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Archive - 2020

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February 26th

Hong Kong Scientists Shed Light On COVID-19 Coronavirus (SARS-CoV-2) Vaccine Development

A team of scientists at the Hong Kong University of Science and Technology (HKUST) has recently made an important discovery in identifying a set of potential vaccine targets for the SARS-CoV-2 coronavirus, providing crucial leads for guiding experimental efforts towards the vaccine development against the novel pneumonia (COVID-19) caused by the virus. Like SARS-CoV, which caused the SARS (Severe Acute Respiratory Syndrome) outbreak in 2003, SARS-CoV-2 belongs to the same Betacoronavirus genus. By considering the genetic similarity between SARS-CoV-2 and SARS-CoV, the team leveraged experimentally-determined immunological data to identify a set of SARS-CoV- derived B cell and T cell epitopes that exactly match to SARS-CoV-2. Epitopes are biomarkers recognized by the immune system to trigger actions against the virus. As no mutation has been observed in the identified epitopes among the available SARS-CoV-2 genetic sequences, immune targeting of these epitopes may potentially offer protection against the novel pneumonia COVID-19. The team, led by data scientists Professor Matthew McKay and Dr. Ahmed Abdul Quadeer, expected that their work can assist in guiding experimental research towards the development of effective vaccines against SARS- CoV-2. Professor McKay highlighted that "Despite similarities between SARS-CoV and SARS-CoV-2, there is genetic variation between the two, and it is not obvious if epitopes that elicit an immune response against SARS-CoV will likely be effective against SARS-CoV-2. We found that only roughly 20% of the SARS-CoV epitopes map identically to SARS-CoV-2, and believe these are promising candidates." "For the identified T cell epitopes, we also performed a population coverage analysis and determined a set of epitopes that is estimated to provide broad coverage globally, as well as in China" said Dr.

February 24th

Artificial Intelligence Yields New Antibiotic (“Hlicin”), “Arguably One of the More Powerful Antibiotics That Has Been Discovered”

A deep-learning model identifies a powerful new drug that can kill many species of antibiotic-resistant bacteria. Using a machine-learning algorithm, MIT researchers have identified a powerful new antibiotic compound. In laboratory tests, the drug killed many of the world’s most problematic disease-causing bacteria, including some strains that are resistant to all known antibiotics. It also cleared infections in two different mouse models. The computer model, which can screen more than a hundred million chemical compounds in a matter of days, is designed to pick out potential antibiotics that kill bacteria using different mechanisms than those of existing drugs.“ We wanted to develop a platform that would allow us to harness the power of artificial intelligence to usher in a new age of antibiotic drug discovery,” says James Collins, PhD, the Termeer Professor of Medical Engineering and Science in MIT’s Institute for Medical Engineering and Science (IMES) and Department of Biological Engineering. “Our approach revealed this amazing molecule which is arguably one of the more powerful antibiotics that has been discovered.” In their new study, the researchers also identified several other promising antibiotic candidates, which they plan to test further. They believe the model could also be used to design new drugs, based on what it has learned about chemical structures that enable drugs to kill bacteria. “The machine learning model can explore, in silico, large chemical spaces that can be prohibitively expensive for traditional experimental approaches,” says Regina Barzilay, PhD, the Delta Electronics Professor of Electrical Engineering and Computer Science in MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL). Dr. Barzilay and Dr.

February 23rd

Model for X-Linked Adrenoleukodystrophy (X-ALD) Identified in C. elegans Worm

The IDIBELL Neurometabolic Diseases group, with international collaboration, has identified a model of chromosome X-linked adrenoleukodystrophy (x-ALD) in the earthworm C. elegans. X-ALD is a rare disorder of the nervous system with no treatment available. The model should permit the acceleration of research and a reduction in the price of that research, which is studying the mechanisms and the possible pharmacological targets for the neuronal alterations of this disease. The earliest results of studies with this organism point to glial cells as responsible for the neurological damage caused by the disease. X-ALD is a rare genetic disease in which long-chain fatty acids accumulate in the blood and the nervous tissue, and where the myelin in the neurons is damaged. People who suffer from X-ALD (1 in 14,700 newborns) may have, among other things, brain and mobility problems, as well as hormonal disorders. The cause is a deficiency in the ABCD1 gene, which encodes the adrenoleukodystrophy protein (ALDP), which transports long-chain fatty acids to peroxisomes. These organelles play a very important role in lipid degradation and their subsequent cell use. This work has identified and characterized the worm C. elegans as a model of the disease, this model is deficient for the human analog protein (homologous) ALDP. The research team, co-led by Dr. Aurora Pujol and Esther Dalfó, analyzed the consequences of this deficit on a cellular level and found that, as in human and in existing mouse models, exist an accumulation of long-chain fatty acids, changes in lipid metabolism, oxidative imbalances in the mitochondria, and neuronal disorders. The model will allow accelerating the study of this disease, for which there is currently no treatment.

