Research

The main theme of our research is to understand host-pathogen interactions for the goal of developing host-directed therapy (HDT) for infectious diseases. We are particularly interested in how the host controls or tolerates acute and chronic infections using functional genomics approaches.

1. Sepsis is an ultimate outcome of any uncontrolled infection and defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Despite considerable advances over the last decades, sepsis is still a leading cause of death in intensive care units, and patients develop prolonged immune paralysis leading to a high incidence of recurrent infections. The team is investigating a) how the host interacts differentially with pathogens during successful and failed control of infections and b) how the host immune system becomes dysfunctional during sepsis. The goals of our current research are to develop HDT against pan-respiratory viruses and to elucidate the mechanisms of immune paralysis in sepsis, using clinical samples and animal models. 

2. Virus-induced cancers account for more than 10 percent of all cancers in humans and all cancer deaths worldwide. The team is currently working on the host genetic landscape of human papillomavirus (HPV)-driven cellular immortalization and transformation. Infection with ‘high-risk’ HPVs cause cervical cancer, oropharyngeal cancer, and other anogenital cancers. Although vaccination could prevent the majority of high-risk HPV infections, vaccine uptake rates remain low in many parts of the world, and HPV vaccination cannot treat precancerous lesions or cancers. Therefore, HPV-associated cancers present an important public health need. The essential drivers of HPV-mediated carcinogenesis are the HPV E6 and E7 oncoproteins, and inhibiting key transforming activities of the high-risk HPV oncoproteins has high potential to treat HPV-positive cancers. The goal of our current research is to understand and inhibit the carcinogenesis by HPV E6/E7, using the functional genomics screens of the human genes.