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June 20th, 2020

AACR Recognizes Cigall Kadoch with 2020 Award for Outstanding Achievement in Basic Cancer Research for Pioneering Characterization of Normal & Aberrant SWI/SNF Chromatin Remodeling Complexes; Disruption Contributes to 20% of All Cancers

On June 17, 2020, the American Association for Cancer Research (AACR) announced that it is honoring Cigall Kadoch, PhD, with the 2020 AACR Award for Outstanding Achievement in Basic Cancer Research. Dr. Kadoch (https://www.dfhcc.harvard.edu/insider/member-detail/member/cigall-kadoch...) is Assistant Professor of Pediatric Oncology at Dana-Farber Cancer Institute, Assistant Professor Of Pediatrics at Harvard Medical School, and an Institute Member at the Broad Institute of MIT and Harvard. She is being recognized for her pioneering biochemical and functional characterization of normal and aberrant SWI/SNF chromatin remodeling complexes and her elucidation of the mechanisms by which the disruption of these complexes contributes to over one-fifth of human cancers. The AACR Award for Outstanding Achievement in Basic Cancer Research was established by the AACR to recognize an early-career investigator for meritorious achievements in basic cancer research. The award is intended to recognize an individual who has not yet reached 46 years of age at the time of his/her award presentation. Dr. Kadoch is world-renowned for her seminal work involving the biology of ATP-dependent chromatin remodeling complexes, which are groups of proteins that influence how DNA is packaged, thereby controlling when and how strongly genes are expressed. In a landmark study (https://advances.sciencemag.org/content/1/5/e1500447) early in her career, Dr. Kadoch discovered that more than 20 percent of all cancers have mutations in genes encoding proteins that are part of mammalian SWI/SNF chromatin remodeling complexes.

June 20th

AACR Honors Jedd D. Wolchok, MD, PhD, with 2020 Award for Outstanding Achievement in Clinical Cancer Research; Sloan-Kettering Scientist/Physician Recognized for Leadership in Ground-Breaking Clinical Development of CTLA-4 Antibody Therapy for Melanoma

On June 17, 2020, the American Association for Cancer Research (AACR) announced that it is recognizing Jedd D. Wolchok (photo), MD, PhD, with the 2020 AACR-Joseph Burchenal Award for Outstanding Achievement in Clinical Cancer Research. Dr. Wolchok is the Lloyd J. Old/Virginia and Daniel K. Ludwig Chair in Clinical Investigation and Chief of the Immuno-Oncology Service at Memorial Sloan Kettering Cancer Center (MSKCC). He also serves as Director of the Parker Institute for Cancer Immunotherapy at MSKCC, Associate Director of the Ludwig Center for Cancer Immunotherapy, and Professor of Medicine at Weill Medical College of Cornell University. Dr. Wolchok is being recognized for his leadership in the groundbreaking clinical development of CTLA-4 antibody therapy for melanoma and for his pivotal role in ushering in the field of checkpoint inhibitor therapies for cancer. The AACR and Bristol-Myers Squibb established this award (xxxx) in 1996 to recognize outstanding achievements in clinical cancer research. The award honors Dr. Joseph H. Burchenal, honorary member and Past President of the AACR, and a major figure in clinical cancer research. Dr. Wolchok is internationally recognized for his seminal role in developing ipilimumab (Yervoy), an anti-CTLA-4 monoclonal antibody that promotes the release of cancer-fighting T cells in the body. He led the pivotal phase III clinical trial demonstrating that treatment with ipilimumab and the chemotherapeutic dacarbazine yields superior overall survival in patients with metastatic melanoma compared with dacarbazine treatment alone. Through his work with ipilimumab, Dr. Wolchok discovered differences in the kinetics of clinical tumor responses to immunotherapy and chemotherapy, which prompted him and his team to develop new criteria for evaluating treatment responses to immunotherapy.

