Lacy-Hulbert Lab

Adam Lacy-Hulbert Laboratory

The overall interest of the Lacy-Hulbert lab is to understand the mechanisms and consequences of recognition of self and foreign particles by cells of the innate immune system. Innate immunity is the first line of defense against infection and the specialised phagocytes, Dendritic Cells (DCs) and macrophages, are essential regulators of both innate and adaptive immune responses. Innate immune cells also play important roles in development and tissue repair, and contribute to many pathological processes including chronic inflammatory diseases, aging-related disorders and cancer. Finding out how macrophages and DCs recognize potential targets and respond appropriately will be essential for our understanding of both normal developmental processes and a wide range of diseases.

Current work in the laboratory focuses on three main areas:

1. Recognition and removal of apoptotic cells

2. Alpha (v) integrins and immune regulation

3. Development of new methods for gene knockdown and study in vivo

We use a variety of cell and molecular biology approaches including conditional gene targeting in mice and RNAi-mediated gene knockdown in vivo and in vitro to understand how macrophages and DCs recognize and respond to targets, and orchestrate immune responses. Our lab is one of six independent, interdisciplinary, collaborative laboratories that makes up the Program of Developmental Immunology in the Department of Pediatrics at Massachusetts General Hospital/ Harvard Medical School.

Selected Publications

  • Lacy-Hulbert A, Smith AM, Tissire H, Barry M, Crowley D, Bronson RT, Roes JT, Savill JS and Hynes RO. Ulcerative colitis and autoimmunity induced by loss of myeloid av integrins. Proc Natl Acad Sci U S A 2007:104:15823-8.
  • Lacy-Hulbert A, Ueno T, Ito T, Jurewicz M, Izawa A, Smith RN, Chase CM, Tanaka K, Fiorina P, Russell PS, Auchincloss H Jr, Sayegh MH, Hynes RO and Abdi R. Beta 3 integrins regulate lymphocyte migration and cytokine responses in heart transplant rejection. Am J Transplant 2007:7:1080-90.
  • Lucas M, Stuart LM, Zhang A, Hodivala-Dilke K, Febbraio M, Silverstein R, Savill J and Lacy-Hulbert A. Requirements for apoptotic cell contact in regulation of macrophage responses. J Immunol 2006:177:4047-54.
  • Reynolds LE, Conti FJ, Lucas M, Grose R, Robinson S, Stone M, Saunders G, Dickson C, Hynes RO, Lacy-Hulbert A and Hodivala-Dilke K. Accelerated re-epithelialization in beta3-integrin-deficient- mice is associated with enhanced TGF-beta1 signaling. Nat Med 2005: 11:167-74.
  • Devitt A, Parker KG, Ogden CA, Oldreive C, Clay MF, Melville LA, Bellamy CO, Lacy-Hulbert A, Gangloff SC, Goyert SM and Gregory CD. Persistence of apoptotic cells without autoimmune disease or inflammation in CD14-/- mice. J Cell Biol 2004: 167:1161-70.
  • McCarty JH, Lacy-Hulbert A, Charest A, Bronson RT, Crowley D, Housman D, Savill J, Roes J and Hynes RO. Selective ablation of av integrins in the central nervous system leads to cerebral hemorrhage, seizures, axonal degeneration and premature death. Development 2005: 132:165-76.
  • Lucas M, Stuart LM, Savill J and Lacy-Hulbert A. Apoptotic cells and innate immune stimuli combine to regulate macrophage cytokine secretion. J Immunol 2003: 171:2610-5.
  • Stuart LM, Lucas M, Simpson C, Lamb J, Savill J and Lacy-Hulbert A. Inhibitory effects of apoptotic cell ingestion upon endotoxin-driven myeloid dendritic cell maturation. J Immunol 2002:168:1627-35.