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Systemic Inflammatory Diseases as Crohn’s disease, Rheumatoid Arthritis and Longer Psoriasis Duration May Mean Higher CVD Risk

Reporter: Aviva Lev-Ari, PhD, RN

Longer Psoriasis Duration May Mean Higher CVD Risk

Effect size ‘similar to that of smoking’

Several studies have shown that methotrexate, which has anti-inflammatory effects, reduces CV risk in patients with rheumatoid arthritis, suggesting that good anti-inflammatory control may be expected to reduce CV risk in patients with psoriasis.

Menter has worked closely with the senior author of the current study, Nehal Mehta, MD, of the University of Pennsylvania in Philadelphia, to identify cardiovascular issues in the psoriasis population. In one recent study, investigators found that the prevalence of moderate-to-severe coronary calcification was similar between patients with psoriasis and those with type 2 diabetes, and approximately five times greater than healthy controls.

Investigators found that moderate-to-severe psoriasis was a significantly stronger predictor of coronary calcification than type 2 diabetes, and the effect was independent of known CV and cardiometabolic risk factors.

 

SOURCE

https://www.medpagetoday.com/Dermatology/Psoriasis/68429?xid=nl_mpt_cardiodaily_2017-10-09&eun=g99985d0r

QIAGEN – International Leader in NGS and RNA Sequencing, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 1: Next Generation Sequencing (NGS)

QIAGEN – International Leader in NGS and RNA Sequencing

Reporter: Aviva Lev-Ari, PhD, RN

 

The reader is encouraged to review all the products of QIAGEN on the company web site.

miRCURY Exosome Kits

For enrichment of exosomes and other extracellular vesicles from serum/plasma or cell/urine/CSF samples
  • Excellent recovery of exosomes and other extracellular vesicles
  • Easy and straightforward protocol that takes less than 2 hours
  • No ultracentrifugation or phenol/chloroform steps required
  • Fully compatible with the miRCURY LNA miRNA PCR System
  • Suited for a variety of applications, such as miRNA or RNA profiling

miRCURY Exosome Kits enable high-quality and scalable exosome isolation with an easy protocol that does not require special laboratory equipment. The miRCURY Exosome Serum/Plasma Kit is optimized for serum and plasma samples, while the miRCURY Exosome Cell/Urine/CSF Kit is designed for processing cell-conditioned media, urine and CSF samples. Both kits provide high exosomal recovery and seamless integration with different downstream assays.

SOURCE

https://www.qiagen.com/us/shop/sample-technologies/tumor-cells-and-exosomes/mircury-exosome-kits/#orderinginformation

QIAGEN – Product Profile

The Role of Exosomes in Metabolic Regulation

Author: Larry H. Bernstein, MD, FCAP

 

On 9/25/2017, Aviva Lev-Ari, PhD, RN commissioned Dr. Larry H. Bernstein to write a short article on the following topic reported on 9/22/2017 in sciencemission.com

 

We are publishing, below the new article created by Larry H. Bernstein, MD, FCAP.

 

Background

During the period between 9/2015  and 6/2017 the Team at Leaders in Pharmaceutical Business Intelligence (LPBI)  has launched an R&D effort lead by Aviva Lev-Ari, PhD, RN in conjunction with SBH Sciences, Inc. headed by Dr. Raphael Nir.

This effort, also known as, “DrugDiscovery @LPBI Group”  has yielded several publications on EXOSOMES on this Open Access Online Scientific Journal. Among them are included the following:

 

QIAGEN – International Leader in NGS and RNA Sequencing, 10/08/2017

Reporter: Aviva Lev-Ari, PhD, RN

 

cell-free DNA (cfDNA) tests could become the ultimate “Molecular Stethoscope” that opens up a whole new way of practicing Medicine, 09/08/2017

Reporter: Aviva Lev-Ari, PhD, RN

 

Detecting Multiple Types of Cancer With a Single Blood Test (Human Exomes Galore), 07/02/2017

Reporter and Curator: Irina Robu, PhD

 

Exosomes: Natural Carriers for siRNA Delivery, 04/24/2017

Reporter: Aviva Lev-Ari, PhD, RN

 

One blood sample can be tested for a comprehensive array of cancer cell biomarkers: R&D at WPI, 01/05/2017

Curator: Marzan Khan, B.Sc

 

SBI’s Exosome Research Technologies, 12/29/2016

Reporter: Aviva Lev-Ari, PhD, RN

 

A novel 5-gene pancreatic adenocarcinoma classifier: Meta-analysis of transcriptome data – Clinical Genomics Research @BIDMC, 12/28/2016

Curator: Tilda Barliya, PhD

 

Liquid Biopsy Chip detects an array of metastatic cancer cell markers in blood – R&D @Worcester Polytechnic Institute, Micro and Nanotechnology Lab, 12/28/2016

Reporters: Tilda Barliya, PhD and Aviva Lev-Ari, PhD, RN

 

Exosomes – History and Promise, 04/28/2016

Reporter: Aviva Lev-Ari, PhD, RN

 

Exosomes, 11/17/2015

Curator: Larry H. Bernstein, MD, FCAP

 

Liquid Biopsy Assay May Predict Drug Resistance, 11/16/2015

Curator: Larry H. Bernstein, MD, FCAP

 

Glypican-1 identifies cancer exosomes, 10/31/2015

Curator: Larry H. Bernstein, MD, FCAP

 

Circulating Biomarkers World Congress, March 23-24, 2015, Boston: Exosomes, Microvesicles, Circulating DNA, Circulating RNA, Circulating Tumor Cells, Sample Preparation, 03/24/2015

Reporter: Aviva Lev-Ari, PhD, RN

 

Cambridge Healthtech Institute’s Second Annual Exosomes and Microvesicles as Biomarkers and Diagnostics Conference, March 16-17, 2015 in Cambridge, MA, 03/17, 2015

Reporter: Aviva Lev-Ari, PhD, RN

 

The newly created think-piece on the relationship between regulatory functions of Exosomes and Metabolic processes is developed conceptually, below.

 

The Role of Exosomes in Metabolic Regulation

Author: Larry H. Bernstein, MD, FCAP

We have had more than a half century of research into the genetic code and transcription leading to abundant work on RNA and proteomics. However, more recent work in the last two decades has identified RNA interference in siRNA. These molecules may be found in the circulation, but it has been a challenge to find their use in therapeutics. Exosomes were first discovered in the 1980s, but only recently there has been a huge amount of research into their origin, structure and function. Exosomes are 30–120 nm endocytic membrane-bound extracellular vesicles (EVs)(1-23) , and more specifically multiple vesicle bodies (MVBs) by a budding process from invagination of the outer cell membrane that carry microRNA (miRNA), and have structures composed of protein and lipids (1,23-27 ). EVs are the membrane vesicles secreted by eukaryotic cells for intracellular communication by transferring the proteins, lipids, and RNA under various physiologic conditions as well as during the disease stage. EVs also act as a signalosomes in many biological processes. Inward budding of the plasma membrane forms small vesicles that fuse. Intraluminal vesicles (ILVs) are formed by invagination of the limiting endosomal membrane during the maturation process of early endosome.

EVs are the MVBs secreted that serve in intracellular communication by transferring a cargo consisting of proteins, lipids, and RNA under various physiologic conditions (4, 23). Exosome-mediated miRNA transfer between cells is considered to be necessary for intercellular signaling and exosome-associated miRNAs in biofluids (23). Exosomes carry various molecular constituents of their cell of origin, including proteins, lipids, mRNAs, and microRNAs (miRNAs) (. They are released from many cell types, such as dendritic cells (DCs), lymphocytes, platelets, mast cells, epithelial cells, endothelial cells, and neurons, and can be found in most bodily fluids including blood, urine, saliva, amniotic fluid, breast milk, hydrothoracic fluid, and ascitic fluid, as well as in culture medium of most cell types.Exosomes have also been shown to be involved in noncoding RNA surveillance machinery in generating antibody diversity (24). There are also a vast number of long non-coding RNAs (lncRNAs) and enhancer RNAs (eRNAs) that accumulate R-loop structures upon RNA exosome ablation, thereby, resolving deleterious DNA/RNA hybrids arising from active enhancers and distal divergent eRNA-expressing elements (lncRNA-CSR) engaged in long-range DNA interactions (25). RNA exosomes are large multimeric 3′-5′ exo- and endonucleases representing the central RNA 3′-end processing factor and are implicated in processing, quality control, and turnover of both coding and noncoding RNAs. They are large macromolecular cages that channel RNA to the ribonuclease sites (29). A major interest has been developed to characterize of exosomal cargo, which includes numerous non-randomly packed proteins and nucleic acids (1). Moreover, exosomes play an active role in tumorigenesis, metastasis, and response to therapy through the transfer of oncogenes and onco-miRNAs between cancer cells and the tumor stroma. Blood cells and the vascular endothelium is also exosomal shedding, which has significance for cardiovascular,   neurologicological disorders, stroke, and antiphospholipid syndrome (1). Dysregulation of microRNAs and the affected pathways is seen in numerous pathologies their expression can reflect molecular processes of tumor onset and progression qualifying microRNAs as potential diagnostic and prognostic biomarkers (30).

Exosomes are secreted by many cells like B lymphocytes and dendritic cells of hematopoietic and non-hematopoietic origin viz. platelets, Schwann cells, neurons, mast cells, cytotoxic T cells, oligodendrocytes, intestinal epithelial cells were also found to be releasing exosomes (4). They are engaged in complex functions like persuading immune response as the exosomes secreted by antigen presenting cells activate T cells (4). They all have a common set of proteins e.g. Rab family of GTPases, Alix and ESCRT (required for transport) protein and they maintain their cytoskeleton dynamics and participate in membrane fusion. However, they are involved in retrovirus disease pathology as a result of recruitment of the host`s endosomal compartments in order to generate viral vesicles, and they can either spread or limit an infection based on the type of pathogen and its target cells (5).

Upon further consideration, it is understandable how this growing biological work on exosomes has enormous significance for laboratory diagnostics (1, 3, 5, 6, 11, 14, 15, 17-20, 23,30-41) . They are released from many cell types, such as dendritic cells (DCs), lymphocytes, platelets, mast cells, epithelial cells, endothelial cells, and neurons, and can be found in most bodily fluids including blood, urine, saliva, amniotic fluid, breast milk, thoracic and abdominal effusions, and ascitic fluid (1). The involvement of exosomes in disease is broad, and includes: cancer, autoimmune and infectious disease, hematologic disorders, neurodegenerative diseases, and cardiovascular disease. Proteins frequently identified in exosomes include membrane transporters and fusion proteins (e.g., GTPases, annexins, and flotillin), heat shock proteins (e.g., HSC70), tetraspanins (e.g., CD9, CD63, and CD81), MVB biogenesis proteins (e.g., alix and TSG101), and lipid-related proteins and phospholipases. The exosomal lipid composition has been thoroughly analyzed in exosomes secreted from several cell types including DCs and mast cells, reticulocytes, and B-lymphocytes (1). Dysregulation of microRNAs of pathways observed in numerous pathologies (5, 10, 12, 21, 27, 35, 37) including cancers (30), particularly, colon, pancreas, breast, liver, brain, lung (2, 6, 17-20, 30, 33-36, 38, 39). Following these considerations, it is important that we characterize the content of exosomal cargo to gain clues to their biogenesis, targeting, and cellular effects which may lead to identification of biomarkers for disease diagnosis, prognosis and response to treatment (42).

