The focus of our research is the role of dead or dying cells in health and disease, especially that within the kidney and the immune system. This has involved two complementary sets of studies and perspectives: (1) alterations in the function of live cells, especially kidney epithelial cells and macrophages, following their receptor-mediated interaction with nearby dead or dying cells (apoptotic and necrotic); and (2) dead cells as a source of auto-antigen and/or immunogen in autoimmune disease, especially systemic lupus erythematosus (SLE) and the anti-phospholipid syndrome (APLS). Within the kidney, interaction with neighboring apoptotic cells causes live cells to stop dividing, cease metabolic activity, and even to die. This effect is specific to kidney cells, as interaction with apoptotic cells causes cells from other organs to proliferate and grow. Our lab is actively studying the mechanisms and consequences of these phenomena.
Patel VA, Massenburg D, Vujicic S, Feng L, Tang M, Litbarg N, Antoni A, Rauch J, Lieberthal W, Levine JS. Apoptotic cells activate AMPK and inhibit epithelial cell growth without change in intracellular energy stores. J. Biol. Chem. 290: 22352-22369 2015 [PMID: 26183782].
Patel VA, Feng L, Lee DJ, Massenburg D, Pattabiraman G, Antoni A, Schwartz JH, Lieberthal W, Rauch J, Ucker DS, Levine JS. Recognition-dependent signaling events in response to apoptotic targets inhibit epithelial cell viability by multiple mechanisms: implications for non-immune tissue homeostasis. J. Biol. Chem. 287: 13761-13777, 2012 [PMID: 22396534].
Levine JS, Subang R, Nasr SH, Fournier S, Lajoie G, Wither J, Rauch J. Immunization with the apoptotic cell binding protein, β2-glycoprotein I, in the presence of lipopolysaccharide recapitulates both autoantibody emergence and nephritis of human SLE. J. Immunol. 177: 6504–6516, 2006 (PMID: 17056583).