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Archive - 2020

November 8th

Vaccine Candidate Against COVID-19 Achieves Greater Than 90% Effectiveness in First Interim Analysis from Ongoing Phase 3 Study, Pfizer and BioNTech Announce; "Great Day for Science & Humanity," Pfizer CEO States

On November 9, 2020, Pfizer Inc. (NYSE: PFE) and BioNTech SE (Nasdaq: BNTX) announced that their mRNA-based vaccine candidate, BNT162b2, against SARS-CoV-2 has demonstrated evidence of efficacy against COVID-19 in participants without prior evidence of SARS-CoV-2 infection, based on the first interim efficacy analysis conducted on November 8, 2020 by an external, independent Data Monitoring Committee (DMC) from the Phase 3 clinical study. After discussion with the FDA, the companies recently elected to drop the 32-case interim analysis and conduct the first interim analysis at a minimum of 62 cases. Upon the conclusion of those discussions, the evaluable case count reached 94 and the DMC performed its first analysis on all cases. The case split between vaccinated individuals and those who received the placebo indicates a vaccine efficacy rate above 90%, at 7 days after the second dose. This means that protection is achieved 28 days after the initiation of the vaccination, which consists of a 2-dose schedule. As the study continues, the final vaccine efficacy percentage may vary. The DMC has not reported any serious safety concerns and recommends that the study continue to collect additional safety and efficacy data as planned. The data will be discussed with regulatory authorities worldwide. “Today is a great day for science and humanity. The first set of results from our Phase 3 COVID-19 vaccine trial provides the initial evidence of our vaccine’s ability to prevent COVID-19,” said Albert Bourla, PhD, Chairman and CEO of Pfizer. “We are reaching this critical milestone in our vaccine development program at a time when the world needs it most with infection rates setting new records, hospitals nearing over-capacity, and economies struggling to reopen.

November 8th

Bacterial Origins of Trench Fever in Humans Traced Back Centuries by Real-Time PCR-Based DNA Analysis of Ancient Remains; Remnants of Infections Demonstrated in Civilians As Well As Soldiers

First observed among British Expeditionary Forces in 1915, trench fever sickened an estimated 500,000 soldiers during World War I. Since then, the disease has become synonymous with the battlefield. But now, new research from an international team of scientists has uncovered evidence challenging this long-held belief. The research, published online on November 4, 2020 in PLOS ONE, outlines the discovery of DNA evidence of the disease in civilian remains predating WWI by thousands of years. In total, the team analyzed bone fragments and teeth of 145 individuals alive between the 1st and 19th centuries. Approximately 20% of those remains contained traces of Bartonella quintana, the bacteria responsible for trench fever. Davide Tanasi, PhD, an Associate Professor with the University of South Florida (USF) History Department and member of the Institute for the Advanced Study of Culture and the Environment, excavated remains for this project from a Roman cemetery in Syracuse, Sicily. Dr. Tanasi, who is also the Director of USF's Institute for Digital Exploration, first began work at the site to better understand the dietary habits and health of the Christian population living there during the 3rd and 4th centuries. Through a collaboration with French epidemiologists, researchers used real-time polymerase chain reaction (PCR) testing to detect B. quintana DNA within the remains.
"Once contracted, there are diseases, like trench fever, that can leave traces within your DNA and can integrate your DNA with further information," Dr. Tanasi said. "This means that once a person dies, even as far back as 2,000 years ago, it is still possible to find traces of the bacterium that infected them."

November 7th

Hyperacylation of Key Enzymes in Pathways Known to Be Dysregulated In MMA (Methylmalonic Acidemia) Likely Contributes to Altered Metabolism and Identifies New Set of Targets for Therapeutic Intervention