We might continue in pursuit of a particular noteworthy exosome, the NLRP3 inflammasome, which is activated by a variety of external or host-derived stimuli, thereby, initiating an inflammatory response through caspase-1 activation, resulting in inflammatory cytokine IL-1b maturation and secretion (43).
Inflammasomes are multi-protein signaling complexes that activate the inflammatory caspases and the maturation of interleukin-1b. The NLRP3 inflammasome is linked with human autoinflammatory and autoimmune diseases (44). This makes the NLRP3 inflammasome a promising target for anti-inflammatory therapies. The NLRP3 inflammasome is activated in response to a variety of signals that indicate tissue damage, metabolic stress, and infection (45). Upon activation, the NLRP3 inflammasome serves as a platform for activation of the cysteine protease caspase-1, which leads to the processing and secretion of the proinflammatory cytokines interleukin-1β (IL-1β) and IL-18. Heritable and acquired inflammatory diseases are both characterized by dysregulation of NLRP3 inflammasome activation (45).
Receptors of innate immunity recognize conserved moieties associated with either cellular damage [danger-associated molecular patterns (DAMPs)] or invading organisms [pathogen-associated molecular patterns (PAMPs)](45). Either chronic stimulation or overwhelming tissue damage is injurious and responsible for the pathology seen in a number of autoinflammatory and autoimmune disorders, such as arthritis and diabetes. The nucleotide-binding domain leucine-rich repeat (LRR)-containing receptors (NLRs) are PRRs are found intracellularly and they share a unique domain architecture. It consists of a central nucleotide binding and oligomerization domain called the NACHT domain that is located between an N-terminal effector domain and a C-terminal LRR domain (45). The NLR family members NLRP1, NLRP3, and NLRC4 are capable of forming multiprotein complexes called inflammasomes when activated.

The (NLRP3) inflammasome is important in chronic airway diseases such as asthma and chronic obstructive pulmonary disease because the activation results, in pro-IL-1β processing and the secretion of the proinflammatory cytokine IL-1β (46). It has been proposed that Activation of the NLRP3 inflammasome by invading pathogens may prove cell type-specific in exacerbations of airway inflammation in asthma (46). First, NLRP3 interacts with the adaptor protein ASC by sensing microbial pathogens and self-danger signals. Then pro-caspase-1 is recruited and the large protein complex called the NLRP3 inflammasome is formed. This is followed by autocleavage and activation of caspase-1, after which pro-IL-1β and pro-IL-18 are converted into their mature forms. Ion fluxes disrupt membrane integrity, and also mitochondrial damage both play key roles in NLRP3 inflammasome activation (47). Depletion of mitochondria as well as inhibitors that block mitochondrial respiration and ROS production prevented NLRP3 inflammasome activation. Futhermore, genetic ablation of VDAC channels (namely VDAC1 and VDAC3) that are located on the mitochondrial outer membrane and that are responsible for exchanging ions and metabolites with the cytoplasm, leads to diminished mitochondrial (mt) ROS production and inhibition of NLRP3 inflammasome activation (47). Inflammasome activation not only occurs in immune cells, primarily macrophages and dendritic cells, but also in kidney cells, specifically the renal tubular epithelium. The NLRP3 inflammasome is probably involved in the pathogenesis of acute kidney injury, chronic kidney disease, diabetic nephropathy and crystal-related nephropathy (48). The inflammasome also plays a role in autoimmune kidney disease. IL-1 blockade and two recently identified specific NLRP3 inflammasome blockers, MCC950 and β-hydroxybutyrate, may prove to have value in the treatment of inflammasome-mediated conditions.

Autophagosomes derived from tumor cells are referred to as defective ribosomal products in blebs (DRibbles). DRibbles mediate tumor regression by stimulating potent T-cell responses and, thus, have been used as therapeutic cancer vaccines in multiple preclinical cancer models (49). It has been found that DRibbles could induce a rapid differentiation of monocytes and DC precursor (pre-DC) cells into functional APCs (49). Consequently, DRibbles could potentially induce strong innate immune responses via multiple pattern recognition receptors. This explains why DRibbles might be excellent antigen carriers to induce adaptive immune responses to both tumor cells and viruses. This suggests that isolated autophagosomes (DRibbles) from antigen donor cells activate inflammasomes by providing the necessary signals required for IL-1β production.

The Hsp90 system is characterized by a cohort of co-chaperones that bind to Hsp90 and affect its function (50). The co-chaperones enable Hsp90 to chaperone structurally and functionally diverse client proteins. Sahasrabudhe et al. (50) show that the nature of the client protein dictates the contribution of a co-chaperone to its maturation. The study reveals the general importance of the cochaperone Sgt1 (50). In addition to Hsp90, we have to consider Hsp60. Adult cardiac myocytes release heat shock protein (HSP)60 in exosomes. Extracellular HSP60, when not in exosomes, causes cardiac myocyte apoptosis via the activation of Toll-like receptor 4. the protein content of cardiac exosomes differed significantly from other types of exosomes in the literature and contained cytosolic, sarcomeric, and mitochondrial proteins (21).

A new Protein Organic Solvent Precipitation (PROSPR) method efficiently isolates the EV repertoire from human biological samples. Proteomic profiling of PROSPR-enriched CNS EVs indicated that > 75 % of the proteins identified matched previously reported exosomal and microvesicle cargoes. In addition lipidomic characterization of enriched CNS vesicles identified previously reported EV-specific lipid families and novel lipid isoforms not previously detected in human EVs. The characterization of these structures from central nervous system (CNS) tissues is relevant to current neuroscience, especially to advance the understanding of neurodegeneration in amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD) and Alzheimer’s disease (AD)(15). In addition, study of EVs in brain will enable characterization of the degenerative posttranslational modifications (DPMs) occurring in those proteins.
Neurodegenerative disease is characterized by dysregulation because of NLRP3 inflammasome activation. Alzheimer’s disease (AD) and Parkinson’s disease (PD), both neurodegenerative diseases are associated with the NLRP3 inflammasome. PD is characterized by accumulation of Lewy bodies (LB) formed by a-synuclein (aSyn) aggregation. A recent study revealed that aSyn induces synthesis of pro-IL-1b by an interaction with TLR2 and activates NLRP3 inflammasome resulting in caspase-1 activation and IL-1b maturation in human primary monocytes (43). In addition mitophagy downregulates NLRP3 inflammasome activation by eliminating damaged mitochondria, blocking NLRP3 inflammasome activating signals. It is notable that in this aberrant activation mitophagy downregulates NLRP3 inflammasome activation by eliminating damaged mitochondria, blocking NLRP3 inflammasome activating signals (43).

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Development of 3D Human Tissue Models Awarded NIH Grants Worth $15M

Reporter: Irina Robu, PhD

NIH has awarded $15 million for Tissue Chip for Disease Modeling and Efficacy Testing to develop 3D human tissue models. The 3D platforms, also called tissue chips support living cells and human tissues, it mimics the complex biological functions of organs/tissues and at the same time provide a new way to test potential drugs and their effectiveness. The awards will allow scientists to study and understand diseases mechanism and forecast how patients respond and is part of the first phase of a five-year program.  According to NCATS Director, Dr. Christopher P. Austin “these tissue chips to provide more accurate platforms to understand diseases, and to be more predictive of the human response to drugs than current research models, thereby improving the success rate of candidate drugs in human clinical trials”.

The awards will be used to study common and rare diseases including rheumatoid arthritis, influenza A, kidney disease, amyotrophic lateral sclerosis, or ALS, arrhythmogenic cardiomyopathy, and hemorrhagic telangiectasia. Award recipients are Brigham and Women’s Hospital, Cedars-Sinai Medical Center, Columbia University, Duke University, Harvard University, Northwestern University, University of California Davis, University of California Irvine, University of Pittsburgh, University of Rochester, University of Washington Seattle and Vanderbilt University.

SOURCE

https://www.mdtmag.com/news/2017/09/nih-grants-15m-development-3d-human-tissue-models

 

Brain Surgeons Use 3D printing to Practice

Reporter: Irina Robu, PhD

Mechanical thrombectomy is a hopeful new modality of interventional stroke treatment. The countless devices on the market differ with regard to where they apply force on the thrombus, taking a proximal approach such as aspiration devices or a distal approach such as basket-like devices. In 2012, the Food and Drug Administration (FDA) approved mechanical thrombectomy – using a wire to pull clots out of the brains of stroke victims. At the end of the wire a trap exists which is like a noose that that captures the clot. Considering that the mechanical thrombectomy is a very risky procedure, interventional radiologists and neurosurgeons need to train extensively before they work on a real person.

Because of the procedure is very risky, a UConn Health radiologist and medical physicist made it easier for surgeons to practice first before the actual procedure. The team made a life size model of the arteries that the wire must pass through using brain scans and a 3D printer. The life size model will allow the surgeon to be more confident when guiding the wire and will give them the basic techniques on how to move the catheter. Holding the life size model of arteries, brings home how small they are even in an adult man. According to Dr. Ketan Bulsara, this life size model will be used a training model to learn mechanical thrombectomy and being able to model the tumor in advance could personalize and advance patient care.

SOURCE

https://www.mdtmag.com/news/2017/09/uconn-healths-new-3-d-printed-model-allows-brain-surgeons-practice

 

3D-printed body parts could replace cadavers for medical training

Reporter: Irina Robu, PhD

Even though, the 3-D printing based tissue modeling is still in early phases it is considered a promising approach for anatomy training. Models that are produced on a computer screen can be reproduced as tangible objects that students can examine and even dissect. According to a recent report in Medical Science Educator, the latest advancement in 3D printing can revolutionize how anatomy students learn.

For now, human cadavers have been the norm for studying human anatomy but they come with financial and logistical concerns both on storage and disposal. However, with the advancement of custom designed 3D organs, made possible by using 3D printing the need to keep large collection of physical models are reduced. With just a 3D printer, a digital model of the organ needed to study can be reproduced either with resin, thermoplastics, photopolymers and other material. Different materials can be used to allow construction of complex models with hard, soft, opaque and transparent conditions. The printed body parts will look exactly the same as the real thing because they are falsely colored to help students distinguish between the different parts of the anatomy including ligaments, muscles and blood vessels. Medical schools and hospitals around the world would be able to buy just an arm or a foot or the entire body depending on their training need.

Furthermore, to customizing anatomy lessons, 3D printed models can be used for teaching pathology/radiology by comparing CT images of the organs to their 3D-printed counterparts which students can examine and understand. Yet, the methods of 3D printing vary by materials used, resolution accuracy, long term stability, cost, speed and more. The printer cost is still a concern at this point partly because 3D bioprinters cost thousands of dollars nonetheless the cost is dropping due to the introduction of innovative printing materials.

