Category Archives: Molecular Medicine

Neither substance is sufficient alone, said Dr. Chen-Yu Zhang, co-author of the study and a professor of biochemistry at Nanjing University in China. The royal jelly and plant microRNA work together to affect caste formation.

Were taking you on a journey to help you understand how bees, while hunting for pollen, use all of their senses taste, touch, smell and more to decide what to pick up and bring home.

Researchers raised honeybees in the lab to study the effects of the plant microRNA in bee bread. They found that larvae raised on diets supplemented with the plant material had smaller bodies and smaller ovaries than those raised without the supplement. Further experiments showed that one of the most common types of plant microRNA found in bee bread targets a gene in honeybees, TOR, which helps determine caste.

They did a nice job documenting the specific role of microRNA that has a very profound impact on this development, said Xiangdong Fu, a professor of cellular and molecular medicine at UC San Diego who was not involved with the study. Its fascinating. Depending on what you eat, you can end up a different way.

This information could provide new insight into the mysterious trend of rising honeybee deaths in the last decade, which could have a large impact on agriculture.

Xi Chen, a co-author of the paper and a professor of biochemistry at Nanjing University, said plant microRNA could play a role. We could check if changing microRNA in certain plants can cause the disappearance of the honeybee, he said.

The study also points to the interdependence of plants and honeybees. The plant substance that affects bee development is also important for the formation of certain flowers, Dr. Zhang said. The molecules can make a flower larger and more colorful, which attracts more bees and helps spread its seed, a sign of plant and insect co-evolution.

This is a large, emerging area of research, according to Dr. Philip Askenase, a professor of medicine and pathology at Yale University School of Medicine, who was not involved in the study. Here you have evolutionary dependence of the creature and the plants, he said. MicroRNA from plants can influence bee development and microRNA from bees can influence the pollen they spread, affecting the next generation of plants. They are mutually contributing microRNA to each other. Thats a big deal.

Learning more about how these molecules can affect species in different kingdoms like plants and insects or plants and humans could help identify therapeutic applications for cancer treatments or to suppress allergic reactions, Dr. Askenase said. Some important biological problems could now be addressed with this new knowledge of how nature works, he said.

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The Secret Ingredient That Stops Honeybees From Becoming Queens - New York Times

31 Aug 2017

Arriving at the same conclusion, essentially at the same time, three research groups have independently mapped the site where proteases snip off the extracellular portion of TREM2. Two papers in the August 30 issue of EMBO Molecular Medicine and one under review and posted on the BioRiv preprint server report that the site coincides exactly with a mutation in the microglial receptor, H157Y, that boosts AD risk by as much as 11-fold. Its incredible that all three results are essentially identical, said Christian Haass of Ludwig-Maximilians-Universitt, Munich, the senior author on one of the EMBO Molecular Medicine papers. Peter St. George-Hyslop of the University of Toronto, who co-led the second published study with Damian Crowther and Iain Chessell of AstraZeneca in Cambridge, U.K., presented their findings earlier this year at the 13th International Conference on Alzheimers and Parkinsons Diseases in Vienna (Apr 2017 news). Ulf Neumann at Novartis in Basel, Switzerland, led the thirdgroup.

TREM2 binds anionic lipids released during neuronal and glial damage. It supports microglial metabolism and it promotes the migration, cytokine release, phagocytosis, proliferation, and survival of the cells (Aug 2017 news;Feb 2015 news). Evidence suggests that TREM2 spurs microglia to form a neuroprotective barrier around amyloid plaques and to clear A (May 2016 news; Jul 2016 news). Motivated by the discovery of roughly a dozen TREM2 genetic variants that increase the risk of frontotemporal dementia, AD, and possibly other neurodegenerative diseases, including amyotrophic lateral sclerosis and Parkinsons disease, researchers are searching for ways to bolster TREM2s protective function. Thinking that limiting ectodomain shedding might improve TREM2 signaling (see image below), the three research groups set out to find the cleavagesite.

Snip Site. ADAM10, or other proteases, may shed TREM2s extracellular ligand binding domain, abolishing TREM2-mediated signaling. (Courtesy of Yeh et al., 2017, Trends MolMed.)

In Haasss lab, first author Kai Schlepckow focused on the TREM2 C-terminal fragment (CTF) left over after shedding. Because -secretase quickly chews up the CTF in microglia, much as it does the C-terminal fragment of amyloid precursor protein in neurons, Schlepckow generated human embryonic kidney 293 (HEK293) cells expressing TREM2 and treated them with DAPT, a -secretase inhibitor. After immunoprecipitating the TREM2 CTF, he analyzed it by mass spectrometry. The result was crystal clear: a single major peak corresponding to a fragment with an N-terminus at serine 158. That amino acid lies in the extracellular domain of TREM2, 17 amino acids from the predicted transmembrane domain. Ive had experience mapping other cleavage sites and this one is super-precise. Ive never seen something like it, saidHaass.

