Viral Mechanisms of Metabolic Reprogramming
Viruses depend on cellular metabolic resources to supply the energy and biochemical building blocks necessary for their rapid replication. We find that the cell’s metabolic resources represent a contested host-pathogen interaction that can determine the outcome of infection. We have identified several virally-induced metabolic activities that are essential for productive infection. A major goal of our laboratory is to elucidate the mechanisms through which viruses modulate cellular metabolism to support infection, and thereby identify potential therapeutic targets to block virally-associated disease.
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High Throughput Pharmacological Screening for Anti-coronaviral Compounds
The global SARS-CoV-2 pandemic is responsible for hundreds of thousands of deaths globally. Anti-viral therapeutic strategies are desperately needed to attenuate SARS-CoV-2-associated disease. We have initiated a high-throughput pharmacologic screen of a unique metabolism-focused compound library to identify drugs that limit coronavirus infection in pulmonary human fibroblasts. Our preliminary data has identified several compounds that substantially inhibit coronavirus infection.
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Viral Manipulation of Cellular Anti-viral Signaling
Cells express numerous sensors to detect viral infection. Upon detection of viral components, cells enter an anti-viral state that limits viral spread. Many viruses express genes that antagonize the establishment of this anti-viral state so as to support infection. A major project in the lab is to elucidate the mechanisms through which viral gene products modify the sensing, establishment, and down-stream implementation of the anti-viral state. We couple viral recombineering and CRISPR-mediated cellular DNA editing with classical biochemical and LC-MS/MS-based proteomic techniques to dissect these issues.
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Oncogene-Induced Metabolic Reprogramming
It has been known for decades that the cancer cell transformation induces gross metabolic changes in normal cells. Many of these metabolic changes are essential for tumorigenesis, highlighting the likelihood that inhibition of these activities could prevent cancer-associated disease. Our lab is interested in how oncogenic mutations reprogram the metabolic network, thus enabling tumorigenesis. We utilize LC-MS/MS-based metabolomic analysis to identify novel activities induced by oncogenic mutations.
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Viral Vectors For Gene Therapy And Cancer Cell Killing
Viruses can be engineered to express genes to treat genetic disorders or specifically kill cancer cells. We are currently utilizing molecular recombineering techniques to optimize viral vectors for gene delivery, modulation of immune activation, and cancer cell-specific killing.
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