Kimm Hamann, Ph.D.

Roles and Mechanisms of Apoptosis in Hematopoiesis and Inflammation.

Research Summary

Our research focuses primarily on the role of the TNF family death receptors, particularly Fas/CD95 receptor, in hematopoiesis and inflammation, and on the mitochondrial pathways of cell death in ischemia/reperfusion injury of cardiomyocytes. Studies currently are focused on inflammatory cells, whose numbers increase dramatically and chronically in certain disease states, and examine the role(s) of apoptosis in both the production (hematopoiesis) of these cells and the resolution of inflammation. Further, we are examining the expression of FasL by airway epithelial cells and their interactions with eosinophils in pulmonary inflammatory states such as asthma. Additional asthma-related studies include investigations of corticosteroid and beta-agonist effects on inflammatory cell apoptosis, and the effects of therapeutics on molecular pathways involved in cell survival. As another major and related focus of our laboratory, we are investigating Fas-mediated, "downstream" activation of the nuclear transcription factor, NF-kB, and the role of its gene targets in apoptosis of inflammatory cells. In cardiomyocytes, we currently are studying molecular mechanisms of apoptosis and "preconditioning"-induced protection against apoptosis, including NF-kB-mediated events, and involvement of other protective molecules.

Selected Papers

Hamann KJ, Dorscheid DR, Sperling AI, Ko F, Adams K, Gruenert DC and White SR. (1998). Co-expression of Fas (CD95) and FasL (CD95L) in human airway epithelial cells. Am J Respir Cell Molec Biol 19:537-542.

Hamann KJ, Viera JE, Halayko AJ, Dorscheid D, White SR, Forsythe SM, Camoretti-Mercado B, Rabe KF and Solway J. (2000). Fas (CD95) crosslinking induces apoptosis in human airway smooth muscle cells. Am J Physiol 278:L618-624.

Farrokh-siar L, Rezai K, Palmer E, Van Seventer J, Hamann K, Rajadurai H, Patel S, Ernest T and Van Seventer G. (2002). Human fetal retinal pigment epithelium induces apoptosis in human T-cell line Jurkat which is independent from its expression of TRAIL. Curr. Eye Research 24:206-13.

Qin Y, Camoretti-Mercado B, Blokh L, Long CG, Ko FD and Hamann KJ. (2002). Fas resistance of leukemic eosinophils is due to activation of NF-kB by Fas ligation. J Immunol 169:3536-3544.

Qin Y, Vanden Hoek TL, Wojcik K, Li CQ, Shao ZH, Anderson T, Becker LB and Hamann KJ. (2003). Reperfusion, not simulated ischemia, initiates intrinsic apoptosis injury in cardiomyocytes. Am J Physiol 284:H141-H150.

Qin Y, Vanden Hoek TL, Wojcik K, Li CQ, Shao ZH, Anderson T, Becker LB and Hamann KJ. (2003). Caspase-dependent cytochrome c relaease in reperfusion-induced apoptosis of ischemic cardiomyocytes (Submitted).