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The Roles of Autophagic SNARE proteins SNAP29 and SNAP47 in Autophagy and Enterovirus D68 Replication Item Type dissertation Authors Corona, Abigail Publication Date 2019 Abstract Enterovirus-D68 (EV-D68) is a positive-sense, single-stranded RNA virus of the Picornaviridae family that causes respiratory disease in children and has been implicated in recent outbreaks of acute flaccid myelitis, a severe paralysis syndrome. We ha... Keywords Virology; Cellular biology; amphisome; picornavirus; SNAP29; SNAP47; Autophagy; Enterovirus D, Human; Picornaviridae Download date 04/10/2021 22:18:40 Link to Item http://hdl.handle.net/10713/11615 Curriculum Vitae Abigail Kristen Corona Formerly: Abigail Kristen McGillivray [email protected] Education Doctor of Philosophy* to be conferred - 2019 Degree in Molecular Microbiology and Immunology University of Maryland-Baltimore; Baltimore, Maryland 21201 Advisor: William T. Jackson, PhD Bachelor of Science 2014 Degree in Biochemistry Carroll University; Waukesha, Wisconsin 53186 Publications Corona AK and Jackson WT. “Finding the middle ground for autophagic fusion requirements.” Trends in Cell Biology 2018. 28 (11): 869-881. Corona AK, Mohamud Y, Jackson WT, Luo H. “Oh, SNAP! How enteroviruses redirect autophagic traffic away from degradation.” Autophagy 2018. 14 (8): 1469-1471. Corona Velazquez AF, Corona AK, Klein KA, Jackson WT. “Poliovirus induces autophagic signaling independent of the ULK1 complex.” Autophagy 2018. 14 (7):1201-1213. Corona AK, Saulsbery HM, Corona Velazquez AF, Jackson WT. “Enteroviruses remodel autophagic trafficking through regulation of host SNARE proteins to promote virus replication and cell exit.” Cell Reports 2018. 22 (12): 3304-3314. Singh RK, Lall N, Leedahl TS, McGillivray A, Mandal T, Haldar M, Mallik S, Cook G, Srivastava DK. “Kinetic and thermodynamic rationale for suberolyanilide hydroxamic acid being a preferential human histone deacetylase 8 inhibitor as compared to the structurally similar ligand, trichostatin a” Biochemistry 2013. (45): 8139-49. Presentations Oral Presentations Corona AK, Jackson WT. “The roles of SNAP29 and SNAP47 during Enterovirus D68 Infection and Autophagy.” The Tenth Annual UMB/UMCP Research Symposium on Host-Pathogen Interactions, June 18, 2019. Corona AK, Saulsbery HM, Corona Velazquez AF, Jackson WT. “Enteroviruses remodel autophagic trafficking through regulation of host SNARE proteins to promote virus replication and cell exit.” Molecular Microbiology and Immunology Annual Graduate Student Symposium, Baltimore MD, June 4th-5th 2018. Corona AK, Jackson WT. “The effects of autophagy and the manipulation of autophagy on EVD68.” 36th American Society for Virology National Meeting, Madison WI, June 24th-28nd, 2017. Corona AK, Jackson WT. “The effects of autophagy and the manipulation of autophagy on EVD68.” Molecular Microbiology and Immunology Annual Graduate Student Symposium, Baltimore MD, June 7th-8th, 2017. McGillivray AK, Corona Velazquez AF, Jackson WT. “Differential effects of members of an autophagy fusion complex on the growth of a model picornavirus.” 35th American Society for Virology National Meeting, Blacksburg VA, June 18th-22nd, 2016 McGillivray AK, Corona Velazquez AF, Jackson WT. “Differential effects of members of an autophagy fusion complex on the growth of a model picornavirus.” Molecular Microbiology and Immunology Annual Graduate Student Symposium, Baltimore MD, June 8th-9th, 2017. Poster Presentations Corona AK and Jackson WT. “Autophagy SNARES SNAP29 and SNAP47 have novel roles revealed during virus infection” ASM, San Francisco CA, June 21, 2019. Corona AK and Jackson WT. “Autophagy SNARES SNAP29 and SNAP47 have novel roles revealed during virus infection” ASCB/EMBO, San Diego CA, December 10, 2018. Corona AK, Saulsbery HM, Corona Velazquez AF, Jackson WT. “Enteroviruses remodel autophagic trafficking through regulation of host SNARE proteins to promote virus replication and cell exit.” The Ninth Annual UMB/UMCP Microbiology & Immunology Research Symposium, Baltimore MD, June 19th 2018. Corona AK, Saulsbery HM, Corona Velazquez AF, Jackson WT. “Enteroviruses remodel autophagic trafficking through regulation of host SNARE proteins to promote virus replication and cell exit.” Training Program in Integrative Membrane Biology Retreat, Baltimore MD, April 6th 2018. McGillivray AK. “Discovery of Novel Inhibitors for the SIRT5 Enzyme” 247th American Chemical Society National Meeting & Exposition, Dallas TX, March 16-20, 2014. Schoeberle A, McGillivray AK and Marks GT. “Determining the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on expression of 3β/17β-hydroxysteroid dehydrogenase and 17α hydroxylase-17,20 lyase in human granulosa cells using RT-qPCR” 247th American