Our research aims to understand the molecular mechanisms responsible for protective or pathological immune responses during cancer, viral infection and obesity. We will use this knowledge to design effective strategies for the treatment of type II diabetes and cancer with potential clinical applications. Our research plan consists of three main directions:
1. Immune surveillance and immune escape mechanism of cancer
Our goal is to analyze the cellular and molecular mechanisms controlling tissue residence and circulation, innate immune surveillance and tumor escape. Our previous work has shown that the innate immune system can protect mice from tumor development (O'Sullivan et al., J exp Med 2012).
We are interested in the following questions:
-How are tissue resident immune cells activated by the development of cancer?
-How are circulating natural killer (NK) cells recruited into the tumor microenvironment?
-What are the molecular and cellular mechanisms leading to NK cell dysfunction in the tumor microenvironment?
2. Mechanism of adipose tissue inflammation and insulin resistance during diet induced obesity
Our study first identified the protective and pathological role of tissue resident type 1 innate lymphocytes (ilc1) during viral infection, liver injury and obesity (O'Sullivan et al., immunity 2016; weizman et al., cell 2017; nabekura et al., immunity 2019).
We are interested in the following questions:
-What is the complete cellular composition of mammalian adipose tissue?
-How do cells interact in the adipose tissue microenvironment during homeostasis and obesity?
-What is the cause of adipose tissue inflammation during obesity?
3. Response of ILC to virus infection and generation of immune memory
The innate immune system was previously thought to consist of short-lived cells that perform effector functions during infection and die quickly once they complete their tasks. However, our and other studies have shown that ILC has the characteristics of adaptive immune system, such as clonal amplification, longevity and immune memory (O'Sullivan et al., immunity 2015; weizman et al., Nature Immunology 2019)
We are interested in the following questions:
-What are the transcriptional and epigenetic mechanisms that control the formation of memory cells?
-How do effector lymphocytes survive to form memory cells?