| VAMC
111R
4150 Clement St.
San Francisco, CA 94121
phone:
415-750-2104
fax: 415-750-6920
email: bseaman@medicine.ucsf.edu
Dr. Seaman received his M.D. from Harvard Medical School in 1969. He completed his medical residency at the Massachusetts General Hospital and was a postdoctoral fellow in the Arthritis and Rheumatism Branch of the NIAMDD/NIH. He then joined the faculty of the Department of Medicine at UCSF, where he served as Chief of the Arthritis/Immunology Section at the San Francisco VA Medical Center (1981-92) and as Chief of the Medical Service at San Francisco VA Medical Center (1992-1999). In addition to his own research, directs the San Francisco Laboratory within the Alliance for Cellular Signaling, a consortium of laboratories dedicated to the definition of pathways for transmembrane and intracellular signaling.
Research Interests
The Seaman laboratory is interested in the cell surface receptors that either activate or inhibit leukocytes involved in the regulation of immunity and autoimmunity. These cells include T cells, natural killer (NK) cells, and cells of monocyte/macrophage lineage. Our current work is focused in particular on a receptor called TREM-2 and on receptors for ferritin.
TREM-2 is expressed on activated macrophages and on cells derived from this lineage, including microglia, osteoclasts, and dendritic cells. The ligands from TREM-2 are not known, but we have demonstrated that TREM-2 binds to astrocytes and neurons and to a broad range of bacteria. We are studying the role of TREM-2 in response to pathogens by macrophages and in the response by microglia to brain injury and inflammation.
In 2005, we demonstrated in mice that TIM-2, a receptor that is structurally to TREM‑2, serves as a receptor for H-ferritin, allowing the uptake of ferritin by cells. This was the first demonstration of a receptor for H-ferritin. Tim-2 is not expressed in humans, but part of our current work regards cloning a ferritin receptor in humans.
Studies in the Seaman lab relate to the Alliance for Cellular Signaling, a consortium of laboratories directed by Al Gilman, Ph.D., University of Texas Southwestern Medical Center, Dallas (http://www.signaling-gateway.org ). The focus of the Alliance is cell signaling by macrophages. Dr. Seaman directs The San Francisco Laboratory, which has been studying in particular the mechanisms by which different G-protein-coupled receptors synergize in activating macrophages.
Recent Publications
Daws MR, Sullam PM, Niemi EC, Chen TT, Seaman WE. Ligand binding by TREM-2: pattern recognition of anionic ligands. J Immunol. 171:594-599, 2003
Chen TT, Brown EJ, Huang EJ, Seaman WE. Expression and activation of signal regulatory protein a on astrocytomas. Cancer Res. 64:117-27, 2004.
Chen TT, Li L, Chung D-H, Allen CDC, Torti SV, Torti FM, Cyster JG, Chen C, Brodsky, FM, Niemi EC, Nakamura MC,Seaman WE, Daws MR. TIM-2 is expressed on B cells and in liver and kidney and it is a receptor for H‑ ferritin endocytosis. J Exp Med. 202:955-65, 2005.
Charles JF, Humphrey MB, Zhao X, Quarles E, Nakamura MC, Aderem A, Seaman WE, Smith KD. The innate immune response to Salmonella by macrophages is dependent on TREM2-DAP12. Infect Immun 2008 Apr 7 (Epub ahead of print].
Roach TI, Rebres RA, Fraser ID, Decamp DL, Mean-Lin K, Sternweis PC, Simon MI, Seaman WE. Signaling and crosstalk by C5a and UDP in macrophages selectively use PLC b 3 to regulate intracellular free calcium. J Biol Chem. 2008 Apr 14 [Epub ahead of print].
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