Research

We are studying the dynamic interactions between immune cells, epithelial cells, and microbes in barrier tissues that interface with the environment. Drawing from the fields of immunology, microbiology and stem cell biology we use an interdisciplinary approach to mechanistically understand the factors that dictate barrier tissue fitness and function. By leveraging the abundant clinical resources of the NYU medical center, we are uniquely able to translate our bench side findings to gain a better understanding of human immunity and its role in health and disease.

Inflammation, Tissue Regeneration, and Cancer

Our body’s epithelial barriers, such as the skin, lungs and gut, interface with the external world and consequently are exposed to inflammation inducing stimuli. We are studying how immune and parenchymal cells sense and cope with inflammation in an effort to identify mechanisms of inflammatory resolution. Tissue regeneration, namely the repair of tissues during the re-establishment of homeostasis, is an essential component of resolution.

Conversely, inflammation is critical to achieve optimal healing. We aim to define the immune factors that promote healing, but may also be hijacked to promote cancer. Moreover, we have recently shown that the epithelia, and in particular epithelial stem cells, maintain a memory of inflammation, enhancing their regenerative capacity. These findings point to an altered tissue state following inflammation that extends beyond immunity and suggests that targeting the long-lived cells of a tissue may be a viable strategy for the treatment of inflammatory conditions. Thus, we are dissecting how inflammatory memory in epithelial stem cells and other long lived non-immune cells contribute to recurrent inflammatory disorders.

Host-Microbe Interactions

A veritable garden of commensal bacteria, fungi, and viruses reside in and on our bodies. Far from bystanders, these microbes are essential for maintaining host physiology, providing vital signals to sustain health.

Our lab studies how host-commensal interactions train our epithelial barriers. In particular, we are interested in identifying the spatial and functional interactions between commensal microbes and epithelial stem and differentiated cells at steady state and during wounding. Do certain microbial signals stimulate regeneration and other delay it? Can stem cells sense commensals or is this sensing relegated to their differentiated progeny? Do microbial metabolites condition the epithelia?

Additionally, the invading pathogens that penetrate our boundaries cause tissue damage. The fascinating antagonism between an infection and wound repair is central to the pathology of many diseases including Staphylococcusaureus infections and chronic non-healing wounds. By disentangling the dynamic interactions between-host and pathogen we aim to uncover new ways to combat these conditions.

Early in Life Immunity

An immunologically tolerogenic environment supports gestation, ensuring that the developing fetus is protected from harmful stimuli. Birth is a critical immunological transition from this aseptic intrauterine environment to a terrestrial environment. At birth, how environmental stimuli, such as commensal colonization, are first experienced and then integrated to establish immunological set points is unclear. Moreover, if and how exposures to harmful agents in utero influence formation of epithelial barriers and the context in which the first environmental antigens are perceived is unknown.

We are systematically defining the factors that educate epithelial barriers and immune function early in life. These studies greatly add to our understanding of how neonatal exposure to environmental stimuli establish health and conversely, how harmful exposures may contribute to disease in the long-term.