrow cells, using transmissible ER stress (TERS) to activate Wnt signaling in recipient cancer cells. Wnt is a cellular signaling pathway linked to carcinogenesis in many types of cancer.

"We noticed that TERS-experienced cells survived better than their unexperienced counterparts when nutrient-starved or treated with common chemotherapies like bortezomib or paclitaxel," said Jeffrey J. Rodvold, a member of Zanetti's lab and first author of the study. "In each instance, receiving stress signals caused cells to survive better. Understanding how cellular fitness is gained within the tumor microenvironment is key to understand cooperativity among cancer cells as a way to collective resilience to nutrient starvation and therapies."

When cancer cells subject to TERS were implanted in mice, they produced faster growing tumors.

"Our data demonstrate that transmissible ER stress is a mechanism of intercellular communication," said Zanetti. "We know that tumor cells live in difficult environments, exposed to nutrient deprivation and lack of oxygen, which in principle should restrict tumor growth. Through stress transmission, tumor cells help neighboring tumor cells to cope with these adverse conditions and eventually survive and acquire growth advantages."

Importantly, he said the research may explain previous findings by other groups showing that individual tumor cells within a uniform genetic lineage can acquire functionally different behaviors in vivo. In other words, some cells acquire greater fitness and extended survivalanother way to generate intra-tumor heterogeneity, which currently represents one of the major obstacles to cancer treatment. This implies that mutations peppered throughout the cancer genome of an individual are not the only source of intra-tumor heterogeneity.

Zanetti said researchers and physicians need to consider these changing cellular dynamics in the tumor microenvironment in developing both a better understanding of cancer and more effective treatments.

Explore further: Cancer cells co-opt immune response to escape destruction

More information: Science Signaling (2017). DOI: 10.1126/scisignal.aah7177

Researchers at the University of California, San Diego School of Medicine report that tumor cells use stress signals to subvert responding immune cells, exploiting them to actually boost conditions beneficial to cancer growth.

A new study has identified a mechanism used by tumors to recruit stem cells from bone and convert them into cancer-associated fibroblasts (CAFs) that facilitate tumor progression. This work, which pinpoints the specific biochemical ...

A very high mortality rate is associated with ovarian cancer, in part due to difficulties in detecting and diagnosing the disease at early stages before tumors have spread, or metastasized, to other locations in the body.

Researchers from Oregon Health and Science University and Oregon State University have found that aspirin may slow the spread of some types of colon and pancreatic cancer cells. The paper is published in the American Journal ...

Tumor growth is dependent on interactions between cancer cells and adjacent normal tissue, or stroma. Stromal cells can stimulate the growth of tumor cells; however it is unclear if tumor cells can influence the stroma.

Researchers at University of California San Diego School of Medicine report that cancer cells appear to communicate to other cancer cells, activating an internal mechanism that boosts resistance to common chemotherapies and ...

A research study led by University of Minnesota engineers gives new insight into how cancer cells move based on their ability to sense their environment. The discovery could have a major impact on therapies to prevent the ...

The chemotherapy drug capecitabine gives patients a better quality of life and is as effective at preventing breast cancer from returning as the alternative regimen called CMF, when given following epirubicin. These are the ...

When you dine on curry and baked apples, enjoy the fact that you are eating something that could play a role starvingor even preventingcancer.

Scientists at Karolinska Institutet in Sweden report that cancer cells and normal cells use different 'gene switches' in order to regulate the expression of genes that control growth. In mice, the removal of a large regulatory ...

Doctors are reporting unprecedented success from a new cell and gene therapy for multiple myeloma, a blood cancer that's on the rise. Although it's early and the study is small35 peopleevery patient responded and all ...

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Read more from the original source:
Cancer cells send signals boosting survival and drug resistance in other cancer cells - Medical Xpress

Newswise The University of Illinois at Chicago College of Medicine will launch a new center that will focus on understanding tissue regeneration and pioneering future developments in stem cell biology as a means to repair diseased organs and tissues.

The center will partner with colleges and departments across the University of Illinois System.

