The research focus of this laboratory is the signaling and activities of myeloid cells, especially neutrophils and macrophages, during inflammation and its resolution.

One area of active research is the identification and harnessing of signals for the normal resolution of inflammation, recognizing that such signals could provide therapeutic strategies to curtail inappropriate, injurious, or chronic inflammation. For example, with collaborators, we have investigated programmed cell death by apoptosis and identified signals and pathways for corpse clearance in an anti-inflammatory process termed efferocytosis.

A second area of research has been defining the role of activated neutrophils in programming of macrophages in acute inflammation, and more specifically, signals downstream of the active NADPH oxidase.

Using mass spectrometry, my laboratory with collaborators identified lysophosphatidylserine (lysoPS), an oxidant-modified lipid accumulating in neutrophils following activation of the NADPH oxidase. This led to the discovery that activated neutrophils displaying lysoPS are recognized by g-protein coupled receptors on macrophages leading to their removal often prior to any evidence of their cell death. In the absence of a functioning NADPH oxidase, e.g., Chronic Granulomatous Disease (CGD), lysoPS is not made by neutrophils and these cells are poorly cleared from inflammatory lesions.

We have also demonstrated that the absence of NADPH oxidase activity leads to deficient PPARγ signaling in CGD macrophages altering their programming and diminishing their capacity to clear apoptotic cells. Investigation of the PPARγ agonist, pioglitazone has shown promise in rectifying this deficiency and is currently under investigation in a trial of a PPARγ agonist in human CGD with our collaborator Dr. Seven Holland at the NIH.

Recently, in collaboration with Dr. Henson, we have shown that the neutrophil NADPH oxidase plays a central orchestrating role over the recruitment of monocytes, and more broadly, the activities and fate of these cells and monocyte-derived macrophages in acute inflammation.

Armed with the means of precisely identifying, isolating and analyzing macrophage populations and programming, we embark on this new project to determine the key signals between activated neutrophils and macrophages in this intimate relationship. An understanding of such signals may provide therapeutic insights for chronic inflammation, not only in CGD, but in other inflammatory settings as well. 

 

Learn about Open Positions in the Lab

The Bratton Lab is currently recruiting a senior researcher and postdoctoral fellows. Interested candidates should visit our career website for more information.

 

Collaborators

Peter Henson, Ph.D.

William Janssen, M.D.

David Riches, Ph.D.

Claudia Jakubzick, Ph.D.

Elizabeth Redente, Ph.D. 

 

Current Funding

  • R01AI141389 Neutrophil Nox2 controls mononuclear cell functions in inflammation: Role in CGD

  • U01AI122269 Treatment of CGD with the PPAR-gamma agonist, pioglitazone, enhances phagocyte anti-inflammatory and antimicrobial responses

  • R01AI110408 - Reversal of inflammatory processes in CGD

 

Contact Information

brattond@njhealth.org

 

Publications

http://www.ncbi.nlm.nih.gov/sites/myncbi/donna.bratton.1/bibliography/43657942/public/?sort=date&direction=ascending