Research interests

Innate Immunology

“Innate” – Merriam-Webster.com
in•nate adjective

: existing from the time a person or animal is born

: existing as part of the basic nature of something

 

Natural (innate) immunity as described by Elie Metchnikoff in Immunity in Infective Diseases (1907):

“In natural immunity, the motile phagocytes, having come up to the invaders, perform a second physiological function; they ingest the micro-organisms. Sometimes the leucocytes (sic) devour at one swoop whole masses of these organisms, and carry out their work in a very short time.”

  • Since the time of Metchnikoff, our understanding of natural innate immunity has grown to include a complex interplay of many cell types which have evolved to provide a first line of defense against infection by bacteria, viruses, fungi and parasites
  • In some cases, innate immunity can be turned against the host where unwanted inflammatory responses contribute to various acquired or inherited diseases
  • In the Wallet lab, we study functions of two innate immune cell types – macrophages and dendritic cells (DCs) with the overall goal of understanding how these cells contribute to human disease

 

A key interest is to understand the role of macrophages in HIV-1 infection. As a target for productive HIV infection, macrophages contribute to pathogenesis and persistence of the disease. Once infected by HIV, macrophages become hyper-responsive to subsequent activating stimuli creating an inflammatory environment that is harmful to the patient. We are working to understand the biochemical and molecular mechanisms underlying this hyper-inflammatory phenotype of HIV-infected macrophages.

The greatest challenges facing global efforts to combat HIV are lack of an effective vaccine and lack of a cure. We hope to contribute to finding a cure by pursuing strategies to eliminate persistently-HIV-infected macrophages. As a lentivirus, HIV is able to insert its own genetic material into the DNA of the cells which it infects. Because the virus is now part of the patient, it is necessary to eliminate the infected cells for the patient to be cured. Many researchers are working on strategies to eliminate T lymphocytes that carry HIV DNA. Our approach will focus on targeting HIV-infected macrophages and together we can work towards a cure.

Dendritic cells are the most potent member of a class of cells known as antigen presenting cells (APCs). Upon encounter with a pathogen, DCs are able to ingest the microbe via phagocytosis, become activated, and then digest the microbe to present antigenic peptides to T lymphocytes. In the autoimmune disease type 1 diabetes, the immune system malfunctions by attacking normal tissue (the insulin-producing beta-cells in the pancreas). We are studying the genes which regulate activation of DCs with the goal of uncovering what role DCs play in triggering autoimmune damage to beta-cells.