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Ebola virus causes severe hemorrhagic fever and is readily transmitted through contact with or inhalation of aerosolized biological fluids from infected individuals. Vaccines against this deadly virus are currently in development. As Ebola outbreaks often occur in areas of Africa that lack infrastructure and trained medical personal, development of a needle-free vaccine would be advantageous. In this episode, Alexander Bukreyev and Michelle Meyer discuss their work, which demonstrates that an aerosolized formulation of an Ebola vaccine protects rhesus macaques from infection. The aerosolized version of the vaccine elicited an Ebola-specific response that was on par or better that an injected, liquid form of the same vaccine. Importantly, a single vaccination with the aerosolized formulation conferred 100% protection to macaques exposed to a lethal dose of Ebola virus. Together, these results support evaluation of the aerosolized vaccine formulation in clinical trials.
Dr. Robert Schrier is a nephrologist and Professor of Medicine at the University of Colorado School of Medicine, where he served as Chair of the Department of Medicine and Chief of the Kidney Division for more than 20 years. He is an expert in patient-oriented research on acute kidney injury, autosomal dominant polycystic kidney disease, hypertension, and diabetic nephropathy. Dr. Schrier has authored over 1,000 papers and several books and has been continuously funded by the NIH for 45 years. In an interview with JCI Editor-at-Large Ushma Neill, Schrier discusses his love of sports, his studies in Germany as a Fulbright scholar, his decision to go to medical school, and his entry into research at the Walter Reed Army Medical Center, where he became interested in kidney failure.
Alcohol abuse is a major risk factor for morbidity and disability throughout the world, and treatment options are limited for this complex psychiatric condition. In this episode, Leandro Vendruscolo and colleagues demonstrate that administration of the glucocorticoid receptor antagonist mifepristone reduces alcohol intake in alcohol-dependent rats, but not in nondependent animals. Moreover, in a double-blinded study of 56 alcohol-dependent human subjects, mifepristone treatment substantially reduced alcohol craving and alcohol consumption compared to placebo. The results of this study support further evaluation of mifepristone as a therapeutic strategy for the treatment of alcoholism.
The autoimmune disease systemic lupus erythematosus (SLE) is characterized by increased type I IFN and circulating apoptotic cell-derived autoantigens (AC-Ags), both of which drive autoantibody production by B cells. In this episode, John Mountz, Hui-Chen Hsu, and Hao Li describe a mechanism by which type 1 IFN prevents clearance of ACs by marginal zone macrophages (MZMs) in SLE. The authors found that in murine SLE models, type I IFN increased follicular translocation of MZ B cells in the spleen, which disrupted the interaction between these B cells and MZ macrophages (MZMs). The interaction between MZ B cells and MZMs was shown to activate the megakaryoblastic leukemia 1–mediated (MKL1-mediated) mechanosensing pathway, which was essential for MZMs to phagocytize ACs and thereby prevent follicular entry of AC-Ags. Moreover, these defects were also present in spleens from patients with SLE. The results of this study suggest that strategies to maintain this mechanosensing pathway may block follicular entry of AC-Ags and prevent the development of autoantibodies against these antigens.
Craig Thompson, MD, president and CEO of Memorial Sloan Kettering Cancer Center, has made fundamental contributions to our understanding of how cells survive and replicate. His current research focuses on the role of metabolic pathways in tumorigenesis. In an interview with JCI Editor at Large Ushma Neill, Thompson discusses the evolution of his research focus. He initially studied platelet physiology while working at the Naval Blood Research Laboratory. Thompson then became a Howard Hughes Medical Institute Investigator studying the processes that regulate cell death and the mechanisms that shape lymphocyte development and immune homeostasis. After moving to the University of Pennsylvania, Thompson began to focus on the role of cellular metabolism in proliferation and survival when he found that elimination of apoptosis in mice did not completely regulate cellular survival. These processes have since been shown to play a critical role in cancer development and progression.
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