Animal Kingdom Should Have a Father’s Day Too !! BioQuick & Ananya Sen Salute Nature's Top Pops

[This timely article was written by Ananya Sen, a graduate student in microbiology at the University of Illinois at Urbana-Champaign, and is reprinted here with her permission. Ms. Sen is also a science writer and her articles can be found at http://ananyasen.web.illinois.edu/. This article was originally published as a Spotlight piece in Nautilus (http://nautil.us/)] Becoming a parent brings out the best in many animals. Although parenting is usually left to the females, males from many species go above and beyond to care for the offspring. Take anemonefish. In “Finding Nemo,” Marlin swims over 1,000 miles from the Great Barrier Reef to Sydney to rescue his son Nemo, who had been captured by scuba divers. In reality, anemonefish rarely stray so far away from their home. But, like Marlin, they are excellent fathers. Anemonefish, commonly called clownfish (photo by Dr. Justin Rhodes), live in sea anemones (https://link.springer.com/chapter/10.1007/978-3-319-31305-4_27), and reside in the same location for most of their lives. Although sea anemones are one of the most venomous creatures in the sea, clownfish are immune because they have a mucus layer on their skin that protects them. This setup helps both animals. Clownfish usually lay their eggs on a patch of bare rock that is protected by the poisonous tentacles of sea anemones. In exchange, the territorial fish defend the sea anemones from predators. “The males are spectacular fathers,” said Justin Rhodes (https://psychology.illinois.edu/directory/profile/jrhodes), PhD from University of Wisconsin-Madison, a Psychology Professor at the University of Illinois, Urbana-Champaign.

Nanosponges Coated with Membranes from Lung Cells or Macrophages Could Intercept SARS-CoV-2 & Block Virus Infectivity

Nanoparticles cloaked in human lung cell membranes and human immune cell membranes can attract and neutralize the SARS-CoV-2 virus in cell culture, causing the virus to lose its ability to hijack host cells and reproduce. The first data describing this new direction for fighting COVID-19 were published on June 17, 2020 in Nano Letters. The open-access article is titled “"Cellular Nanosponges Inhibit SARS-CoV-2 Infectivity.” The "nanosponges" were developed by engineers at the University of California (UC) San Diego and tested by researchers at Boston University. The UC San Diego researchers call their nano-scale particles "nanosponges" because they soak up harmful pathogens and toxins. In lab experiments, both the lung cell and immune cell types of nanosponges caused the SARS-CoV-2 virus to lose nearly 90% of its "viral infectivity" in a dose-dependent manner. Viral infectivity is a measure of the ability of the virus to enter the host cell and exploit its resources to replicate and produce additional infectious viral particles. Instead of targeting the virus itself, these nanosponges are designed to protect the healthy cells the virus invades. "Traditionally, drug developers for infectious diseases dive deep on the details of the pathogen in order to find druggable targets. Our approach is different. We only need to know what the target cells are. And then we aim to protect the targets by creating biomimetic decoys," said Liangfang Zhang, PhD, a nanoengineering professor at the UC San Diego Jacobs School of Engineering. Dr. Zhang’s lab first created this biomimetic nanosponge platform more than a decade ago and has been developing it for a wide range of applications ever since.

Nobel Laureate Phillip A. Sharp, PhD, Honored with 2020 AACR Award for Lifetime Achievement in Cancer Research: Sharp Co-Discovered Phenomenon of RNA Splicing

On May 26, 2020, the American Association for Cancer Research (AACR) announced that it is recognizing Phillip A. Sharp, PhD, Fellow of the AACR Academy and Nobel Laureate, with the 17th AACR Award for Lifetime Achievement in Cancer Research. Dr. Sharp, an Institute professor at Massachusetts Institute of Technology’s David H. Koch Institute for Integrative Cancer Research, is being honored for his exceptional body of groundbreaking and high-impact basic research, including his seminal co-discovery of RNA splicing. For this discovery, Dr. Sharp was awarded the 1993 Nobel Prize in Physiology or Medicine, along with Sir Richard J. Roberts, PhD. This body of research fundamentally changed scientists’ understanding of the structure of genes, shaping our understanding of RNA biology and our knowledge of the genetic causes of cancer and other diseases. “Dr. Sharp is a luminary in the fields of molecular biology and biochemistry who has dedicated his research career to advancing our understanding of the molecular biology of gene expression as it pertains to cancer and the mechanisms of RNA splicing,” said Margaret Foti, PhD, MD (hc), Chief Executive Officer of the AACR. “He is one of the most creative scientific thinkers of our time, always looking to push the boundaries to address the enormous challenges that cancer still poses. We are very proud to honor him with this special award.” The AACR Award for Lifetime Achievement in Cancer Research was established in 2004 to honor individuals who have made significant fundamental contributions to cancer research, either through a single scientific discovery or a collective body of work. These contributions, whether they have been in research, leadership, or mentorship, must have had a lasting impact on the cancer field and must have demonstrated a lifetime commitment to progress against cancer.