Researchers in the new center will investigate the molecular signals that drive stem cellsto matureinto different cell types, such as blood, heart and blood vessel cells. The center will also study the epigenetic regulation of stem cells; determine the best approaches to transplant engineered cells, tissues and organs; and look for ways to efficiently produce the regenerative cells neededfor novel treatments.

The center will use a team-oriented multi-disciplinary approach that incorporates experts in biochemistry, biophysics, bioengineering and the clinical sciences to investigate stem cell biology and tissue regeneration, says Asrar Malik, the Schweppe Family Distinguished Professor and head of pharmacology, who is guiding the effort. Asearch is underway to recruit a director and additional faculty members, he said.

The current program in stem cell biology and regenerative medicine already includes seven faculty members, most within the department of pharmacology, who together have more than $10 million in research grants from the National Institutes of Health. Malik saidthat the intent in the next few years will be to carry out additional recruitments with other departments, to build from this interdisciplinary foundation and capitalize on our strengths.

Three new faculty members have joined the center in the last two years. Owen Tamplin studies stem cells in zebrafish; Konstandin Pajcini investigates the role of stem cells in the development of leukemia; and Jae-Won Shin engineers stem cells and tissues with an eye towards transplantation.

This will be the only dedicated stem cell and regenerative medicine center in Chicago with a focus on basic biology and translational science, and will affirm UICs leadership role in these fields, and help attract additional talent to our team, said Malik.

The opening of the center will be commemorated with a June 12 symposium on stem cell and regenerative medicine from 9 a.m. to 4 p.m. in the Faculty Alumni Lounge, UIC College of Medicine West building, 1853 W. Polk Street.

Speakers include:

More:
UIC Launches Center for Stem Cell and Regenerative Medicine - Newswise (press release)

In news that may bring hope to asthma sufferers, scientists discover a mechanism that provides a possible new target for allergy treatments.

By observing the allergic response in mice with asthma, scientists at the Francis Crick Institute found that white blood cells that normally reduce the symptoms of asthma convert into cells that make allergies worse. The research was funded by the Medical Research Council and the Francis Crick Institute.

"If we can work out what makes the cells change, and how to stop them changing, we might be able to find new ways of tackling allergic responses that make conditions such as asthma worse," says Mark Wilson, Group Leader at the Francis Crick Institute, who led the research.

The findings, published in The Journal of Experimental Medicine, also reveal that this cell-changing mechanism could boost immunity to worms in the intestine, which affect nearly half of the world's population, providing a new approach for vaccines.

"The conversion of immune-suppressing cells to immune-boosting cells is beneficial for providing immunity against intestinal worms, but can make allergies worse," explains Victoria Pelly, first author of the paper, and researcher at the Francis Crick Institute. "If we can find a way to target this mechanism, it will be extremely useful in the clinic."

After infecting mice with intestinal worms, the team took their white blood cells and injected them into non-infected mice, as a sort of 'vaccine', before infecting these mice with intestinal worms. Using a combination of genetic and imaging tools, the team monitored the white blood cells and found that a large proportion of immune-suppressing cells turned into immune-boosting cells to help fight the infection.

To investigate whether the same cell conversion happened in conditions beside worm infection, the team observed what happened to immune-suppressing cells in the lungs of mice with asthma. They found that up to 60% of these cells converted to immune-boosting cells, worsening the symptoms of asthma.

"Even though we notice the same cell conversion in worm infection and asthma, we think that the molecular mechanisms underlying this process are different," says Mark.

This article has been republished frommaterialsprovided by The Francis Crick Institute. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference:

Pelly, V. S., Coomes, S. M., Kannan, Y., Gialitakis, M., Entwistle, L. J., Perez-Lloret, J., . . . Wilson, M. S. (2017). Interleukin 4 promotes the development of ex-Foxp3 Th2 cells during immunity to intestinal helminths. The Journal of Experimental Medicine, 214(6), 1809-1826. doi:10.1084/jem.20161104

Originally posted here:
Cells Change Type to Help or Hinder Immunity - Technology Networks

JERUSALEM, June 5, 2017 /PRNewswire/ -- Gamida Cell, a leader in cellular and immune therapies for the treatment of cancer and orphan genetic diseases, announced today the appointment of Nobel Prize Laureate Professor Roger Kornberg and immune oncology expert and recently retired Novartis executive Dr. Michael Perry to its Board of Directors.

