Description of Research Expertise

Research Interests:
The Taabazuing lab is interested in understanding the molecular mechanisms of cell death pathways that regulate immunity.

Keywords:
Pyroptosis, Apoptosis, Cell Death, Cytokines, Inflammasomes, Innate Immunity, Cancer Immunotherapy, Pathogen Defense

Research Details:
How cells adapt to extracellular and intracellular dangers such as pathogens or DNA damage is important for host survival. The response is usually mediated by large multi-protein signaling platforms known as supramolecular organizing centers (SMOCs) that either eliminate the damaged cells or in some instances promote pro-survival pathways. Dysregulation of SMOCs can lead to inflammation, autoimmune disorder, cancer, and even permit immune evasion by pathogens.

SMOCs serve as hubs for activation of proteases known as caspases, which then cleave several important substrates that regulate a myriad of biological pathways. The SMOCs my lab is interested in regulate cell death pathways known as pyroptosis and apoptosis. The major questions my research program is addressing include: 1) what are the specific insults or danger signals sensed by the PRRs that trigger their activation, 2) what is the molecular mechanism of SMOC assembly and caspase activation, and 3) what are the downstream substrates of caspases and the biological outputs that they regulate? We utilize a variety of techniques to address these questions, including genetics, biochemistry, microscopy, proteomics, and chemical biology. Answers to these key questions will help us develop strategies to modulate the immune system for therapeutic purposes.

Rotation Projects:
Pyroptosis is a type of cell death that is induced by intracellular pathogens or host derived danger signals. Typically, pattern recognition receptors sense the danger signal, bind to the adaptor protein ASC, and recruit the pro-caspase-1 zymogen into a multiprotein signaling platform known as the inflammasome. The oligomerization of pro-caspase-1 enables caspase-1 auto-proteolytic maturation, which then activates cytokines, including IL-1β and IL-18, as ­­­­well as the pore forming protein GSDMD that induces pyroptosis. Some inflammasomes activate caspase-1 without the ASC adaptor protein, resulting in pyroptosis without cytokine maturation. Our goal is to uncover the molecular mechanisms of inflammasome assembly leading to the diverse downstream signaling outputs. This knowledge will aid in developing therapeutics for auto-inflammatory disorders and cancer.

Apoptosis is a type of programmed cell death that is important for maintaining cellular homeostasis. Apoptosis can be activated by a number of diverse stimuli, including genotoxic stress. As DNA damage can lead to oncogenic transformations and many chemotherapeutic drugs induce DNA damage to cause apoptotic cell death in cancer cells, it underscores the need to understand the molecular regulation of apoptosis. We are particularly interested in understanding the regulation of genotoxic stress induced apoptosis. PIDD is a protein that senses genotoxic stress and forms distinct multiprotein signaling platforms like the inflammasome. Depending on the severity of the genotoxic stress, PIDD is thought to initiate a cell survival signaling cascade or a pro-death signaling cascade. Our goal is to elucidate the molecular mechanism of how PIDD senses DNA damage, becomes activated, and regulates cell fate decisions.

Lab Personnel:
The Taabazuing lab is comprised of undergraduates, graduate students, and postdocs. We are looking to accept more trainees at all levels if space is available.