Quan Lu

Quan Lu

Associate Professor of Environmental Genetics and Pathophysiology

Department of Environmental Health
Department of Genetics and Complex Diseases

665 Huntington Avenue
Building 1, Room 305
Boston, Massachusetts 02115

Research Interests

As the interface between a cell and its environment, the plasma membrane (PM) controls the trafficking into and out of the cell and regulates the signaling of resident receptor proteins. My lab studies how PM trafficking regulates receptor signaling, with a particular focus on how such regulation is perturbed in environmental and lung diseases. Our research is aided by the cutting-edge functional genetics tools (e.g., RNAi and CRISPR screens and Next-Generation sequencing) and by a combination of molecular, cellular and biochemical approaches as well as animal models. Through collaborations with epidemiologists and clinicians, we also aim to understand how individual genetic variations in PM receptor regulation contribute to the susceptibility to environmental and lung diseases in the human population. Major ongoing projects in the lab include:

Signaling and regulation of GPCRs in lung biology and asthma therapy: G-protein-coupled receptors (GPCRs) are the largest protein family encoded by the human genome and play critical physiological roles in the lung. We have focused on the beta-2 adrenergic receptor (B2AR), which mediates the relaxation of airway smooth muscle and is the target of beta-agonists, the mainstay drug for asthma. Using genome-wide RNAi screen, we have identified a number of novel B2AR regulators, including arrestin domain-containing protein 3 (ARRDC3) and farnesyl diphosphate synthase (FDPS). Our work on FDPS directly led to an ongoing pilot clinical trial that aims to test the efficacy of alendronate, an FDPS inhibitor, in improving beta-agonist efficacy in asthmatic patients. More recently, we found that human airway cells express a number of GPCRs that were best known for their functions in the brain and gut. We are testing the hypothesis that these GPCRs and their hormone ligands may provide a signaling link between the lung and the brain/gut. Better understanding of these GPCRs in the lung could lead to new therapeutic targets for asthma and other respiratory diseases. Finally, we are also exploring the role of microRNAs in regulating the expression and signaling of B2AR and other GPCRs in the lung.

Dysregulation of receptor signaling by environmental metal toxicants: Exposure to metal toxicants in the environment such as arsenic and lead (Pb) is linked to a myriad of human diseases and thus is of great concern to public health; yet the underlying molecular mechanisms remain poorly understood. Arsenic is proteotoxic and causes misfolding of cellular proteins; and PM receptors that contain hydrophobic transmembrane domains and are made in the endoplasmic reticulum are particularly vulnerable to the arsenic proteotoxicity. Using genome-wide RNAi screen, my lab identified several genes that regulate arsenic-induced ER stress response. Recently we also obtained evidence that lead (Pb) affects the expression and activity of several PM receptors in cultured neuron stem cells. We are testing a unifying hypothesis that perturbation of the expression and/or integrity of PM receptors represent a common mechanism underlying the pleotropic effects of environmental metal toxicants.

Novel roles of PM-derived microvesicles in receptor signaling and cell communication: We recently discovered that mammalian cells secrete extracellularly a novel type of small vesicles that we named ARMMs (ARRDC1-Mediated Microvesicles). ARMMs are directly generated at the PM and carry receptor proteins. We showed that ARMMs can deliver these receptor proteins into recipient cells to initiate specific signaling. We are investigating the physiological role of ARMMs as a new way of intercellular signaling and inter-tissue communication. We are also exploring the exciting possibility that ARMMs may be harnessed as a novel vehicle for delivering therapeutic molecules into targeted cells.

updated 05/2015

Photo: Kent Dayton/HSPH