"We are pleased to welcome Professor Kornberg and Dr. Perry to our Board, especially now as Gamida Cell completes the final stages of clinical development of its flagship product NiCord and plans for potential commercialization. We look forward to their important guidance during this crucial time in the Company's development and in preserving Gamida's leading position in bone marrow transplantation," said Gamida Cell Chairman of the Board, Julian Adams, Ph.D.

Professor Roger Kornberg has been a Professor of Structural Biology atStanford Medical Schoolsince 1978. He won the Nobel Prize for Chemistry in 2006 for his studies of the molecular basis of transcription, the process whereby information in DNA is read out for the direction of all activities of all organisms, including humans. Professor Kornberg began his career as apostdoctoral researchfellow at theLaboratory of Molecular Biologyin Cambridge, England and went on to be an Assistant Professor of Biological Chemistry at Harvard Medical School in 1976, before moving to his present position. Professor Kornberg is also the recipient of the 2006Dickson PrizefromUniversity of Pittsburgh and the 2006Louisa Gross Horwitz PrizefromColumbia University. In 2009, he was elected a Foreign Member of the Royal Society. Professor Kornberg earned hisbachelor's degreeinchemistryfromHarvard Universityin 1967 and hisPh.D.inchemical physicsfrom Stanford in 1972 supervised byHarden M. McConnell.

"Gamida Cell's novel platform technology and scientific approach to expand functional cells in culture have broad potential to change the way cell based therapies are used clinically. NiCord, has demonstrated clinically that it could fill the unmet need in bone marrow transplantation," said Professor Kornberg.

Dr. Michael Perry recently retired from Novartis, following a highly successful tenure where he served as SVP and Chief Scientific Officer, Global BD&L, Chief Scientific Officer, Cell & Gene Therapy Unit, Global Head, Cellular Therapy/VP, Integrated Hospital Care Franchise and as Novartis' observer on the Gamida Cell Board of Directors. Novartis is a major shareholder in Gamida Cell. He is currently a Director and Operating Partner at venture capital firm Bioscience Managers Pty Ltd. Dr. Perry currently serves on the Boards of Avita Medical Ltd (AVH:ASX), Arrowhead Pharmaceuticals (ARWR:NASDAQ) and AmpliPhi Biosciences (APBH:NYSE). He is an Adjunct Professor at the University of Colorado, School of Medicine, Gates Center for Regenerative Medicine and Stem Cell Biology and serves as Chair of the Translational Medicine Advisory Board of the Houston Methodist Research Institute. Dr. Perry holds a Hon. B.Sc., in Physics from the University of Guelph in Ontario, Canada. He also earned a Doctorate in Veterinary Medicine & Surgery from the Ontario Veterinary College and a Ph.D. in Biomedical Science/Pharmacology from the University of Guelph.

Dr. Perry said, "Gamida Cell is a very attractive commercial opportunity with its cutting edge science, a lead product with FDA Breakthrough Therapy designation, compelling clinical data in bone marrow transplantation, an experienced and strong team, and a robust and cost effective manufacturing process. I am very much looking forward to supporting Gamida Cell to help translate these achievements into a business success."

About NiCord

NiCord is a stand-alone graft derived from a single umbilical cord blood unit which has been expanded in culture and enriched with stem and progenitor cells using Gamida Cell's proprietary NAM technology. NiCord leverages the advantage of umbilical cord blood which does not need full tissue matching to the patient, and can therefore be available to practically all patients in need. It also aims to address the major barrier of umbilical cord blood transplantation - delayed hematopoietic recovery - by demonstrating an advantage with a primary endpoint that is clinically meaningful.

Results from the Phase 1 and Phase 2 studies of NiCord were recently published in an article published by the Journal of Biology of Blood and Marrow Transplantation (BBMT, the official publication of theAmerican Society for Blood and Marrow Transplantation) entitled "Transplantation of Ex Vivo Expanded Umbilical Cord Blood (NiCord) Decreases Early Infection and Hospitalization".