Therefore, in order for 3-D printing to become more widely used, costs must be reduced while resolution must continue to improve. Instructors can potentially print one model per student in a material of their choosing that can be dissected. And no matter how much medical science moves with the times, there would always be the requisite skeleton model in the corner of most anatomy rooms.

SOURCE

http://www.abc.net.au/news/2014-07-22/an-3d-body-parts-could-replace-cadavers-for-medical-training/5615210

 

Additional Resources

Medical Science Educator, June 2015, Volume 25, Issue 2, pp 183–194| Cite as

Anatomical Models: a Digital Revolution

https://link.springer.com/article/10.1007/s40670-015-0115-9/fulltext.html

 

Goodbye to Cadavers?

https://consultqd.clevelandclinic.org/2015/09/goodbye-to-cadavers/

 

3-D Printing: Innovation Allows Customized Airway Stents

https://consultqd.clevelandclinic.org/2014/12/3-d-printing-innovation-allows-customized-airway-stents/

 

Exploring 3-D Printing’s Potential in Renal Surgery

https://consultqd.clevelandclinic.org/2015/06/exploring-3-d-printings-potential-in-renal-surgery/

 

How 3-D Printing Is Revolutionizing Medicine at Cleveland Clinic

https://consultqd.clevelandclinic.org/2015/11/how-3-d-printing-is-revolutionizing-medicine-at-cleveland-clinic/

Economic Potential of a Drug Invention (Prof. Zelig Eshhar, Weitzman Institute, registered the patent) versus a Cancer Drug in Clinical Trials: CAR-T as a Case in Point, developed by Kite Pharma, under Arie Belldegrun, CEO, acquired by Gilead for $11.9 billion, 8/2017.

Curator: Aviva Lev-Ari, PhD, RN

Article ID #245: Economic Potential of a Drug Invention (Prof. Zelig Eshhar, Weitzman Institute, registered the patent) versus a Cancer Drug in Clinical Trials: CAR-T as a Case in Point, developed by Kite Pharma, under Arie Belldegrun, CEO, acquired by Gilead for $11.9 billion, 8/2017. Published on 10/4/2017

WordCloud Image Produced by Adam Tubman

UPDATED on 2/21/2021

The Announcement of the 2021 Dan David Prize Laureates – YouTube – PRIZE $1MM per Winner for contributors to CAR-T MOA leading to development of immunotherapy anti cancer drugs

  • Prof. Zelig Eshhar – Weitzmann Institute his student Arie S. Belldegrun was CEO at Kate Pharmaceutics sold to Gilead for $12Bil
  • Prof. Carl June of UPenn
  • Steven Rosenberg, PhD, NIH

UPDATED on 10/15/2020

Hooked by the science, Arie Belldegrun joins a group of influentials who believe Dewpoint may have the key to the next big thing in biotech
John Carroll
Editor & Founder
Amir Nashat knew he had years of preclinical work to do when he talked to me at the beginning of 2019 about Dewpoint Therapeutics and its rare focus on the role bimolecular condensates could play in crafting a wide-ranging pipeline of therapeutics.

SOURCE

The Cambridge, MA-based Dewpoint team, which will now double in size over the next year, doesn’t have a late-stage preclinical program it can shove into the clinic. The biotech is investing in neurodegeneration, cancer, cardiovascular and other areas for a platform that could, eventually, have extensive applications. But asked about a timeline to proof-of-concept data, Nashat frankly estimates that it will take 4-5 years to birth some hard human data. The money should get them through 3 years and a considerable de-risking approach to their preclinical efforts

The CSO is Mark Murcko, an experienced and well known startup player.

Mark Murcko
“When I think about new companies a lot of it is about timing; is it too soon or too late?” Murcko notes enthusiastically in our interview. “Is there enough information available to make you think you can take that and use it toward new drugs? Five years ago it was too early, too nascent.”

Now, Murcko adds, seems like a great time to give this a go.

SOURCE

UPDATED on 7/16/2019

Part club, part guide, part landlord: Arie Belldegrun is blueprinting a string of bespoke biotech complexes in global boomtowns — starting with Boston

UPDATED on 3/11/2019

At California Central District Court Juno Therapeutics, Inc. et al v. Kite Pharma, Inc. – Multi-party Patent Infringement

UPDATED on 2/6/2019

Gilead takes an $820M hit after axing a Kite CAR-T. Are billions more going to be incinerated?

 

Gilead is writing off its anti-BCMA CAR-T for multiple myeloma, eliminating one of the many efforts focused on that target and driving a big part of the company’s $820 million impairment charge for R&D in the 4th quarter of last year.  But this could just be a taste of what’s to come.

A $12 billion buyout of Kite Pharma in 2017 brought with it the CAR-T therapy Yescarta (axicabtagene ciloleucel) and a foothold in immuno-oncology. But last year’s results make clear that return on that investment will be slow to materialize.

https://www.biopharmadive.com/news/gilead-earnings-q4-investors-trial-readouts/547697/

Buried in among Gilead’s fourth-quarter results statement is a line revealing it has abandoned an anti-BCMA cell therapy for multiple myeloma, part of its $12 billion acquisition of Kite Pharma.

The failed KITE-585 program and other costs associated with the acquisition resulted in a whopping $820 million impairment charge in the quarter and add to analyst speculation that with sales of approved CAR-T Yescarta still disappointing, Gilead may have to write down the value of the Kite deal entirely, according to a Bloomberg report.

Gilead’s decision to drop the KITE-585 CAR-T program reflects the increasing competition in the anti-BCMA category and doesn’t come out of the blue. The company said at the J.P. Morgan conference (JPM) last month that it would only press ahead with development of KITE-585 if its profile was very compelling.

https://www.fiercebiotech.com/biotech/gilead-drops-anti-bcma-car-t-from-kite-takes-820m-charge

Yescarta Projections

Street sees sales rising to $2.3 billion by 2025

Robert W. Baird & Co. analyst Brian Skorney says Gilead may have to write down the deal, which the company values at $11.9 billion. That means lowering the projections on its balance sheet, if the multi billion-dollar sales Wall Street expects don’t materialize. The long-time bull cut his rating on the stock to neutral in July following the management exodus.

UPDATED on 1/23/2018

Two CARTs, Two Charts: Dissecting Returns From T-Cell Therapy M&A

Bruce Booth

1/22/2018 Celgene finalized its acquisition of Juno Therapeutics for $9B, only a few short months after Gilead bought Kite Pharma for $11.9B.

It’s also clear that public investors did quite well in these deals – unlike some outcomes, both private and public investors can only be happy with these deals. Kite’s IPO investors made over a whopping 10x, and Juno’s nearly a 3.6x (in 3 years, so still a very strong public market return). Even the follow-on financing participants made handsome returns: both Kite’s and Juno’s follow-on financings about 4-6 months prior to acquisition delivered a 2x return in a short period. What’s clear is that participating at any point only these price curves was a positive for investors. Obviously that doesn’t always happen, but great to see when it does.

A final takeaway is that there is “no one size fits all” for how to build business models that can work in biotech these days, even to get to similar product and patient outcomes. While Kite and Juno have remarkably similar products, similar platforms, and similar overall acquisition valuations, the stories were built quite differently when it comes to financing their growth.

https://www.forbes.com/sites/brucebooth/2018/01/23/two-carts-two-charts-dissecting-returns-from-t-cell-therapy-ma/#23f0b7a2459e

UPDATED on 10/18/2017

Kite Pharma, under Arie Belldegrun, CEO, acquired by Gilead for $11.9 billion, 8/2017.

Kite’s Yescarta™ (Axicabtagene Ciloleucel) Becomes First CAR T Therapy Approved by the FDA for the Treatment of Adult Patients With Relapsed or Refractory Large B-Cell Lymphoma After Two or More Lines of Systemic Therapy

— Manufacturing Success Rate of 99 Percent in ZUMA-1 Pivotal Trial with a Median 17 Day Turnaround Time —

CAR T therapy is a breakthrough in hematologic cancer treatment in which a patient’s own T cells are engineered to seek and destroy cancer cells. CAR T therapy is manufactured specifically for each individual patient.

“The FDA approval of Yescarta is a landmark for patients with relapsed or refractory large B-cell lymphoma. This approval would not have been possible without the courageous commitment of patients and clinicians, as well as the ongoing dedication of Kite’s employees,” said Arie Belldegrun, MD, FACS, Founder of Kite. “We must also recognize the FDA for their ability to embrace and support transformational new technologies that treat life-threatening illnesses. We believe this is only the beginning for CAR T therapies.”

“Today is an important day for patients with relapsed or refractory large B-cell lymphoma who have run out of options and have been waiting for new treatments that may help them in their fight against cancer,” said John Milligan, PhD, President and Chief Executive Officer of Gilead Sciences. “With the combined innovation, talent and drive of the Kite and Gilead teams, we will rapidly advance cell therapy research and aim to bring new options to patients with many other types of cancer.”

The list price of Yescarta in the United States is $373,000.

Yescarta has been granted Priority Medicines (PRIME) regulatory support for DLBCL in the European Union. A Marketing Authorization Application (MAA) for axicabtagene ciloleucel is currently under review with the European Medicines Agency (EMA) and potential approval is expected in the first half of 2018.

Yescarta (axicabtagene ciloleucel) Pivotal Trial Results

The approval of Yescarta is supported by data from the ZUMA-1 pivotal trial. In this study, 72 percent of patients treated with a single infusion of Yescarta (n=101) responded to therapy (overall response rate) including 51 percent of patients who had no detectable cancer remaining (complete remission; 95% CI: 41, 62). At a median follow-up of 7.9 months, patients who had achieved a complete remission had not reached the estimated median duration of response (95% CI: 8.1 months, not estimable [NE]).

In the study, 13 percent of patients experienced grade 3 or higher cytokine release syndrome (CRS) and 31 percent experienced neurologic toxicities. The most common (≥ 10%) Grade 3 or higher reactions include febrile neutropenia, fever, CRS, encephalopathy, infections-pathogen unspecified, hypotension, hypoxia and lung infections. Serious adverse reactions occurred in 52% of patients and included CRS, neurologic toxicity, prolonged cytopenias (including neutropenia, thrombocytopenia and anemia), and serious infections. Fatal cases of CRS and neurologic toxicity occurred. FDA approved Yescarta with a Risk Evaluation and Mitigation Strategy.

Yescarta Indication

Yescarta is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.

Yescarta is not indicated for the treatment of patients with primary central nervous system lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma (NHL), accounting for three out of every five cases. In the United States each year, there are approximately 7,500 patients with refractory DLBCL who are eligible for CAR T therapy. Historically, when treated with the current standard of care, patients with refractory large B-cell lymphoma had a median overall survival of approximately six months, with only seven percent attaining a complete response. Currently, patients with large B-cell lymphoma in second or later lines of therapy have poor outcomes and greater unmet need, since nearly half of them either do not respond or relapse shortly after transplant.

