The goal of this project is to define how basic cellular mechanisms suppress, activate and execute the process of apoptosis or programmed cell death. Apoptosis is a fundamental component of virtually all aspects of biology, being critical for both developmental and cellular homeostasis in all multi-cellular organisms. Extensive studies worldwide have now implicated either excess or impaired apoptosis in numerous human diseases including cancer, AIDS, autoimmune diseases, sepsis, as well as toxic responses to environmental agents. Additionally, many of the therapies used for the treatment of cancer work by the activation of inherent cellular apoptotic programs. A clear understanding of the cellular mechanisms involved in the control of apoptosis will have considerable impact on human health. Although an enormous literature describes agents that induce apoptosis and the signaling pathways that transduce these death signals, very little information exists on how different signals impinge on the common genetic pathway of apoptosis, particularly from a cell biological perspective.

Project Start
Project End
Budget Start
Budget End
Support Year
15
Fiscal Year
2010
Total Cost
$1,096,379
Indirect Cost
City
State
Country
Zip Code
Oakley, Robert H; Ramamoorthy, Sivapriya; Foley, Julie F et al. (2018) Glucocorticoid receptor isoform-specific regulation of development, circadian rhythm, and inflammation in mice. FASEB J :fj201701153R
Whirledge, Shannon D; Kisanga, Edwina P; Oakley, Robert H et al. (2018) Neonatal Genistein Exposure and Glucocorticoid Signaling in the Adult Mouse Uterus. Environ Health Perspect 126:047002
Olivares-Morales, Mauricio Javier; De La Fuente, Marjorie Katherine; Dubois-Camacho, Karen et al. (2018) Glucocorticoids Impair Phagocytosis and Inflammatory Response Against Crohn's Disease-Associated Adherent-Invasive Escherichia coli. Front Immunol 9:1026
Santen, Richard J; Jewell, Christine M; Yue, Wei et al. (2018) Glucocorticoid receptor mutations and hypersensitivity to endogenous and exogenous glucocorticoids. J Clin Endocrinol Metab :
Cain, Derek W; Cidlowski, John A (2017) Immune regulation by glucocorticoids. Nat Rev Immunol 17:233-247
Oakley, Robert H; Busillo, John M; Cidlowski, John A (2017) Cross-talk between the glucocorticoid receptor and MyoD family inhibitor domain-containing protein provides a new mechanism for generating tissue-specific responses to glucocorticoids. J Biol Chem 292:5825-5844
Whirledge, Shannon; Cidlowski, John A (2017) Glucocorticoids and Reproduction: Traffic Control on the Road to Reproduction. Trends Endocrinol Metab 28:399-415
Busada, Jonathan T; Cidlowski, John A (2017) Mechanisms of Glucocorticoid Action During Development. Curr Top Dev Biol 125:147-170
Ramamoorthy, Sivapriya; Cidlowski, John A (2016) Corticosteroids: Mechanisms of Action in Health and Disease. Rheum Dis Clin North Am 42:15-31, vii
Regan Anderson, Tarah M; Ma, Shi Hong; Raj, Ganesh V et al. (2016) Breast Tumor Kinase (Brk/PTK6) Is Induced by HIF, Glucocorticoid Receptor, and PELP1-Mediated Stress Signaling in Triple-Negative Breast Cancer. Cancer Res 76:1653-63

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