February 17th

Novel Formulation Permits Use of Toxin from Rattlesnake Venom to Treat Chronic Pain

Crotoxin, extracted from the venom of the South American rattlesnake Crotalus durissus terrificus, has been studied for almost a century for its analgesic, anti-inflammatory, and antitumor activities and as an even more powerful muscle paralyzer than botulinum toxin. However, the toxicity of crotoxin limits its medicinal use. A new study, published online on November 20, 2019, by Brazilian researchers in the journal Toxins, shows that crotoxin's therapeutic effects can be enhanced and its toxicity reduced when it is encapsulated in nanostructured SBA-15 silica, a material originally developed for use in vaccine formulations. The open-access Toxins article is titled “Crotoxin Conjugated to SBA-15 Nanostructured Mesoporous Silica Induces Long-Last Analgesic Effect in the Neuropathic Pain Model in Mice. The study was conducted under the aegis of Brazil's National Science and Technology Institute (INCT) on Toxins, one of the INCTs supported by FAPESP (São Paulo Research Foundation) in São Paulo State in partnership with the National Council for Scientific and Technological Development (CNPq), an agency of the Brazilian government. The INCT's principal investigator is Osvaldo Augusto Sant'Anna, PhD. The study was part of the doctoral research of Morena Brazil Sant'Anna, whose thesis advisor is Gisele Picolo, PhD. Dr. Picolo herself was the principal investigator for a project on the same topic. Researchers Flavia Souza Ribeiro Lopes and Louise Faggionato Kimura participated in the study, which was performed at Butantan Institute in São Paulo. Dr.

HIF-2α Is Pivotal for Progression of Clear Cell Renal Cell Carcinomas (ccRCC) and Can Be Disabled by New Experimental Drug, PT2385

An experimental drug already shown to be safe and to help some patients with clear cell renal cell carcinoma (ccRCC), a deadly form of kidney cancer, effectively disables its molecular target. The finding from a team of researchers at the UT Southwestern Medical Center’s Kidney Cancer Program, was published in the February 14, 2020 issue of Clinical Cancer Research, reveals a weakness in this cancer that could be further exploited with other targeted treatments in the future. The article is titled “HIF-2 Complex Dissociation, Target Inhibition, and Acquired Resistance with PT2385, a First-in-Class HIF-2 Inhibitor, in Patients with Clear Cell Renal Cell Carcinoma.” Approximately 70,000 new cases of ccRCC are diagnosed every year in the U.S. The five-year life expectancy after diagnosis is low compared with other cancers, at about 10-12 percent. Unlike many other forms of cancer, ccRCC doesn’t respond to chemotherapy or conventional radiation. When study lead author James Brugarolas, MD, PhD, Professor of Internal Medicine (Hematology/Oncology) and Director of the Kidney Cancer Program at UT Southwestern, began his career two decades ago, only one medication was approved to treat this cancer. There are now over a dozen approved drugs for ccRCC; however, says Dr. Brugarolas, each offers only a modest effect on survival and comes with a host of side effects. Searching for better pharmaceuticals to fight this cancer, researchers at the Kidney Cancer Program focused on a protein known as hypoxia-inducible factor 2α (HIF-2α), which investigators at UTSW first discovered and described in the late 1990s. HIF-2α is a target of a tumor suppressor protein called von Hippel-Lindau (VHL) protein that’s characteristically inactivated in most cases of ccRCC.

