GeneTex Webinar Series

Viral and Host Determinants of Arbovirus Viremia and Dissemination

Arboviruses are major public health threats. Major determinants of arbovirus transmission, geographic spread and pathogenesis are the magnitude and duration of viremia in the vertebrate host. However, the factors that dictate viremia following arbovirus infection are poorly defined. Dr. Morrison’s team used mouse models to find that a panel of arboviruses display distinct clearance kinetics from the circulation. Moreover, for several different alphaviruses, bunyaviruses, and flaviviruses, they discovered that clearance requires blood-exposed liver Kupffer cells. However, while the clearance of dengue virus (DENV) and eastern equine encephalitis virus (EEEV) also requires Kupffer cells, distinct pathways including mannose binding lectin (MBL) and glycosaminoglycans (GAGs), respectively, promote clearance. In his talk, Dr. Morrison will describe the mechanisms underlying these differences, host species specificity, and a previously unrecognized arbovirus-scavenging role for lymphatic endothelial cells. Collectively, his team’s work provides new insight into virus-host interactions that influence arbovirus viremia, dissemination, and pathogenesis.

When: Thursday, Nov 29, 2023 at 11:00 a.m. (EST)

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The interface of the ovary and fallopian tube during ovarian cancer formation and spread

Dr. Joanna E. Burdette earned her B.S. from Emory University in Biology and her Ph.D. at the University of Illinois at Chicago. She was a postdoctoral fellow at Northwestern University. She is the Edward and Josephine Chair in Pharmacognosy and Medicinal Chemistry as well as the Associate Dean for Research and Graduate Studies in the College of Pharmacy. She serves as the co-Director for the Cancer Biology Program in the UI Cancer Center and the co-director of the IRACDA program, which focuses on training postdoctoral fellows in research and teaching with an emphasis on diversity and inclusion. Her research has helped to develop three-dimensional models of the fallopian tube epithelium, which is thought to be the source for the deadliest type of ovarian cancer, high grade serous cancer. She has held leadership roles in the Endocrine Society, the Society for the Study of Reproduction, and in the Gynecologic Oncology Group. She has been the recipient of the Liz Tilberis Scholar Award from the Ovarian Cancer Research Fund, the UIC Rising Star, UIC Distinguished Researcher, and University Scholar.

When: Wednesday, April 5, 2023 at 10:00 a.m. (EDT)

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SARS-CoV-2 Omicron therapeutics: Getting to know the unknown and the road ahead

François Jean, PhD, is an expert in antiviral drug discovery and professor of molecular virology at the University of British Columbia (UBC). He is the founder of the UBC’s Facility for Infectious Disease and Epidemic Research (FINDER), one of the largest university-based containment level 3 (CL-3) facilities in the world. He is currently leading major international research initiatives funded by the Canadian Institutes of Health Research (CIHR) to discover broad-spectrum drugs active against current infections with the circulating SARS-CoV-2 variants and future pandemic-causing viral pathogens. He is the Lead of Pillar 10, Antiviral Strategies & Antiviral Therapeutics, at the Coronavirus Variants Rapid Response Network (CoVaRR-Net). He has won several prestigious scholarly awards including the CIHR New Investigator Salary Award, the UBC Peter Wall Institute for Advanced Studies Early Career Scholar Start-Up Research Grant, the Thermo Fisher Scientific Award from the Canadian Society for Microbiologists, and UBC’s Faculty of Science Excellence in Service Award in recognition of his leadership role in establishing FINDER. His webinar will highlight the exciting and ongoing advances his lab has made in novel SARS-CoV-2 antiviral drug discovery since he last spoke in the GeneTex Webinar Series.

When: Wednesday, February 22, 2023 at 11:30 a.m. (EST)

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Blood plasma-derived extracellular vesicles: A minimally invasive tool for predicting response to cancer treatment

My laboratory investigates how host factors expressed in host cells or present in the extracellular milieu, such as extracellular vesicles and extracellular condensates, regulate response against infective agents and disease pathogenesis. Our translational experiments use primary cells, animal models, and human clinical specimens to study spatiotemporal regulation of host factors and their effects on clinical outcomes. We use integrative scientific approaches including multimodal datasets, computational modeling, Omics technologies, and cellular and molecular biology experimental tools in our studies. Discoveries made through this area of research will expand our knowledge and may lay the foundation for development of new tools and strategies for treatment and prevention of diseases. My laboratory provides an environment that encourages, nurtures, and values diversity, inclusivity, and innovation. My laboratory is funded by multiple active grants. We also have multiple pending grants.

