Guest Editors
Bertram Jacobs
Arizona State University
Dr. Jacobs is Professor of Virology, former Director of the School of Life Sciences, and a member of the Biodesign Center for Immunotherapy, Vaccines and Virotherapy at Arizona State University. The main interest of Dr. Jacobs’ lab is poxvirus: host interactions, in particular evasion of the innate immune interferon defenses by poxviruses. Most recently, we have shown that one of the ways that poxviruses evade the interferon system is by inhibiting induction of interferon-mediated necroptotic cell death. Disabling of the immune evasion genes in vaccinia virus has allowed the generation of highly attenuated strains of vaccinia virus as improved vaccine vectors for diseases such as HIV, as well as viruses to potentially treat cancer. Dr. Jacobs was awarded the Arizona Governor’s Innovator of the Year Award in Academia for the work in vaccine development. Dr. Jacobs received his PhD in Biochemistry from the University of California, Berkeley and did post-doctoral research at the University of California, Santa Barbara, before taking a faculty position at Arizona State University. Dr. Jacobs has been a member of the NIH Virology Study Section and has served on numerous biodefense- and vaccine-related study sections. He has been an active collaborator with Russian scientists at VECTOR, home of the Russian smallpox repository. Dr. Jacobs serves as Chair of the Arizona State University Institutional Biosafety Committee. Dr. Jacobs’ teaching interests include HIV prevention education to lay audiences. In this regard, Dr. Jacobs teaches a highly regarded interdisciplinary HIV class at ASU and spends several weeks each year in Africa teaching HIV prevention. Dr. Jacobs has served on the Board of Directors of two non-profit organizations dealing with public health, Aunt Rita’s Foundation and HEAL, International.
Heather Koehler
Emory University School of Medicine
Dr. Koehler graduated in 2013 with a Doctor of Naturopathic Medicine (N.D.) where she conducted the research characterizing and validating traditional botanical medicines used in immune stimulation and anti-microbial applications. She then completed her PhD in molecular and cellular biology at Arizona State University using poxviruses to study viral host interactions. Here, her thesis work focused on characterizing the function of a viral Z-DNA binding protein. Her work demonstrated that the viral Z-DNA binding protein blocks virus-induced necroptosis in vaccinia virus-infected cells by restricting sensing by the nucleic acid sensor known as DAI/ZBP1. This demonstrated a novel mechanism of inhibition of virally induced necroptosis mediated by blocking the pathogen recognition system. She then began a postdoctoral fellowship at Emory University School of Medicine in the Emory Vaccine Center and the Department of Microbiology and Immunology. During her fellowship, she demonstrated that the ZBP1:E3 axis was in competition for Z-RNA specific sensing, thereby identifying a novel PAMP. Thorough my postdoctoral training, she broadened her perspective by shifting the focus of her research to the host by studying the function of ZBP1 that plays a role in regulating the innate immune system both at a tonic level as well as in response to viral infections. Most recently, she has transitioned to Washington State University College of Veterinary Medicine where she serves as an Assistant Professor in the School of Molecular Biosciences. Here, she will study how Z-RNA serves as a specialized PAMP to activate the immune system.
Collection Overview
Necroptosis is a relatively newly discovered, explosive, pro-inflammatory type of programmed cell death that is caspase-independent, and in fact is even inhibited by activated caspase 8. While necroptosis is caspase-independent, it is dependent on activation of the Ser/Thr protein kinase, RIPK3, which phosphorylates and activates the executioner of necroptosis, MLKL. MLKL can then migrate to the plasma membrane where it can be phosphorylated by the tyrosine TAM kinases, trimerize and form pores, leading to osmotic bursting. Necroptosis has been shown to act downstream of death receptors such as TNF, TRAIL, and Fas receptors to be a part of the interferon-inducible anti-viral pathway and to act downstream of activation of TLR3. More recently necroptosis has been shown to be induced by glucose deprivation in tumor cells, even though many tumor cell lines are deficient in RIPK3 and thus do not induce necroptosis. In this methods collection, we will demonstrate methods to identify necroptotic cell death and to characterize the initiators of the necroptotic pathway with the hope that investigators will broaden the scope of systems analyzed for this important form of programmed cell death.
Articles