Chemical Society National Meeting & Exposition, Dallas TX, March 16-20, 2014. McGillivray AK. “Discovery of Novel Inhibitors for the SIRT5 Enzyme” Poster Competition by American Chemical Society, Milwaukee Section, University of Wisconsin-Milwaukee, November, 2013. McGillivray AK. “Discovery of Novel Inhibitors for the SIRT5 Enzyme” Poster Celebration for National Science Foundation sponsored Research Experience for Undergraduates, North Dakota State University, Fargo ND, August 2013. Research Experience March 2015-Present:* PhD Candidate, Virology, Principle Investigator: Dr. William T. Jackson Research has focused on understanding the role of autophagy on Enterovirus D68 replication. Autophagy is marked by the formation of an isolated double-membrane that engulfs specific or non-specific cargo. The membrane fuses around cargo to form an autophagosome, which then sequentially fuses with an endosome and a lysosome, referred to as an amphisomes and autolysosome respectively, and the contents are degraded. Several picornaviruses have been shown to exploit canonical autophagy as a means to benefit their own survival and replication. These studies focus on the subversion of specific proteins that facilitate the fusion of the autophagosome and endosome/lysosome and the redirection of this pathway to benefit EV-D68 replication. August 2011 – May 2014: Undergraduate Researcher, Biochemistry, Mentor: Dr. Gregory T. Marks. Carroll University. Research focused on the effects of dioxin exposure on the estrogen synthesis pathway in primary human granulosa cells via qRT-PCR. Studies have previously shown that exposure to 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) have affected the estrogen pathway. These studies were a focused effort to elucidate the precise step in the pathway that is affected by the exposure to TCDD. June-August 2013: Undergraduate Researcher, Biochemistry, Mentor: Dr. DK Srivastava. North Dakota State University. Research focused on the effects of many small molecule barbiturate derivatives for inhibitors of the kinetics of human histone deactylases (HDACs) and, furthermore, a family of HDACs known as the sirtuins. Many sirtuins have a high impact in the proliferation and prolongation of cancer cells, so it would be advantageous to be able to modulate the activity of these enzymes. Teaching and Mentoring Experience Teaching at an Undergraduate University Workshop May 2019 • Attended sessions that related to how fund a laboratory at a Primarily Undergraduate Institution and how to balance research, teaching and service at the PUI research level Collaborative Teaching Fellow Sept 2018-March 2019 • Training completed in Bloom’s Taxonomy application to learning outcomes and assessments, interactive teaching technologies, active learning techniques, and course development Graduate Mentor Summers 2017 and 2018 • Mentored undergraduate students in research design, data collection, data analysis and presentation preparation for the Nathan Schnaper Internship Program Laboratory Teaching Assistant 2011-2014 • Assisted faculty in 100-level chemistry laboratory courses • Aided 15-20 students per course during laboratory assignments and experiments • Collected, organized and graded laboratory assignments and reports Abstract Title of Dissertation: The Roles of Autophagic SNARE proteins SNAP29 and SNAP47 in Autophagy and Enterovirus D68 Replication Abigail Corona, Doctor of Philosophy, 2019 Dissertation Directed by: Dr. William T. Jackson, Associate Professor, Department of Microbiology and Immunology Enterovirus-D68 (EV-D68) is a positive-sense, single-stranded RNA virus of the Picornaviridae family that causes respiratory disease in children and has been implicated in recent outbreaks of acute flaccid myelitis, a severe paralysis syndrome. We have demonstrated that EV-D68 induces autophagy upon infection and modifies the autophagic process to benefit its own replication. Autophagy is a regulated process of cytosolic degradation in eukaryotic cells which maintains cellular homeostasis by degrading damaged organelles, protein aggregates, microbes and other xenobiotics in the cytoplasm. The autophagic process is characterized by the formation of double- membraned autophagosomes around cytosolic cargo, which then undergo a series of fusion steps with endosomes and lysosomes to degrade the vesicle’s contents. The autophagy pathway is targeted by many pathogens, either to protect themselves from degradation or to utilize components to benefit replication. EV-D68 uses virally-encoded proteases to cleave an autophagosome fusion SNARE protein, SNAP29, blocking delivery of autophagosome contents, including nascent viruses, to the lysosome. Our data show that relocalization occurs for SNAP47 during autophagy induction, and is required for normal