PLEASANTON, Calif.--(BUSINESS WIRE)--10x Genomics, a company focused on enabling the mastery of biology by accelerating genomic discovery, today announced publication of an article in the journal Nature of a collaborative research study with researchers at the Stanford University School of Medicine. The article entitled, Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal, utilizes the 10x Genomics Single Cell 3 Solution for single-cell RNA-seq (scRNA-seq) to unravel the priming and self-renewal mechanisms of intestinal stem cells (ISCs).

The renewal and differentiation of Lgr5+ ISCs is critical to the continuous regeneration of the epithelial lining of the gut, which enables us to absorb nutrients and provides a barrier to protect us from the external environment. Disruptions in this process can lead to or worsen human intestinal disorders such as inflammatory bowel disease (IBD), gastrointestinal cancer and Celiac disease.

This carefully regulated process occurs within a stem-cell niche called the intestinal crypt, and depends on Wnt signaling, which can be turned up by Wnt and R-spondin (RSPO) ligands. The authors sought to identify the unique functional roles of Wnt and RSPO ligands for regulating Lgr5+ ISCs and the relative contributions of both ligands to in vivo Wnt signaling and stem-cell biology.

The authors were able to show using in vivo experiments that Wnt and RSPO are not redundant signals. RSPO was shown to expand stem cell number. Although Wnt was needed to maintain Lgr5+ ISCs in the presence of RSPO, Wnt was not sufficient to induce additional numbers of Lgr5+ ISCs above a certain threshold, demonstrating that RSPO, and not Wnt, establishes the set point for Lgr5+ ISC number. The authors performed single-cell RNA-seq to definitively show that the signaling contributions of Wnt and RSPO elicited distinct effects on ISCs, by fully characterizing the expression profile for each unique cellular subtype on a cell-by-cell basis upon perturbation of those signals in vivo.

By characterizing gene expression from 13,102 single cells, Yan and colleagues were able to show that Lgr5- control cells represented differentiated cell types of the small intestinal lineages, including Paneth, goblet, enteroendocrine, enterocyte, pre-enterocyte, and tuft cells. The Lgr5+ cells consisted of three cellular sub-populations, corresponding to cycling stem cells, non-cycling stem cells, and transit amplifying cells. The authors were able to further show that these three distinct sub-populations of Lgr5+ cells were each uniquely affected by perturbations in Wnt and RSPO signaling, conclusively demonstrating that Wnts are priming factors that enable stem cells to be competent by expressing RSPO receptors on their cell surface, whereas RSPOs are actual self-renewal factors that expand stem cell number.

Single-cell analysis provided conclusive evidence for the unique roles of Wnt and RSPO signaling to their respective function, either co-operatively priming Lgr5+ cells for competency, or for RSPO-mediated self-renewal. said Grace Zheng, Ph.D., research scientist at 10x Genomics. This powerfully illustrates the utility of single-cell RNA-seq to monitor discrete stem-cell states and their dynamic perturbation. To do this with any other technology would have been extremely cumbersome, if not impossible.

We are very excited about this result, and it opens up the possibility that analogous multi-tiered regulation by priming and self-renewal factors may be a generalized property of stem cells across other organ systems, either through Wnt and RSPO or functionally equivalent stem-cell niche components, said Ben Hindson, Ph.D., president, co-founder, and chief scientific officer of 10x Genomics. This could have wide reaching implications for stem-cell research and potentially yield new insight towards therapeutic applications in the future.

The lead author of the study is Kelley Yan, M.D. Ph.D., lead author of the study, formerly a postdoctoral fellow at Stanford and now an Assistant Professor of Medicine and of Genetics and Development in the Columbia Center for Human Development at Columbia University Medical Center. The senior author is Calvin Kuo, M.D. Ph.D., Professor of Medicine at Stanford.

