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Alexander Hoffmann
Biochemistry: signaling, transcription, computational network; stress and immune responses, apoptosis, proliferation |
| Contact Information |
| Office: NSB 3328 |
| Phone: (858) 822-4670 |
| Fax: (858) 822-4671 |
| Email: ahoffmann@ucsd.edu |
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| Education and Appointments |
| 1994 |
Ph.D., Rockefeller University
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| 1988 |
B.A., Cambridge University
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| Awards and Academic Honors |
| 2007 |
Hellman Faculty Fellow |
| 2005 |
Ellison Medical Foundation New Scholar in Aging |
| 1998-2002 |
postdoctoral associate, Caltech |
| 1998-2000 |
Gordon Ross Medical Foundation postdoctoral fellowship |
| 1996-98 |
Jane Coffin Child postdoctoral fellowship |
| 1995-1998 |
postdoctoral associate, MIT |
| 1993-1994 |
Arnold and Mabel Beckman graduate fellowship |
| 1991-1993 |
Boehringer Ingelheim Foundation Graduate Fellowship |
| Research Interests |
Mammalian cells respond to the environmental stresses and pathogens, and to inter-cellular signals in order to protect the organism, and coordinate an immune response. Each signal activates the expression of a specific set of genes, utilizing signaling pathways in the cell.
Our interest focuses on the IºB/NF-ºB signaling network, which transmits signals that regulate inflammation, immunity, and environmental stress responses. In many human diseases (e.g. cancer, immunodeficiencies, and arthritis) this pathway is deregulated. Multiple IºB and NF-ºB proteins form protein families and mediate stimulus-specific signal transduction through overlapping but distinct functions. The goal of our research program is to elucidate signal transduction mechanisms within the IºB/NF-ºB pathway and the specificity of its components as they relate to the stimulus-specific, gene-specific, and cell type-specific responses underlying diverse physiological functions.
In our research we combine genetics (knockout mice and cell lines, and retroviral transgenic approaches to perturb signaling), immunology and cancer cell biology (characterize phenotypes of mutant mice), biochemistry (track signaling intermediates and identify novel signal transducers), molecular biology (construct mutants, genome wide expression studies) to develop a computational model of IºB/NF-ºB signaling that allows in silico exploration of cell signaling. Computational simulations lead to predictions about natural responses and disease processes - these are then tested experimentally. We hope not only to contribute generalizable insights into cellular signaling, but also to provide leads for therapeutic strategies for a number of human diseases.
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| Primary Research Area: |
Interdisciplinary Specialties: |
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Biochemistry
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Cellular Biochemistry
Computational and Theoretical
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| Selected Publications |
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Cooperation of multiple signaling pathways in CD-40-regulated gene expression in B lymphocytes. With H. Dadgostar, B. Zanegar, X-F. Qin, U. Truong, G. Rao, D. Baltimore, and G. Cheng. Proc. Natl. Acad. Sci. USA 99, 1497 (2002).
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The NF-ºB/IºB signaling module: temporal control and selective gene activation. With A. Levchenko, M. Scott, and D. Baltimore. Science 298, 1241 (2002).
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Genetic analysis of NF-ºB/Rel transcription factors reveals molecular specificities. With T.H. Leung and D. Baltimore, EMBO J., 22, pp.5530-9 (2003).
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CK2 is a C-terminal IºB kinase responsible for NF-ºB activation during the UV response. With T. Kato, M Delhase, and M. Karin. Mol. Cell, 12, 829 (2003).
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Unique CD40-mediated biological program in B-cell activation requires both type 1 and type 2 NF-ºB pathways. With B. Zarnegar, J. He, D. Baltimore, and G. Cheng. Proc. Natl. Acad. Sci. USA, 101, 8108 (2004).
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One nucleotide in a ºB site can determine cofactor specificity for NF-ºB dimers. With T.H. Leung and D. Baltimore. Cell 118, pp.453-464 (2004).
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Comment on Oscillations in NF-ºB Signaling Control of Dynamics of Gene Expression . With D. Barken, C.J. Wang, J. Kearns, R. Cheong, and A. Levchenko. Science 308, pp.52a. (2005)
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Initiation and termination of NF-ºB signaling by the intracellular protozoan Toxoplasma gondii. With S. Shapira, O.S. Harb, J. Margarit, M. Matrajt, J. Han , J., B. Freedman, M.J. May, D.S. Roos, C.A. Hunter. J. Cell Sci. 118, pp.3501-3508 (2005).
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Induction of NR4A orphan nuclear receptor expression in macrophages in response to inflammatory stimuli. With L. Pei, A. Castrillo, M. Chen, P. Tontonoz. J. Biol. Chem., 280, pp.29256-62 (2005).
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Molecular determinants of crosstalk between nuclear receptors and Toll-like Receptors mediating counter-regulation of inflammatory responses. With S. Ogawa, J. Lozach, C. Benner, G. Pascual, R.K. Tangirala, S. Westin, S. Subramaniam, M. David, M.G. Rosenfeld, and C.K. Glass. Cell 122, pp.707-21 (2005).
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