Indeed, the result was so clean, Haass wondered if it was real. He had the researchers analyze the sequence on the other side of the break. Because sTREM2, the soluble extracellular domain, is too big to analyze by mass spectrometry, Schlepckow created a TREM2 construct with a tobacco etch virus protease cleavage site shortly before the proposed sheddase site. That way, the researchers could immunoprecipitate sTREM2 from the cell medium, shorten it with the TEV protease, and then determine its mass. Consistent with the CTF results, they obtained a single sharp peak corresponding to a peptide terminating at histidine 157. The researchers got the same results using human THP-1 cells, which are similar to monocytes, the cells that give rise tomicroglia.

Crowthers group also relied on mass spectrometry. First we used a library of peptide protease inhibitors to get a quick-and-dirty answer to where the site might be, said Crowther. First author Peter Thornton at AstraZeneca synthesized a set of D-amino acid polypeptides that overlapped TREM2 amino acids 140-176, where they thought metalloprotease likely cleaved. Then they used these peptides to compete with TREM2 for the protease in primary humanmacrophages.

All peptides that spanned TREM2 amino acids 158-160 reduced TREM2 ectodomain shedding, whereas peptides mapping to nearby regions did not. Interestingly, the most effective peptide worked equally well when its sequence was reversed, suggesting that the responsible metalloproteases recognize biophysical properties, such as charge, to target a specific sequence. To map that sequence more precisely, Thornton immunoprecipitated sTREM2 from the conditioned media of several cell types, isolated it by gel chromatography, digested it with trypsin and analyzed the fragments by mass spectrometry. From human macrophages, primary murine microglia, and HEK293 cells expressing human TREM2, H157 surfaced as the most likely sheddasesite.

Neumanns group tackled the question by generating a series of TREM2 constructs with deletions or amino acid replacements in the stalk region, located between the transmembrane and extracellular domains (see image above). They identified two regions, amino acids 169-172 and 156-164, in which mutations strongly reduced TREM2 cleavage induced by the protein kinase C activator PMA. To pinpoint the cleavage site, they designed a series of labeled peptides spanning the stalk region, incubated them with the metalloprotease ADAM17 in a test tube, and analyzed the resulting fragments using high-performance liquid chromatography and mass spectrometry. The researchers used ADAM17 because their prior data indicated it was a major TREM2sheddase.

Data from Dominik Feuerbach at Novartis also revealed the H157-S158 bond as the cleavage site. The researchers repeated the experiments using liquid chromatography and mass spec to analyze sTREM2 generated by HEK293 cells expressing human TREM2 and TYROBP, which forms a complex with the cytoplasmic portion of TREM2 (see image above). Feuerbach said they included TYROBP to mimic TREM2s physiological state as closely as possible. Again, they found cleavage occurred at the H157-S158site.

Researchers have reported that a histidine to tyrosine mutation at position 157 increases the risk for late-onset AD in Han Chinese and affects shedding (Ma et al., 2014). How might this change affect TREM2 processing? Haass and Crowthers groups compared shedding in cells expressing wild-type or the H157Y mutant. Crowther found that the extracellular domain of the wild-type protein has a half-life of less than one hour on the cells surface. Although the researchers didnt measure the mutant extracellular domain half-life directly, they found cells more rapidly pumped mutant sTREM2 into the conditioned medium. Shedding is fast in healthy cells, but it gets even faster with the variant, he said. Haass group obtained similar results. This was a surprise, said Haass, who was expecting the H157Y mutation to reduce sTREM2 production, just like other mutations that increase risk for neurodegeneration. The T66M and Y38C mutations associated with frontotemporal dementia, for example, preclude TREM2 from reaching the cell surface where shedding predominantly occurs, shutting down production of sTREM2. We got exactly the opposite of what we expected, saidHaass.

On further reflection, Haass and colleagues realized that increased shedding could have the same biological effect as reducing cell surface TREM2 because it reduced the amount of signaling-competent TREM2 on the cell surface. Indeed, Schlepckow found that monocytes expressing H157Y TREM2 phagocytosed a third less Escherichia coli than monocytes expressing the wild-type receptor. These findings support the idea that loss of function is key to the risk associated with H157Y TREM2, in line with most other TREM2 variants whose mechanisms have been dissected. Marco Colonna of Washington University in St. Louis noted that except for two TREM2 variants that increased ligand binding but were only weakly tied to AD risk, all other variants dampened TREM2 function, either by decreasing ligand binding, preventing TREM2 from reaching the cell surface, or, in this case, increasing TREM2 shedding. Feuerbach said the case for trying to therapeutically boost membrane-bound TREM2 is more compelling than ever. From a genetic point of view, this is one of the most attractive targets, said Feuerbach, first author of the BioRivpaper.