“With CAR T therapy, we are reengineering a patient’s own immune system to detect and kill cancer cells, and the results have been impressive,” said Frederick L. Locke, MD, ZUMA-1 Co-Lead Investigator and Vice Chair of the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center in Tampa, Florida. “Many of the patients that received CAR T therapy had already relapsed several times with traditional treatments such as chemotherapy or hematopoietic stem cell transplant. Now, thanks to this new therapy many patients are in remission for months.”

“This therapy is a new option for patients with relapsed or refractory large B-cell lymphoma who have run out of treatment options and face a dire prognosis,” said Louis J. DeGennaro, PhD, President and Chief Executive Officer of The Leukemia & Lymphoma Society (LLS). “Early on, LLS recognized the potential of CAR T therapy and we are proud to be part of making this historic approval possible.”

“Engineered cell therapies like Yescarta represent the potential for a changing treatment paradigm for cancer patients,” said David Chang, MD, PhD, Worldwide Head of Research and Development and Chief Medical Officer at Kite. “Together, Gilead and Kite will accelerate studies of CAR T therapy in multiple blood cancers and advance other cell therapy approaches for solid tumors, with the goal of helping patients with diverse cancers benefit from this new era of personalized cancer therapy.”

http://www.businesswire.com/news/home/20171018006639/en/Kite%E2%80%99s-Yescarta%E2%84%A2-Axicabtagene-Ciloleucel-CAR-Therapy-Approved

This article has the following structure:

  • ABOUT Drug Invention (Prof. Zelig Eshhar, Weitzman Institute, registered the patent)
  • ABOUT Gilead’s $12 billion buy of Kite Pharma
  • ABOUT  the Drug Development process and the COMMERCIALIZATION GENIUS of Arie Belldegrun – Interviewed by Globes
  • ABOUT the Perspective of Drug Invention (Prof. Zelig Eshhar, Weitzman Institute, registered the patent) following the Gilead’s $12 billion buy of Kite Pharma – Interviewed by Globes
  • ABOUT the Economic significance of Kite Pharma Acquisition for the Venture Capital Investment in Biotech in Israel
  • Key Opinion Leader’s View: Aviva Lev-Ari, PhD, RN
  1. I agree with Prof. Zelig Eshhar that this Case in Point is “one more invention, or parts of an invention, came from an Israeli laboratory (at the Weizmann Institute in this case) and fell into foreign hands. It is another enormous missed opportunity in the field of biomedicine and ethical drugs.”
  2. I agree with Prof. Zelig Eshhar that this Case in Point should have been a TEVA commercialization effort. It is a regrettable reality that the development and the manufacturing will not benefit the State of Israel, home of the Weitzman Institute where the Patentable invention took place by Prof. Zelig Eshhar.
  3. It is to be acknowledged that for CAR-T – the process of treatment using the drug – personalized genetic engineering of each patient’s cells – a grafting process with no precedent in the pharmaceutical industry (Juno has related process) – is bringing to the Oncology arena a NOVEL treatment for hematological malignancies cancer patients
  4. I agree with Prof. Zelig Eshhar that the Barriers in the pharmaceutical industry are especially high. Developing ethical drugs is a process requiring huge amounts of time, patience, money, and failures. It is exactly, therefore, all need to acknowledge that the Drug Development process and the COMMERCIALIZATION GENIUS of Arie Belldegrun is inseparable from the breakthrough invention of Prof. Zelig Eshhar to develop the drug from the Lab bench to the FDA accelerated process of Drug approval.
  5. The Biotech industry in Israel needs to develop more MDs, PhDs with the level of training of Arie Belldegrun and with his entrepreneur acumen, keenness and depth of perception, discernmentdiscrimination especially in practical aspects of Translation Medicine, Clinical Research, Clinical Trial Design and abilities to engage in innovating the FDA processes.
  6. The Biotech industry in US needs to develop more MDs, PhDs with the level of training of Prof. Zelig Eshhar to carry the scientific gravitas and the creativity to become inventors of novel drugs.

ABOUT Drug Invention (Prof. Zelig Eshhar, Weitzman Institute, registered the patent)

Pioneers of Cancer Cell Therapy:  Turbocharging the Immune System to Battle Cancer Cells — Success in Hematological Cancers vs. Solid Tumors

Curator: Aviva Lev-Ari, PhD, RN

ABOUT Gilead’s $12 billion buy of Kite Pharma

FDA has approved the world’s first CAR-T therapy, Novartis for Kymriah (tisagenlecleucel) and Gilead’s $12 billion buy of Kite Pharma, no approved drug and Canakinumab for Lung Cancer (may be?)

Curator: Aviva Lev-Ari, PhD, RN

ABOUT  the Drug Development process and the COMMERCIALIZATION GENIUS of Arie Belldegrun – Interviewed by Globes

“Chemotherapy will become just a bad memory”

More energetic than ever, Arie Belldegrun talks to “Globes” about Kite Pharma’s remarkable journey and the future of cancer treatment.

http://www.globes.co.il/en/article-chemotherapy-will-become-just-a-bad-memory-1001206978

ABOUT the Perspective of Drug Invention (Prof. Zelig Eshhar, Weitzman Institute, registered the patent) following the Gilead’s $12 billion buy of Kite Pharma – Interviewed by Globes

Kite Pharma was a $12b missed opportunity for Israel – Interview with Professor Zelig Eshhar

Some Israeli media headlines depicted Kite as an Israeli exit. But it is a US company that does no business in Israel and has no employees here.

Professor Zelig Eshhar is the man who registered the patent on the cancer treatment drug developed by Kite Pharma, recently acquired by Gilead for $11.9 billion.

“Globes”: Do you believe that any party in Israel could have financed the product and brought it where it is today?

Eshhar: “On the one hand, yes. The level of investment in the product before it reached Nasdaq was something that an Israeli concern could certainly have financed. On the other hand, Kite Pharma founder Professor Arie Belldegrun, with his energy and connections, brought it to a completely different place (Eshhar previously tried to interest various concerns in Israel in financing the drug, but all of them told him that it was too early, or that the product was not effective enough, E.T.).

Was the development already in its final form in the 1980s?

“Almost. I went to the National Institutes of Health (NIH), where I met for the first time Professor Steven Rosenberg, who later became the first doctor to conduct clinical trials with the technology. Rosenberg heard about my technology, and offered me exceptional conditions. We set up a team there, and had the best of everything. I only wish I had it now.”

They say that Belldegrun didn’t want the product at first. Today, he’s devoting all his efforts to it.

“When Arie founded Cougar Biotechnology, which developed a drug for prostate cancer, and was eventually sold to Johnson & Johnson for $1 billion, I contacted him and offered him the technology, but he was busy with Cougar’s product, and maybe didn’t think that he had enough capital for such a production. Only after he sold Cougar did he get back to me with an offer to buy the rights to my patent. At that time (2009-2010), the technology was already arousing great interest, and there were negotiations with several large companies.” (from an April 2015 “Globes” interview with Eshhar, who was awarded the Israel Prize).

Israelis can be very provincial. In at least some of the media headlines, Kite Pharma was portrayed as a “huge Israeli exit,” and the impression was given that it was an Israeli company. The truth is very different. Kite Pharma is not an Israeli company; it is a 100% US company. It does no business in Israel; its nearly $12 billion exit has no significance whatsoever for the Israeli economy, and will contribute nothing to it: no jobs, and the tax contribution will be marginal, and certainly not on the scale of Mobileye, for example. Let me say it again: Kite Pharma does not have even one employee in Israel (and has no reason to employ anyone here), and certainly does not pay taxes in Israel. There are no Israelis on the company’s management team or board of directors. This is a US company for all intents and purposes. The word “Israel” appears exactly once in the company’s full documents – where registration of the company’s patents is concerned. The fact that every story about the company mentions the small holdings of several Israeli financial institutions in it is a bad joke. Everyone should remember that Israeli financial institutions are of course entitled to invest in any foreign share, such as Google, Amazon, Facebook, Apple Computers, and so forth. Kite Pharma is one of those foreign shares, and nothing more.

Of course, there is cause for pride in the fact that Eshhar, owner of the patent for Kite Pharma’s drug is “one of ours,” i.e. an Israeli researcher at the Weizmann Institute of Science. Another source of pride is Kite Pharma founder and CEO Arie Belldegrun, a graduate of the Hebrew University Medical School who did his post-doctorate at the Weizmann Institute, where he met Eshhar, and Kite Pharma later bought his patent for the cancer drug. Belldegrun was also a director at Teva Pharmaceutical Industries Ltd. (NYSE: TEVA; TASE: TEVA) until recently, resigning at the peak of that company’s crisis. Beyond this Israeli connection, however, the Kite Pharma exit has no great significance for Israel. All it means is that one more invention, or parts of an invention, came from an Israeli laboratory (at the Weizmann Institute in this case) and fell into foreign hands. It is another enormous missed opportunity in the field of biomedicine and ethical drugs.

It is necessary to realize that while Belldegrun is indeed a big biomedical brain with many achievements in the field, he is a brain that has left Israel, and we all have to ask ourselves why he left, why Kite Pharma is not an Israeli company, and why its (as yet non-existent) product was not developed in Israel and will not be manufactured there. The headline in Israel for the Kite Pharma exit should ask why Israel lost out on it, even though the patent came from Israeli laboratories, albeit with US cooperation.

Belldegrun is likely to keep his experiences on the Teva board of directors to himself. Of all the directors in the company, what he has to say is the most interesting, but he is unlikely to divulge what happened there with the inflated deal with Allergan, and exactly what he said at the board of directors meeting that approved the deal that led Teva into its current major crisis. The Kite Pharma exit and his other exits only highlight the lost opportunity. Kite Pharma, still without a product and without approval for a product, was sold for $11.9 billion in cash. Teva yesterday hit another low point, with a market cap of $16 billion. It is simply inconceivable: a company with an enormous potential, but no product, is worth three quarters of a huge veteran company with at least dozens of products, including products in the ethical drug sector. Kite Pharma is actually one of the indirect reasons for Teva’s decline – for the fact that Teva, which could have been a hothouse for developments like Copaxone, chose a huge inflated gamble on the generics market – a gamble that is now jeopardizing Teva’s future and very existence.

It is true that developing drugs is a very long process, requires huge amounts of capital, and involves many failures, but Teva decided to neglect it, and when a major company like Teva neglects Israeli developments, there are enough competitors in the pharma industry ready to turn Israeli research into gold. Kite Pharma is one example of this research.

The Weizmann Institute is a fruitful source of biomedical research. According to previous estimates published in “Globes,” the Weizmann Institute gets NIS 1 billion each year in royalties on medical and other developments, amounting to half of its budget. Directly and indirectly, the Weizmann Institute, together with other universities in Israel, is responsible for tens of billions of pharmaceutical sales. Only a few billions of this, however, results from drugs developed in Israel, like Copaxone, and far less than that is also made in Israel. The reports by Yeda R&D Company Ltd., the technology transfer arm of the Weizmann Institute of Science, are top secret, and there is a good reason for that. Exposing them will only highlight the scale of the missed opportunities. Instead of these inventions providing a base for a major pharmaceutical industry here, the commercialization companies are benefiting only the inventors and the Weizmann Institute itself (that is certainly natural and legitimate, and they are entitled to it), even though the research infrastructure from which they sprung is Israeli know-how, as in the case of Eshhar.