Gamida Cell is currently enrolling patients in an international, multi-center, Phase 3 registration study of NiCord as a graft for bone marrow transplantation for patients with blood cancer who do not have a rapidly available fully matched donor. The Company announced in February 2017 that the first patient in the study had been transplanted. NiCord has an FDA Breakthrough Therapy Designation as well as FDA and EMA orphan drug designations, the most recent granted in March 2017. For more information on enrolling transplantation centers and study inclusion and exclusion criteria please click here.

About Gamida Cell

Gamida Cell is a world leader in cellular and immune therapies for the treatment of cancer and orphan genetic diseases. The company's pipeline of products are in development to treat a wide range of conditions including cancer, genetic hematological diseases such as sickle cell disease and thalassemia, bone marrow failure syndromes such as aplastic anemia, genetic metabolic diseases and refractory autoimmune diseases. Gamida Cell's current shareholders include Novartis, Elbit Imaging, Clal Biotechnology Industries, Israel Healthcare Venture, Denali Ventures and Auriga Ventures. For more information please visit http://www.gamida-cell.com.

Press Contact: Marjie Hadad MH Communications +972-54-536-5220 marjierhadad@gmail.com

Investor Contact: Beth DelGiacco Stern Investor Relations, Inc. +1-212-362-1200 beth@sternir.com

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/gamida-cell-appoints-nobel-prize-laureate-professor-roger-kornberg-and-immune-oncology-expert-dr-michael-perry-to-its-board-of-directors-300468459.html

SOURCE Gamida Cell

Homepage

More here:
Gamida Cell Appoints Nobel Prize Laureate Professor Roger Kornberg and Immune Oncology Expert Dr. Michael Perry ... - PR Newswire (press release)

Tissue-specific stem cells

Tissue-specific stem cells, which are sometimes referred to as adult or somatic stem cells, are already somewhat specialized and can produce some or all of the mature cell types found within the particular tissue or organ in which they reside. Because of their ability to generate multiple, organ-specific, cell types, they are described as multipotent. For example, stem cells found

Stem cells are the foundation cells for every organ and tissue in our bodies. The highly specialized cells that make up these tissues originally came from an initial pool of stem cells formed shortly after fertilization. Throughout our lives, we continue to rely on stem cells to replace injured tissues and cells that are lost every day, such as those in our skin, hair, blood and the lining of our gut. Stem cells have two key properties: 1) the ability to self-renew, dividing in a way that makes copies of themselves, and 2) the ability to differentiate, giving rise to the mature types of cells that make up our organs and tissues.