To identify the proteases responsible for wild-type and mutant TREM2 shedding, Thornton and colleagues used various protease inhibitors, as well as siRNA, to block or knock down the expression of ADAM17 or ADAM10,a.k.a. a-secretase, which process the A precursor protein (APP). Previous work implicated ADAM10 in TREM2 cleavage (Kleinberger et al., 2014). Lowering or blocking ADAM10, but not ADAM17, reduced TREM2 shedding. However, neither an inhibitor, nor ADAM10 siRNA, blocked shedding of the H157Y mutant as effectively as they blocked that of the wild-type. Crowther hypothesized the existence of a novel sheddase to account for the difference, but also acknowledged the mutant site might simply be more prone to ADAM10 cleavage and, thus, harder to fully block. It could just be that the H157Y conformation is so tasty, that ADAM10 just continues to nibble away, he said. Haass favors this latterpossibility.

Feuerbach, however, said his data points to ADAM17, rather than ADAM10, as the major TREM2 sheddase. In contrast to Crowthers group, which used HEK273 cells expressing human TREM2, but not TYROBP, Feuerbach used Chinese hamster ovary cells expressing both proteins, as well as human M2A macrophages, which are related to microglia and endogenously express TREM2 and TYROBP. To probe TREM2 cleavage, he used protease inhibitors, and ADAM10 or ADAM17 knockouts. His results indicate that TREM2 shedding depends much more on the activity of ADAM17. We would not exclude ADAM10 or other proteases from playing a role, but Id say ADAM17 probably accounts for 90 percent of the shedding, he said. Colonna and Thomas Brett, also at Washington University, thought that differences in cell types might account for the discrepancy. Different proteases might be more prevalent in different cellsprobably multiple proteases can do the job, said Colonna. Also, Feuerbach pointed out that TYROBP might affect the conformation of the cleavagesite.

From a therapeutic standpoint, researchers agreed the proteases matter less than the location of the TREM2 cleavage site. No one is interested in developing an ADAM10 inhibitor for AD, said Crowther, noting it would have too many undesirable secondary effects. Indeed, ADAM10s cutting of APP prevents the generation of A, noted Terrence Town, University of Southern California, Los Angeles. Hoping to more specifically target TREM2 clipping, Haass has begun generating antibodies against the TREM2 cleavage site. Not only could such antibodies help people with the rare H157Y mutation, but they might also help nearly anyone with AD, he believes. Antibodies against the TREM2 cleavage site could have a very potent effect, said Crowther. A boost in membrane-bound TREM2 that would rev up A phagocytosis would be beneficial. Indeed, evidence suggests people with sporadic and familial AD have increased levels of freewheeling sTREM2 in their spinal fluid, which may reflect an uptick in TREM2 shedding (Jan 2016 news;Suarez-Calvet et al., 2016). Nonetheless, Haass cautioned that it will be complicated to develop such a therapy because excessive TREM2 activity could beharmful.

Furthermore, any therapy that keeps TREM2 from casting off its extracellular domain will also cause a drop in sTREM2 levels. Brett wondered about the consequences, noting that, at least according to one study, sTREM2 causes inflammation, which is harmful, but also promotes microglial survival (Feb 2017 news). Colonna agreed. At the end of the day, we dont know if blocking sTREM2 production will have a positive, negative, or neutral effect, hesaid.

Regardless of whether regulating TREM2 processing has a future in the clinic, the new studies offer important basic insights, said Colonna. By looking at every single mutation, well understand TREM2 better.MarinaChicurel

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TREM2 Cleavage Site Pinpointed: A Gateway to New Therapies? - Alzforum

Donald and Barbara Zuckers foundation donated $61 million to the medical school founded by Hofstra University and Northwell Health, the organizations announced on Wednesday, leading to renaming the school for the couple.

Most of the donation or $50 million will go towards a permanent endowment to provide students need-based scholarship support in the Zucker School of Medicine.

Some $10 million meanwhile goes towards creating and endowing the Barbara Hrbek Zucker Emerging Scientists Program at the Feinstein Institute for Medical Research, which is headquartered in Manhasset.

The program is intended to prepare postdoctoral fellows for successful careers and support early career faculty in developing research programs.

More so than any other donors in our history, Don and Barbara Zucker have been extraordinary supporters of causes where we have historically struggled to get financial support, Michael J. Dowling, president and chief executive officer of Northwell Health, said in a statement.