When: Tuesday, November 29, 2022 at 10:00 am (EST)

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RAS Genes in Development and Cancer

Matthias Drosten studied Biology at the University of Bochum in Germany. He later joined the laboratory of Professor Brigitte Pützer at the University of Essen Medical School (Germany) where he obtained his Ph.D. for his work on the role of the RET oncogene in thyroid cancer. In 2004 he moved to Spain and joined the laboratory of Dr. Mariano Barbacid at the Spanish National Cancer Research Center (CNIO) in Madrid as a postdoctoral fellow to work on RAS signaling and biology. In 2008 he acquired a permanent position as a staff scientist in the same group and expanded his research interests to the role of KRAS in lung cancer with special emphasis on the generation of genetically-engineered mouse models. In 2021 he joined the Cancer Research Center (CIC) in Salamanca (Spain) as a group leader where he continues to focus his research efforts on KRAS signaling and lung cancer.

When: Wednesday, October 5, 2022 at 10:00 am (EDT)

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Restoring stem cell fate and behavior outside their native niche

Adult stem cells reside in defined niches and depend on specialized cues to preserve their identity and instruct behavior. Early in my career, I studied the dynamic interplay between stem cells and their microenvironment in skeletal muscle. Stem cells played executive and adaptive roles, autonomously remodeling physical cues to balance growth and repair while remaining susceptible to inflammatory cues that could promote chronic degeneration. In various tissues, the dissection of stem cell-niche interactions has informed therapeutic strategies that aim to exploit their regenerative potential for a range of conditions, from wounding to aging. In the hair follicle, a particularly rich set of stem cell-niche interactions control self-renewal and differentiation not only to each hair lineage, but can unlock a wound-related plasticity that yields all skin lineages. As a postdoctoral fellow, I became interested in the signals that control stem cell plasticity across tissue compartments during epidermal repair. Timely resolution of this multipotent state has long remained elusive and can act as a barrier to appendage formation in wounded or grafted skin. By leveraging our discovery that hair follicle stem cells exhibit a wound-like epigenetic signature in culture, I identified key niche signals that lie at the intersection between homeostatic regeneration and wound-enabled plasticity. Local production of these signals is dysregulated upon wounding and can be manipulated to push stem cell contribution to hair regrowth or wound re-epithelialization. Outside the niche, temporal control of their activity enabled the ex vivo modeling of stem cell fate decisions normally observed only within the intact hair follicle. Together, this work demonstrates the effectiveness of targeting wound-related niche signals to restore proper stem cell function in the skin. It also establishes a highly tractable platform for the reconstruction and future interrogation of stem cell-niche crosstalk.

When: Tuesday, June 28, 2022 at 10:00 a.m. (EDT)

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The SARS-CoV-2 RNA-protein interactome at subgenome resolution

Characterizing the interactions that SARS-CoV-2 viral RNAs make with host cell proteins during infection can improve our understanding of viral RNA functions and the host innate immune response. Using RNA antisense purification and mass spectrometry (RAP-MS), we recently characterized the first atlas of human and viral proteins that directly and specifically bind to SARS-CoV-2 RNAs in infected human cells. We now expand these results to different cell types and resolve the interactomes of genomic and subgenomic viral RNAs separately. We report a subgenome-resolved network of host RNA binders and find quantitative differences in the enrichment of host factors towards different viral RNA types, indicative of distinct binding preferences within the SARS-CoV-2 RNA-protein interactome. We globally map direct interaction sites of viral and host cell proteins on SARS-CoV-2 RNAs and use genetic perturbation together with pharmacological inhibition to demonstrate the functional relevance of several direct RNA binders in SARS-CoV-2 infections. The identification of host dependency factors and defense strategies as presented here provides a general roadmap for dissecting the biology of RNA viruses and the interactions between hosts and pathogens at the molecular level with therapeutic implications.

When: Thursday, April 21, 2022 at 10:00 a.m. (EDT)

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RNA vaccines against emerging viruses

Viral pandemics in modern times were associated primarily with specific strains of influenza until SARS-CoV-2 arose. Nevertheless, other RNA viruses like SARS-CoV, MERS, and ZIKV have all evoked illness, fear, and death within the last two decades, while DENV and other flaviviruses have caused misery over a much longer timeframe. The Richner laboratory at the University of Illinois, Chicago College of Medicine studies the biology of these pathogens and dissects the underlying signaling, cytokine, and cellular interplay responsible for generating an effective adaptive immune response and immunologic memory following viral infection or vaccination. Other major areas of focus include understanding the biological basis of age-related diminution of the immune response and application of mRNA vaccine technology against flaviviruses and coronaviruses. His webinar will concentrate primarily on his compelling findings related to mRNA vaccines against ZIKV and DENV as well as his quest to develop a pan-coronavirus vaccine.

When: Thursday, March 10, 2022 at 10:00 a.m. (EST)

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Neuroinflammation and Neurodegenerative Disease

Astrocytes are a functionally diverse cell population that exerts a complex range of effects on neurons in the central nervous system (CNS). These include actions both supportive to neuron homeostasis (i.e., release of lactate and promotion of post-traumatic tissue repair) as well as destructive (i.e., driving CNS inflammation and neurodegeneration). These negative processes can involve multiple mechanisms including neurotoxicity, modulation of microglial responses, and recruitment of inflammatory cells. Using a combination of proteomic, metabolomic, transcriptomic, and perturbation approaches, Dr. Chun-Cheih Chao found that sphingolipid metabolism in astrocytes trigger the interaction of cytosolic phospholipase A2 (cPLA2) with mitochondrial antiviral signaling protein (MAVS). This stimulates NF-κB-driven transcriptional programs leading to CNS inflammation and disruption of MAVS-hexokinase 2 (HK2) interactions that result in decreased lactate production and compromised neuronal metabolism. Dr. Chao will describe how this sequence of events can be pharmacologically targeted to treat neuroinflammation.

