Alexander Hoffmann
Biochemistry: signaling, transcription, computational network; stress and immune responses, apoptosis, proliferation
Biochemistry: signaling, transcription, computational network; stress and immune responses, apoptosis, proliferation
Contact Information
Adjunct Professor of Chemistry and Biochemistry
Office: Natural Sciences Bldg
Phone:
Email: ahoffmann@ucsd.edu
Web: signalingsystems.ucsd.edu
Group: View group members
Office: Natural Sciences Bldg
Phone:
Email: ahoffmann@ucsd.edu
Web: signalingsystems.ucsd.edu
Group: View group members
Education
1994 Ph.D., Rockefeller University
1988 B.A., Cambridge University
1994 Ph.D., Rockefeller University
1988 B.A., Cambridge University
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.
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.
Primary Research Area
Biochemistry
Biochemistry
Interdisciplinary interests
Cellular Biochemistry
Computational and Theoretical
Computational and Theoretical
Image Gallery
Selected Publications
- Cheng CS, Feldman KE, Lee J, Verma S, Huang DB, Huynh K, Chang M, Ponomarenko JV, Sun SC, Benedict CA, Ghosh G, Hoffmann A, "The specificity of innate immune responses is enforced by repression of interferon response elements by NF-κB p50.", Sci Signal, 2011, Vol. 4, Issue 161, ra11 [View Abstract]
- O'Dea E, Hoffmann A, "The regulatory logic of the NF-kappaB signaling system.", Cold Spring Harb Perspect Biol, 2010, Vol. 2, Issue 1, a000216 [View Abstract]
- Shih VF, Kearns JD, Basak S, Savinova OV, Ghosh G, Hoffmann A, "Kinetic control of negative feedback regulators of NF-kappaB/RelA determines their pathogen- and cytokine-receptor signaling specificity.", Proc Natl Acad Sci U S A, 2009, Vol. 106, Issue 24, 9619-24 [View Abstract]
- O'Dea EL, Kearns JD, Hoffmann A, "UV as an amplifier rather than inducer of NF-kappaB activity.", Mol Cell, 2008, Vol. 30, Issue 5, 632-41 [View Abstract]
- Werner SL, Kearns JD, Zadorozhnaya V, Lynch C, O'Dea E, Boldin MP, Ma A, Baltimore D, Hoffmann A, "Encoding NF-kappaB temporal control in response to TNF: distinct roles for the negative regulators IkappaBalpha and A20.", Genes Dev, 2008, Vol. 22, Issue 15, 2093-101 [View Abstract]
- Basak S, Kim H, Kearns JD, Tergaonkar V, O'Dea E, Werner SL, Benedict CA, Ware CF, Ghosh G, Verma IM, Hoffmann A, "A fourth IkappaB protein within the NF-kappaB signaling module.", Cell, 2007, Vol. 128, Issue 2, 369-81 [View Abstract]
- O'Dea EL, Barken D, Peralta RQ, Tran KT, Werner SL, Kearns JD, Levchenko A, Hoffmann A, "A homeostatic model of IkappaB metabolism to control constitutive NF-kappaB activity.", Mol Syst Biol, 2007, Vol. 3, 111 [View Abstract]
- Kearns JD, Basak S, Werner SL, Huang CS, Hoffmann A, "IkappaBepsilon provides negative feedback to control NF-kappaB oscillations, signaling dynamics, and inflammatory gene expression.", J Cell Biol, 2006, Vol. 173, Issue 5, 659-64 [View Abstract]
- Werner SL, Barken D, Hoffmann A, "Stimulus specificity of gene expression programs determined by temporal control of IKK activity.", Science, 2005, Vol. 309, Issue 5742, 1857-61 [View Abstract]
- Hoffmann A, Levchenko A, Scott ML, Baltimore D, "The IkappaB-NF-kappaB signaling module: temporal control and selective gene activation.", Science, 2002, Vol. 298, Issue 5596, 1241-5 [View Abstract]