Their latest gifts are a testament to the Zuckers leadership as philanthropists who recognize the vital role of medical education and research in transforming the future of medicine.

Donald Zucker, 86, a New York City real estate developer from Sands Point, and his wife Barbara, donated to Northwell in the past. The couple gave to organizations like the Zucker Hillside Hospital in Glen Oaks, Lenox Hill Hospital in Manhattan and the Elmezzi Graduate School of Molecular Medicine in Manhasset.

Lawrence Smith, the founding dean of the Zucker School of Medicine and physician-in-chief at Northwell Health, said that the couple recognized how important it is to support students financially.

Their generosity will ensure that our medical school will continue to be represented by a highly diverse, talented student body that reflects the communities we serve throughout the New York metropolitan area, Smith said.

Hofstra University and Northwell Health first launched the medical school in 2008. It currently has 400 students enrolled and had more than 7,000 applicants competing for 100 spaces in 2016.

Almost a decade ago, we set out to create a new model of medical education that would improve health care in our region and today we mark another milestone in that journey, said Stuart Rabinowitz, the president of Hofstra University. The Zuckers support solidifies and expands our commitment to train innovative physicians whose backgrounds and experiences are as diverse as the people they treat.

See more here:
Hofstra and Northwell rename medical school following $61 million donation - The Island Now

The virtual embryo offers predictions which cells express -- for example -- the genes even skipped (red) and twist (green). To appreciate the spatial distribution, researchers can look at the fly embryo from all angles. Credit: Drosophila Virtual Expression eXplorer, BIMSB at the MDC

After 13 rapid divisions a fertilized fly egg consists of about 6,000 cells. They all look alike under the microscope. However, each cell of a Drosophila melanogaster embryo already knows by then whether it is destined to become a neuron or a muscle cellor part of the gut, the head, or the tail. Now, Nikolaus Rajewsky's and Robert Zinzen's teams at the Berlin Institute of Medical Systems Biology (BIMSB) of the Max Delbrck Center for Molecular Medicine in the Helmholtz Association (MDC) have analyzed the unique gene expression profiles of thousands of single cells and reassembled the embryo from these data using a new spatial mapping algorithm. The result is a virtual fly embryo showing exactly which genes are active where at this point in time. "It is basically a transcriptomic blueprint of early development," says Robert Zinzen, head of the Systems Biology of Neural Tissue Differentiation Lab. Their paper appears as a First Release in the online issue of Science.

"Only recently has it become possible to analyze genome-wide gene expression of individual cells at a large scale. Nikolaus recognized the potential of this technology very early on and established it in his lab," says Zinzen. "He started to wonder whethergiven a complex organized tissueone would be able to compute genome-wide spatial gene expression patterns from single-cell transcriptome data alone." BIMSB combines laboratories with different backgrounds and expertise, emphasizing the need of bringing computing power to biological problems. It turns out the institute had not only the perfect model systemthe Drosophila embryoto address Rajewsky's question, but also the right people with the right expertise, from physics and mathematics to biochemistry and developmental biology.

"The virtual embryo is much more than merely a cell mapping exercise," says Nikolaus Rajewsky, head of the Systems Biology of Gene Regulatory Elements Lab, who enjoyed returning to fly development 15 years after studying gene regulatory elements in Drosophila embryos during his post-doctoral time at the Rockefeller University. Using the interactive Drosophila Virtual Expression eXplorer (DVEX) database, researchers can now look at any of about 8,000 expressed genes in each cell and ask, "Gene X, where are you expressed and at what level? What other genes are active at the same time and in the same cells?" It also works with the enigmatic long non-coding RNAs. "Instead of time-consuming imaging experiments, scientists can do virtual ones to identify new regulatory players and even get ideas for biological mechanisms," says Rajewsky. "What would normally take years using standard approaches can now be done in a couple of hours."

Breaking the synchronicity of the first cell divisions

In their paper, the MDC researchers describe a dozen new transcription factors and many more long non-coding RNAs that have never been studied before. Also, they propose an answer to a question that has puzzled scientists for 35 years: How does the embryo break synchronicity of cell divisions to develop more complex structures?

In a process called gastrulation, distinct germ layers form and cells become restricted with regard to which tissues and organs they may differentiate into. "We believe that the Hippo signaling pathway is at least partly responsible for setting up gastrulation," says Rajewsky. The pathway controls organ size, cell cycles and cell proliferation, but had never been implicated in the development of the early embryo. "We not only showed that Hippo is active in the fly, but we could even predict in which regions of the embryo this would lead to a different onset of mitosis and therefore break synchronicity. And that is just one example for how useful our tool is to understand mechanisms that have escaped traditional science."

