Eusondia Arnett, Ph.D.

Staff Scientist II | Dr. Larry Schlesinger's Lab | Host Pathogen Interaction

Tuberculosis (TB) is a leading cause of death worldwide, and is caused by the intracellular bacterium Mycobacterium tuberculosis. M. tuberculosis infects and resides within alveolar macrophages, which are unable to clear the bacteria.  Dr. Arnett’s research goal is to further elucidate the interactions that occur between M. tuberculosis and the host macrophage, to increase understanding regarding why these macrophages are unable to clear M. tuberculosis.

 


Inside the Lab

In Dr. Larry Schlesinger’s lab, Dr. Arnett studies the nuclear receptor peroxisome proliferator-activated receptor (PPAR) gamma, which is critical for M. tuberculosis growth in macrophages. Her work has identified molecules upstream of PPAR gamma activation as well as novel effectors of PPAR gamma which regulate apoptosis during M. tuberculosis infection. Apoptosis is an important defense mechanism that prevents M. tuberculosis growth, and she has found that targeting this pathway significantly reduces M. tuberculosis growth, providing new potential targets for host-directed therapy for M. tuberculosis.

Granulomas are a histopathologic hallmark of TB that have classically been thought of as a host response to limit M. tuberculosis growth. However, granulomas, which are recalcitrant to antibiotics, also provide a niche for M. tuberculosis persistence. Through use of an in vitro granuloma model, the lab has started to interrogate the role of the host immune response in granuloma formation and development. Dr. Arnett is involved in expanding this in vitro granuloma model, and is using it to study HIV and TB co-infections. HIV and TB are well established co-morbidities, but the underlying mechanisms for this are incompletely understood. Dr. Arnett will use this model to elucidate the role of the host response and HIV on M. tuberculosis granulomas.

Main Technologies and Methods Used

  • Isolation and differentiation of primary human cells
  • Gene knockdown and over expression
  • qRT-PCR
  • Western blotting
  • Immunofluorescence microscopy