DMS • 1 Rope Ferry Road • Hanover, NH 03755-1404 • Voice 603 650-1200 • Fax 603 650-1202 • Toll Free 1 877 DMS 1797
News • Publications • Calendar • Departments • Biomedical Libraries • Computing • Support the School • Directory
| | |
Seth A. Brooks, Ph.D.
Title(s):
Research Assistant Professor of Medicine (Connective Tissue Disease)
Department(s):
Medicine
Microbiology and Immunology
Education:
University of. Pennsylvania, BA Philosophy 1989
University of California, Berkeley, PhD Integrative Biology 1996
Programs:
Immunology Program
Curriculum Vitae:
Brooks_S_CV_2009-02-05.pdf
NIH Biosketch:
Brooks_S_BIO_2009-02-05.pdf
Websites:
http://dms.dartmouth.edu/microbio/
Contact Information:
|
Dartmouth Medical School HB 7506 Hanover NH 03755 |
|
|
Office: 630 East Borwell Phone: 603-650-8065 Email: seth.brooks@dartmouth.edu |
|
Selected Publications: |
|
Emmons J, Townley-Tilson WH, Deleault KM, Skinner SJ, Gross RH, Whitfield ML, Brooks SA |
|
Professional Interests:
Posttranscriptional Regulation of Cytokine Expression
The primary focus of our lab is the study of posttranscriptional regulation of TNF-a. TNF-a is a central mediator of inflammation and is critical to the control of infection and activation of immune response. TNF-a overexpression contributes to a number of disease states, including rheumatoid arthritis, Crohn's Disease, and the cachexia associated with AIDS and malignancy.
At the molecular level, TNF-a biosynthesis is largely regulated at the levels of mRNA stability and translation, each of which is orders of magnitude more important than regulation of gene transcription. The importance of TNF-a post-transcriptional regulation in disease was demonstrated with the generation of mice containing a germ line deletion of the TNF-a 3'UTR ARE. Macrophages and T cells from these mice produced 3 to 10 fold more TNF-a protein than their wild-type counterparts. This effect was mediated solely through increased TNF-a mRNA stability and translation. In addition to insights into the regulation of TNF-a biosynthesis, the relevance of these mice was apparent by the spontaneous development of disease pathology indistinguishable from Rheumatoid Arthritis, Crohn¡¦s Disease and cachexia.
We are currently studying several proteins involved in TNF-a posttranscriptional regulation, including tristetraprolin (TTP), which regulates TNF-a mRNA stability in monocyte/macrophages. Loss of TTP results in increased TNF-a message stability and a consequent increase in TNF-a protein expression, resulting in inflammatory arthritis and cachexia in TTP (-/-) animals. We are also in the process of characterizing the role of several additional proteins we have identified as specifically interacting with the TNF-a 3'UTR In Vivo.
Cancer Immunotherapy
We are also involved in a larger collaborative effort in cancer immunotherapy. These studies focus on the development and optimization dendritic cell based vaccine strategies.
Courses Taught:
Grant Information:
VA Merit Award - 2005-2008. Identification of Proteins Mediating Posttranscriptional TNFa Expression
VA MREP Award - 2002-2005. Characterization of the Mechanism of Action of TTP on mRNA Stability
Hitchcock Foundation - 2003. Identification of the In Vivo mRNA Ligands of Tristetraprolin in Monocytes
Arthrits Foundation Post Doctoral Fellowship - 2000-2002. Identification and Characterization of TTP Interacting Proteins
NRSA Post Doctoral Fellowship -1998-2000. Identification of the mRNA ligands bound by hnRNP A2
Copyright © 2009 Trustees of Dartmouth College