February 16th

Precision Medicine World Conference (PMWC 2020) Ends Last of Three Full-Day Sessions on Friday, January 24, in California's Silicon Valley

Friday, January 24, was the third and last day of the Precision Medicine World Conference 2020 (PMWC 2020) in California’s Silicon Valley, with seven parallel tracks of talks focusing on different aspects of precision medicine. The tracks were Emerging Therapeutics; AI and Data Intelligence; Diagnostics in Clinical Practice; Molecular Profiling—From Research to Clinic; Health Data, Microbiome, and Patient Education; Showcase 1; and Showcase 2. The first five tracks consisted of leaders in the field discussing the latest advances, sometimes in individual presentations and sometimes in panel discussions. The two Showcase tracks gave new companies the opportunity to present their work in crisp 15-minute talks. This year’s PMWC, the 11th annual PMWC conference in Silicon Valley, and the 17th PMWC meeting overall, including smaller, more regional meetings, was the largest annual meeting ever, with over 2,300 attendees from around the world and over 400 presentations given over the full three days. The conference took place in the Santa Clara Convention Center in the heart of California’s Silicon Valley. The theme of this year’s conference was “How Do We Accelerate Precision Medicine and Deliver on Its Proses?” This year’s conference was co-hosted by UCSF, Stanford Health Care/Stanford Medicine, the University of Michigan, the University of Pittsburgh, and Duke Health. Sponsors of the conference included Illumina, Agendia, Bio-Rad, QIAGEN, RubAdaptive, Agilent, Caprion, GO, Google Cloud, Gritstone, Karius, Molecular Health, RubrYc, Oncocyte, Siemens Healthineers, Sophia, Thermo-Fisher Scientific, Quanterix, and Tabula Rasa HealthCare. Neary 100 companies were exhibitors at the meeting.

Precision Medicine World Conference (PMWC 2020) Continues on Second Day of Three Full-Day Sessions on Thursday, January 23, in California's Silicon Valley

Thursday, January 23, was the second full day of the Precision Medicine World Conference 2020 (PMWC 2020) in California’s Silicon Valley, and consisted of seven parallel tracks of talks focusing on different aspects of precision medicine. The tracks were Emerging Therapeutics; AI and Data Intelligence; Diagnostics in Clinical Practice; Molecular Profiling—From Research to Clinic; Health Data, Microbiome, and Patient Education; Showcase 1; and Showcase 2. The first five tracks consisted of leaders in the field discussing the latest advances, sometimes in individual presentations and sometimes in panel discussions. The two Showcase tracks gave new companies the opportunity to present their work in crisp 15-minute talks. This year’s PMWC, the 11th annual PMWC conference in Silicon Valley, and the 17th PMWC meeting overall, including smaller, more regional meetings, was the largest annual meeting ever, with over 2,300 attendees from around the world and over 400 presentations given over the full three days. The meeting took place in the Santa Clara Convention Center in the heart of California’s Silicon Valley. The theme of this year’s conference was “How Do We Accelerate Precision Medicine and Deliver on Its Promises?” This year’s conference was co-hosted by UCSF, Stanford Health Care/Stanford Medicine, the University of Michigan, the University of Pittsburgh, and Duke Health. Sponsors of the conference included Illumina, Agendia, Bio-Rad, QIAGEN, RubAdaptive, Agilent, Caprion, GO, Google Cloud, Gritstone, Karius, Molecular Health, RubrYc, Oncocyte, Siemens Healthineers, Sophia, Thermo-Fisher Scientific, Quanterix, and Tabula Rasa HealthCare. Nearly 100 companies were exhibitors at the meeting.

February 15th

Precision Medicine World Conference (PMWC 2020) Opened First of Three Full-Day Sessions on Wednesday, January 22, in California’s Silicon Valley

