Thomas A. Hamilton, Ph.D.

Department Chair

Interim Chair Stem Cell Biology and Regenerative Medicine

Lerner Research Institute
9500 Euclid Avenue
Cleveland, Ohio 44195
Location:NE4-314
hamiltt@ccf.org
Phone: (216) 444-6246
Fax: (216) 444-9329



Brief Description

The diversity of the inflammatory process stems from multiple sources, including the complexity of inflammatory stimuli and cell types, the transmembrane and intracellular signaling processes that occur following stimulation, and the large number of independently regulated genes whose expression is subject to modulation during the process.

The primary objective of our research program is to define the molecular events that control the expression of inducible genes during the initiation and resolution of inflammation. An emerging component of these studies includes consideration of the process of cellular stress, also known as the unfolded protein response or endoplasmic reticulum stress. Collectively our research efforts focus on alterations in transcription and mRNA metabolism that can produce significant changes in levels of inflammatory gene products such as chemoattractant cytokines (chemokines) and mediators of cellular stress. Although the mechanisms that increase inflammatory gene expression are important, it is equally necessary to understand negative regulation of these genes since the expression patterns are transient and inappropriate or prolonged expression often results in substantial tissue injury.

The goals of current projects include: (1) identification of mRNA sequence controlling instability and stimulus-induced stabilization, (2) definition of mechanisms through which mRNA decay is achieved, and (3) characterization of the signaling pathways through which inflammatory and cellular stress pathways communicate with one another.

In other words ...

  • Evaluation of mechanisms regulating mRNA half life during inflammatory response
  • Role of upstream open reading frames in regulating cellular stress responses
  • Signal transduction pathways coupling cell stress and inflammatory response in myeloid cells


Shyamasree  Datta Ph.D.
Shyamasree Datta Ph.D.
Research Associate

Location:NE4-300I
Phone:(216) 444-3687
dattas@ccf.org
Fax:(216) 444-9329
laboratory

Paul  Pavicic M.S.
Paul Pavicic M.S.
Lead Research Technologist

Location:NE4-254
Phone:(216) 444-4669
pavicip@ccf.org
Fax:(216) 444-9329
laboratory

Chenyang  Zhao Ph.D.
Chenyang Zhao Ph.D.
Research Associate

Location:NE4-254
Phone:(216) 444-4669
zhaoc@ccf.org
Fax:(216) 444-9329
laboratory


  1. Datta, S., Novotny, M., Pavicic, P.G., Zhao, C., Herjan, T., Hartupee, J., and Hamilton, T.A., Interleukin 17 regulates CXCL1 mRNA stability via an AUUUA/Tristetraprolin independent sequence, J. Immunol. 184 1484-1491, 2010.
  2. Zhao, C., Datta, S., Mandal, P., Xu, D., and Hamilton, T., Stress sensitive reguation of IFRD1 mRNA decay is mediated by an upstream open reading frame (ORF), J. Biol. Chem. 285: 8552-8562, 2010.
  3. Hamilton, T.A., Novotny, M., Pavicic, P. J., Herjan, T., Hartupee, J., Sun, D., Zhao, C., Datta, S., Diversity in Post-Transcriptional Control of Neutrophil Chemoattractant Cytokine Gene Expression, Cytokine, 52: 116-122, 2010
  4. Wan, Y., Xiao, H.,, Affolter, J., Kim, T.W.,, Bulek, K., Chaudhur, S., Carlson, D., Hamilton, T., Mazumder, T., Stark, G.R., Thomas, J., Li, X., IL-1 receptor-associated kinase 2 is critical for LPS-mediated post-transcriptional control, J.Biol. Chem. 284: 20041 - 20051, 2009
  5. Hartupee, J., Liu, C., Novotny, M., Sun, D., Xiaoxia Li, and Thomas A. Hamilton. IL-17 Signaling for mRNA Stabilization Does Not Require TNF Receptor-Associated Factor 6, J. Immunol. 182: 1660 - 1666, 2009
  6. Datta S, Biswas R, Novotny M, Pavicic PG Jr, Herjan T, Mandal P and Hamilton TA. Tristetraprolin regulates CXCL1 (KC) mRNA stability. J. Immunol. 180(4):2545-2552, 2008.
  7. Hartupee, J., Li, X., and Hamilton, T.A., IL-1alpha -induced NFkappaB activation and chemokine mRNA stabilization diverge at IRAK1. J. Biol. Chem. 283:15689-15693 2008