Tissue-specific stem cells Tissue-specific stem cells, which are sometimes referred to as adult or somatic stem cells, are already somewhat specialized and can produce some or all of the mature cell types found within the particular tissue or organ in which they reside. Because of their ability to generate multiple, organ-specific, cell types, they are described as multipotent. For example, stem cells found within the adult brain are capable of making neurons and two types of glial cells, astrocytes and oligodendrocytes. Tissue-specific stem cells have been found in several organs that need to continuously replenish themselves, such as the blood, skin and gut and have even been found in other, less regenerative, organs such as the brain. These types of stem cells represent a very small population and are often buried deep within a given tissue, making them difficult to identify, isolate and grow in a laboratory setting. Neuron Dr. Gerry Shaw, EnCor Biotechnology Inc. Astrocyte Abcam Inc. Oligodendrocyte Dhaunchak and Nave (2007). Proc Natl Acad Sci USA 104:17813-8 http://www.isscr.org Embryonic stem cells Embryonic stem cells have been derived from a variety of species, including humans, and are described as pluripotent, meaning that they can generate all the different types of cells in the body. Embryonic stem cells can be obtained from the blastocyst, a very early stage of development that consists of a mostly hollow ball of approximately 150-200 cells and is barely visible to the naked eye. At this stage, there are no organs, not even blood, just an inner cell mass from which embryonic stem cells can be obtained. Human embryonic stem cells are derived primarily from blastocysts that were created by in vitro fertilization (IVF) for assisted reproduction but were no longer needed. The fertilized egg and the cells that immediately arise in the first few divisions are totipotent. This means that, under the right conditions, they can generate a viable embryo (including support tissues such as the placenta). Within a matter of days, however, these cells transition to become pluripotent. None of the currently studied embryonic stem cell lines are alone capable of generating a viable embryo (i.e., they are pluripotent, not totipotent). Why are embryonic stem cells so valuable? Unlike tissue-specific (adult) stem cells, embryonic stem cells have the potential to generate every cell type found in the body. Just as importantly, these cells can, under the right conditions, be grown and expanded indefinitely in this unspecialized or undifferentiated state. These cells help researchers learn about early human developmental processes that are otherwise inaccessible, study diseases and establish strategies that could ultimately lead to therapies designed to replace or restore damaged tissues. Induced pluripotent stem cells One of the hottest topics in stem cell research today is the study of induced pluripotent stem cells (iPS cells). These are adult cells (e.g., skin cells) that are engineered, or reprogrammed, to become pluripotent, i.e., behave like an embryonic stem cell. While these iPS cells share many of the same characteristics of embryonic stem cells, including the ability to give rise to all the cell types in the body, it is important to understand that they are not identical. The original iPS cells were produced by using viruses to insert extra copies of three to four genes known to be important in embryonic stem cells into the specialized cell. It is not yet completely understood how these three to four reprogramming genes are able to induce pluripotency; this question is the focus of ongoing research. In addition, recent studies have focused on alternative ways of reprogramming cells using methods that are safer for use in clinical settings. Disease- or patient-specific pluripotent stem cells One of the major advantages of iPS cells, and one of the reasons that researchers are very interested in studying them, is that they are a very good way to make pluripotent stem cell lines that are specific to a disease or even to an individual patient. Disease-specific stem cells are powerful tools for studying the cause of a particular disease and then for testing drugs or discovering other approaches to treat or cure that disease. The development of patientspecific stem cells is also very attractive for cell therapy, as these cell lines are from the patient themselves and may minimize some of the serious complications of rejection and immunosuppression that can occur following transplants from unrelated donors. Moving stem cells into the clinic Clinical translation is the process used to turn scientific knowledge into real world medical treatments. Researchers take what they have learned about how a tissue usually works and what goes wrong in a particular disease or injury and use this information to develop new ways to diagnose, stop or fix what goes wrong. Before being marketed or adopted as standard of care, most treatments are tested through clinical trials. Sometimes, in attempting new surgical techniques or where the disease or condition is rare and does not have a large enough group of people to form a clinical trial, certain treatments might be tried on one or two people, a form of testing sometimes referred to as innovative medicine. For more information on how science becomes medicine, please visit http://www.closerlookatstemcells.org. Current therapies Blood stem cells are currently the most frequently used stem cells for therapy. For more than 50 years, doctors have been using bone marrow transplants to transfer blood stem cells to patients, and more advanced techniques for collecting blood stem cells are now being used to treat leukemia, lymphoma and several inherited blood disorders. Umbilical cord blood, like bone marrow, is often collected as a source of blood stem cells and in certain cases is being used as an alternative to bone marrow transplantation. Additionally, some bone, skin and corneal diseases or injuries can be treated