Human tissue health is shaped not only by genes and local microenvironments, but also by systemic factors such as neural and endocrine activity, nutritional metabolism, immune responses, environmental stress, and aging. The Zhang laboratory focuses on the systemic regulation of tissue health. We study how brain–body communication at the organismal level and stem cell–immune microenvironment interactions at the tissue level jointly maintain local tissue homeostasis and influence tissue regeneration, barrier defense, and disease.
Using the skin as a primary model and extending into other tissues and extreme physiological states, the laboratory aims to establish a cross-scale framework linking organismal states to local tissue health. We further seek to develop new strategies to promote tissue regeneration, intervene in complex diseases, advance artificial hibernation technologies, and protect tissues and organs.
1. Systemic regulation of local tissue health and aging: Adult stem cells are central to tissue homeostasis, injury repair, and lifelong regeneration. Local tissue states are regulated not only by their microenvironments, but also by systemic physiological signals, including neural and endocrine activity, nutritional metabolism, immune responses, and environmental stress. We study how these signals act through interorgan communication to regulate adult stem cells and their microenvironments, thereby shaping tissue regeneration, homeostasis, adaptation, and aging.
Previous work from the laboratory showed that psychological stress activates cutaneous sympathetic nerves to release norepinephrine, directly driving aberrant activation and depletion of melanocyte stem cells (Nature, 2020) . We also found that intermittent fasting suppresses hair follicle stem cell regeneration through the HPA axis and local adipose metabolic remodeling (Cell, 2025) . These studies demonstrate that systemic physiological states are key determinants of local tissue health. Moving forward, we will further define how neural/endocrine and metabolic signals shape stem cell behavior and tissue microenvironments, and explore intervention strategies to enhance tissue regeneration, delay degenerative changes, and promote tissue rejuvenation.
2. Disease memory mechanisms and intervention in autoimmune diseases: Many autoimmune and chronic inflammatory diseases are characterized by recurrence, local relapse, and long-term persistence. Tissue-resident memory T cells (TRM) and other local immune cells in barrier tissues are essential for rapid immune defense, but under disease conditions they can also drive relapse and chronic inflammation. We study how tissue immune memory is established, maintained, positioned, and reactivated, and how these processes are regulated by epithelial cells, local microenvironments, and systemic neural/endocrine signals.
Recent work from the laboratory revealed that sympathetic–epithelial crosstalk regulates the recruitment, positioning, and immunosurveillance function of skin CD8+ TRM cells, thereby shaping antitumor defense in barrier tissues (Cell, 2026) . This finding suggests that the nervous system can remodel local immune memory through epithelial cells. Building on this direction, we will investigate disease memory mechanisms in recurrent autoimmune diseases such as vitiligo, psoriasis, and alopecia areata. We aim to define how neuro–epithelial–immune interactions determine disease relapse, remission, and tissue injury, and to explore intervention strategies targeting tissue-resident immune cells, chemokine axes, and local neural regulatory pathways.
3. Brain–body communication, stem cell adaptation, and tissue protection during hibernation: Hibernating animals maintain tissue integrity under low body temperature, hypometabolism, and prolonged energetic stress, and rapidly restore physiological function during periodic arousal. This phenomenon provides a unique model for studying tissue protection, stem cell maintenance, and reversible adaptation under extreme physiological conditions. We use laboratory-induced hibernation in hamsters and torpor-like mouse models to investigate how stem cell states, niche architecture, and regenerative programs are dynamically remodeled across the hibernation cycle.
This direction focuses on brain–body communication among brain circuits, circulating hormones, metabolites, and peripheral tissues. We investigate how the central nervous system senses and drives hibernation state transitions, and how these transitions coordinate adaptive changes in the skin and other peripheral tissues. By combining physiological monitoring, neural manipulation, single-cell and spatial multi-omics, tissue functional analysis, cross-species comparison, and AI-assisted analysis, we aim to establish a framework for tissue regeneration control during extreme physiological adaptation and uncover new mechanisms relevant to tissue protection, aging, metabolic adaptation, and regenerative medicine.
