Alexander Hoffmann
Professor, Chemistry and Biochemistry
Ph.D. The Rockefeller University, New York
Email: ahoffmann@ucsd.edu
Research Interests:
My laboratory is interested in the signaling networks that control immune responses. Over the past few years many important signaling proteins have been identified, but understanding how they control immune responses requires us to look at how they function together within networks. We have developed a mechanistic Systems Biology approach that combines biochemical, cell biological, genome-wide measurements and computational modeling to understand the responses to pathogens. This allows us to focus on the signaling systems’ emergent properties, such as dynamic control, signaling crosstalk, and memory that play important roles in determining the specificity and effectiveness of immune responses. We study tissue cells, macrophages, dendritic cells, B-cell and T-cells, as well as their interaction with each other. NFκB and interferon signaling systems are the primary focus.
Track(s)
Microbiology/Immunology
Molecular Pharmacology
BMS Focus Areas:
Cancer Biology
Bioinformatics
Selected Publications:
25. Hoffmann, A., Levchenko, A., Scott, M., Baltimore, D. 2002 The NF-kB/IkB signaling module: temporal control and selective gene activation. Science, 298, pp. 1241-1245.
37. Werner, S.L., Barken, D., Hoffmann, A. 2005 Stimulus-specificity of gene expression programs determined by temporal control of IKK activity. Science, 309, pp.1857-61.
42. Hoffmann, A., Baltimore, D. 2006 Circuitry of NF-kB Signaling. Immunological Reviews, 210, pp.171-186.
43. Kearns, J.D., Basak, S., Werner, S.L., Huang, C.S., Hoffmann, A. 2006 IkBe provides negative feedback to control NF-kB oscillations, signaling dynamics, and inflammatory gene expression. J. Cell Biol., 173, pp.659-664.
44. Hoffmann, A., Natoli, G., Ghosh, G. 2006 Transcriptional Regulation via the NF-kB Signaling Module. Oncogene 25, pp.6706-6716.
45. Basak, S., Kim, H., Kearns, J.D., Tergaonkar, V., O’Dea, E., Werner, S.L., Benedict, C.A., Ware, C.F., Ghosh, G., Verma, I.M., Hoffmann, A. 2007. A fourth IkB protein within the NF-kB Signaling Module. Cell, 128, pp.369-381.
46. Hoffmann, A., Xia, Y., Verma, I.M. 2007. Inflammatory Tales of Liver Cancer. Cancer Cell, 11, pp.99-101.
47. O’Dea, E.L., Barken, D., Peralta, R.Q., Tran K.T., Werner, S.L., Kearns, J.D., Levchenko, A., Hoffmann, A. 2007. A homeostatic model of IkB metabolism to control constitutive activity. Molecular Systems Biology, 3:111, p.1-7.
49. Basak, S., Shih, V. F.-S., Hoffmann, A. 2008. Generation and activation of multiple dimeric transcription factors within the NF-kB signaling system. Molec. Cell. Biol., 28, pp.3139-3150.
54. O’Dea, E.L., Kearns, J.D., Hoffmann, A. 2008. UV as an amplifier rather than inducer of NF-kB activity. Molecular Cell, 30, pp.632-641.
55. Basak, S., Hoffmann, A. 2008. Crosstalk via the NF-kB Signaling System. Cytokine and Growth Factor Reviews, 19 pp.187-197.
56. Ch’en, I.L., Hedrick, S.M., Hoffmann, A. 2008. NF-kB as a determinant of distinct cell death pathways. Methods in Enzymology, 146, pp.175-187.
57. Werner, S.L., Kearns, J.D., Zadorozhnaya, V., Lynch, C., O’Dea, E., Boldin, M.P., Ma, A., Baltimore, D., Hoffmann, A. 2008. Encoding NF-kB temporal control in response to TNF: distinct roles for the negative regulators IkBa and A20. Genes Dev., 22. pp.2093-2101.
