Laboratório de Sinalização Celular na Resposta Inflamatória

Líder(es): Larissa Dias da Cunha

Telefone(s): (16) 3315 – 3319

Linha de Pesquisa

Mecanismos moleculares de regulação da imunidade inata por processos autofágicos

Linha gerais/ General outline

Investigação dos mecanismos de sinalização extra- e intracelular e seu papel na regulação da ativação de células da imunidade inata.

Linha de Pesquisa/ Research areas

In our lab, we use a multidisciplinary approach working towards understanding how signaling transduction cascades initiate, progress and ultimately regulate the function of innate immune cells upon activation of a primary function such as phagocytosis. This knowledge is used to gain insight into the pathogenesis of inflammatory disorders (such as autoimmune diseases and cancer), as well as in the mechanisms driving the balance between resistance and tolerance to infections. We currently aim to use cellular and molecular biology, protein biochemistry and immunoassays to investigate the role of the autophagy machinery, a bonafide mechanism of coping with metabolic stresses, in the regulation of phagocytosis by innate immune cells. Phagocytosis of invading microorganisms and dead cells is a primordial function of the immune system, and the phagosome has emerged as an autonomous signaling compartment within the cells. During phagocytosis, diverse components of the autophagy machinery can be recruited to the phagosome membrane, ultimately impacting cell function. In this context, our main current research projects include:

1. To determine the mechanisms of LC3-associated phagocytosis (LAP) induction and
LAPosome maturation.

2. To investigate the molecular mechanisms for the regulation of macrophage function
by LAP.

3. To investigate the consequences of LAP activation in innate immune cells in the pathogenesis of inflammatory diseases and cancer.

Principais Artigos dos últimos 5 anos:

1) Cunha LD, Yang M, Carter R, Clifford G, Harris L, Crawford JC, Quarato G, Boada-Romero E, Kalkavan H, Johnson, MDL; Sivaraman N, Turnis ME, Finkelstein D, Opferman JT, Gawad C, Green DR. 2018LC3-Associated Phagocytosis in Myeloid Cells Promotes Tumor Immune Tolerance. Cell, 175: 1-13.

2) Heckmann BL, Boada-Romero E, Cunha LD, Magne J, Green DR. 2017. LC3-Associated Phagocytosis and Inflammation. Journal of Molecular Biology, epub.

3) Martinez J, Cunha LD, Park S, Yang M, Lu Q, Orchard R, Li Q, Yan M, Janke L, Guy C, Linkermann A, Virgin HW, Green DR. 2016. Noncanonical autophagy inhibits the autoinflammatory, lupus-like response to dying cells. Nature, 533 (7601): 115-19.

4) Martinez J, Malireddi RK, Lu Q, Cunha LD, Pelletier S, Gingras S, Orchard R, Guan JL, Tan H, Peng J, Kanneganti TD, Virgin HW, Green DR. 2015. Molecular characterization of LC3-associated phagocytosis reveals distinct roles for Rubicon, NOX2 and autophagy proteins. Nature Cell Biology, 17(7): 893-906.