At the Dinh Lab, we are committed to advancing our understanding of the vascular system, particularly its role in immune cell trafficking and disease pathophysiology. By studying these processes, we aim to uncover insights that could lead to new therapeutic strategies for a range of diseases.
Our research focuses on post-capillary venules (PCVs), a specialized type of venular endothelial cell that plays a key role in immune cell extravasation. This process is facilitated by specific interactions between cell surface receptors on PCVs and ligands on immune cells. Understanding these interactions and the molecular mechanisms that regulate them is essential for understanding inflammation and immune responses.
In Peyer’s Patch vasculature, cell specialization is guided by transcription factors such as NKX2-3, COUP-TFII, and HEY1, which regulate mucosal addresins like MAdCAM1 and St6gal1. These genes drive the transformation of capillary endothelial cells (CapECs) into high endothelial venules (HEVs), a process essential for supporting immune cell trafficking. The diagram illustrates how these molecular pathways collaborate to define endothelial cell identity and ensure proper immune function in the gut.
Transcription factor (TF) interactions play a key role in defining the diversity and function of endothelial cells (ECs) involved in immune cell trafficking. Our research focuses on understanding how transcription factors may work together to regulate gene expression programs that define post-capillary venule (PCV) identity, potentially supporting their role in myeloid cell trafficking. Early findings suggest that endothelial cell populations exhibit significant transcriptional diversity, likely driven by TF activity.
Our lab uses single-cell sequencing datasets to study how COUP-TFII (COUP) regulates peripheral node addressin+, which are crucial for immune cell recruitment in secondary lymphoid tissues. By integrating transcriptomic and epigenomic data from wild-type, COUP overexpression (OE), and knockout (KO) endothelial cells, we identify key genes and regulatory elements involved in PCV identity.
We use tools like Loupe, JMP, and AlphaFold to analyze gene expression, predict transcription factor interactions, and pinpoint COUP's role in shaping PCV function. This research enhances our understanding of immune responses and vascular biology.
MSBI students work in collaboration with The Lee Lab @ SJSU to perform more detailed scRNA-seq analysis and build pipelines.