Barriers in the pharmaceutical industry are especially high. Developing ethical drugs is a process requiring huge amounts of time, patience, money, and failures. When it succeeds, however, the profit is enormous – for the industry, the employees, and the state (provided that some tax is paid). For example, Pfizer’s peak sales of Lipitor, a very popular drug for reducing cholesterol and fat in the bloodstream, reached $11 billion, and its profit on the drug was $9 billion, before competition from a generic version began. In addition to money, a great deal of experience and marketing power is required, and that is the reason why most developments wind up in the hands of major companies like Pfizer, Merck, and others at some stage. After all these qualifying statements, everyone who celebrated Kite Pharma’s exit should weep over it – it is another part of the sale of Israeli know-how overseas for a mess of pottage. Instead of consolidating a splendid pharma industry here, Israel is selling the brains with their know-how to foreigners. More than anything else, Teva’s decline and the Kite Pharma exit epitomize this sad and dangerous trend.

Published by Globes [online], Israel Business News – www.globes-online.com – on August 30, 2017

© Copyright of Globes Publisher Itonut (1983) Ltd. 2017

http://www.globes.co.il/en/article-kite-pharma-the-huge-exit-that-israel-missed-1001203173

ABOUT the Economic significance of Kite Pharma Acquisition for the Venture Capital Investment in Biotech in Israel

Israeli investors profit from $11.9b Kite acquisition

Pontifax fund and Israeli institutional investors will profit from the US personalized cancer drug company’s huge sale.  Part of the technology was developed at the Weizmann Institute

Pharmaceutical company Gilead Sciences Inc. has announced that it will acquire US company Kite Pharma Inc., developer of personalized cancer treatment drugs, at a company value of $11.9 billion. This is one of the biggest ever acquisitions of a company whose products have not yet been approved for marketing. The company value for the acquisition reflects a 29% premium on the market price.

Kite Pharma has developed a new method for genetically engineering immune system cells, so that they will make a focused attack on the malignant tumor. The company was founded in the US by Israeli-American Professor Arie Belldegrun, who already has two exits to his credit. He is also a former director at Teva Pharmaceutical Industries Ltd. (NYSE: TEVA; TASE: TEVA) (whose current value is not much more than the value at which Kite Pharma, a company with no products approved for marketing yet, is being acquired).

A significant part of the technology on which the product is based was developed by Professor Zelig Eshhar of the Weizmann Institute of Science.

The main Israeli beneficiary of the acquisition is the Pontifax fund, which invested $3.8 million in Kite Pharma at an early stage, but which distributed Kite Pharma shares worth $120 million to its investors. Among the investors in Pontifax that received shares in Kite Pharma are Menorah Mivtachim Holdings Ltd. (TASE: MORA) (which also bought shares on the market, and whose stake in the company is now worth over $100 million), The Phoenix Holdings Ltd. (TASE: PHOE1;PHOE5), Altshuler Shaham Ltd.Meitav Dash Investments Ltd. (TASE:MTDS), Harel Insurance Investments and Financial Services Ltd. (TASE: HARL), and Mori Arkin.

Kite Pharma is waiting for marketing approval of its first product, following a successful trial on 100 patients on a very abbreviated track for innovative cancer products. The product was initially designed for treatment of blood cancer, but it is now hoped that its use can later be expanded to treatment of other types of cancer. Gilead is making a big gamble, first of all that the US Food and Drug Administration (FDA) will fulfill its commitment to approve the product, even though the development plan it devised, together with the company, was very short and limited. The second gamble involves the process of treatment using the drug – personalized genetic engineering of each patient’s cells – a grafting process with no precedent in the pharmaceutical industry.

Speaking about the talks to sell Kite, Prof. Arie Belldegrun told “Globes.” “We handled like in the IDF 669 unit. Nobody knew anything. Nobody heard anything. We held meetings in places where nobody would see us. And before we announced it only five employees knew about it.”

Published by Globes [online], Israel Business News – www.globes-online.com – on August 28, 2017

© Copyright of Globes Publisher Itonut (1983) Ltd. 2017

http://www.globes.co.il/en/article-israeli-investors-profit-from-119b-kite-acquisition-1001202841

Other related articles published in this Open Access Online Scientific Journal include the following: 

Curators: Stephen J Williams, PhD and Aviva Lev-Ari, PhD, RN

  • Cancer Biology & Genomics for Disease Diagnosis, on Amazon since 8/11/2015

http://www.amazon.com/dp/B013RVYR2K

  • Cancer Therapies: Metabolic, Genomics, Interventional, Immunotherapy and Nanotechnology in Therapy Delivery (Series C Book 2) – on Amazon since 5/18/2017

http://www.amazon.com/dp/B071VQ6YYK

2017 Nobel Prize in Physiology or Medicine jointly to Jeffrey C. Hall (ex-Brandeis, University of Maine), Michael Rosbash (Brandeis University) and Michael W. Young (Rockefeller University in New York) for their discoveries of molecular mechanisms controlling the circadian rhythm

Curator: Aviva Lev-Ari, PhD, RN

Article ID #244: 2017 Nobel Prize in Physiology or Medicine jointly to Jeffrey C. Hall, Michael Rosbash and Michael W. Young for their discoveries of molecular mechanisms controlling the circadian rhythm. Published on 10/2/2017

WordCloud Image Produced by Adam Tubman

Press Release

2017-10-02

The Nobel Assembly at Karolinska Institutet has today decided to award

the 2017 Nobel Prize in Physiology or Medicine

jointly to

Jeffrey C. Hall, Michael Rosbash and Michael W. Young

for their discoveries of molecular mechanisms controlling the circadian rhythm

READ the Summary

https://www.nobelprize.org/nobel_prizes/medicine/laureates/2017/press.html

Jeffrey C. Hall was born 1945 in New York, USA. He received his doctoral degree in 1971 at the University of Washington in Seattle and was a postdoctoral fellow at the California Institute of Technology in Pasadena from 1971 to 1973. He joined the faculty at Brandeis University in Waltham in 1974. In 2002, he became associated with University of Maine.

Michael Rosbash was born in 1944 in Kansas City, USA. He received his doctoral degree in 1970 at the Massachusetts Institute of Technology in Cambridge. During the following three years, he was a postdoctoral fellow at the University of Edinburgh in Scotland. Since 1974, he has been on faculty at Brandeis University in Waltham, USA.

Michael W. Young was born in 1949 in Miami, USA. He received his doctoral degree at the University of Texas in Austin in 1975. Between 1975 and 1977, he was a postdoctoral fellow at Stanford University in Palo Alto. From 1978, he has been on faculty at the Rockefeller University in New York.

Key publications

Zehring, W.A., Wheeler, D.A., Reddy, P., Konopka, R.J., Kyriacou, C.P., Rosbash, M., and Hall, J.C. (1984). P-element transformation with period locus DNA restores rhythmicity to mutant, arrhythmic Drosophila melanogaster. Cell 39, 369–376.

Bargiello, T.A., Jackson, F.R., and Young, M.W. (1984). Restoration of circadian behavioural rhythms by gene transfer in Drosophila. Nature 312, 752–754.

Siwicki, K.K., Eastman, C., Petersen, G., Rosbash, M., and Hall, J.C. (1988). Antibodies to the period gene product of Drosophila reveal diverse tissue distribution and rhythmic changes in the visual system. Neuron 1, 141–150.

Hardin, P.E., Hall, J.C., and Rosbash, M. (1990). Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels. Nature 343, 536–540.

Liu, X., Zwiebel, L.J., Hinton, D., Benzer, S., Hall, J.C., and Rosbash, M. (1992). The period gene encodes a predominantly nuclear protein in adult Drosophila. J Neurosci 12, 2735–2744.

Vosshall, L.B., Price, J.L., Sehgal, A., Saez, L., and Young, M.W. (1994). Block in nuclear localization of period protein by a second clock mutation, timeless. Science 263, 1606–1609.

Price, J.L., Blau, J., Rothenfluh, A., Abodeely, M., Kloss, B., and Young, M.W. (1998). double-time is a novel Drosophila clock gene that regulates PERIOD protein accumulation. Cell 94, 83–95.

Keeping time on our human physiology

The biological clock is involved in many aspects of our complex physiology. We now know that all multicellular organisms, including humans, utilize a similar mechanism to control circadian rhythms. A large proportion of our genes are regulated by the biological clock and, consequently, a carefully calibrated circadian rhythm adapts our physiology to the different phases of the day (Figure 3). Since the seminal discoveries by the three laureates, circadian biology has developed into a vast and highly dynamic research field, with implications for our health and wellbeing.

The circadian clock

Figure 3. The circadian clock anticipates and adapts our physiology to the different phases of the day. Our biological clock helps to regulate sleep patterns, feeding behavior, hormone release, blood pressure, and body temperature.

SOURCE

https://www.nobelprize.org/nobel_prizes/medicine/laureates/2017/press.html

Medicine Nobel awarded for work on circadian clocks, Jeffrey Hall, Michael Rosbash and Michael Young unpicked molecular workings of cells’ daily rhythms.

Ewen CallawayHeidi Ledford

02 October 2017

https://www.nature.com/news/medicine-nobel-awarded-for-work-on-circadian-clocks-1.22736?WT.ec_id=NEWSDAILY-20171002

Other Related Research 

Charles Weitz, Ph.D., M.D.
Robert Henry Pfeiffer Professor of Neurobiology

Mammalian Circadian Clocks

Circadian clocks are molecular oscillators with ~24-hour periods that drive daily biological rhythms.  Such clocks are found in all of the major branches of life, and they likely represent ancient timekeeping systems important for predicting daily environmental cycles on our rotating planet.  In mammals, circadian clocks are present in most if not all cells. These distributed clocks control a myriad of processes, in aggregate creating coherent 24-hour programs of physiology and behavior.

A picture of how circadian clocks are built has emerged in the last two decades.  The core mechanism is a transcriptional feedback loop, wherein the protein products of several clock genes build the molecular machinery to inhibit the transcription factor responsible for their own production.  The molecular components of circadian clocks are conserved from insects to humans.

The Weitz lab uses molecular biology, biochemistry, genetics, and structural biology to investigate the mammalian circadian clock.  The focus of our efforts at present is to understand the circadian clock in terms of the integrated functions of its several multi-protein machines.  This effort is principally based on the purification of endogenous circadian clock protein complexes from mouse tissues and their biochemical analysis and structural study by cryo-electron microscopy.

Fig. 1.  Class-average electron microscopy images of the mouse nuclear PER complex, a core circadian clock machine.  It is a 1.9-MDa assembly of about thirty proteins that appears as a quasi-spherical, beaded particle of 40-nm diameter. Our current work provides an initial low-resolution view of the structural organization of endogenous clock machinery from a eukaryote.  We aim to obtain high-resolution structures.

Selected papers:

Duong HA, Robles MS, Knutti K, Weitz CJ.  A molecular mechanism for circadian clock negative feedback. Science  332, 1436-1439 (2011).