59. Kearns, J.D., Hoffmann, A. 2009. A biochemist’s perspective on computational modeling: lessons from NF-kB. J. Biological Chemistry, 284, pp.5439-43.
60. Loriaux, P., Hoffmann, A. 2009. Of Elections and Cell Death Decisions. Molec Cell, 257, pp.257-8.
62. Shih, V.F.-S., Kearns, J.D., Basak,S., Savinova, O.V., Ghosh, G., Hoffmann, A., 2009, Kinetic control of negative feedback regulators of NF-kB/RelA determines their pathogen- and cytokine-receptor signaling specificity. Proc. Natl. Acad. Sci. USA, 106, pp.9619-9624.
66. O’Dea, E., Hoffmann, A. 2010. The Regulatory Logic of the NFkB Signaling System. Cold Spring Harb Perspect Biol. 2:a000216.
68. Takeda, N., O’Dea, E.L., Doedens, A., Kim, J., Weidemann, A., Stockmann, C., Simon, M.C., Asagiri, M., Hoffmann, A., Johnson, R.S. 2010 Nitric oxide homeostasis is regulated by HIF-1a versus HIF-2a antagonism. Genes Dev, 24, pp.491-501.
69. von Vietinghoff, S., Asagiri, M., Azar, D., Hoffmann, A., Ley, K. 2010 Defective regulation of CXCR2 facilitates neutrophil release from bone marrow causing spontaneous inflammation in severely NF-kappaB-deficient mice. J Immunol. 185, pp.670-8.
70. Rao, P., Hayden, M.S., Long, M., Scott, M.S., West, A.P., Zhang, D., Oeckinghaus, A., Lynch, C., Hoffmann, A., Baltimore, D., Ghosh, S. 2010 IkBb acts to both inhibit and activate gene expression at different stages of the inflammatory response. Nature, 466, pp.1115-9. PMID: 20740013
71. Hasty, J, Hoffmann, A., Golden, S. 2010 Systems Biology of cellular rhythms: from cacophony to symphony. Current Opinion in Genetics and Development, 20, pp.571-3. PMID: 21036033
72. Behar, M., Hoffmann, A. 2010 Temporal Codes of Intra-Cellular Signals. Current Opinion in Genetics and Development, 20, pp.684-693. PMID: 20956081
73. Huxford, T., Hoffmann, A., Ghosh, G. 2011 Understanding the Logic of IkB:NF-kB Regulation in Structural Terms. Current Topics in Microbiology and Immunology, 349, pp.1-24. PMID: 20845107
74. Shih, V., F.-S., Tsui, R., Caldwell, A., Hoffmann, A. 2011 A single NFkB system for both canonical and non-canonical signaling. Cell Research, 21, pp.86-102. PMID: 21102550
75. Ho, J., Asagiri, M., Hoffmann, A., Ghosh, G. 2011 NF-kB potentiates caspase-independent hydrogen peroxide-induced death. PLOS One, 6(2):e16815 PMID: 21347231
76. Cheng, C.S., Feldman, K., Lee, J., Verma, S., Huang, D.-B., Huynh, K., Chang, M., Ponomarenko, J., Sun, S.-C., Benedict, C.A., Ghosh, G., Hoffmann, A. 2011 The specificity of innate immune responses is enforced by NFkB p50 repressing interferon-regulatory elements (IREs). Science Signaling, 4(161):ra11. PMID: 21343618, PMC3096068.
77. Wuerzberger, S.M, Chen, Y., Yang, D.T., Kearns, J.D., Bates, P.W., Lynch, C., Ladell, N.C., Yu, M., Podd, A., Zeng, H., Huang, T.T., Wen, R., Hoffmann, A., Wang, D., Miyamoto, S. 2011 A critical role of IkBa nuclear export in B-cell maturation and formation of secondary lymphoid tissues. Immunity, 34(2):188-200. PMID: 21333553
78. Schröfelbauer, B., Hoffmann, A. 2011. How do pleiotropic kinase hubs mediate specific signaling by TNFR superfamily members? Immunological Reviews, in press.