Project underwent a tough gestation period

When the researchers started creating the virtual embryo, they did not know whether it would be possible. A key pillar of their eventual success is the Drop-Seq technology, a droplet-based, microfluidic method that allows the transcriptional profiling of thousands of individual cells at low cost. This technique had been newly set up in the Rajewsky lab by Jonathan Alles, a summer student.

However, the fly embryos needed to be selected precisely at the onset of gastrulation. Philipp Wahle, a PhD student in Robert Zinzen's lab, hand-picked about 5,000 of them before dissociating them into single cells. "I was convinced this would give us a large and completely unique data set. This was a great motivation for me," says Wahle. That laborious process created a new challenge. "You need to collect over several sessions to have enough material for a sequencing run," says Christine Kocks, who led the single-cell sequencing team. It was composed of Jonathan Alles, Salah Ayoub and Anastasiya Boltengagen, who jointly with computational scientist Nikos Karaiskos optimized the droplet-based sequencing. "So we had to find a way to stabilize the transcriptomes in the cells," added Kocks. "Finally, based on his earlier work with C. elegans embryos, Nikolaus suggested using methanol." The new single-cell fixation method was published in BMC Biology in May 2017.

As the data got better and better, Nikos Karaiskos, a theoretical physicist and computational expert in Rajewsky's lab, took on the challenge of spatially mapping such a large number of cells to their precise embryonic position. None of the existing approaches in the field of spatial transcriptomics was suitable to reconstruct the Drosophila embryo. "It was a reiterative process to filter the data, see what is inside and try to map it. It changed many times along the way," says Karaiskos. There was a lot of back and forth between members of the computer lab and wet labexchanges that are a defining characteristic of the BIMSB. "I had to question my work all the time, see where it was lacking and develop something better." He came up with a new algorithm called DistMap that can map transcriptomic data of cells back to their original position in the virtual embryo.

Navigating unchartered territory

The construction of the virtual embryo allowed Karaiskos to readily predict the expression of thousands of genes, an almost impossible task by traditional experimental means. Philipp Wahle, supported by Claudia Kipar, validated these predictions by visualizing the gene expression profiles at the bench with a traditional approach: In situ hybridization allows visualizing patterns of gene expression with colorful dyes that are visible under the microscope. "At this stage, a single layer of cells surrounds the entire fly embryo," says Wahle. "This makes it very accessible, thus enabling you to compare the computational data with imaging."

It is the first time that it has been possible to look at the about 6,000 cells of the embryo individually, assess their gene expression profilesand understand what determines their behavior in the embryo. "The most important technological advance of this study is that we don't lose the spatial information that is required to understand how embryonic cells act in concert," say the scientists. "This really is unchartered territory and requires new bioinformatics approaches to make sense of the collected data. This worked beautifully in our collaboration, not least because of the unique make-up of the Rajewsky lab, which integrates wet lab and computational approaches." One major advantage is that both groups are not only interested in technology but have specific biological questions that motivate them, says Rajewsky. "Robert has a deep understanding of early development. We can do single-cell sequencing runs and have the computational power to develop the tools that help us actually understand the underlying gene regulatory interactions."

The groups are already planning follow-up projects. One example would be to map the cells at different time points to see how they work together to form organs and tissues. Another would be to check whether the mapping approaches are applicable to more complex tissues.

Explore further: Lockdown genes to reduce IVF failure rates

More information: "The Drosophila Embryo at Single Cell Transcriptome Resolution" Science (2017). science.sciencemag.org/lookup/ 1126/science.aan3235

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Reconstructing life at its beginning, cell by cell - Phys.Org

Newswise New York (August 31, 2017) Scientific innovator and physician Dr. Pawel Muranski has joined NewYork-Presbyterian and Columbia University Medical Center (CUMC) as director of cellular immunotherapy at the newly established Good Manufacturing Practices (GMP) cell production lab and assistant director of Transfusion Medicine and Cellular Therapy. He will also serve on the faculty of CUMC as Assistant Professor of Medicine, Pathology and Cell Biology, a principal investigator at Columbia Center for Translational Immunology (CCTI) and a member of Columbias Herbert Irving Comprehensive Cancer Center.

Were thrilled to have Dr. Muranski joining us to continue his innovative work, said Dr. Gary Schwartz, chief of the Division of Hematology/Oncology at NewYork-Presbyterian/CUMC and the Clyde 56 and Helen Wu Professor of Oncology (in medicine) at CUMC. His approach to T cell-based therapy holds so much potential and could revolutionize care for cancer patients, transplant patients and others.

Dr. Muranski is a hematologist who specializes in bone marrow transplantation and in developing adoptive T cell therapies, in which white blood cells called T lymphocytes are removed from a patient or a donor and then programmed to target viral infections, leukemic cells and solid tumors. Adoptive transfer of T cells, including Chimeric Antigen Receptor (CAR)-T therapy has shown great promise in early trials of patients with leukemia, lymphoma and several solid cancersin some cases leading to a complete remission.

