Dr. Dorothy E. Lewis
The University of Texas Health Science Center at Houston
Department of Internal Medicine - Infectious Diseases
- HIV immunology and pathogenesis
- Mechanisms of chronic activation in HIV
- Mechanisms of HIV-associated lipodystrophy
- Microparticles in maternal plasma for fetal genetic diagnosis
- Mechanisms of pre-eclampsia
- Flow cytometric methods
HIV pathogenesis is associated with loss of CD4 T cells, levels of viremia and a third component, chronic activation. Although antiretroviral drugs can limit CD4 loss and stop viremia, chronic activation of the immune system remains a problem and is associated with failure to fully reconstitute CD4 T cells. The mechanisms are unclear but seem to involve chronic exposure of cells of the immune system to microbial products, such as LPS that drive chronic activation. This occurs because of damage to the gut, CD4 loss and intestinal breach. Dr. Lewis has found that memory CD4 T cells make and release massive amounts of the proteolytic enzyme, Granzyme B, which causes bystander cell death and reduced barrier function in an in vitro model of intestinal permeability. Future experiments will address mechanisms of action, as well as examine non human primate models for evidence of granzyme B mediated affects on the intestine.
Chronic HIV infection also causes dysregulation of fat metabolism and Dr. Lewis is interested in immune cell interactions with fat cells. She has shown that monocytes increase pre-adipocyte proliferation, but reduce differentiation in an in vitro model. In vivo experiments with an HIV protein, vpr, shows that fat metabolism is changed in the mice. Future experiments will examine mechanisms for how the immune system in HIV influences fat metabolism and glucose utilization.
Another major area of interest involves non-invasive diagnosis of genetic abnormalities and pathologic pregnancies. Dr. Lewis’s lab has found that fetal DNA is contained within membranes that express cell surface molecules indicative of fetal origin. In addition these bits of cells, called microparticles, are increased in women who develop preeclampsia. Future experiments will perfect the DNA isolation methods and study mechanisms of preeclampsia development.
Dr. Lewis is also an expert in flow cytometry and many of her projects involve assays using this instrument for detection of immune function, cell division and cytokine secretion. The microparticles in plasma are also quantitated and characterized using this instrument.
Graduate student projects could include aspects of HIV pathogenesis or development of non-invasive strategies in pregnancy. Most experiments are done with specimens from humans and in vitro cell lines.
Singh M, S Basu, C Camell, J Couturier, RJ Nudelman, MA Medina, JR Rodgers, DE Lewis. Selective expansion of memory CD4+ T cells by mitogenic human CD28 generates inflammatory cytokines and regulatory T cells. Eur J Immunol 38:1522-1532, 2008.
Feske M, RJ Nudelman, M Medina, J Lew, M Singh, J Couturier, EA Graviss, DE Lewis. IL-7 enhances human antigen-specific memory T-cell responses: importance for improved diagnosis of tuberculosis infection. Clin Vaccine Immunol 15:1616-1622, 2008.
Orozco A, Jorgez C., Ramos W, Popek E., Bischoff F, and DE Lewis. Placental Release of Distinct DNA-associated Microparticles into maternal circulation: Reflective of gestation time and pre-eclampsia. Placenta 30:891-897, 2009
Orozco AF, Lewis DE. Flow cytometric analysis of circulating microparticles in plasma. Cytometry A, 2010 March 16.