When: Thursday, February 24, 2022 at 3:00 p.m. (CET)

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From Skin to Brain: The Epigenetic Basis of Inflammatory Training

Inflammatory training is the generation of an epigenetic memory that leads to an augmented state of responsiveness to a broad range of secondary stimuli. Though previously thought to be exclusive to the innate immune system, Dr. Samantha Larsen discovered that epithelial stem cells can undergo inflammatory training that accelerates tissue repair. She revealed this phenomenon hinges on the coordinated efforts of stimulus-specific, stress-responsive, and homeostatic transcription factors that extend to diverse stimuli, cell types, and species. She has now extended her interests in the long-term consequences of inflammation to the brain, where she has identified that neurons, much like other long-lived cell types, undergo inflammatory training that may predispose them to subsequent neurodegeneration. Moving forward, she is addressing the persistent transcriptional and electrophysiological changes that follow concussive brain injury with the ultimate goal of treating and preventing injury-induced neuropathogenesis.

When: Tuesday, November 9, 2021 at 9:00 a.m. (EST)

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新型コロナウイルスの進化　～これまでとこれから～

2019年末に突如出現した新型コロナウイルスは、瞬く間に全世界に広がった。これまで、全世界において2億人以上が新型コロナウイルスに感染し、450万人以上が新型コロナウイルス感染症COVID-19によって死亡している。未曾有の新型コロナウイルスパンデミックは、発生から約2年あまりが経過した現在においても、リアルタイムの災禍であり、いまだ収束の兆しは見えない。
演者は、新型コロナウイルスの発生当初からこれまで、そのウイルス学的な性状の理解に向けたシステムウイルス学研究を展開してきた。本講演では、新型コロナウイルスについて、これまでの研究からわかってきたことを概説するとともに、これからの研究と流行の展望について広く議論したい。

When: 2021年11月5日(金), 11:00 a.m.

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Genetic and Metabolic Determinants of Tumor Evolution and Metastasis

Dr. Ngo’s research examines the complex interplay between genomic instability, nutrient constraints, and metabolic synthetic processes that impacts a cancer cell’s ability to proliferate in diverse metastatic tissue environments. He will describe two independent studies that (i) connect a form of genetic instability with its causal role in inflammation-driven metastasis, and (ii) uncover a novel therapeutic paradigm that exploits the link between extracellular nutrient availability and cell-intrinsic serine synthesis in brain metastases. Dr. Ngo’s work provides new insight into the mechanisms driving metastasis and how this could lead to innovative therapies.

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Discovery of Novel Antiviral Agents Against Human Pathogenic Viruses: A Tale of Two Emerging Viruses – SARS-CoV-2 and Zika Virus

Dr. Jean will discuss his work with novel small-molecule inhibitors and protein-based therapeutics that function against human pathogenic viruses of global public health concern, including SARS-CoV-2 and Zika virus. He will further explain the importance of his research findings for (i) generating effective tools for dissecting pathways in vivo, (ii) defining the biological impact of new therapeutics, and (iii) generating insights into clinical approaches for treating viral diseases caused by emerging human coronaviruses and flaviviruses.

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Inflammation, Infection, and Brain: Neuro-immune communication

Dr. Lin will present an overview of neuro-immune communication and an introduction to the impacts of COVID-19 on neurological complications. The webinar objectives include Neuro-immune communication, Neurodegenerative disorders and the impacts of SARS-CoV-2 infection on neurological complications.

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The ALS-Reproducible Antibody Platform (ALS-RAP): Identification of high-quality antibodies for ALS research

Dr. Laflamme will discuss his published work describing the systematic assessment of antibodies against the C9ORF72 protein as part of ALS-RAP. He will then present intriguing data regarding C9ORF72 biology in macrophages, and will introduce his very exciting and potentially revolutionary efforts to expand the ALS-RAP methodology for antibodies against additional ALS disease proteins as well as those of other neurodegenerative disorders.

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COVID-19 and the Brain

Dr. Eric Song of Yale University will discuss his work that revealed the ability of SARS-CoV-2 to directly infect the mammalian brain (Song et al., J. Exp. Med. 2021). This important study entailed the use of several elegant approaches to demonstrate SARS-CoV-2 infection of both mouse and human brains, with clear implications for the subset of COVID-19 patients experiencing persistent neurological and neuropsychiatric symptoms after resolution of the acute disease. Dr. Song will also provide updates on his current efforts and offer perspectives on future directions of SARS-CoV-2/COVID-19 research.

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