Padmanabhan K, Robles MS, Westerling T, Weitz CJ.  Feedback regulation of transcriptional termination by the mammalian circadian clock PERIOD complex. Science  337, 599-602 (2012).

Kim JY, Kwak PB, Weitz CJ. Specificity in circadian clock feedback from targeted reconstitution of the NuRD co-repressor.  Mol. Cell  56, 738-748 (2014).

Aryal RA, Kwak PB, Tamayo AG, Chiu PL, Walz T, Weitz CJ.  Macromolecular assemblies of the mammalian circadian clock.  Mol. Cell  (2017, in press).

SOURCE

http://neuro.hms.harvard.edu/people/faculty/charles-weitz

Circadian Clock’s Inner Gears

https://hms.harvard.edu/news/circadian-clock%E2%80%99s-inner-gears?utm_source=linkedin&utm_medium=social&utm_campaign=hms-linkedin-general

Other related articles Published in this Open Access Online Scientific Journal included the following: 

Search Keyword “Sleep” – 161 Scientific Articles

https://pharmaceuticalintelligence.com/?s=Sleep

Search Keyword “Circadian” Rhythm

Ultra-Pure Melatonin Product Helps Maintain Sleep for Up to 7 Hours

Curator: Gail S. Thornton, M.A.

Alteration in Reduced Glutathione level in Red Blood Cells: Role of Melatonin

Author: Shilpa Chakrabarti, PhD

Melatonin and its effect on acetylcholinesterase activity in erythrocytes

Author: S. Chakravarty, PhD

Day and Night Variation in Melatonin Level affects Plasma Membrane Redox System in Red Blood Cells

Author: Shilpa Chakravarty, PhD

Prolonged Wakefulness: Lack of Sufficient Duration of Sleep as a Risk Factor for Cardiovascular Diseases – – Indications for Cardiovascular Chrono-therapeutics

Curator: Aviva Lev-Ari, PhD, RN

Winners of 2017 Blavatnik National Awards for Young Scientists

Reporter: Aviva Lev-Ari, PhD, RN

 

presented by to Life Sciences Laureate

 

NEW YORK – June 27, 2017 – The Blavatnik Family Foundation and the New York Academy of Sciences today announced the 2017 Laureates of the Blavatnik National Awards for Young Scientists. Starting with a pool of 308 nominees – the most promising scientific researchers aged 42 years and younger nominated by America’s top academic and research institutions – a distinguished jury first narrowed their selections to 30 Finalists, and then to three outstanding Laureates, one each from the disciplines of Life Sciences, Chemistry and Physical Sciences & Engineering. Each Laureate will receive $250,000 – the largest unrestricted award of its kind for early career scientists and engineers. This year’s Blavatnik National Laureates are:

  • Feng Zhang, PhD, Core Member, Broad Institute of MIT and Harvard; Associate Professor of Brain and Cognitive Sciences and Biomedical Engineering, MIT; Robertson Investigator, New York Stem Cell Foundation; James and Patricia Poitras ’63 Professor in Neuroscience, McGovern Institute for Brain Research at MIT.Dr. Zhang is being recognized for his role in developing the CRISPR-Cas9 gene-editing system and demonstrating pioneering uses in mammalian cells, and for his development of revolutionary technologies in neuroscience.
  • Melanie S. Sanford, PhD, Moses Gomberg Distinguished University Professor and Arthur F. Thurnau Professor of Chemistry, University of Michigan. Dr. Sanford is being celebrated for developing simpler chemical approaches – with less environmental impact – to the synthesis of molecules that have applications ranging from carbon dioxide recycling to drug discovery.
  • Yi Cui, PhD, Professor of Materials Science and Engineering, Photon Science and Chemistry, Stanford University and SLAC National Accelerator Laboratory. Dr. Cui is being honored for his technological innovations in the use of nanomaterials for environmental protection and the development of sustainable energy sources.

“The work of these three brilliant Laureates demonstrates the exceptional science being performed at America’s premiere research institutions and the discoveries that will make the lives of future generations immeasurably better,” said Len Blavatnik, Founder and Chairman of Access Industries, head of the Blavatnik Family Foundation, and an Academy Board Governor.

“Each of our 2017 National Laureates is shifting paradigms in areas that profoundly affect the way we tackle the health of our population and our planet — improved ways to store energy, “greener” drug and fuel production, and novel tools to correct disease-causing genetic mutations,” said Ellis Rubinstein, President and CEO of the Academy and Chair of the Awards’ Scientific Advisory Council. “Recognition programs like the Blavatnik Awards provide incentives and resources for rising stars, and help them to continue their important work. We look forward to learning where their innovations and future discoveries will take us in the years ahead.”

The annual Blavatnik Awards, established in 2007 by the Blavatnik Family Foundation and administered by the New York Academy of Sciences, recognize exceptional young researchers who will drive the next generation of innovation by answering today’s most complex and intriguing scientific questions.

SOURCE

http://blavatnikawards.org/news/items/winners-2017-blavatnik-national-awards-young-scientists-include-pioneering-bioengineer-chemist-and-nanoscientist-will-receive-250000-prizes/

LIVE HubWeek – Harvard, MIT, MGH, Boston multiple locations, 10/10 – 10/15, 2017

Reporter: Aviva Lev-Ari, PhD, RN

 

I attended several events on THU, October 12, 2017

DEEP DIVE: The AI Revolution in Medicine

9AM — 11:30AM Faneuil Hall

Panelists:

Jayashree Kalpathy-Cramer, PhD, co-director of the Quantitative Tumor Imaging at Martinos (QTIM) Lab at the A.A. Martinos Center for Biomedical Imaging at MGH

Tina Kapur, PhD, executive director of Image Guided Therapy, Department of Radiology, BWH

Katherine P. Andriole, PhD, FSIIM, director of Research Strategy and Operations, MGH and BWH Center for Clinical Data Science

Dina Katabi, PhD, Andrew & Erna Viterbi Professor of EE and CS at MIT, director of MIT Center for Wireless Networks and Mobile Computing

10:30 – 11:00AM: Generating data and other AI challenges

Highlights

  • Dina Katabi, PhD – presented 21st Century technologies under development at MIT
  • Katherine P. Andriole, PhD described innovations in EMR

Voices of Oncology Discovery – Presented by HMS Executive Education

Red Dome, 1:30-3PM

  • Thomas Lynch Jr., MD, Executive VP, CSO, BMS
  • Alice Shaw, MD, PhD, Paula O’Keeffe Endowed Chair of Thoracis Oncology, MGH, Associate Professor of Medicine, HMS
  • Arlene Sharpe, PhD, George Fabyan Prof. of Comparative Pathology, Co-Director Evergrande Center for Immunologic Disease, HMS
  • Linnea Olson, Artist, blogger, advocate and long-term cancer survivor
  • Stanley Y Shaw, MD, PhD, Associate Dean for Executive Education, HMS

Highlights

  • Success reported with targeted therapies, biomarkers facilitate Clinical Trial design provide benefits for translation to approval of therapies
  • Biomarkers enable to achieve enriched population in Clinical Trials
  • Genomics vs Tissue Agnostics – FDA approved a drug based on genomics ALONE
  • FDA – has a new directive requiring feedback from Patients
  • KRAS Mutation – no targeted therapy in existance yet
  • Targeted therapies are available for: EDFR, PD-L!, PD-L2, ALK
  • Price of Durg and Value to Patients: Impact on Big Pharma
  • Combination drug therapy is KING
  • Data analytics, Urgency for response to drugs, clinical trials have accelerated path to approval if no alternative on the market

VOICE of the Cancer survival patient:

  1. Don’t give up
  2. Patient must have a seat at the Table
  3. Cancer as chronic disease while a search for cure continues

The Personalized Cell Therapy Challenge: A Race against Time

Green Dome, 4:00PM – 5PM

Udit Batra, Dr. Shashi Murthy, David Williams, Bruce Levine, Goeff Hodge

 

Healthy Brain, Enlightened Brain

Faneuil Hall, 5;30PM – 7PM

Deepak Chopra, MD and Dr. Rudy Tanzi, Reverend Liz Walker

Highlights

  • Importance of Sleep

Health Buzz: Why How Much You Sleep Could Affect Your Risk for Alzheimer’s Disease

  • Importance od De-Stress Methods
  • Nutrition and Microbiome
  • Early detection of AD – 20 years before onset of symptomes

Book signing:

MGH- Institute for Brain Health

Jonathan Rosand, MD
Dr. Jonathan Rosand is a Co-Director and Co-Founder of the Mass General Institute for Brain Health, Professor of Neurology at Harvard, the J. P. Kistler Chair in Neurology, and Neurologist at Massachusetts General Hospital where he is Chief of the Division of Neurocritical Care and Emergency Neurology. A clinician-scientist with expertise in prevention of cerebrovascular diseases and preservation of brain function following stroke and brain injury, he brings the most advanced techniques of personalized medicine to his practice. In his laboratory within the Mass General Center for Human Genetic Research, Dr. Rosand directs a world-class research program in genetics that continues to discover new genes that influence susceptibility to and recovery from stroke.

Rudolph Tanzi, PhD
Dr. Rudy Tanzi is a Co-Director and Co-Founder of the Mass General Institute for Brain Health, Professor of Neurology and holder of the Joseph P. and Rose F. Kennedy Endowed Chair in Neurology and Mental Retardation at Harvard University, Vice-Chair of Neurology (Research) at MGH and Co-Chair of the Mass General Research Council. He received his Ph.D. in Neurobiology from Harvard University. The four new AD candidates discovered by the Alzheimer’s Genome Project, headed by Tanzi, were named as one of the ten top medical breakthroughs of 2008 by Time magazine. He has received the two highest awards in the field of AD research: The Metropolitan Life Award for Biomedical Research and the Potamkin Prize. Dr. Tanzi has co-authored over 450 research publications, and in 2012, co-authored the New York Times Best Selling book, “Super Brain”.

