MD/PhD- Julius Maximilian University, Germany, 1988
Residency- MetroHealth Medical Center, 1991
Pulmonary and Critical Care- MetroHealth Medical Center, 1994
Research
The focus of my research is the study of the immune response during human tuberculosis (TB); particularly cytokine responses to M. tuberculosis (MTB) and its components and their role in depressed anti-MTB defense mechanisms in the peripheral blood and at the site most commonly affected by TB, the lung.
More recently these studies have focused on identifying the contribution of both T-cell and macrophage apoptosis on host immune reactivity in HIV-infected and -uninfected persons with MTB infection/disease, and on identifying the mediators and mechanisms involved.
MTB infection remains a major source of morbidity and mortality worldwide. Yet immune mechanisms involved in preventing initial MTB infection to activate TB are only incompletly understood. Our previous experience using peripheral blood and lung mononuclear cells from TB patients and healty control subjects indicate that immune mechanisms involved in a lack of control of MTB infection likely are multiple, and involve diverse factors such as overproduction of cytokines associated with intense immune activation (TNF) suppressive cytokines (TGF, IL-10) and increased susceptibility of MTB-responsive T-cells newly recruited to the lung to apoptosis.
Studies currently ongoing in my lab are designed to establish the mechanisms involved in apoptosis of (MTB-responsive) T-cells and to identify whether and how cytokine-mediated pathways are involved in the process.
• Hirsch CS, Toossi Z, Vanham G, Johnson JL, Peters P, Okwera A, Mugerwa R, Mugeyenyi P, and Ellner JJ. Apoptosis and T-cell hyporesponsiveness in pulmonary tuberculosis. J Inf Dis 179:945-53, 1999.
• Hirsch CS, Toossi Z, Othieno C, Johnson JL, Schwander S, Robertson S, Wallis RS, Okwera A, Mugerwa R, Edmonds K, Peters P, and Ellner JJ. Depressed T-cell IFN-? responses in pulmonary tuberculosis: Analysis of underlying mechanisms and modulation with therapy. J Inf Dis 180:2069-73, 1999.
• Hirsch CS, Toossi Z, Johnson JL, Luzze H, Ntambi E, Peters P, McHugh M, Okwera A, Joloba M, Mugeyenyi P, Mugerwa RD, Terebuh P, and Ellner JJ. Augmentation of apoptosis and IFN-? production at sites of active MTB infection in human tuberculosis. J Inf Dis,183: 779-88, 2001.
• Ribeiro-Rodrigues R, Resende Co T, Ribeiro F, Palaci M, Johnson JL, Sá RT, Maciel EL, Pereira Lima FL, Dettoni V, Toossi Z, Boom WH, Dietze R, Ellner JJ, and Hirsch CS. Sputum cytokine levels in patients with pulmonary tuberculosis as markers of response to treatment. Clin Diag Lab Immunol, 9:818-823, 2002.
