Li Zhou

There are three major ongoing research projects in my lab:

1.	Epigenetic regulation of skin Langerhans cells and dendritic epidermal T cells
Langerhans cells (LCs) and dendritic epidermal T cells (DETCs) are the two major immune cell populations within the mouse skin epidermis, playing crucial role in skin immunity and disease pathogenesis. Previous lineage tracing studies have disclosed that both LC and DETC derive from embryonic precursors and self-maintaining postnatally. However, comprehensive insights into the regulatory mechanisms governing their ontogeny, homeostasis and function remain elusive. Our laboratory has been focusing on exploring the roles of epigenetic factors, with a specific emphasis on miRNAs and chromatin modulators, including histone lysine demethylase 4 (Kdm4) in the intricate regulation of LCs and DETCs.  

2.	Investigating diversified TGFβ beta signaling pathways in the regulation of skin Langerhans cells 
Langerhans cells (LCs), the skin residing dendritic cells (DCs), control both adaptive immunity and immune tolerance in skin. Transforming growth factor-β1 (TGFβ1) is recognized as a critical factor influencing LC maintenance and function, and TGFβ signals through the interaction of TGFβ receptors to activate distinct intracellular canonical Smad2/3/4 and non-canonical Smad-independent pathways. But detailed TGFβ signaling pathways involved in LC regulation remain elusive.  Using mouse models with spatial- and temporal-specific mutations in TGFβ receptors and related signaling molecules, this project aims to elucidate the context-dependent specificities of TGFβ signaling pathways and the molecular mechanisms governing the regulation of LC embryonic ontogeny, postnatal homeostasis, function, and inflammation-induced repopulation.

3.	The role of histone H2AZ chaperon VPS72 in regulating regulatory T cell functional plasticity in tumor microenvironment 
The immune-suppressive niche within the tumor microenvironment (TME) is a critical factor contributing to tumor immune evasion and progression. Regulatory T cells (Tregs) play a pivotal role in this context. Vacuolar protein sorting 72 homolog (VPS72), a histone chaperone for H2AZ, plays a crucial role in chromatin modification and gene expression. Our previous research has demonstrated a positive correlation between VPS72 and Treg function within the TME. In the upcoming studies, we aim to employ gene deletion mouse models to elucidate the specific roles and underlying mechanisms of VPS72 and the histone variant H2AZ in Treg maintenance, stability, and function within the tumor microenvironment. The findings from this proposed research will not only advance our comprehension of Treg biology but also pave the way for the development of more effective strategies for Treg-based interventions in cancer treatment.