 

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Designing Biology: New Paradigms for Collaboration
Oct 10, 2017, 10:30 AM – 12:15 PM
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Leveraging Sustainable Design to Achieve Social Equity

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Tuesday, October 10, 2017, 8:00 AM – 10:00 AM
The Organ Generation

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Tuesday, October 10, 2017, 8:30 AM – 10:00 AM
Creating Connected Communities with Design Thinking–Ideation

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Tuesday, October 10, 2017, 9:00 AM – 12:00 PM
Boston Landing Development Presentation Tuesday, October 10, 2017, 10:00 AM – 11:00 AM
Maximize Innovation with Universal Design Tuesday, October 10, 2017, 10:00 AM – 12:00 PM
Mobile @Scale Tuesday, October 10, 2017, 10:00 AM – 5:00 PM
Designing Biology: New Paradigms for Collaboration Tuesday, October 10, 2017, 10:30 AM – 12:15 PM
Fitness Class at Athlete’s Park Tuesday, October 10, 2017, 11:00 AM – 12:00 PM
Public Skate at the Warrior Ice Arena Tuesday, October 10, 2017, 12:00 PM – 3:00 PM
Women in Science Luncheon Tuesday, October 10, 2017, 12:00 PM – 2:00 PM
Programming the Future of AI: Ethics, Governance, and Justice

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Tuesday, October 10, 2017, 12:00 PM – 1:00 PM
Salesforce Growth Camp Tuesday, October 10, 2017, 12:00 PM – 6:00 PM
Presentation Skills & Public Speaking Workshop

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Tuesday, October 10, 2017, 12:45 PM – 2:15 PM
The Human Face of AI

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Tuesday, October 10, 2017, 12:45 PM
Giza 3D: Visualizing the Pyramids

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Tuesday, October 10, 2017, 1:00 PM – 2:00 PM
Ancient DNA: Mediterranean Pathogens and Mobility Tuesday, October 10, 2017, 2:00 PM – 5:00 PM
Building a Startup in Boston

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Tuesday, October 10, 2017, 2:30 PM – 3:15 PM
The Art of Storytelling

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Tuesday, October 10, 2017, 2:45 PM – 4:15 PM
Innovation at Boston Health Care for the Homeless Tuesday, October 10, 2017, 3:00 PM – 4:30 PM
Breaking Into Biotech

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Tuesday, October 10, 2017, 3:30 PM – 5:00 PM
How AI Makes Us More Human

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Tuesday, October 10, 2017, 4:00 PM – 5:00 PM
“Walk A Mile” Poverty Simulation Tuesday, October 10, 2017, 4:00 PM – 6:30 PM
How the Hub is Steering the Digital Health Revolution Tuesday, October 10, 2017, 4:30 PM – 7:00 PM
How To Connect With Anyone Tuesday, October 10, 2017, 4:45 PM – 6:15 PM
The Future of Robotics

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Tuesday, October 10, 2017, 5:00 PM – 6:00 PM
Aging & Caregiving Digital Health Reverse Pitches Tuesday, October 10, 2017, 5:00 PM – 8:00 PM
The Neuroscience Behind Consumer Decision-Making Tuesday, October 10, 2017, 5:00 PM – 6:00 PM
Reducing & Managing Stress: Walking the Labyrinth Tuesday, October 10, 2017, 5:30 PM – 6:30 PM
Diversity in Business: How to Bring Meaningful Change Tuesday, October 10, 2017, 5:30 PM – 7:30 PM
Innovation in the Regional Food System Tuesday, October 10, 2017, 6:00 PM – 8:00 PM
When the Best Idea Fails Tuesday, October 10, 2017, 6:00 PM – 7:30 PM
Activating Purpose in the Workplace Tuesday, October 10, 2017, 6:00 PM – 8:00 PM
Venture Café Kendall Connect Tuesday, October 10, 2017, 6:00 PM – 7:30 PM
Open House at The Engine Tuesday, October 10, 2017, 6:00 PM
HUBweek Roxbury Innovation Showcase Tuesday, October 10, 2017, 6:00 PM – 9:00 PM
Hiring & Reskilling for the Future Tuesday, October 10, 2017, 6:30 PM – 8:30 PM
Create, Engage & Change: Urbano Project Open Studio Tuesday, October 10, 2017, 6:30 PM – 9:30 PM
Are You Truly Connected? Tuesday, October 10, 2017, 6:30 PM – 9:00 PM
The Changing Boston Designscape Tuesday, October 10, 2017, 6:30 PM – 8:30 PM
How To Be A Successful Networker Tuesday, October 10, 2017, 6:45 PM – 8:15 PM
The Science of 3D Knitting Tuesday, October 10, 2017, 7:45 PM
Finding Heaven Under Our Feet Tuesday, October 10, 2017, 8:00 PM – 9:45 PM
Behind The Scenes Of Successful Entrepreneurs Wednesday, October 11, 2017, 8:00 AM – 10:00 AM
Tour: Design Biennial Boston Wednesday, October 11, 2017, 8:30 AM – 9:30 AM
Engineering + Entrepreneurship: Innovation in Healthcare Wednesday, October 11, 2017, 9:00 AM – 3:00 PM
The Silk Road: Taking Breakthroughs Global Wednesday, October 11, 2017, 9:00 AM
Cancer Disparities + Diversity in Life Sciences Wednesday, October 11, 2017, 10:00 AM – 11:00 AM
MIT Public Art and Architecture Tour (Morning)

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Wednesday, October 11, 2017, 10:00 AM – 11:00 AM
War on Cancer 3.0 Wednesday, October 11, 2017, 11:00 AM – 12:00 PM
Kendall Square: Innovation Playground Wednesday, October 11, 2017, 12:00 PM
How to Attract Global Entrepreneurs to Boston Wednesday, October 11, 2017, 12:00 PM – 1:00 PM
AAUW Work Smart in Boston Salary Negotiation Workshop I Wednesday, October 11, 2017, 12:00 PM – 2:00 PM
Free Yoga & Meditation Class Wednesday, October 11, 2017, 12:15 PM – 2:00 PM
Creating Connected Communities with Design Thinking–Rapid Prototyping Wednesday, October 11, 2017, 1:00 PM – 4:00 PM
Bully Boy Distillery Tour Wednesday, October 11, 2017, 1:30 PM – 3:30 PM
Art of Talking Science Competition: Rise of the Machines Wednesday, October 11, 2017, 2:00 PM – 4:00 PM
MIT Public Art and Architecture Tour (Afternoon)

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Wednesday, October 11, 2017, 2:00 PM – 3:00 PM
The Harvard Yard Archaeology Project Wednesday, October 11, 2017, 2:30 PM – 3:30 PM
Inside the Brigham: Innovation in Action Wednesday, October 11, 2017, 3:00 PM – 6:00 PM
Marine Science Boston Harbor Cruise

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Wednesday, October 11, 2017, 3:00 PM – 5:00 PM
5th Annual BUILD Entrepreneur Games Wednesday, October 11, 2017, 3:00 PM – 7:30 PM
Healthcare Redesign Collaborative Wednesday, October 11, 2017, 3:30 PM – 6:00 PM
Ramp-Up E-commerce Conversions Wednesday, October 11, 2017, 3:45 PM – 5:45 PM
Healthcare and the Experience Economy Wednesday, October 11, 2017, 4:00 PM – 6:30 PM
Harvard Innovation Labs Startup Showcase and Stories Wednesday, October 11, 2017, 4:00 PM – 6:00 PM
Green Innovation Industry Night Wednesday, October 11, 2017, 4:00 PM – 8:00 PM
Decoding the Dynaymic Cyber Threat Landscape Wednesday, October 11, 2017, 4:00 PM – 6:30 PM
IoT for Good: Connected, Inclusive, Smart Cities

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Wednesday, October 11, 2017, 4:30 PM – 6:30 PM
Rare Rights. Common Cause. Wednesday, October 11, 2017, 4:45 PM
Dell PolicyHack Wednesday, October 11, 2017, 5:00 PM – 9:00 PM
The Female Entrepreneur’s Experience in Boston Wednesday, October 11, 2017, 5:00 PM – 7:00 PM
Love the Problem Showcase! Innovation That Solves Wednesday, October 11, 2017, 5:30 PM – 7:30 PM
AAUW Work Smart in Boston Salary Negotiation Workshop II Wednesday, October 11, 2017, 5:30 PM – 7:30 PM
Fall Café Night: District Hall’s 4th Birthday Party Wednesday, October 11, 2017, 5:30 PM – 9:00 PM
Geometry As Public Art: The Immigrant Experience Wednesday, October 11, 2017, 5:30 PM – 6:30 PM
Artificial Intelligence (and More) in Healthcare Wednesday, October 11, 2017, 5:30 PM – 7:30 PM
Celebration of Student Entrepreneurship in Boston Wednesday, October 11, 2017, 6:00 PM – 8:00 PM
Two Lenses: Communicating Science Wednesday, October 11, 2017, 6:00 PM – 8:00 PM
Innovation, the New Foundation of Urban Living Wednesday, October 11, 2017, 6:00 PM – 7:30 PM
Twilight: Exploring the Unconscious Mind Wednesday, October 11, 2017, 6:00 PM – 7:30 PM
The City Talks: STEAM Wednesday, October 11, 2017, 6:00 PM – 7:00 PM
Fact/Fiction: Driving Truth into Policy Debates Wednesday, October 11, 2017, 6:00 PM – 7:30 PM
Civic Series presents: Breaking Through Gridlock Wednesday, October 11, 2017, 6:00 PM – 8:30 PM
Runnin’: A circle of friends. An American epidemic. Wednesday, October 11, 2017, 6:30 PM – 8:00 PM
GlobeDocs: Opening Night Film–Bending the Arc Wednesday, October 11, 2017, 7:00 PM – 9:00 PM
GlobeDocs: Opening Night Film–Bending the Arc + Reception Wednesday, October 11, 2017, 7:00 PM – 11:00 PM
Environmental Film Festival: Happening – A Clean Energy Revolution Wednesday, October 11, 2017, 7:00 PM – 9:00 PM
The City Talks: Art and Medicine Wednesday, October 11, 2017, 7:30 PM – 8:30 PM
Innovation Women Pop-up (Thursday) Thursday, October 12, 2017, 8:00 AM
Deep Dive: The A.I. Revolution in Medicine Thursday, October 12, 2017, 9:00 AM – 12:00 PM
What it Means to be Part of a Movement Thursday, October 12, 2017, 11:00 AM – 12:00 PM
Exploration Phase I (Thursday) Thursday, October 12, 2017, 12:00 PM – 1:00 PM
Swiss-Made: Fulldome Immersive I (Thursday) Thursday, October 12, 2017, 1:00 PM – 1:30 PM
Swiss-Made: Fulldome Immersive II (Thursday) Thursday, October 12, 2017, 1:30 PM – 2:00 PM
Made in USA: Fulldome Immersive I (Thursday) Thursday, October 12, 2017, 2:00 PM – 2:30 PM
Deep Dive: Voices of Oncology Thursday, October 12, 2017, 2:00 PM – 3:30 PM
Do We Trust Our Digital Economy? Thursday, October 12, 2017, 2:30 PM – 3:30 PM
Abstract Superconscious (Thursday) Thursday, October 12, 2017, 2:30 PM
SAT FEST 2017 (Thursday) Thursday, October 12, 2017, 3:00 PM – 3:45 PM
Uncharted Domain (Thursday) Thursday, October 12, 2017, 3:00 PM
Linked Threats: Climate Change and Social Inequality Thursday, October 12, 2017, 3:35 PM – 4:15 PM
Made in USA: Fulldome Immersive II (Thursday) Thursday, October 12, 2017, 3:45 PM – 4:45 PM
Social Justice and the New Food Activism Thursday, October 12, 2017, 4:00 PM – 5:30 PM
Investing in American Jobs Thursday, October 12, 2017, 4:15 PM – 5:00 PM
Fullscale Dome-ination (Thursday) Thursday, October 12, 2017, 4:30 PM – 5:00 PM
Future Forum: Thursday Night Session Thursday, October 12, 2017, 5:00 PM – 7:00 PM
Swiss-Made: Fulldome Immersive III (Thursday) Thursday, October 12, 2017, 5:00 PM – 5:30 PM
Swiss-Made: Fulldome Immersive IV (Thursday) Thursday, October 12, 2017, 5:30 PM – 6:00 PM
MIT IDE Inclusive Innovation Challenge Celebration Thursday, October 12, 2017, 6:00 PM – 7:30 PM
Immersion Artists Talk Series Thursday, October 12, 2017, 6:30 PM – 8:30 PM
LIVE Silent Disco Thursday, October 12, 2017, 7:00 PM – 10:00 PM
Exploration Phase II (Thursday) Thursday, October 12, 2017, 7:00 PM – 8:00 PM
Wasted! The Story of Food Waste Thursday, October 12, 2017, 7:00 PM – 9:00 PM
GlobeDocs: Unrest Thursday, October 12, 2017, 7:30 PM – 9:30 PM
Live: Disorder 3D–Digital Choreography (Thursday) Thursday, October 12, 2017, 8:00 PM – 8:30 PM
Live: Disorder 3D–Digital Choreography (Friday) Thursday, October 12, 2017, 8:45 PM – 9:15 PM
Live: Disorder 3D–Digital Choreography (Saturday) Thursday, October 12, 2017, 9:30 PM – 10:00 PM
Innovation Women Pop-up (Friday) Friday, October 13, 2017, 8:00 AM
Deep Dive: Climate Change Friday, October 13, 2017, 9:00 AM – 12:00 PM
Swiss-Made: Fulldome Immersive I (Friday) Friday, October 13, 2017, 9:00 AM – 9:30 AM
Disrupting Poaching Networks Before They Kill Friday, October 13, 2017, 9:15 AM – 10:00 AM
Swiss-Made: Fulldome Immersive II (Friday) Friday, October 13, 2017, 9:30 AM – 10:00 AM
Made in USA: Fulldome Immersive II (Friday) Friday, October 13, 2017, 10:00 AM – 10:45 AM
Around Us. On Us. Within Us. Friday, October 13, 2017, 10:30 AM – 11:15 AM
Abstract Superconscious (Friday) Friday, October 13, 2017, 10:45 AM
Housing the Workforce:Typology Technology & Tectonics Friday, October 13, 2017, 11:05 AM – 11:55 AM
Initiative: The Women Behind Digital Health Friday, October 13, 2017, 12:00 PM – 1:15 PM
Exploration Phase I (Friday) Friday, October 13, 2017, 12:00 PM – 1:00 PM
Deep Dive: Innovations in Opioid Treatment and Recovery Friday, October 13, 2017, 1:00 PM – 4:00 PM
Swiss-Made: Fulldome Immersive III (Friday) Friday, October 13, 2017, 1:00 PM – 1:30 PM
Swiss-Made: Fulldome Immersive IV (Friday) Friday, October 13, 2017, 1:30 PM – 2:00 PM
Made in USA: Fulldome Immersive I (Friday) Friday, October 13, 2017, 2:00 PM – 2:30 PM
Planetary Explorations (Friday) Friday, October 13, 2017, 2:30 PM – 3:00 PM
Leading for Creativity Friday, October 13, 2017, 3:50 PM – 4:30 PM
Stories Under the Stars (Friday) Friday, October 13, 2017, 4:00 PM
Friday Night Session: Saving As Many Lives As Penicillin

