Panganiban Lab
Projects

Studying the Molecular Mechanisms Underlying Gene-Environment Interplay in Allergic Diseases

Our lab is focused on the genetic and environmental mechanisms that contribute to the pathogenesis of asthma. By leveraging a combination of laboratory and cross-disciplinary collaborations with scientists from fields such as computational biology, bioinformatics, and epidemiology we aim to better understand the complex factors that drive asthma. By identifying key environmental and genetic factors involved in asthma pathogenesis, we aim to develop new therapeutic strategies that can benefit patients.

Lab Projects (2)

The functional role of GSDMB in asthma

Pyroptosis is a highly inflammatory cell death pathway implicated in various inflammatory diseases. The execution of pyroptosis relies on the activation of gasdermins, which are pore-forming proteins (GSDMA-E and PJVK) expressed in various epithelial tissues, including the airway. When activated, gasdermins release their N-terminal fragment, which forms membrane pores that serve as conduits for the release of inflammatory cytokines. Sustained formation of these pores leads to pyroptosis-mediated cell lysis. Genetic association studies have strongly linked gasdermins in allergic diseases, where GSDMB is strongly associated with asthma by GWAS. However, the molecular mechanisms underlying this association remain unknown. Building on our previous findings that GSDMB is highly expressed in airway epithelial cells and is a pyroptotic executioner (Panganiban et al JACI 2023; Panganiban et al Allergy 2023), we investigate the regulation of GSDMB-mediated pyroptosis in airway epithelial cells through genome-wide CRISPR screen and explore the role of GSDMB and pyroptosis in animal models of asthma.

Mechanistic investigations of the role of polycyclic aromatic hydrocarbons in lung diseases

An emerging focus in our lab is understanding how exposure to polycyclic aromatic hydrocarbons (PAHs) causes airway epithelial dysfunction. Exposure to PAHs has been linked to obstructive airway diseases such as asthma and COPD. PAHs are widespread environmental contaminants produced both from natural sources (e.g. by forest fires and volcanic eruptions) and from human activities (e.g. burning fossil fuels, motor vehicle emissions, cigarette smoking). We are investigating how PAHs, particularly benzo(a)pyrene, contribute to the development of asthma-relevant cellular phenotypes. To achieve this, we are using genome-wide CRISPR screens to identify regulators and suppressors of benzo(a)pyrene-induced NF-ĸB activation in lung epithelial cells. Understanding these molecular processes will advance our mechanistic insights into how exposure to PAHs is linked with lung diseases.

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