This laboratory has several major interests related to bioregulation
and the molecular biology of disease. Two major research
problems we are currently exploring are:
I. The molecular biological mechanisms through which the immune system and the nervous system interact in health and disease (neuro-immunology). The major hypothesis that guides this work is that the nervous system regulates the immune system through the release of signaling molecules; catecholamines and steroids, which act to modulate genes that regulate ligand-receptor interaction necessary to regulate immune function. Recently we have discovered a catecholamine, cyclic AMP dependent mRNA destabilization system which regulates the availability of mRNA for lymphocyte cell surface proteins. Currently, we are investigating mechanisms that dictate this system. The biomedical importance of this research is that it promises to yield new understandings of the biological basis of stress and its relationship to disease as well as the modulation of anti-tumor immunity.
II. The molecular mechanisms of wound healing. In this research, we had previously found that proteases classically associated with blood clotting, plasminogen activators (PAs) and plasminogen activator inhibitors (PAI), may function in the control of keratinocyte (skin cell) proliferation and differentiation. By utilizing biochemical (enzyme kinetic and substrate studies) and molecular biological (use of transgenic knockout mice and anti-sense RNA) techniques, we are learning how these PAs and PAIs relate to the maintenance of tissue homeostasis, developmental biology and molecular medicine. In addition to gaining new insights into the nature of tissue renewal, this research also relates to cardiovascular disease, molecular hematology and tumor biology.
Other projects being carried out in the laboratory include:
The signal transduction mechanisms through which biologic response modifiers including tumor promoters, cyclic nucleotides and neurotransmitters affect lymphocytes and keratinocytes.
The function and regulation of Thy 1 protein and other cell surface recognition proteins in lymphocytes and keratinocytes. The role of cyclic nucleotides in host-microbe interactions.
The use of the enzyme aspartate amino transferase to diagnose active
destructive inflammatory disease (e.g., chronic
inflammatory periodontal diseases).
Publications
Chambers DA, Perlman RL, and Cohen RL (1993): Neuroimmune modulation:
Signal transduction and catecholamines.
Neurochem International. 22:95Ð110.
Cook-Mills J, Mokyr MB, Cohen RL, Perlman RL, and Chambers DA (1995):
Neurotransmitter suppression of the in vitro
generation of a cytotoxic T-lymphocyte response against the syngeneic
MOPC-315 plasmacytoma. Cancer Immunol
Immunother. 40:79Ð87.
Chambers DA (1995): The double helix, 40 years, prospective and perspective. Ann NY Acad Sci. 758:1Ð471
Cook-Mills J, Perlman RL, and Chambers DA (1995): Inhibition of lymphocyte
activation by catecholamines: Evidence for a
non-classical mechanism of catecholamine action. Immunology 85:544Ð549.
Wajeman-Chao SA, Lancaster SA, Graf LH Jr, and Chambers DA (1998): Mechanism of catecholamine-mediated destabilization of mRNA encoding Thy-1 protein in T lineage cells. J Immunol. 161:4825Ð4833.
Bator JM, Cohen RL, and Chambers DA (1998): Hydrocortisone regulates
the dynamics of plasminogen activator and
plasminogen activator inhibitor expression in cultured murine keratinocytes.
Exp Cell Res. 242:110Ð119.
Kalinichenko VV, Mokyr MB, Graf LH Jr, Cohen RL, and Chambers DA (1999):
Norepinephrine-mediated inhibition of antitumor cytototic lymophocyte generation
involves a-, b- adrenergic receptor mechanism and decreased TNF-a expression.
J Immun. 162, Sept. 1.