On Day 3 (Thursday, October 29) of the American Society of Human Genetics (ASHG) 2020 Virtual Annual Meeting (, one of the multiple stimulating morning sessions was “From Genes to Therapeutic Targets and Clinical Trials” (#031). Among the six presentations given during this session was a particularly interesting one titled “Aberrant Post-Translational Modifications Contribute to MMA Pathophysiology and Identify New Targets for Therapy,” delivered by PamelaSara Head (photo), PhD, Prat Fellow, National Institute of General Medical Sciences, NIH. In the abstract for her talk, Dr. Head noted that organic acidemias (OAs), such as methylmalonic acidemia (MMA), are a group of inborn errors of metabolism that typically arise from defects in the catabolism of amino- and fatty acids. She said that OAs are difficult to treat and have multisystemic manifestations such as hyperammonemia and ketotic hyperglycinemia (KH), leading to increased morbidity and mortality. Build-up of acyl-CoA species is postulated to cause intracellular toxicity. In the work reported here, Dr. Head and colleagues explored an alternative pathophysiological consequence of impaired acyl-CoA metabolism: i.e., the accumulation of aberrant post-translational modifications (PTMs) that modify enzymes in critical intracellular pathways. Using a mouse model that recapitulates the hepatic mitochondriopathy of MMA, the group surveyed PTMs in hepatic extracts with propionyl- and malonyl-lysine antibodies. The team discovered widespread hyper-acylation in the MMA mice compared to controls, but not in animals with Acsf3 deficiency, a disorder of acyl-CoA synthesis.

Dramatic Clinical Improvement Described in Rare Skin Disease (ILVEN) That Has Previously Proved Highly Treatment-Resistant; Treatment Choice Guided by Molecular Genetic Dissection of Disease in Two Patients That Revealed Mosaic Mutations in CARD14 Gene

On Day 3 (Thursday, October 29) of the American Society of Human Genetics (ASHG) 2020 Virtual Annual Meeting (, one of the multiple stimulating morning sessions was “From Genes to Therapeutic Targets and Clinical Trials” (#031). Among the six presentations given during this session was a particularly interesting one titled “Molecular Genetic Dissection of Inflammatory Linear Verrucous Epidermal Naevus Leads to Successful Targeted Therapy,” delivered by Melissa Riachi (photo), PhD, Post-Doctoral Research Associate, Francis Crick Institute (UK). In the abstract to her talk, Dr. Riachi noted that inflammatory linear verrucous epidermal naevus (ILVEN) is a rare childhood disease characterized by Blaschko-linear erythematous scaly skin. The disease is highly pruritic, causes distressing disfigurement, and is so notoriously treatment-resistant that this characteristic forms part of the diagnostic criteria. The cause has been unknown, other than a recent single case of GJA1 mosaicism [Editor’s Note: GJA1 is the abbreviation for gap junction protein alpha 1.] Using deep next-generation whole exome sequencing of affected skin and blood, Dr. Riachi’s group discovered mosaic mutations in the gene CARD14 as the cause of ILVEN in two patients with treatment-resistant disease. [Editor’s Note: CARD14 is the acronym for caspase recruitment domain family member 14.] Functional characterization of patient cultured keratinocytes demonstrated two increased interleukins (IL-12A and IL-23A) at expression and protein levels in a non-NF-kB-dependent manner. Dramatic clinical improvement was seen with IL12/IL23-inhibitor ustekinumab, chosen as a direct result of the genetic finding.

Inhibition of HDL-Related Protein Improves Survival in Sepsis—Results Presented at American Society of Human Genetics (ASHG) 2020 Virtual Annual Meeting (October 27-30)

On Day 3 (Thursday, October 29) of the American Society of Human Genetics (ASHG) 2020 Virtual Annual Meeting (, one of the multiple stimulating morning sessions was “From Genes to Therapeutic Targets and Clinical Trials” (#031) (!/9070/presentation/1474). Among the six presentations given during this session was a particularly interesting one titled “Genetic and Pharmacological Inhibition of Cholesteryl Ester Transfer Protein Improves Survival in Sepsis,” delivered by Mark Trinder (photo), MD/PhD Candidate and Vanier Scholar at the University of British Columbia, University of British Columbia. In the abstract to his talk, Trinder noted that sepsis is a dysregulated host response to infection that is responsible for up to 1 of 5 deaths globally. He said that numerous clinical trials have failed to identify drugs that improve outcomes from sepsis, suggesting the need for therapies that target pathways causal to the pathogenesis of the condition. Along these lines, he noted that high-density lipoprotein (HDL) particles, although best-known for their inverse association with coronary artery disease, possess many properties that are relevant to sepsis. The quantity of HDL, as reflected by the concentration of HDL cholesterol (HDL-C), declines drastically during severe infections such as sepsis and greater decline of HDL-C is associated with worse clinical outcomes. In the work described at the ASHG meeting, Trinder and colleagues tested the hypothesis that genetic or pharmacologic inhibition of cholesteryl ester transfer protein (CETP), which facilitates the metabolism of HDL-C, would decrease mortality from sepsis in humans and mice.

