Laboratory Edward Pearce

Current Affiliation: Bloomberg Distinguished Professor at the Johns Hopkins University, Baltimore, USA

New contact details

Edward Pearce, Bloomberg Distinguished Professor
Johns Hopkins University
School of Medicine
600 N. Wolfe Street
Baltimore MD 21287
USA

Phone +1 410 955-7866
epearce7@jhmi.edu

The laboratory emphasizes two overlapping areas of research:

**Anabolic metabolism vs catabolic metabolism and the control of dendritic cell immunogenicity vs. tolerogenicity.** PRR agonists, cytokines and nutrient and O2 levels can influence the balance of anabolic to catabolic metabolism, as shown. mTOR and AMPK are important regulators of this metabolic balance and their activation states are highly responsive to a broad array of intracelllar and extracellular signals. Glycolysis coupled to the TCA cycle and citrate export from mitochondria supports an array of biosynthetic processes that are critical for DC activation. In contrast, autophagy and the oxidation of fatty acids and glutamine can create a state in which DCs are tolerogenic.

© O'Neill LA/Pearce EJ 2016

Cells of the innate immune system play important roles in tissue hemostasis and in defense against infection. To a great extent the ability of these cells to serve multiple functions reflects their ability to enact different gene expression programs in response to distinct extra- and intra-cellular activating signals. Recent work has revealed that innate cell activation is highly dependent on metabolic reprogramming. The laboratory is focused on elucidating the mechanisms involved in innate immune cell metabolic reprogramming and the underlying reasons why different types of metabolism are essential to support different activation states in these cells.

Different types of infection stimulate distinct types of immune responses. The laboratory is particularly interested in the responses induced by helminth parasites. These multicellular pathogens, which cause disease primarily in developing countries, induce type 2 immunity, which shares features in common with the responses which cause allergy/asthma. Moreover, facets of type 2 immunity are implicated in wound healing, tumor progression and adipose tissue homeostasis. Research in the laboratory asks how type 2 immunity is initiated and maintained, and examines mechanisms that mediate downstream sequelae of these types of immune responses, both beneficial, such as immunity to helminth parasites, and detrimental, such as tissue fibrosis and cancer progression. Many of the effects of type 2 immunity are mediated by the effects of cytokines made by CD4⁺ Th2 lymphocytes and type 2 innate lymphoid cells on macrophages, and the laboratory focuses on the biology of macrophages in these settings, especially from an immunometabolic perspective.