by grafting tissues that are derived from or maintained by stem cells. These therapies have also been shown to be safe and effective. Potential therapies Other stem cell treatments, while promising, are still at very early experimental stages. For example, the mesenchymal stem cell, found throughout the body including in the bone marrow, can be directed to become bone, cartilage, fat and possibly even muscle. In certain experimental models, these cells also have some ability to modify immune functions. These abilities have created considerable interest in developing ways of using mesenchymal stem cells to treat a range of musculoskeletal abnormalities, cardiac disease and some immune abnormalities such as graft-versus-host disease following bone marrow transplant. Remaining challenges Despite the successes we have seen so far, there are several major challenges that must be addressed before stem cells can be used as cell therapies to treat a wider range of diseases. First, we need to identify an abundant source of stem cells. Identifying, isolating and growing the right kind of stem cell, particularly in the case of rare adult stem cells, are painstaking and difficult processes. Pluripotent stem cells, such as embryonic stem cells, can be grown indefinitely in the lab and have the advantage of having the potential to become any cell in the body, but these processes are again very complex and must be tightly controlled. iPS cells, while promising, are also limited by these concerns. In both cases, considerable work remains to be done to ensure that these cells can be isolated and used safely and routinely. Second, as with organ transplants, it is very important to have a close match between the donor tissue and the recipient; the more closely the tissue matches the recipient, the lower the risk of rejection. Being able to avoid the lifelong use of immunosuppressants would also be preferable. The discovery of iPS cells has opened the door to developing patient-specific pluripotent stem cell lines that can later be developed into a needed cell type without the problems of rejection and immunosuppression that occur from transplants from unrelated donors. Third, a system for delivering the cells to the right part of the body must be developed. Once in the right location, the new cells must then be encouraged to integrate and function together with the bodys other cells. http://www.isscr.org Glossary Blastocyst A very early embryo that has the shape of a ball and consists of approximately 150-200 cells. It contains the inner cell mass, from which embryonic stem cells are derived, and an outer layer of cells called the trophoblast that forms the placenta. Cell line Cells that can be maintained and grown in a dish outside of the body. Clinical translation The process of using scientific knowledge to design, develop and apply new ways to diagnose, stop or fix what goes wrong in a particular disease or injury. Differentiation The process of development with an increase in the level of organization or complexity of a cell or tissue, accompanied by a more specialized function. Embryo The early developing organism; this term denotes the period of development between the fertilized egg and the fetal stage. Embryonic stem cell Cells derived from very early in development, usually the inner cell mass of a developing blastocyst. These cells are self-renewing (can replicate themselves) and pluripotent (can form all cell types found in the body). Induced pluripotent stem (iPS) cell Induced pluripotent cells (iPS cells) are stem cells that were engineered (induced) from non-pluripotent cells to become pluripotent. In other words, a cell with a specialized function (for example, a skin cell) that has been reprogrammed to an unspecialized state similar to that of an embryonic stem cell. Innovative medicine Treatments that are performed on a small number of people and are designed to test a novel technique or treat a rare disease. These are done outside of a typical clinical trial framework. In vitro fertilization A procedure in which an egg cell and sperm cells are brought together in a dish to fertilize the egg. The fertilized egg will start dividing and, after several divisions, forms the embryo that can be implanted into the womb of a woman and give rise to pregnancy. Mesenchymal stem cells Mesenchymal stem cells were originally discovered in the bone marrow, but have since been found throughout the body and can give rise to a large number of connective tissue types such as bone, cartilage and fat. Multipotent stem cells Stem cells that can give rise to several different types of specialized cells, but in contrast to a pluripotent stem cell, are restricted to a certain organ or tissue types. For example, blood stem cells are multipotent cells that can produce all the different cell types that make up the blood but not the cells of other organs such as the liver or brain. Pluripotent stem cells Stem cells that can become all the cell types that are found in an implanted embryo, fetus or developed organism. Embryonic stem cells are pluripotent stem cells. Self-renewal The process by which a cell divides to generate another cell that has the same potential. Stem cells Cells that have both the capacity to self-renew (make more stem cells by cell division) and to differentiate into mature, specialized cells. Tissue-specific stem cells (also known as adult or somatic stem cells) Stem cells found in different tissues of the body that can give rise to some or all of the mature cell types found within the particular tissue or organ from which they came, i.e., blood stem cells can give rise to all the cells that make up the blood, but not the cells of organs such as the liver or brain. Totipotent stem cells Stem cells that, under the right conditions, are wholly capable of generating a viable embryo (including the placenta) and, for humans, exist until about four days after fertilization, prior to the blastocyst stage from which embryonic stem cells are derived.

