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 Langone 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 Repair, and Cancer

Our body’s epithelial barriers, such as the skin, lungs and gut, interface with the external world and are routinely exposed to injurious, microbial, and carcinogenic stimuli. We are studying how barrier tissues sense, respond to, and remember these encounters. We have recently shown that the epithelia, and in particular epithelial stem cells, maintain a memory of inflammation. In this context, we examine how tissue adaptation promotes anti-pathogen responses and repair. On the other hand, maladaptations of inflammatory memory underlie recurrent autoimmune disease and cancers. We thus seek to understand the mechanisms controlling the delicate balance between beneficial and deleterious features of inflammatory memory.

We also aim to understand the role of immune cells in tissue repair and regeneration by studying mechanisms of immune-tissue crosstalk following acute damage and in chronic non-healing conditions such as skin ulcers and intestinal fistulae. Here, we take unbiased approaches to track the evolution of immune populations in wounds and then examine their pro- or anti- repair functions. Cancers have long been called “wounds that don’t heal” and so we parallel our studies in acute wounds with an understanding of cancer development and progression.

Early in Life Immunity

Far from inert, we now appreciate that the early life immune system is dynamic and highly responsive to environmental stimuli. While the development pathways and seeding of immune cells in tissues has been carefully studied, their functional interactions in embryonic and neonatal tissues is poorly understood. We examine how immune cells dialog with tissue stem cells and direct their activation and differentiation. Using sophisticated mouse genetic and in utero gene manipulations systems we are able to deplete specific immune populations or hamper their communications with tissue stem cells. In addition to studying immune-tissue stem cell crosstalk in development, we also evaluate how neonatal immune cells respond to microbial and allergic stimuli in an effort to understand why infants and children are more susceptible to certain infectious and allergic diseases.

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 this 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 Staphylococcus aureus infections and chronic non-healing wounds. By untangling the dynamic interactions between-host and pathogen we aim to uncover new ways to combat these conditions.

Research Support