November 6th

MSC-Derived Exosomes and Exosome-Educated Macrophages Can Differentially Improve Ligament Healing

Each year, ligament injuries sideline thousands of athletes and regular citizens. Recovery is long and painful, and sometimes a return to full function is never realized due to scar formation--a factor that makes ligament injuries prone to further damage. A new, exosome-based study published on Tuesday (November 3, 2020) in Stem Cells may lead to a welcome solution in the future. The open-access article is titled “Exosome‐Educated Macrophages and Exosomes Differentially Improve Ligament Healing.” (See image at left and, in larger view, at bottom). This study demonstrates how certain exosomes and exosome-educated macrophages can each promote ligament healing and reduce scarring. Exosomes are tiny sub-cellular membrane-bounded sacs that are released by all cells studied thus far and that can shuttle proteins and genetic information between cells. Macrophages are a type of white blood cell that typically kills microorganisms and removes dead cells, but can also stimulate the action of other immune system cells. “Educated macrophages” (EEMs) are macrophages that have been “educated” by interaction with information-conveying exosomes—in this case, mesenchymal stromal cell (MSC)-derived exosomes. Last year, the team behind the current study, researchers at the University of Wisconsin-Madison (UW-Madison), released another study (also published as an open-access article in Stem Cells) ( that showed how treating an Achilles tendon with EEMs reduces inflammation and improves tendon strength. The EEMs were generated by exposing CD14+ macrophages to MSC-derived exosomes. "Our previous study was done on a mouse model," said Ray Vanderby, PhD, Professor of Orthopedics and Rehabilitation at UW-Madison.

November 5th

35-Year Mystery of Retrons Solved—Unusual Molecules Combining RNA and DNA Strands Are Part of Bacterial Defense Mechanism Against Phage; Similarities Noted to “Guard” Mechanism Used by Plants

Peculiar hybrid structures called retrons (image at left; see graphic summary at end) that are half RNA, half single-strand DNA are found in many species of bacteria. Since their discovery around 35 years ago, researchers have learned how to use retrons for producing single strands of DNA in the lab, but no one knew what their function was in the bacteria, despite much research into the matter. In a paper published online on November 5, 2020 in Cell, a Weizmann Institute of Science (Israel) team reports on solving the long-standing mystery. The article is titled “Bacterial Retrons Function in Anti-Phage Defense.” Retrons are immune system "guards" that ensure the survival of the bacterial colony when it is infected by viruses. In addition to uncovering a new strategy used by bacteria to protect themselves against viral infection--one that is surprisingly similar to that employed by plant immune systems--the research revealed many new retrons that may, in the future, add to the genome-editing toolkit. The study, conducted in the Microbial Genomics lab ( of Weizman Professor Rotem Sorek of the Institute's Molecular Genetics Department, was led by Adi Millman, Dr. Aude Bernheim, and Avigail Stokar-Avihail in Professor Sorek’s lab. Professor Sorek and his team did not set out to solve the retron mystery; they were seeking new elements of the bacterial immune system, specifically elements that help bacteria to fend off viral infection. Their search was made easier by their recent finding that bacteria's immune system genes tend to cluster together in the genome within so-called “defense islands.” When the researchers uncovered the unique signature of a retron within a bacterial defense island, the team decided to investigate further.