High-Throughput Analyses of Small Substances in Coyote Tobacco Plant Reveal That Plants Can Re-Organize Their Metabolism to Produce Highly-Specific Defense Metabolites After Insect Attack; Results Support “Optimal Defense” Theory of Directional Response

Do plants attacked by herbivores produce substances that are most effective against attackers in a targeted manner, or are herbivore-induced changes in a plant metabolism random, which could thwart the performance of herbivores? Scientists at the Max Planck Institute for Chemical Ecology in Jena, Germany, and at the CNRS Institute of Plant Molecular Biology/University of Strasbourg, France, tested these long-standing hypotheses for the first time using the coyote tobacco plant Nicotiana attenuata and its close relatives. The researchers combined extensive measurements of known and unknown plant metabolites using mass spectrometry with statistical measures derived from information theory. The results show that plants regulate their metabolism directionally to produce effective defenses. Furthermore, a comparative approach using different populations and closely related species demonstrated that the amounts of certain plant hormones are crucial for the directionality of the plant's response to its enemy. This research was reported online on June 10, 2020 in Science advances. The open-access article is titled “Information Theory Tests Critical Predictions of Plant Defense Theory for Specialized Metabolism.” All living organisms on earth can be divided into two major groups: those that produce their own food from abiotic sources, such as light, and those that feed on other organisms. These different ways of feeding affect an organism's metabolism. Plants, which gain their energy from light, produce a much greater diversity of metabolites than animals. Scientists have long wondered which evolutionary forces are behind this difference. As early as in the 1950s, researchers assumed that that the ability of plants to produce certain substances to defend themselves could be one reason.

Viruses Like SARS-CoV-2 Mimic Normal Ligands to Bind Cell-Surface Receptors and Initiate “Lipid Raft” Formation; Lipid Rafts Can Then Ferry Viruses into the Cell

Rescue rafts are a lifesaver, but other types of rafts may put our lives in danger—that is the case with “lipid rafts,” which are exploited by coronaviruses to attack human cells. An interdisciplinary research group, coordinated by the University of Trento and the University of Napoli-Federico II in Italy, set out to understand what happens when a virus jumps on this type of raft to invade a cell. To penetrate the human cell, the virus tricks the cell membrane that surrounds the cell. The membrane has a crucial role, because it ensures the regular functioning of the cell which is essential for tissue growth and development and organ functionality. When a virus sneaks into a cell pretending to be something friendly--a ligand, namely a molecule that binds to a chemically affine receptor and forms a complex capable of causing a cellular response--the membrane responds by creating localized thickened zones, called “lipid rafts.” Indeed, that is where receptors find favorable sites for binding. Indeed, receptors must change their configuration as they bind to their ligand and this can be done more easily across suitable stress-relieved zones of the cell membrane, namely on the rafts. Also, these thickenings turn out to be energetically favorable for the system, thereby becoming entryways for viruses and ligands in general. The researchers adopted a mechanobiological approach to explain how the microstructural properties of the membrane interact with biochemical processes to form lipid rafts. The study may suggest new strategies to limit virus attacks and prevent or combat diseases like SARS and Covid-19 based on biomedical and engineering principles.

June 19th

Genes & Blood Type Tied to Risk of Severe COVID-19 in Study Published in New England Journal of Medicine; Blood Type A Associated with 50% Higher Than Normal Risk of Severe COVID-19 If Infected; Blood Type O Associated with 50% Reduced Risk

