The laboratory of Kun Ling, Ph.D., is interested in the mechanisms modulating cell communications. The status of cells in association with the surrounding microenvironment, including attaching to and communicating with the neighboring cells and underlying matrix, is essential for their morphology and behavior. In turn, it affects numerous life events, such as embryogenesis, differentiation, angiogenesis, tissue repair, immune response and cancer progression.
Dr. Ling's laboratory is focused on the roles of phosphoinositide signaling, especially the type I phosphatidylinositol phosphate kinases, in cell adhesion, migration and primary cilia-mediated cell communication, as well as in the related human diseases.
- Molecular mechanisms underlying cell adhesion and migration. Researchers in Dr. Ling's lab have been working on how type Iγ phosphatidylinositol bisphosphate kinase (PIPKIγ), generating lipid second messenger phosphatidylinositol 4,5-bisphosphate (PI4,5P2), regulates cell adhesion and migration, two essential cellular events during embryonic development and cancer metastasis.
- Role of PIPKIγ in cancer progression. Dr. Ling's team has observed that PIPKIγ directly interacts with multiple structural and signaling molecules to support the progression of pancreatic and breast cancers. The team is investigating the underlying mechanism and the possibility of targeting PIPKIγ during clinical practice involving pancreatic or breast cancers.
- PIPKIγ and heart development and function. PI4,5P2 plays a critical role in regulating cytoskeleton organization and intercellular adhesions, which are essential for the development and function of the heart. Using PIPKIγ knockout mice that exhibit cardiomyopathy phenotype, Dr. Ling's group is investigating the connection between defective PIPKIγ and congenital cardiovascular diseases.
- Phosphoinositide signaling and ciliopathies. Ciliopathies are a group of hereditary human syndromes caused by defective primary cilia, the chemical and mechanical sensors of cells. Dr. Ling's group focuses on determining how phosphoinositide signaling, especially PIPKIγ, participates in the biogenesis and function of primary cilia and human ciliopathies, such as polycystic diseases.
Significance to patient care
Phosphoinositide signaling plays important roles in many life events. These include cell adhesion, epithelial morphogenesis, cell migration, vesicular trafficking and tumor metastasis, as well as the development and function of organs such as the kidney and heart.
The goal of Dr. Ling's lab is to understand the role of PIPKIγ in these important cellular processes and life events. The lab's published and preliminary results clearly support that PIPKIγ is required for cancer progression, and its phosphorylation levels are highly correlated with cancer grade. This knowledge will open up new avenues toward the identification of novel therapeutic targets for clinical practices against cancer, cardiovascular diseases and ciliopathies.