Dr. Muranskis research will continue to focus on exploiting and enhancing the capability of engineered T cells to recognize and target cancerous cells or dangerous viruses. He has a particular interest in developing CD4+ T helper cellsthe master orchestrators of immune responseas a potentially powerful weapon against cancer. His T cells can also target viral infections in patients whose immune systems have been weakened by bone marrow or organ transplantation, cancer treatment, or autoimmune diseases.

Despite recent spectacular advances in the field of cancer immunotherapy, very few institutions have GMP laboratories with the capacity to grow and manipulate T cells, said Dr. Muranski. NewYork-Presbyterian and Columbia University Medical Center are now positioned to become leaders in cutting-edge cellular immunotherapies. Im excited to work with the team here on developing a comprehensive program that brings these innovative treatments to our patients.

In addition to his work in the GMP lab, Dr. Muranski will be working with Dr. Prakash Satwani, a pediatric hematologist and oncologist at NewYork-Presbyterian and associate professor of pediatrics at CUMC, on an upcoming major CAR-T cell initiative. He will also work closely with Dr. Markus Mapara, director of the Adult Blood and Marrow Transplantation Program at NewYork-Presbyterian/Columbia and professor of medicine at CUMC.

Dr. Muranski trained as a fellow at the Surgery Branch, National Cancer Institute (NCI), National Institutes of Health (NIH) in Bethesda, Maryland, where he performed innovative studies aimed at understanding of the role of CD4+ T cells as mediators of curative anti-tumor immunity. Most recently, he served in Hematology Branch, National Heart, Lung and Blood Institute (NHLBI) at the NIH, where his research focused on using T cell-based therapies to prevent viral infections in patients undergoing donor-based stem cell transplantation for blood cancers.

He earned his medical degree from the Medical University of Warsaw in Poland before completing a research fellowship at the Institute for Molecular Medicine and Genetics, Medical College of Georgia and a residency at St. Francis Hospital in Evanston, Illinois. He completed a clinical fellowship in hematology and oncology at the National Institutes of Health in Bethesda, Maryland.

NewYork-Presbyterian

NewYork-Presbyterian is one of the nations most comprehensive, integrated academic healthcare delivery systems, whose organizations are dedicated to providing the highest quality, most compassionate care and service to patients in the New York metropolitan area, nationally, and throughout the globe. In collaboration with two renowned medical schools, Weill Cornell Medicine and Columbia University Medical Center, NewYork-Presbyterian is consistently recognized as a leader in medical education, groundbreaking research and innovative, patient-centered clinical care.

NewYork-Presbyterian has four major divisions:

Columbia University Medical Center

Columbia University Medical Centerprovides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. The campus that Columbia University Medical Center shares with its hospital partner, NewYork-Presbyterian, is now called the Columbia University Irving Medical Center. For more information, visit cumc.columbia.eduorcolumbiadoctors.org.

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Dr. Pawel Muranski to Head New Cellular Immunotherapy Laboratory at NewYork-Presbyterian/Columbia University ... - Newswise (press release)

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Thailand, August 28, 2017 An investigation is launched in Thailand after a woman fell from the 31stfloor of a hotel to her death, that woman is a Turks and Caicos Islander identified as #MaxineVerniceMissick. Missick was a medical student studying at Keele University in the UK but was on a trip to Thailand when she somehow plunged to her death and was found in an alley between two hotels with a broken neck and other broken bones around 5am Friday.

The 23 year old is a graduate of Clement Howell High, and had reportedly been accepted recently to work at the Institute for Molecular Medicine Research in Penang, Malaysia. Police explained that her room was not ransacked, that her hotel room door was locked and that Missick checked in, alone and arrived in the country on August 18. Her hotel check out date was August 31.

Friends of Maxine, who was described as a British citizen in news reports out of Thailand is also Haitian and was called a woman who loved the Lord, loved African culture, always had a smile on her face and loved meeting people.

Police in Thailand have not ruled out suicide, promise a thorough investigation and say an autopsy will be performed to determine exact cause of death. Condolences to Maxines friends and family.

#MagneticMediaNews

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TCI woman fell 31 floors, due to work in molecular medicine in Malaysia - Magnetic Media (press release)

The Graduate Program in Molecular Medicine at the University of Maryland Baltimore offers research and training opportunities with internationally-renowned scientists. Our Molecular Medicine Program is an interdisciplinary program of study leading to a Ph.D. degree. There are four different research tracks: Cancer Biology, Genome Biology, Molecular and Cell Physiology, and Toxicology and Pharmacology. Each provides for a unique interdisciplinary research and graduate training experience that is ideally suited for developing scientists of the post-genomic era.

