Hongbo R. Luo

Department of Pathology, Harvard Medical School

Department of Lab Medicine, Children’s Hospital Boston

10214 Karp Building, 1 Blackfan Circle

Boston, MA 02115

Tel: 617-910-2303

One of the major players in innate immune system is neutrophil which is the most abundant cell type among circulating white blood cells and constitutes the first line of host defense against invading bacteria and other pathogens. The long-term objective of our research is to elucidate the molecular mechanisms and cellular signaling pathways that control various neutrophil functions. The ultimate goal is to control the number and function of neutrophils during infection and inflammation. Currently, we are particularly interested in signaling pathways mediated by inositol phospholipid PtdIns(3,4,5)P3, inositol phosphates (e.g. InsP4), and reactive oxygen species (ROS). We utilize a wide variety of approaches ranging from basic molecular and cell biology methods to high throughput chemical genetic screening and animal inflammation models to dissect these pathways.

Ongoing studies:

1) Signal pathways mediating neutrophil directional movement.

2) Molecular mechanism of neutrophil spontaneous cell death.

3) Neutrophil homeostasis under normal and inflammatory conditions.

4) Regulation of neutrophil function in bacterial pneumonia.

5) Improving neutrophil performance in granulocyte transfusion.

6) Regulation of hematopoiesis by neutrophils.

References:

Hattori, H., Subramanian, K.K., Sakai, J., Jia, Y., Li, Y., Porter, T.F., Loison, F., Sarraj, B., Kasorn, A., Jo, H., Blanchard, C., Zirkle, D., McDonald, D., Pai, S.Y., Serhan, C.N., and Luo, H.R. (2010). Small-molecule screen identifies reactive oxygen species as key regulators of neutrophil chemotaxis. Proc Natl Acad Sci U S A 107, 3546-3551.

Xu, Y., Loison, F., and Luo, H.R. (2010). Neutrophil spontaneous death is mediated by down-regulation of autocrine signaling through GPCR, PI3Kgamma, ROS, and actin. Proc Natl Acad Sci U S A 107, 2950-2955.

Li, Y., Jia, Y., Pichavant, M., Loison, F., Sarraj, B., Kasorn, A., You, J., Robson, B. E., Umetsu, D. T., Mizgerd, J. P., Ye K., and Luo, H. R. (2009). Targeted deletion of tumor suppressor PTEN augments neutrophil function and enhances host defense in neutropenia-associated pneumonia. Blood 113, 4930-4941.

Jia, Y., F. Loison, H. Hattori, Y. Li, C. Erneux, S. Y. Park, C. Gao, L. Chai, L. E. Silberstein, S. Schurmans, and H. R. Luo (2008). Inositol trisphosphate 3-kinase B (InsP3KB) as a physiological modulator of myelopoiesis. Proc Natl Acad Sci U S A 105: 4739-4744.

Yonghui Jia, Kulandayan K. Subramanian, Christophe Erneux, Valerie Pouillon, Hidenori Hattori, Hakryul Jo, Jian You, Daocheng Zhu, Stephane Schurmans, and Hongbo R. Luo (2007). Inositol 1,3,4,5-tetrakisphosphate negatively regulates chemoattractant-elicited PtdIns(3,4,5)P3 signaling in neutrophils. Immunity 27: 453-467.

Subramanian, K. K., Jia, Y., Jo, H., Loison, F., You, J., Benjamin T. Simms E.J, Mizgerd J.P, and Luo, H. R. Tumor suppressor PTEN is a physiological suppressor of neutrophil function. Blood 2007 109: 4028-4037.

Immunology webpage updated 11/10/2010