[On June 18, 2020, NIH Director Francis Collins, MD, PhD, posted his Director’s Blog on the topic of blood type and risk of severe COVID-19. This report reproduces Dr. Collins’ blog (https://directorsblog.nih.gov/2020/06/18/genes-blood-type-tied-to-covid-...), with a small number of minor editorial changes. Dr. Collins blog is titled “Genes, Blood Type Tied to Risk of Severe COVID-19.” This blog follows below.] Many people who contract COVID-19 have only a mild illness, or sometimes no symptoms at all. But others develop respiratory failure that requires oxygen support or even a ventilator to help them recover. It’s clear that this happens more often in men than in women, as well as in people who are older or who have chronic health conditions. But why does respiratory failure also sometimes occur in people who are young and seemingly healthy? A new study suggests that part of the answer to this question may be found in the genes that each one of us carries. While more research is needed to pinpoint the precise underlying genes and mechanisms responsible, a recent genome-wide association study (GWAS), published online on June 17, 2020 in the New England Journal of Medicine (https://www.nejm.org/doi/full/10.1056/NEJMoa2020283), finds that gene variants in two regions of the human genome are associated with severe COVID-19 and correspondingly carry a greater risk of COVID-19-related death. The two stretches of DNA implicated as harboring risks for severe COVID-19 are known to carry some intriguing genes, including one that determines blood type and others that play various roles in the immune system.

Study Finds “Dark Matter” DNA Vital for Rice Reproduction; Regions of DNA That Give Rise to Non-Coding MicroRNA-2118 Are Required for Proper Development of Plant Reproductive Organs

Researchers from the Okinawa Institute of Science and Technology Graduate University (OIST) have shed light on the reproductive role of “dark matter” DNA, i.e., non-coding DNA sequences that previously seemed to have no function. The findings, published online on June 19, 2020 in Nature Communications, have revealed that a specific non-coding genomic region is essential for the proper development of the male and female reproductive organs in rice. The article is titled “miR2118-Dependent U-Rich PhasiRNA Production in Rice Anther Wall Development.” "Rice is one of the major global crops and is the staple food in many countries, including Japan," said Reina Komiya, PhD, senior author of the research paper and Associate Researcher from the OIST Science and Technology Group. "Further research into how these genomic regions affect plant reproduction could potentially lead to increased productivity and more stable yields of rice." Many previous developmental studies have focused on genes--the regions of DNA that provide instructions for making proteins. But in complex creatures like plants and animals, a large fraction of the genome--typically between 90-98%--does not actually code for proteins. The vast expanse of this once-called “junk DNA” has long puzzled biologists, with many dubbing it the “dark matter” of the genome. But recent research suggests that many of these non-coding genomic regions may have a function after all, giving rise to non-coding RNAs that play a variety of roles in the cell. Scientists have now identified numerous types of non-coding RNA, ranging from small molecules only 20-30 nucleotide bases in length to long molecules of over 200 nucleotides.

Renewed Hope for Treatment of Pain & Depression; Novel Molecule (LIH383) Targets Newly Identified Opioid Receptor with Atypical Properties and Holds Promise for Alternative Therapeutic Strategies; May Also Point to Drugs for Brain & Breast Cancers

Researchers at the Department of Infection and Immunity of the Luxembourg Institute of Health (LIH) have developed LIH383, a novel molecule that binds to and blocks a previously unknown opioid receptor in the brain, thereby modulating the levels of opioid peptides produced in the central nervous system (CNS) and potentiating their natural painkilling and antidepressant properties. Opioid peptides are small proteins that act as neuromodulators by interacting with four “classical” opioid receptors on the surface of CNS cells, playing a key role in mediating pain relief, but also emotions such as euphoria, anxiety, stress, and depression. The molecule was developed by Andy Chevigné (at left in photo), PhD, Head of Immuno-Pharmacology and Interactomics at LIH, and his team, based on their previous research that had identified the atypical chemokine receptor ACKR3 as a novel opioid receptor which binds to natural opioids and “traps” them, thereby dampening their analgesic and antianxiety activity. These findings were published on June 19, 2020 in Nature Communications, carrying important implications for the development of a novel class of drugs for pain, depression, and brain cancer treatment. The open-access article is titled “The Atypical Chemokine Receptor ACKR3/CXCR7 Is a Broad-Spectrum Scavenger for Opioid Peptides.” Opioid-related disorders such as severe pain are, currently, predominantly treated through drugs that act on the opioid system. Opioid prescription drugs against pain -- including morphine, oxycodone, and fentanyl -- work by targeting and activating opioid receptors, preventing the natural “pain message’’ from being transmitted, altering pain perception, and consequently resulting in painkilling effects.