Read the original:
What Are Stem Cells - Checkbiotech.org (press release)

8 October 2001

The Nobel Assembly at Karolinska Institutet has today decided to award The Nobel Prize in Physiology or Medicine for 2001 jointly to&

Leland H. Hartwell, R. Timothy (Tim) Hunt and Paul M. Nurse

for their discoveries of "key regulators of the cell cycle"

All organisms consist of cells that multiply through cell division. An adult human being has approximately 100 000 billion cells, all originating from a single cell, the fertilized egg cell. In adults there is also an enormous number of continuously dividing cells replacing those dying. Before a cell can divide it has to grow in size, duplicate its chromosomes and separate the chromosomes for exact distribution between the two daughter cells. These different processes are coordinated in the cell cycle.

This year's Nobel Laureates in Physiology or Medicine have made seminal discoveries concerning the control of the cell cycle. They have identified key molecules that regulate the cell cycle in all eukaryotic organisms, including yeasts, plants, animals and human. These fundamental discoveries have a great impact on all aspects of cell growth. Defects in cell cycle control may lead to the type of chromosome alterations seen in cancer cells. This may in the long term open new possibilities for cancer treatment.

Leland Hartwell (born 1939), Fred Hutchinson Cancer Research Center, Seattle, USA, is awarded for his discoveries of a specific class of genes that control the cell cycle. One of these genes called "start" was found to have a central role in controlling the first step of each cell cycle. Hartwell also introduced the concept "checkpoint", a valuable aid to understanding the cell cycle.

Paul Nurse (born 1949), Imperial Cancer Research Fund, London, identified, cloned and characterized with genetic and molecular methods, one of the key regulators of the cell cycle, CDK (cyclin dependent kinase). He showed that the function of CDK was highly conserved during evolution. CDK drives the cell through the cell cycle by chemical modification (phosphorylation) of other proteins.

Timothy Hunt (born 1943), Imperial Cancer Research Fund, London, is awarded for his discovery of cyclins, proteins that regulate the CDK function. He showed that cyclins are degraded periodically at each cell division, a mechanism proved to be of general importance for cell cycle control.

Cells having their chromosomes located in a nucleus and separated from the rest of the cell, so called eukaryotic cells, appeared on earth about two billion years ago. Organisms consisting of such cells can either be unicellular, such as yeasts and amoebas, or multi-cellular such as plants and animals. The human body consists of a huge number of cells, on the average about one billion cells per gram tissue. Each cell nucleus contains our entire hereditary material (DNA), located in 46 chromosomes (23 pairs of chromosomes).

It has been known for over one hundred years that cells multiply through division. It is however only during the last two decades that it has become possible to identify the molecular mechanisms that regulate the cell cycle and thereby cell division. These fundamental mechanisms are highly conserved through evolution and operate in the same manner in all eukaryotic organisms.

The cell cycle consists of several phases (see figure). In the first phase (G1) the cell grows and becomes larger. When it has reached a certain size it enters the next phase (S), in which DNA-synthesis takes place. The cell duplicates its hereditary material (DNA-replication) and a copy of each chromosome is formed. During the next phase (G2) the cell checks that DNA-replication is completed and prepares for cell division. The chromosomes are separated (mitosis, M) and the cell divides into two daughter cells. Through this mechanism the daughter cells receive identical chromosome set ups. After division, the cells are back in G1 and the cell cycle is completed.

The duration of the cell cycle varies between different cell types. In most mammalian cells it lasts between 10 and 30 hours. Cells in the first cell cycle phase (G1) do not always continue through the cycle. Instead they can exit from the cell cycle and enter a resting stage (G0).

For all living eukaryotic organisms it is essential that the different phases of the cell cycle are precisely coordinated. The phases must follow in correct order, and one phase must be completed before the next phase can begin. Errors in this coordination may lead to chromosomal alterations. Chromosomes or parts of chromosomes may be lost, rearranged or distributed unequally between the two daughter cells. This type of chromosome alteration is often seen in cancer cells.

It is of central importance in the fields of biology and medicine to understand how the cell cycle is controlled. This year's Nobel Laureates have made seminal discoveries at the molecular level of how the cell is driven from one phase to the next in the cell cycle.

Leland Hartwell realized already at the end of the 1960s the possibility of studying the cell cycle with genetic methods. He used baker's yeast, Saccharomyces cerevisiae, as a model system, which proved to be highly suitable for cell cycle studies. In an elegant series of experiments 1970-71, he isolated yeast cells in which genes controlling the cell cycle were altered (mutated). By this approach he succeeded to identify more than one hundred genes specifically involved in cell cycle control, so called CDC-genes (cell division cycle genes). One of these genes, designated CDC28 by Hartwell, controls the first step in the progression through the G1-phase of the cell cycle, and was therefore also called "start".

