When a virus or bacteria comes calling, protein “sensors” in your cells can detect the invader’s DNA and activate inflammatory responses to prevent infection. One such sensor is cGAS (cyclic GMP-AMP synthase). Normally, cGAS is an asset – something you definitely want to be working for you. However, abnormal responses to intracellular DNA can lead to hyper-inflammatory or autoimmune disorders such as lupus. Turning cGAS off may actually help treat this disease. Manuel Ascano Jr., Ph.D., and colleagues now report the discovery of a class of compounds that can inhibit cGAS. One “chemically improved” compound, RU.521, showed potent and selective inhibition of cGAS activity and lowered inflammatory signaling molecules in immune cells in a mouse model of an autoimmune disease.
Jeff Conn Earns 2017 Excellence in Academic Research Award
Jeff Conn, Lee E. Limbird Professor of Pharmacology, Director of Vanderbilt Center for Neuroscience Drug Discovery, is a recent Excellence in Academic Research Award winner. PhRMA honor Dr. Conn during the 2017 Research & Hope Awards, which took place on October 10 in Washington DC. This year’s program celebrated the progress and promise of Mental Health Research & Care. The Research & Hope Awards illustrate how biopharmaceutical researchers and others in the innovation ecosystem work together to not only bring new medical advances to patients, but thwart deadly diseases through increased awareness, public health efforts and increased collaboration.
Romell Gletten Receives Watkins Student Award
Romell Gletten (Schey Lab, Department of Biochemistry) is the recipient of the 2017 Levi Watkins Jr. Student Award, given annually to a student who has made outstanding contributions to the institution by fostering a more diverse environment that is enriching, encouraging and embracing of all students, faculty and administration.
Although the bacterial topoisomerases gyrase and topoisomerase IV are critical for cell function and are targets for quinolone antibacterials (such as Cipro), little is known about how these enzymes remove positive supercoils on overwound DNA. Neil Osheroff, Ph.D., and colleagues report in Nucleic Acids Research that gyrase removes positive supercoils rapidly and uses a DNA wrapping mechanism to unwind DNA.
Tight regulation of calcium levels in the endoplasmic reticulum (ER) – a cellular organelle with multiple functions – contributes to insulin secretion by pancreatic beta cells. Although ER calcium handling is perturbed in diabetes, the molecular determinants of ER calcium balance are not clear. David Jacobson, Ph.D., and colleagues have now demonstrated that TALK-1 potassium channels located in the ER membrane facilitate calcium release from the ER in mouse and human beta cells.
A trio of Vanderbilt University scientists described their cutting-edge investigations of cellular dynamics and cancer treatment during last week’s Flexner Discovery Lecture: Marija Zanic, Ph.D., assistant professor of Cell and Developmental Biology and Chemical and Biomolecular Engineering; Lauren Parker Jackson, Ph.D., assistant professor of Biological Sciences and Biochemistry; and Christine Lovly, M.D., Ph.D., assistant professor of Medicine and Cancer Biology.
Too much dietary manganese — an essential trace mineral found in leafy green vegetables, fruits and nuts — promotes infection of the heart by the bacterium Staphylococcus aureus(“staph”). “The human body does a wonderful job of regulating nutrient levels, and a traditional Western diet has plenty of minerals in it. The idea of super-dosing nutrients needs to be given careful consideration,” said Eric Skaar, Ph.D., MPH, Ernest W. Goodpasture Professor of Pathology and senior author of the current study.
A research symposium honoring the career of Harold (Hal) Moses, M.D., who founded and served as director emeritus of Vanderbilt-Ingram Cancer Center, has been slated for Wednesday, Oct. 11, 7:45 a.m. – 3:30 p.m., at the Vanderbilt Student Life Center. The free symposium will feature a roster of renowned cancer researchers from Vanderbilt University Medical Center (VUMC) and around the country who will discuss the ways in which Moses’ cancer research has impacted the field. Many of those researchers were mentored by, or worked alongside, Moses, who has been lauded for his ability to instill his commitment to rigorous scientific research in the next generation of investigators.
John Oates, M.D., a pioneering clinical pharmacologist at Vanderbilt University Medical Center (VUMC), has been awarded a one-year, $20,000 grant from the Brain Aneurysm Foundation to support studies of the stroke-reducing potential of acetaminophen. Oates is the Thomas F. Frist Sr. Professor of Medicine, professor of Pharmacology and founding director of the Division of Clinical Pharmacology. He is one of 14 researchers in the United States and Canada to receive grants this year from the Massachusetts-based foundation. The awards will be presented Sept. 28 in Durham, North Carolina.
Craig Lindsley, Ph.D., co-director of the Vanderbilt Center for Neuroscience Drug Discovery, has been honored by the University of Kansas with the 2018 Edward E. Smissman Lectureshipfor his outstanding contributions to the fields of medicinal chemistry and molecular pharmacology.
NAPEs, a family of lipid molecules, are produced in the intestinal tract after food intake and exert leptin-like effects: they reduce food intake and weight gain. Given their potential importance in regulating satiety and inhibiting obesity, Sean Davies, Ph.D., and colleagues are exploring NAPE action.
Three Vanderbilt University scientists on the forefront of research in cellular dynamics and cancer treatment, including Marija Zanic, Ph.D., assistant professor of Cell and Developmental Biology and Chemical and Biomolecular Engineering, will discuss their cutting-edge investigations during the next Flexner Discovery Lecture : “Cutting-Edge Molecular Tools Drive Basic Science Discovery and Patient Care,” will begin at 4 p.m. in room 208 Light Hall.