Researchers Develop Phenome-Risk Classification Machine Learning Algorithm to Identify Patients Who Are at High Risk for Developmental Stuttering; Results Presented at ASHG 2020 Virtual Annual Meeting (October 27-30)

On Day 3 (Thursday, October 29) of the American Society of Human Genetics (ASHG) 2020 Virtual Annual Meeting (, one of the most interesting presentations was on the subject of developmental stuttering. Douglas M. Shaw (a graduate student in the Vanderbilt Genetics institute, Vanderbilt University) gave talk entitled “Applying a Phenome Risk Classifying Model to Identify Undiagnosed Developmental Stuttering Cases in a Biobank for Genome Wide Association Analysis.” In the abstract to his talk, Shaw described “developmental stuttering” as a speech disorder characterized by a disturbance in fluency and speech pattern, with an adult prevalence of 1-3% in the US. Despite twin-based studies showing ~50% heritability, the genetic etiology of stuttering is still largely unknown. No population-based genome wide association analysis (GWAS) has yielded variants that reach genome-wide significance, Shaw and colleagues wrote. Shaw noted that within Vanderbilt’s Electronic Health Record-linked biorepository (BioVU), only 142 cases of stuttering have diagnostic ICD9/10 (ICD9-307.0, ICD10-F98.5, ICD9-315.35, ICD10-F80.81, ICD10-R47.82) codes out of 92,762 genotyped samples, suggesting a large portion of people who stutter are not well-captured within the EHR. To address this case acquisition issue and provide a large enough sample set to power a GWAS, Shaw and colleagues developed a phenome-risk classification machine learning algorithm to identify patients who are at high risk for developmental stuttering.

November 3rd

Study Uncovers Subset of COVID-19 Patients Who Recover Quickly and Sustain Antibodies; Results Published in Cell

One of the pressing questions about COVID-19 remains: How long does immunity last? One key indicator of immunity is the presence of virus-specific antibodies. Previous studies have provided conflicting accounts about whether people who have recovered from infection can sustain potentially-protective antibodies or not. A new study led by investigators from Brigham and Women's Hospital in Boston examined blood samples and cells from patients who had recovered from mild to moderate COVID-19 and found that while antibodies against the virus declined in most individuals after disease resolution, a subset of patients sustained anti-virus antibody production several months following infection. These antibody "sustainers" had a shorter course of symptoms, suggesting that some individuals who recover from COVID-19 faster may be mounting a more effective and durable immune response to the virus. Results are published in Cell. The article is titled "Quick COVID-19 Healers Sustain Anti-SARS-CoV-2 Antibody Production.” "We've found a subset of individuals that heal quickly while sustaining virus-specific antibody levels after COVID-19," said Duane Wesemann, MD, PhD, an Immunologist and Associate Physician in the Brigham Division of Allergy and Clinical Immunology and an Associate Professor at Harvard Medical School. "The kind of immune response we're seeing in these individuals is a bit like investing in an insurance policy--it's the immune system's way of adding a potential layer of protection against future encounters with the virus." The Wesemann lab studies the entire set of antibodies a host's immune system produces and how these antibodies learn to recognize pathogens. In the spring of 2020, the team turned its attention to the COVID-19 pandemic and the immune response of people who become infected.

National Human Genome Research Institute (NHGRI) Publishes New Vision for Human Genomics--NHGRI's 2020 Strategic Vision Describes Opportunities in Human Genomics for Improving Human Health—Vision Published in Nature

On October 28, 2020, The National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH¬) published its “Strategic Vision for Improving Human Health at the Forefront of Genomics” ( online in the journal Nature. This vision describes the most compelling research priorities and opportunities in human genomics for the coming decade, signaling a new era in genomics for the Institute and the field. “We crafted our new strategic vision at an important inflection point in human genomics," said Eric Green, MD, PhD, NHGRI Director. "Genomics is now prevalent across the research landscape, and so NHGRI focused its strategic attention on the most cutting-edge aspects of the field. Our criteria for inclusion was that future advances must be widely beneficial and have the greatest impact on understanding genome biology and facilitating the implementation of genomic medicine." Genomics is now prevalent across the research landscape, and so NHGRI focused its strategic attention on the most cutting-edge aspects