Inflammatory Cell Death

Excessive and systemic inflammatory response results in sepsis which rapidly progresses to shock. The high mortality (50-60%) of sepsis patients necessitates an urgent need for therapies. During sepsis the bacterial and mitochondrial DNA levels released from necrotic cells remain elevated till death, suggestive of massive necrosis of host cells.  We are deciphering the role of necrosome signaling in myeloid cells (monocytes, macrophages and neutrophils) during sepsis. The pathways deciphered will lead to the identification of avenues for therapy.

Cystic Fibrosis

Cystic fibrosis is caused by mutation in the CFTR gene which results in impaired chloride transport in cells. As a result, opportunistic pathogens such as Pseudomonas aeruginosa persist in the lungs of cystic fibrosis patients and are considered to exacerbate the disease. Recurrent episodes of pulmonary symptoms termed "exacerbations" are very common in CF patients and are associated with increased airway inflammation and irreversible loss of lung function. Our laboratory is evaluating whether inflammatory cell death induced by lung resident pathogens results in pulmonary exacerbations in cystic fibrosis, and whether blockade of these pathways can result in better host outcome.

Inflammatory Bowel Disease

Our gut is home to trillions of microbes, wherein the host response to invading pathogens, and tolerance to commensal bacteria is delicately balanced. Imbalance in the immune response and the gut microbiome results in inflammatory bowel disease, which is mediated by complex gene-environment interactions and is prevalent in numerous countries with Canada having the highest world-wide incidence. Crohn’s disease is a subset of IBD that affects 1 in 150 Canadians and requires hospitalization and surgical intervention in extreme cases. There is a need for the development of realistic animal models that mimic Crohn’s disease, so that the pathobiology can be deciphered.  We have recently developed a novel animal model of Crohn’s disease in mice that is based on mutation of the “disease susceptibility” and “disease progression” genes.  We aim to decipher the how the interaction of these two sets of genes leads to the development of fulminant Crohn’s disease.


© 2018 David Cai