Faculty mentors in this graduate program are leaders in their respective research areas and reside in various departments and Organized Research Centers in the School of Medicine and Dental School, the Institute for Genomic Sciences (IGS), the Institute of Human Virology (IHV), the Marlene and Stewart Greenebaum Cancer Center, and the Center for Vascular and Inflammatory Diseases (CVID). The over 150 faculty in the Graduate Program in Molecular Medicine are internationally recognized for their research in biotechnology, cancer, cardiovascular and renal biology, functional genomics and genetics, membrane biology, muscle biology, neuroscience and neurotoxicology, reproduction and vascular biology.

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Molecular Medicine | University of Maryland School of Medicine

Next month, the Michigan State University College of Human Medicine will open a new research facility in Grand Rapids.

WKAR's Scott Pohl reports on the new MSU Grand Rapids Research Center, opening in September.

For almost a decade, MSU has leased research space in Grand Rapids from the Van Andel Institute. This new building is the former site of the Grand Rapids Press newspaper. Demolition of that building and the construction of a six-story, 162,800 square foot research center came with a price tag of just over $88-million dollars. Donors include Richard and Helen DeVos, who gave $10-million, and Peter and Joan Secchia, who contributed another $5-million. Other money is coming from the MSU general fund and from tax exempt financing.

MSU College of Human Medicine Dean Dr. Norman Beauchamp credits university President Lou Anna Simon for bringing this dream to life. "The process of creating this really was the university president having a vision for strengthening the research at Michigan State University and having a passion for what we could do to improve health," Dr. Beauchamp states.

MSU research into Parkinsons disease, Alzheimers disease and traumatic brain injury will move here from the Van Andel Institute. Dr. Jack Lipton, chair of Translational Science and Molecular Medicine, says the move will enhance their work. "We were promised when we first came here in 2009 that a building was eventually going to go up," Dr. Lipton explains. "We've been hosted by the Van Andel (Institute) for a few years, and that's been great, but we didn't have the ability to expand. This building is now an extension of the main campus."

Research into womens cancers, prenatal and infant development and infertility will also move to the new facility next month. Obstetrics, Gynecology and Reproductive Biology Chair Dr. Richard Leach says his department has grown from just one researcher in Grand Rapids to a current total of 12. He continues that "this facility enables us to not only bring in state of the art equipment, but the design of this facility enables us to bring our researchers together in teams."

The move wont be done all at once. Certain experiments cant simply be relocated down the street; some researchers will wrap up projects at the Van Andel Institute before occupying space in the new facility.

The MSU Grand Rapids Research Center has scheduled a dedication ceremony for September 20th.

Originally posted here:
MSU Expanding Medical Research In Grand Rapids | WKAR - WKAR

PET scan of a human brain with Alzheimer's disease. Credit: public domain

A gene called triggering receptor expressed on myeloid cells 2, or TREM2, has been associated with numerous neurodegenerative diseases, such as Alzheimer's disease, Frontotemporal lobar degeneration, Parkinson's disease, and Nasu-Hakola disease. Recently, a rare mutation in the gene has been shown to increase the risk for developing Alzheimer's disease.

Independently from each other, two research groups have now revealed the molecular mechanism behind this mutation. Their research, published today in EMBO Molecular Medicine, sheds light on the role of TREM2 in normal brain function and suggests a new therapeutic target in Alzheimer's disease treatment.

Alzheimer's disease, just like other neurodegenerative diseases, is characterized by the accumulation of specific protein aggregates in the brain. Specialized brain immune cells called microglia strive to counter this process by engulfing the toxic buildup. But as the brain ages, microglia eventually lose out and fail to rid all the damaging material.

TREM2 is active on microglia and enables them to carry out their protective function. The protein spans the microglia cell membrane and uses its external region to detect dying cells or lipids associated with toxic protein aggregates. Subsequently, TREM2 is cut in two. The external part is shed from the protein and released, while the remaining part still present in the cell membrane is degraded. To better understand TREM2 function, the two research groups took a closer look at its cleavage. They were led by Christian Haass at the German Center for Neurodegenerative Diseases at the Ludwig-Maximilians-Universitt in Munich, Germany, and Damian Crowther of AstraZeneca's IMED Neuroscience group in Cambridge, UK together with colleagues at the Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto and the Cambridge Institute for Medical Research, University of Cambridge, UK.

Using different technological approaches, both groups first determined the exact site of protein shedding and found it to be at amino acid 157. Amino acid 157 was no unknown. Only recently, researchers from China had uncovered that a mutation at this exact position, referred to as p.H157Y, increased the risk of Alzheimer's disease. Together, these observations indicate that protein cleavage is perturbed in the p.H157 mutant and that this alteration promotes disease development.

