Zhichao Fan, PhD

Neutrophils are the most abundant population of human leukocytes (~60%) and play critical roles in infections and inflammation. Circulating neutrophils are recruited to inflamed or infected tissue. The recruitment cascade is initiated by selectin-mediated rolling and chemokine-triggered integrin-dependent arrest (firm adhesion) of neutrophils on the vascular endothelium under flow. Thus, rolling and arrest are two major processes to target for fighting against inflammatory diseases (decrease rolling and arrest) and infections (increase rolling and arrest). My long-term research interests involve the development of a comprehensive understanding of the mechanism of integrin activation and leukocyte recruitment and how they contribute to human disease, especially inflammation in cardiovascular diseases, which I examine using advanced microscopy, including super-resolution microscopy, high-resolution live-cell imaging, and intravital microscopy. My current ongoing projects include: 1. Molecular mechanism and clinical relevance of the auto-inhibitory in-cis interaction of integrin and their ligands; 2. Identifying new molecules involved in the pathway of integrin activation and clustering; 3. Pharmacology test of drugs targeting integrins in vitro and in disease models (myocardial ischemia-reperfusion injury) 4. High-throughput screening of drugs inhibiting integrin activation and inflammation. 5. Monitoring of leukocyte dynamics in diseases using intravital microscopy and in vivo flow cytometry (IVFC).

[2025] Hypertension-Associated Acetate Deficiency Enhances Platelet Activation and Thrombosis Via Olfr78. [2025] Endolysosomal damage surveillance enables rapid inflammasome sensing of pathogens. [2025] CFTR dictates monocyte adhesion by facilitating integrin clustering but not activation. [2025] Nanoscopy reveals integrin clustering reliant on kindlin-3 but not talin-1. [2025] Different patterns of leukocyte immune responses to infection of ancestral SARS-CoV-2 and its variants. [2024] UBXN9 governs GLUT4-mediated spatial confinement of RIG-I-like receptors and signaling. [2024] Multi-parametric thrombus profiling microfluidics detects intensified biomechanical thrombogenesis associated with hypertension and aging. [2024] Gpx4 Regulates Invariant NKT Cell Homeostasis and Function by Preve