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Friday, October 13, 2017, 5:00 PM – 7:00 PM
The Swiss Touch: Exploring Digital Utopia Friday, October 13, 2017, 5:00 PM – 7:00 PM
Beantown Throwdown Friday, October 13, 2017, 5:30 PM – 8:00 PM
Askwith Forum – Changes in Mind Friday, October 13, 2017, 5:30 PM – 7:00 PM
Coffee & Chocolate: Climate Change, Sustainability, and Gender Equity Friday, October 13, 2017, 6:00 PM – 8:30 PM
The Room Where It Happens: On the Agency of Interior Spaces (Keynote) Friday, October 13, 2017, 6:00 PM – 7:30 PM
Environmental Film Festival: Chasing Coral Friday, October 13, 2017, 6:30 PM – 9:00 PM
Unchained Brain Friday, October 13, 2017, 6:30 PM – 7:45 PM
Exploration Phase II (Friday) Friday, October 13, 2017, 7:00 PM – 8:00 PM
GlobeDocs: Human Flow Friday, October 13, 2017, 7:30 PM – 9:30 PM
On Point Live Friday, October 13, 2017, 7:30 PM – 9:00 PM
The Cypher Friday, October 13, 2017, 8:00 PM – 10:30 PM
SAT FEST 2017 (Friday) Friday, October 13, 2017, 8:45 PM – 9:30 PM
Fullscale Dome-ination (Friday) Friday, October 13, 2017, 9:30 PM – 10:00 PM
Planetary Explorations (Friday Night) Friday, October 13, 2017, 10:00 PM – 10:30 PM
Cosmic Meditation (Saturday) Saturday, October 14, 2017, 8:15 AM
The Room Where It Happens: On the Agency of Interior Spaces (Symposium) Saturday, October 14, 2017, 9:00 AM – 5:00 PM
Made in USA: Fulldome Immersive II (Saturday) Saturday, October 14, 2017, 9:30 AM – 10:15 AM
De-Stress Boston Saturday, October 14, 2017, 10:00 AM – 12:00 PM
Demo Day: Showcase Floor Saturday, October 14, 2017, 10:00 AM
Demo Day: Intro to Startups and Entrepreneurship in Boston Saturday, October 14, 2017, 10:00 AM – 10:50 AM
Intergalactic Yoga (Saturday) Saturday, October 14, 2017, 10:15 AM
Demo Day: Growing a Startup in Boston: Challenges and Advantages Saturday, October 14, 2017, 11:00 AM – 11:50 AM
Uncharted Domain (Saturday) Saturday, October 14, 2017, 11:30 AM
Demo Day: How to be an Ally in the Workplace Saturday, October 14, 2017, 12:00 PM – 12:50 PM
Exploration Phase I (Saturday) Saturday, October 14, 2017, 12:00 PM – 1:00 PM
GlobeDocs: Circle Up/Lenox Street Saturday, October 14, 2017, 12:00 PM – 2:00 PM
Demo Day: Founders Talking About Failure Saturday, October 14, 2017, 1:00 PM – 1:50 PM
Swiss-Made: Fulldome Immersive I (Saturday) Saturday, October 14, 2017, 1:00 PM – 1:30 PM
Swiss-Made: Fulldome Immersive II (Saturday) Saturday, October 14, 2017, 1:30 PM – 2:00 PM
Abstract Superconscious (Saturday) Saturday, October 14, 2017, 2:00 PM
Demo Day: An Introduction to Funding Types Saturday, October 14, 2017, 2:00 PM – 2:50 PM
Swiss-Made: Fulldome Immersive III (Saturday) Saturday, October 14, 2017, 2:30 PM – 3:00 PM
GlobeDocs: Anatomy of a Male Ballet Dancer Saturday, October 14, 2017, 2:30 PM – 4:30 PM
Swiss-Made: Fulldome Immersive IV (Saturday) Saturday, October 14, 2017, 3:00 PM – 3:30 PM
Making a Live Storytelling Show for a Planetarium Saturday, October 14, 2017, 3:45 PM
Stories Under the Stars (Saturday) Saturday, October 14, 2017, 4:30 PM
GlobeDocs: Gladesmen – The Last of the Sawgrass Cowboys Saturday, October 14, 2017, 5:00 PM – 7:00 PM
Krip-Hop Nation: The Crossroads Experience Saturday, October 14, 2017, 5:00 PM – 6:00 PM
Made in USA: Fulldome Immersive I (Saturday) Saturday, October 14, 2017, 5:15 PM – 5:45 PM
SAT FEST 2017 (Saturday) Saturday, October 14, 2017, 5:45 PM – 6:30 PM
Demo Day: Finale Saturday, October 14, 2017, 6:00 PM – 8:00 PM
Fullscale Dome-ination (Saturday) Saturday, October 14, 2017, 6:30 PM – 7:00 PM
Exploration Phase II (Saturday) Saturday, October 14, 2017, 7:00 PM – 8:00 PM
WGBH: First Look: Bill Nye – Science Guy Saturday, October 14, 2017, 7:00 PM – 9:00 PM
GlobeDocs: Jaha’s Promise Saturday, October 14, 2017, 7:30 PM – 9:30 PM
Pico Picante Saturday, October 14, 2017, 8:00 PM – 10:30 PM
Modulate Live–Dance Party Saturday, October 14, 2017, 9:15 PM – 10:45 PM
Intergalactic Yoga (Sunday) Sunday, October 15, 2017, 9:00 AM
Stories Under the Stars (Sunday) Sunday, October 15, 2017, 10:15 AM
Cosmic Meditation (Sunday) Sunday, October 15, 2017, 10:45 AM
Robot Block Party Sunday, October 15, 2017, 11:00 AM
GlobeDocs: Shorts Program–Changing Perspective Sunday, October 15, 2017, 11:30 AM – 1:30 PM
Green Up New England Challenge Sunday, October 15, 2017, 11:45 AM – 12:45 PM
Exploration Phase I (Sunday) Sunday, October 15, 2017, 12:00 PM – 1:00 PM
Butterfly Effect: A Study in Prototyping, Art and Sustainability Sunday, October 15, 2017, 12:00 PM – 1:00 PM
Design Museum: Digitally-Enabled Creativity Sunday, October 15, 2017, 1:00 PM – 2:15 PM
Abstract Superconscious (Sunday) Sunday, October 15, 2017, 1:00 PM
A New Wave of Public Art in the Boston Area Sunday, October 15, 2017, 1:00 PM – 2:15 PM
Made in USA: Fulldome Immersive I (Sunday) Sunday, October 15, 2017, 1:30 PM – 2:00 PM
Planetary Explorations (Saturday) Sunday, October 15, 2017, 2:00 PM – 2:30 PM
GlobeDocs: Hondros Sunday, October 15, 2017, 2:00 PM – 4:00 PM
Designing for Climate Change Sunday, October 15, 2017, 2:20 PM – 3:00 PM
Fullscale Dome-ination (Sunday) Sunday, October 15, 2017, 2:30 PM – 3:00 PM
Creative Placemaking – A View on Tactical Urbanism Sunday, October 15, 2017, 3:30 PM – 4:30 PM
Swiss-Made: Fulldome Immersive III (Sunday) Sunday, October 15, 2017, 3:30 PM – 4:00 PM
GlobeDocs: Quest Sunday, October 15, 2017, 4:30 PM – 6:30 PM
GlobeDocs: I Am Evidence Sunday, October 15, 2017, 4:30 PM – 6:30 PM
GlobeDocs: Closing Night Film–A Fine Line Sunday, October 15, 2017, 7:00 PM – 9:00 PM
WGBH: First Look: Frontline: Putin’s Revenge Sunday, October 15, 2017, 7:00 PM – 9:00 PM
GlobeDocs: Closing Night Film–A Fine Line + Reception Sunday, October 15, 2017, 7:00 PM – 11:00 PM
Immersion Party 3-Pack