Douglas Green, Ph.D.

St. Jude Children’s Research Hospital, Memphis, TN

2014 Distinguished Innovator Awardee

Non-canonical autophagy, phagocytosis, and SLE

The Study and What It Means to Patients

“We will investigate whether a new pathway we discovered that safely disposes of dead cells goes awry in lupus, causing the immune system to attack the body’s cells and tissues. We will apply our innovative approach to the treatment of lupus in animal models, which will lead the way to new strategies for treating lupus in patients.”



SLE may be caused, in part, by a failure to properly dispose of cells that die in our bodies every day.  We have found a process we call LAP that functions in the disposal of dying cells that are eaten by macrophages.  Mice that have macrophage defects in LAP develop lupus-like disease with age.  We will study how LAP serves to prevent disease and develop ways to restore the control of autoimmunity to cells and animals with these defects.  This will pave the way to novel treatment strategies for SLE.

Scientific Abstract

Defects in the clearance of dying cells have been implicated in the process of SLE.  We have identified a novel process, LC3-associated phagocytosis (LAP), in which components of the canonical autophagy pathway are recruited to the phagosomes of macrophages that engulf dying cells.  LAP functions to facilitate the clearance of the cell corpse, and profoundly influences the inflammatory response to dead cell engulfment, decreasing inflammatory cytokine production, increasing anti-inflammatory production, and preventing autoimmunity. 

We will test the hypothesis that LAP contributes to SLE, and may account for genetic associations of autophagy genes with SLE.  Our goals are:  1. To determine if defects in LAP are associated with SLE, and can cause SLE-like disease; 2. To explore how LAP affects specific transcription pathways in phagocytes, and; 3. To identify ways in which to control the inflammatory effects of defective LAP. Our studies will identify pharmacologic approaches to “bypassing” the requirement for LAP to control inflammation and autoimmunity, either by enforcing the process of LAP or by engaging the signaling pathways and transcription factors controlled by LAP.  We will develop animal models of SLE based on defects in LAP and apply our “bypass” approaches to the treatment of disease in these models.