Laboratory of Host Defenses

Sharon H. Jackson, M.D.

Chief, Monocyte Trafficking Unit

Sharon H. Jackson, M.D., received her medical degree from the State University of New York at Buffalo Medical School and completed her pediatrics training at Mount Sinai Hospital, New York. She completed postdoctoral training and subspecialty training in allergy and immunology at NIAID/NIH. Dr. Jackson joined the tenure-track in 2001.

Description of Research Program

Investigations conducted in the Monocyte Trafficking Unit (MTU) are focused on understanding how p47phox, a cytosolic subunit of the phagocyte NADPH oxidase, regulates adaptive and innate immune-cell function. The phagocyte NADPH oxidase has been recognized as the primary innate antimicrobial host defense system used for protection against pathogenic microorganisms. The enzymatic complex consists of the membrane-associated gp91^phox and p22^phox subunits (cytochromeb558) and the cytosolic subunits p47phox, p67^phox , p40phox, and regulatory GTPase Rac2.

January 2009 cover of the American Journal of Pathology, featuring the MTU's image of progressive crystalline macrophage pneumonia. Credit: American Journal of Pathology. Read the journal article.

Chronic granulomatous disease (CGD) is the genetically heterogeneous immunodeficiency syndrome caused by defective or absent NADPH oxidase enzymatic function. 47^phox deficient
(p47^phox-/-) mice are a murine model for the most common autosomal recessive variant of CGD. We are using the p47^phox-/- murine model of CGD as our primary platform to study the specific aim of our research program:

• Understanding how NADPH oxidase p47^phox and/or NADPH oxidase-derived reactive oxygen species (ROS) regulate adaptive immune phenomenon to prevent chronic inflammation and autoimmune disease as well as infection

Ongoing investigations in the MTU revealed that in the absence of NADPH oxidase p47phox, several critical immune cell functions are dysregulated. Specifically, our recent work has shown that NADPH oxidase p47^phox-/- antigen-presenting cells (dendritic cells and macrophages) and T cells exhibit aberrant cytokine responses, and that NADPH oxidase p47^phox-/- T cells also exhibit an intrinsic survival defect. These observations extend the function of p47^phox beyond its recognized role in innate immunity as a regulatory protein in phagocytic cell ROS production, to include the regulation of non-phagocytic cellular networks that affect cell proliferation, cell death, and cytokine secretion.

The interrelated objectives of our research program are to characterize NADPH oxidase p47^phox regulation of the following:

• Antigen-presenting cell maturation and function
• T-cell homeostasis and function
• Antigen-presenting cell-T cell interactions
• Inflammation and autoreactive disease pathogenesis

Research Group Members

Nannan Zhu, M.D. Senior Biologist	Liang Yi, Ph.D. Research Scientist
Brent Elliott, B.A. Research Scientist	Sam Vasilevsky, Ph.D. Postdoctoral Fellow
Qui Liu, M.D. Postdoctoral Fellow	Emmanuel Onyeyirim, B.S. Post-Baccalaureate Student

Information for Prospective Laboratory Trainees

Important objectives of our program are research and training. If you wish to inquire about postdoctoral training or other positions in the MTU, contact Dr. Jackson directly.

Selected Publications

For a complete listing, visit PubMed.

Donaldson M, Antignani A, Milner J, Zhu N, Wood A, Cardwell-Miller L, Changpriroa CM, Jackson SH. p47(phox)-deficient immune microenvironment signals dysregulate naive T-cell apoptosis. Cell Death Differ. 2009 Jan;16(1):125-38.

Liu Q, Cheng LI, Yi L, Wood A, Changpriroa C, Ward JM, Jackson SH. p47^phox deficiency induces macrophage dysfunction resulting in progressive crystalline macrophage pneumonia. Am J Pathol. 2009 Jan;174(1):153-63.

Ge Y, Montano I, Rustici G, Freebern WJ, Haggerty CM, Cui W, Ponciano-Jackson D, Chandramouli GV, Gardner ER, Figg WD, Abu-Asab M, Tsokos M, Jackson SH, Gardner K. Selective leukemic-cell killing by a novel functional class of thalidomide analogs. Blood. 2006 Dec 15;108(13):4126-35.

Jackson SH, Yu CR, Mahdi RM, Ebong S, Egwuagu CE. Dendritic cell maturation requires STAT1 and is under feedback regulation by suppressors of cytokine signaling. J Immunol. 2004 Feb 15;172(4):2307-15.

Jackson SH, Devadas S, Kwon J, Pinto LA, Williams MS. T cells express a phagocyte-type NADPH oxidase that is activated after T cell receptor stimulation. Nat Immunol. 2004 Aug;5(8):818-27.

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