The article entitled, Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal, can be accessed from Nature online: http://dx.doi.org/10.1038/nature22313

For more information about this research, visit the Kuo Lab at Stanford: http://kuolab.stanford.edu/index.html

About 10x Genomics

10x Genomics is changing the definition of sequencing by providing an innovative genomics platform that dramatically upgrades the capabilities of existing sequencing technologies. This is achieved through a combination of new microfluidic science, chemistry and bioinformatics. By implementing GemCode Technology within the Chromium System, researchers can now, for the first time, find new structural variants, haplotypes and other valuable genomic information with comprehensive workflows for Single Cell, V(D)J, Genome, Exome and de novo Assembly applications that incorporate their pre-existing sequencing technologies. http://www.10xGenomics.com.

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Recent Study Published in Nature Unravels a Novel Pathway for ... - Business Wire (press release)

CAMBRIDGE, Mass., May 1, 2017 /PRNewswire/ --Dragonfly Therapeutics, Inc. ("Dragonfly"), today announced the addition of Dr. Asya Grinberg to its senior team. Dr. Grinberg joins Dragonfly from Acceleron Pharma (Nasdaq: XLRN), where she led a multidisciplinary team in cell biology and protein chemistry. As Dragonfly's Head of Biologics, Dr. Grinberg leads its protein engineering, purification, characterization and structural biology team.

Dr. Grinberg brings to Dragonfly an extensive track record of scientific accomplishments and creativity in protein-based drug development. "Asya's experience developing multiple drug candidates from concept deep into the clinic represents a great addition to our company," stated Dragonfly co-founder and head of the Koch Institute for Integrative Cancer Research at MIT, Dr. Tyler Jacks.

Prior to joining Dragonfly, Dr. Grinberg spent 12 years at Acceleron Pharma discovering and developing novel protein therapeutics for treatment of hematopoietic diseases and cancer. She most recently served as Senior Director of Cell Biology and Protein Chemistry and has been a strong scientific and strategic driver of internal innovation. Dr. Grinberg's efforts were instrumental to the development of five clinical candidates, including Luspatercept (currently in Phase III testing) for treatment of beta-thalassemia and MDS. Dr. Grinberg is the key inventor of the IntelliTrap drug discovery platform targeting the TGF-beta superfamily. Dr. Grinberg received her M.Sc. in Bioorganic Chemistry from Moscow State University and did her Ph.D. studies at Max Delbrck Centre for Molecular Medicine in Germany. She completed her post-doctoral fellowship at the University of Michigan supported by the at Howard Hughes Medical Institute. Dr. Grinberg is a co-author of more than 40 scientific publications, and co-inventor on a number of patents.

"We are thrilled to welcome Dr. Grinberg to Dragonfly," said Dragonfly co-founder and CEO Bill Haney. "Her depth of understanding of protein therapeutics, coupled with her talent for innovation, will accelerate our development of novel cancer therapies, which use Natural Killer cells to both enhance the effectiveness of T cell performance and attack cancer directly."

About Dragonfly

Dragonfly Therapeutics is a discovery-stage company developing drugs to stimulate immune responses against cancer.

Our scientific founders are major figures in cancer biology and immunology and launched Dragonfly to harness the power of the innate immune system to provide breakthrough cancer treatments for patients.

For more information visit: http://www.dragonflytx.com, https://www.facebook.com/dragonflytherapeutics/, https://twitter.com/dragonflytx

Media Contact: Maura McCarthy 617-588-0086 x702 rel="nofollow">maura@dragonflytx.com

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/leading-protein-scientist-dr-asya-grinberg-joins-dragonfly-therapeutics-as-head-of-biologics-300448535.html

SOURCE Dragonfly Therapeutics, Inc.

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Leading Protein Scientist Dr. Asya Grinberg Joins Dragonfly ... - Markets Insider

Humanity has come a long way in understanding human biology and the applications of this knowledge to the reduction of human suffering by disease; however, we still have a long way to go. Some of the most basic processes of the cell are still not completely understood, and this lack of understanding leaves humanity in a particularly precarious position.

There are some 20,000 gene-coding proteins in the human cell, and some of the most devastating diseases arise from the dysfunction of just a single gene-product. Niemann-Pick Type C (NPC) represents one of these diseases, and arises when one of two critical NPC genes is mutated in both parents and passed onto their offspring.