On Wednesday, January 22, the full meeting of the Precision Medicine World Conference 2020 (PMWC 2020) opened in California’s Silicon Valley, with seven parallel tracks of talks focusing on different aspects of precision medicine (https://www.pmwcintl.com/). The tracks were Emerging Therapeutics; AI and Data Intelligence; Diagnostics in Clinical Practice; Molecular Profiling—From Research to Clinic; Health Data, Microbiome, and Patient Education; Showcase 1; and Showcase 2. The first five tracks consisted of leaders in the field discussing the latest advances, sometimes in individual presentations and sometimes in panel discussions. The two Showcase tracks gave new companies the opportunity to present their work in crisp 15-minute talks. This year’s PMWC, the 11th annual PMWC conference in Silicon Valley, and the 17th PMWC meeting overall, including small, more regional meetings, was the largest annual meeting ever, with over 2,300 attendees from around the world and over 400 presentations given over the full three days. The meeting took place in the Santa Clara Convention Center in the heart of California’s Silicon Valley. The theme of this year’s conference was “How Do We Accelerate Precision Medicine and Deliver on Its Promises?” This year’s conference was co-hosted by UCSF, Stanford Health Care/Stanford Medicine, the University of Michigan, the University of Pittsburgh, and Duke Health. Sponsors of the conference included Illumina, Agendia, Bio-Rad, QIAGEN, RubAdaptive, Agilent, Caprion, GO, Google Cloud, Gritstone, Karius, Molecular Health, RubrYc, Oncocyte, Siemens Healthineers, Sophia, Thermo-Fisher Scientific, Quanterix, and Tabula Rasa HealthCare. Nearly 100 companies were exhibitors at the meeting.

February 8th

Combination of Cryo-EM and Mass Spec Reveals New Insights into Post-Translational Modifications (PTMs) of Tau Protein; PTMs Mediate Structural Diversity of Toxic Tau Protein in Various Tauopathies Such As Alzheimer’s Disease

The tau protein has long been implicated in Alzheimer's disease and a host of other debilitating brain diseases. But scientists have struggled to understand exactly how tau converts from its normal, functional form into a misfolded, harmful one. Now, researchers at Columbia University's Zuckerman Institute and the Mayo Clinic in Florida, together with colleagues at Emory University and Arizona State University, have used cutting-edge technologies to see tau in unprecedented detail. By analyzing brain tissue from patients, this research team has revealed that modifications to the tau protein may influence the different ways it can misfold in a person's brain cells. These differences are closely linked to the type of neurodegenerative disease that will develop -- and how quickly that disease will spread throughout the brain. The study, published online on February 6, 2020 in Cell, employed two complementary techniques to map the structure of tau and decipher the effects of additional molecules, called post-translational modifications (PTMs), on its surface. These new structural insights could accelerate the fight against neurodegenerative diseases, by helping researchers identify new biomarkers that detect these disorders before symptoms arise and design new drugs that target specific PTMs, preventing the onset of disease before it wreaks havoc on the brain. The Cell article is titled “"Posttranslational Modifications Mediate the Structural Diversity of Tauopathy Strains." "Tau has long been a protein of significant interest due to its prevalence in disease," said Anthony Fitzpatrick, PhD, a Principal Investigator at Columbia's Mortimer B. Zuckerman Mind Brain Behavior Institute, who led the study.

February 6th

Mayo Researchers Discover Way to Prime Cancer Tumors for Immunotherapy

A cancer tumor's ability to mutate allows it to escape from chemotherapy and other attempts to kill it. So, encouraging mutations would not seem to be a logical path for cancer researchers. Yet a Mayo Clinic team and their collaborators took that counterintuitive approach and discovered that, while it created resistance to chemotherapy, it also made tumors sensitive to immunotherapy. They also found that this approach worked successfully across tumor types and individual patient genomes. Their findings, involving mouse models and human cells, were published online on February 7, 2020 in Nature Communications. The open-access article is titled “APOBEC3B-Mediated Corruption of the Tumor Cell Immunopeptidome Induces Heteroclitic Neoepitopes for Cancer Immunotherapy.” The international team of researchers based in Rochester, Minnesota and London, and led by Richard Vile (photo), PhD, a Mayo Clinic Professor of Pediatric Oncology, studied models of both pediatric brain tumors and melanoma. They found that, in mice, high levels of the protein APOBEC3B drove a high rate of tumor mutations. Yet, at the same time, these levels of APOBEC3B also sensitized cells to treatment with immune checkpoint blockade, a major mechanism of immunotherapy. "When you put that in the context of vaccine therapy, the mutations generate neoepitopes, a type of peptide that is a prime target for killer T cells," says Dr. Vile. "So that, combined with the checkpoint blockade, make for a potential cross-tumor therapy." The results showed a high rate of cures in subcutaneous melanoma and brain tumor models, and effectiveness no matter the tumor type or location. The results also showed that an individualized approach for each patient is not required.