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Inflammation & Autoimmunity Group

Directing Immunity to Engulfed Cargo

Jennifer Martinez, Ph.D.
Jennifer A. Martinez, Ph.D.
Principal Investigator
Tel (919) 541-4420
jennifer.martinez3@nih.gov
P.O. Box 12233
Mail Drop D2-01
Research Triangle Park, NC 27709

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Research Summary

Jennifer Martinez, Ph.D. heads the Inflammation and Autoimmunity Group, and holds a secondary appointment in the NIEHS Signal Transduction Laboratory. The Inflammation and Autoimmunity Group investigates the mechanisms by which cargo from the extracellular environment, including pathogens, allergens, and dying cells, is processed by immune cells and how these events influence their pursuant immune response.

The cells of the immune system act as surveyors of the body, patrolling and sampling their surroundings in order to gauge the need for an immune response. Recent evidence revealed that the two evolutionarily conserved pathways of phagocytosis and autophagy can intersect, representing a novel mechanism wherein the crosstalk between engulfment and processing ultimately shapes the immune response. This process, termed LC3-associated phagocytosis (LAP), occurs when an extracellular stimulus is sensed and phagocytosed, triggering the recruitment of some, but not all, components of the autophagy machinery to the pathogen-containing vesicle. It is the activity of these autophagic players that facilitates the rapid destruction of the pathogen via the lysosomal pathway. Not only does LAP play a critical role in the processing of phagocytic cargo, it can also alter the metabolic state of the cells in which it is engaged.

It is well established that the autophagic machinery is often recruited during intracellular infection, and defects in said machinery have been associated with aberrant host defense, inflammatory disease, and age-related disorders. While initial interpretation implicates canonical autophagy in these pathological conditions, it is possible that the defect lies with LAP rather than autophagy. This topic is an emerging field in immunology, and our ability to discriminate between the two processes will have broad applications in tumorigenesis, autoimmunity, and infectious disease.  

LC3-Associated Phagocytosis (LAP)

Major areas of research:

  • Investigating the molecular mechanisms governing the initiation and maintenance of LAP
  • Determining how the molecular mechanisms of LC3-associated phagocytosis regulate other cellular processes, such as innate immunity, antigen presentation, and cellular metabolism
  • Exploring the role of LAP, as opposed to canonical autophagy, in regulating inflammation and autoimmune disorders
  • Identifying LAP-specific infectious pathogens and LAP’s role in controlling these infections
  • Examining the role of LAP in tumorigenesis and clearance of tumor burden
  • Studying the impact of mitophagy deficiency and accumulation of damaged mitochondria on disease pathogenesis

Current projects:

  • Using biochemical and molecular techniques, such immunoprecipitation and siRNA, to delineate the molecular mechanisms that couple receptor-mediated stimulus sensing to recruitment of the autophagic machinery
  • Exploring the mechanisms by which LAP controls lipid/cholesterol sensing and shapes the metabolic profile of the phagocyte
  • Investigating the role of LAP in other phagocytic cells, such as dendritic cells, B cells, and tissue-specific phagocytes
  • Characterizing the Rubicon-/- mouse, where LAP is defective, but canonical autophagy is intact, in models of autoimmunity and infection
  • Using a mouse model where mitophagy is defective ,but canonical autophagy is intact, to study the impact of mitophagy deficiency and accumulation of damaged mitochondria on disease pathogenesis

Martinez earned her B.S. in Cellular and Molecular Biology from Tulane University in 2001 and her Ph.D. in immunology from Duke University in 2010. She began her work on the autophagy machinery and its role in inflammation and host defense as a postdoctoral fellow in the laboratory of Douglas R. Green, Ph.D., at the St. Jude Children’s Research Hospital, Memphis, Tennessee. After completing her fellowship, she joined the NIEHS Immunity, Inflammation, and Disease Laboratory as a Tenure-track Investigator in 2015.

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