As a next step, Haass and Crowther's groups investigated the biochemical properties of the p.H157Y mutant protein more closely. They found that the mutant was cleaved more rapidly than a healthy version of the protein. "Our results provide a detailed molecular mechanism for how this rare mutation alters the function of TREM2 and hence facilitates the progression of Alzheimer's disease," said Crowther.

While most TREM2 mutations affect protein production, the mechanism behind p.H157Y is somewhat different. The p.H157Y mutation allows the protein to be correctly manufactured and transported to the microglia cell surface, but then it is cleaved too quickly. "The end result is the same. In both cases, there is too little full-length TREM protein on microglia," said Haass. "This suggests that stabilizing TREM2, by making it less susceptible to cleavage, may be a viable therapeutic strategy."

Explore further: Phagocytes in the braingood or bad?

More information: TREM2 shedding by cleavage at the H157-S158 bond is accelerated for the Alzheimer's disease-associated H157Y variant EMBO Molecular Medicine, DOI: 10.15252/emmm.201707673

Link:
Stabilizing TREM2 a potential strategy to combat Alzheimer's disease - Medical Xpress

Scientists at the University of Oxford have developed a new method to 3D-print laboratory- grown cells to form living structures.

The approach could revolutionise regenerative medicine, enabling the production of complex tissues and cartilage that would potentially support, repair or augment diseased and damaged areas of the body.

In research published in the journal Scientific Reports, an interdisciplinary team from the Department of Chemistry and the Department of Physiology, Anatomy and Genetics at Oxford and the Centre for Molecular Medicine at Bristol, demonstrated how a range of human and animal cells can be printed into high-resolution tissue constructs.

Interest in 3D printing living tissues has grown in recent years, but, developing an effective way to use the technology has been difficult, particularly since accurately controlling the position of cells in 3D is hard to do.

They often move within printed structures and the soft scaffolding printed to support the cells can collapse on itself.

As a result, it remains a challenge to print high-resolution living tissues. But, led by Professor Hagan Bayley, Professor of Chemical Biology in Oxfords Department of Chemistry, the team devised a way to produce tissues in self-contained cells that support the structures to keep their shape.

The cells were contained within protective nanolitre droplets wrapped in a lipid coating that could be assembled, layer-by-layer, into living structures.

Producing printed tissues in this way improves the survival rate of the individual cells, and allowed the team to improve on current techniques by building each tissue one drop at a time to a more favourable resolution.

To be useful, artificial tissues need to be able to mimic the behaviours and functions of the human body. The method enables the fabrication of patterned cellular constructs, which, once fully grown, mimic or potentially enhance natural tissues.

Dr Alexander Graham, lead author and 3D Bioprinting Scientist at OxSyBio (Oxford Synthetic Biology), said: We were aiming to fabricate three-dimensional living tissues that could display the basic behaviours and physiology found in natural organisms. To date, there are limited examples of printed tissues, which have the complex cellular architecture of native tissues. Hence, we focused on designing a high-resolution cell printing platform, from relatively inexpensive components, that could be used to reproducibly produce artificial tissues with appropriate complexity from a range of cells including stem cells.

The researchers hope that, with further development, the materials could have a wide impact on healthcare worldwide. Potential applications include shaping reproducible human tissue models that could take away the need for clinical animal testing.

The team completed their research last year, and have since taken steps towards commercialising the technique and making it more widely available. In January 2016, OxSyBio officially spun-out from the Bayley Lab. The company aims to commercialise the technique for industrial and biomedical purposes.

Over the coming months they will work to develop new complementary printing techniques, that allow the use of a wider range of living and hybrid materials, to produce tissues at industrial scale. Dr Sam Olof, Chief Technology Officer at OxSyBio, said: There are many potential applications for bioprinting and we believe it will be possible to create personalised treatments by using cells sourced from patients to mimic or enhance natural tissue function. In the future, 3D bio-printed tissues maybe also be used for diagnostic applications for example, for drug or toxin screening.

Dr Adam Perriman from the University of Bristols School of Cellular and Molecular Medicine, added: The bioprinting approach developed with Oxford University is very exciting, as the cellular constructs can be printed efficiently at extremely high resolution with very little waste. The ability to 3D print with adult stem cells and still have them differentiate was remarkable, and really shows the potential of this new methodology to impact regenerative medicine globally

The full citation for the paper is High-resolution patterned cellular constructs by droplet-based 3D printingA.D. Graham et. al. Scientific Reports 7, Article number: 7004 (2017).

Excerpt from:
New method for the 3D printing of living tissues - Scientist Live