Patrick Haslett, M.D.

Assistant Professor of Microbiology and Immunology
Room 743, Batchelor Children's Research Institute
1580 NW 10th Avenue
Telephone: 305-243-2189
Fax: 305-243-7211
Email: phaslett@med.miami.edu

Research Interests:

Our laboratory is concerned with understanding mechanisms of immune damage associated with infection with human immune deficiency virus (HIV). While recent advances in the chemotherapy of HIV infection have dramatically improved the prognosis for sufferers of this disease, perhaps half of all patients do not enjoy the full benefit of treatment, because of drug resistance or difficulty tolerating therapy. Thus, the need for new therapies is underlined by increasing recognition of the limitations of currently available anti-HIV treatments. Based on evidence that host immunity can provide protection from progression of HIV disease, our approach is to evaluate methods of enhancing HIV-specific T cell immunity. Our work is patient-oriented, involving analysis of cellular immune responses in materials derived from HIV-infected individuals. Our long-term goal is to translate findings from such investigations into novel approaches to treatment of HIV disease.

There are two main projects currently under way in the laboratory:

1. We are conducting an analysis of the potent immune modulatory drug thalidomide in patients with chronic HIV disease. Recently, we described the activity of this compound as a costimulator of T cells, and subsequently demonstrated the immune stimulatory effect of this agent when administered to patients with HIV infection. Our data suggest that this drug may have activity as an immune adjuvant, and may be used to enhance desirable immune responses directed against HIV, and to boost responses to vaccines. To test this, we are conducting a controlled clinical trial in patients with chronic HIV infection. Endpoints include boosted HIV-specific CD8 and CD4 T cell responses, and enhanced priming of T cell responses to an experimental immunogen. Together with in depth immunologic analysis, we are conducting studies of viral turnover and genetic diversity to see whether treatment-associated changes in immune function correspond to changes in viral replication. In parallel with these clinical studies, we are pursuing a laboratory-based investigation to analyze the cellular and molecular mechanisms of action of thalidomide and potent analog drugs derived from the parent molecule.

2. HIV-infected patients exhibit a wide range of immune system destruction at the time that treatment with anti-HIV chemotherapy is initiated. Although some studies have shown that the extent of immune destruction, as measured by peripheral blood CD4+ T cell counts, predicts to some extent the degree of immune recovery following effective treatment, there has been very little analysis of the recovery of HIV-specific T cell immunity as a function of pre-treatment immune damage. We are presently devising highly sensitive ex vivo assays of HIV-specific cellular immune function to enable us to address questions such as these. In this regard, our central approach is to exploit the extraordinary efficiency of dendritic cells to stimulate antigen-specific T cell responses, taking advantage of recent advances that have facilitated generating these cells from patient blood. The large and highly diverse HIV-infected population of patients attending University of Miami-affiliated clinics allows us to design studies to investigate questions such as these.

Selected Publications:

Larsson M, Fonteneau JF, Lirvall M, Haslett P, Lifson JD, Bhardwaj N. Activation of HIV-1 specific CD4 and CD8 T cells by human dendritic cells: roles for cross-presentation and non-infectious HIV-1 virus. AIDS. 2002 Jul 5;16(10):1319-29.

Larsson M, Wilkens DT, Fonteneau JF, Beadle TJ, Merritt MJ, Kost RG, Haslett PA, Cu-Uvin S, Bhardwaj N, Nixon DF, Shacklett BL. Amplification of low-frequency antiviral CD8 T cell responses using autologous dendritic cells. AIDS. 2002 Jan 25;16(2):171-80.

Hanekom WA, Hughes J, Haslett PA, Apolles P, Ganiso V, Allin R, Goddard E, Hussey GD, Kaplan G. The immunomodulatory effects of thalidomide on human immunodeficiency virus-infected children. J Infect Dis. 2001 Nov 1;184(9):1192-6.