In addition, Hartwell studied the sensitivity of yeast cells to irradiation. On the basis of his findings he introduced the concept checkpoint, which means that the cell cycle is arrested when DNA is damaged. The purpose of this is to allow time for DNA repair before the cell continues to the next phase of the cycle. Later Hartwell extended the checkpoint concept to include also controls ensuring a correct order between the cell cycle phases.

Paul Nurse followed Hartwell's approach in using genetic methods for cell cycle studies. He used a different type of yeast, Schizosaccharomyces pombe, as a model organism. This yeast is only distantly related to baker's yeast, since they separated from each other during evolution more than one billion years ago.

In the middle of the 1970s, Paul Nurse discovered the gene cdc2 in S. pombe. He showed that this gene had a key function in the control of cell division (transition from G2 to mitosis, M). Later he found that cdc2 had a more general function. It was identical to the gene ("start") that Hartwell earlier had identified in baker's yeast, controlling the transition from G1 to S.

This gene (cdc2) was thus found to regulate different phases of the cell cycle. In 1987 Paul Nurse isolated the corresponding gene in humans, and it was later given the name CDK1 (cyclin dependent kinase 1). The gene encodes a protein that is a member of a family called cyclin dependent kinases, CDK. Nurse showed that activation of CDK is dependent on reversible phosphorylation, i.e. that phosphate groups are linked to or removed from proteins. On the basis of these findings, half a dozen different CDK molecules have been found in humans.

Tim Hunt discovered the first cyclin molecule in the early 1980s. Cyclins are proteins formed and degraded during each cell cycle. They were named cyclins because the levels of these proteins vary periodically during the cell cycle. The cyclins bind to the CDK molecules, thereby regulating the CDK activity and selecting the proteins to be phosphorylated.

The discovery of cyclin, which was made using sea urchins, Arbacia, as a model system, was the result of Hunt's finding that this protein was degraded periodically in the cell cycle. Periodic protein degradation is an important general control mechanism of the cell cycle. Tim Hunt later discovered cyclins in other species and found that also the cyclins were conserved during evolution. Today around ten different cyclins have been found in humans.

The three Nobel Laureates have discovered molecular mechanisms that regulate the cell cycle. The amount of CDK-molecules is constant during the cell cycle, but their activities vary because of the regulatory function of the cyclins. CDK and cyclin together drive the cell from one cell cycle phase to the next. The CDK-molecules can be compared with an engine and the cyclins with a gear box controlling whether the engine will run in the idling state or drive the cell forward in the cell cycle.

Most biomedical research areas will benefit from these basic discoveries, which may result in broad applications within many different fields. The discoveries are important in understanding how chromosomal instability develops in cancer cells, i.e. how parts of chromosomes are rearranged, lost or distributed unequally between daughter cells. It is likely that such chromosome alterations are the result of defective cell cycle control. It has been shown that genes for CDK-molecules and cyclins can function as oncogenes. CDK-molecules and cyclins also collaborate with the products of tumour suppressor genes (e.g. p53 and Rb) during the cell cycle.

The findings in the cell cycle field are about to be applied to tumour diagnostics. Increased levels of CDK-molecules and cyclins are sometimes found in human tumours, such as breast cancer and brain tumours. The discoveries may in the long term also open new principles for cancer therapy. Already now clinical trials are in progress using inhibitors of CDK-molecules.

This year's Nobel Laureates, using genetic and molecular biology methods, have discovered mechanisms controlling the cell cycle. CDK-molecules and cyclins drive the cell from one phase to the next. The CDK-molecules can be compared with an engine and the cyclins with a gear box controlling whether the engine will run in the idling state or drive the cell forward in the cell cycle.

See also high resolution images:

Cell cycle, English version Cellcykel, Swedish version Leland H. Hartwell R. Timothy (Tim) Hunt Paul M. Nurse

To cite this page MLA style: "The Nobel Prize in Physiology or Medicine for 2001 - Press Release". Nobelprize.org. Nobel Media AB 2014. Web. 4 Jun 2017. <http://www.nobelprize.org/nobel_prizes/medicine/laureates/2001/press.html>

More:
The Nobel Prize in Physiology or Medicine for 2001 - Press ...