When the NPC proteins are mutated, the recycling center of the cell, the lysosome, is unable to recycle certain moleculesmost notably, cholesterol. As a result of this inability to recycle certain molecules, they accumulate inside the cell and ultimately lead to the symptoms associated with NPC disease. Some of the more prominent symptoms associated with this devastating disease include an enlarged liver and spleen, balance problems, seizures, and many other neurological symptoms that usually develop during childhood or early adolescence. The prognosis is very poor, and this disease always results in death.

Though NPC disease is not yet completely understood, there are passionate researchers who have dedicated their careers to understanding how this disease develops and how it might be treated. Understanding NPC disease requires scientists to better understand basic processes of cell metabolism and NPC proteins.

These researchers are committed to unlocking these secrets of the cell and using their findings to develop treatments for NPC. One particularly relevant area of NPC research is focused on understanding why neurons are so disproportionately affected by the disease.

Dr. Steven Walkley, a leading researcher in the field of NPC research, is a Neuroscientist at the Albert Einstein College of Medicine. Walkley has a strong interest in genetic brain diseases and strives to understand not only how NPC disease affects neurons, but is also committed to investigating and developing therapies to treat the disease. Unlike most other cells in the body, the neurons that you are born with do not replicate, and must be maintained for a lifetime.

Walkley stresses that this static nature of brain cells contributes to their keen sensitivity of even the slightest changes in homeostasis. As a result, these cells are disproportionately damaged by the accumulation of cholesterol and other molecules as a result of NPC, and Walkley is determined to understand why this happens and how it can be mitigated.

To better understand how neurons are affected by NPC disease, Walkleys lab studies mice with a naturally occurring NPC disease to understand the disease pathology and potential treatments. In fact, he discovered one of the first treatments for NPC diseasemiglustat, a drug that was originally developed as a potential therapy for Tay-Sachs and Gaucher diseases.

Furthermore, his labs discovery of the amazing therapeutic effects of a compound called cyclodextrin was one of his most significant contributions to the field. Cyclodextrin has been shown to significantly increase the lifespan of mice and cats with naturally occurring models of NPC disease.

Another leading researcher in this field is Dr. Charles Vite, a veterinary Neurologist at the University of Pennsylvania. Vite uses a cat as a model to study NPC disease in the brainstriving to understand why neurons are disproportionately affected and how therapies might mitigate this. He explained that sometimes larger models of the disease better mirror what is seen in the human diseaseand he often works in close collaboration with Walkley to understand how findings in the mouse model compare to the larger cat model. A prominent and vital component of Vites contributions to the field are his investigations on how cyclodextrin treats NPC in his cat model; the results have been extremely uplifting. Upon treatment with cyclodextrin, cats with the disease live about three years longer, on average, than they do when left untreated!

I had the great honor of speaking with both of these leading researchers. During our conversations, I came to realize how truly committed these researchers are to their fields. Their love for neuroscience, deep curiosity and passion to better the lives of individuals afflicted with this disease left me in awe. Thanks to dedicated researchers like Walkley and Vite, scientists are understanding more about NPC and basic cell biology every day. Things are finally starting to look brighter for those who are afflicted with NPC and their families.

Walkley and Vite both agree that cyclodextrin is one of the most promising therapies out there for NPC today, and it is currently in clinical trials. Vite believes that one of the greatest difficulties in working with this disease is that too often, individuals do not receive these developing treatments until the disease has already progressed significantly. To avoid this problem, researchers are looking into the development of newborn screening for NPC, and this is something that will likely be established as a concrete treatment for NPC is developed.

As current students, it is critical to realize the importance of the scientific pursuit of knowledge for humanity. With a better understanding of biology comes an ever- increasing freedom from human disease and suffering. With this in mind, we should dive into our coursework with vigor, and look for opportunities to get involved with current research. Walkley stressed the importance for college students to reach out to local scientists to get involved.

The fight for knowledge is by no means finishedwe will continue this trek into the unknown where scientists of today leave off. With every increase in knowledge, we will bring humanity one step closer to a freedom from human suffering by disease.

Denston Carey is a student majoring in cell and molecular biology. He can be reachedat [emailprotected]

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Unlocking the secrets of the cell to heal humanity - Quad (subscription)