Alexander Hoffmann, Ph.D.

Office Address:
570A Boyer Hall
CA

Affiliations
Affiliations
Professor, Microbiology, Immunology & Molecular Genetics
Member, Bioinformatics GPB Home Area, Gene Regulation GPB Home Area, Genetics & Genomics GPB Home Area, Immunity, Microbes & Molecular Pathogenesis GPB Home Area
Biography:

Alexander Hoffmann is the Thomas M Asher Professor of Microbiology and Immunology at UCLA, and the founding director of the Institute for Quantitative and Computational Biosciences (QCBio). Before joining UCLA in 2014, he was Professor of Biochemistry at UCSD; there he founded the San Diego Center for Systems Biology (SDCSB), co-founded the BioCircuits Institute (BCI), and transformed the Graduate Program in Bioinformatics and Systems Biology to span the computational biosciences from biomedical informatics to quantitative biology. He holds degrees in Physics and Zoology (BA, Cambridge University), Biochemistry and Molecular Biology (Ph.D., Rockefeller University) and owes his training to Robert Roeder and David Baltimore, as well as his many computational biology students.

Publications
Hoffmann Alexander Immune Response Signaling: Combinatorial and Dynamic Control. Trends in immunology. 2016; 37(9): 570-2.
Liu Wen-Hsien, Kang Seung Goo, Huang Zhe, Wu Cheng-Jang, Jin Hyun Yong, Maine Christian J, Liu Yi, Shepherd Jovan, Sabouri-Ghomi Mohsen, Gonzalez-Martin Alicia, Xu Shunbin, Hoffmann Alexander, Zheng Ye, Lu Li-Fan, Xiao Nengming, Fu Guo, Xiao Changchun A miR-155-Peli1-c-Rel pathway controls the generation and function of T follicular helper cells. The Journal of experimental medicine. 2016; 213(9): 1901-19.
Mitchell Simon, Vargas Jesse, Hoffmann Alexander Signaling via the NFκB system. Wiley interdisciplinary reviews. Systems biology and medicine. 2016; 8(3): 227-41.
Cheng Zhang, Hoffmann Alexander A stochastic spatio-temporal (SST) model to study cell-to-cell variability in HIV-1 infection. Journal of theoretical biology. 2016; 395(3): 87-96.
Junkin Michael, Kaestli Alicia J, Cheng Zhang, Jordi Christian, Albayrak Cem, Hoffmann Alexander, Tay Savaş High-Content Quantification of Single-Cell Immune Dynamics. Cell reports. 2016; 15(2): 411-22.
Almaden Jonathan V, Liu Yi C, Yang Edward, Otero Dennis C, Birnbaum Harry, Davis-Turak Jeremy, Asagiri Masataka, David Michael, Goldrath Ananda W, Hoffmann Alexander B-cell survival and development controlled by the coordination of NF-κB family members RelB and cRel. Blood. 2016; 127(10): 1276-86.
Xu Jinjin, Zhou Lei, Ji Lei, Chen Fengyuan, Fortmann Karen, Zhang Kun, Liu Qingwu, Li Ke, Wang Weicang, Wang Hao, Xie Wei, Wang Qingwei, Liu Jiang, Zheng Biao, Zhang Pei, Huang Shixia, Shi Tieliu, Zhang Biaohong, Dang Yongyan, Chen Jiwu, O'Malley Bert W, Moses Robb E, Wang Ping, Li Lei, Xiao Jianru, Hoffmann Alexander, Li Xiaotao The REGγ-proteasome forms a regulatory circuit with IκBɛ and NFκB in experimental colitis. Nature communications. 2016; 7(10): 10761.
Suryawanshi Gajendra W, Hoffmann Alexander A multi-scale mathematical modeling framework to investigate anti-viral therapeutic opportunities in targeting HIV-1 accessory proteins. Journal of theoretical biology. 2015; 386(10): 89-104.
Fagerlund Riku, Behar Marcelo, Fortmann Karen T, Lin Y Eason, Vargas Jesse D, Hoffmann Alexander Anatomy of a negative feedback loop: the case of IκBα. Journal of the Royal Society, Interface. 2015; 12(110): 0262.
Fortmann Karen T, Lewis Russell D, Ngo Kim A, Fagerlund Riku, Hoffmann Alexander A Regulated, Ubiquitin-Independent Degron in IκBα. Journal of molecular biology. 2015; 427(17): 2748-56.
Cheng Zhang, Taylor Brooks, Ourthiague Diana R, Hoffmann Alexander Distinct single-cell signaling characteristics are conferred by the MyD88 and TRIF pathways during TLR4 activation. Science signaling. 2015; 8(385): ra69.
Ourthiague Diana R, Birnbaum Harry, Ortenlöf Niklas, Vargas Jesse D, Wollman Roy, Hoffmann Alexander Limited specificity of IRF3 and ISGF3 in the transcriptional innate-immune response to double-stranded RNA. Journal of leukocyte biology. 2015; 98(1): 119-28.
Tsui Rachel, Kearns Jeffrey D, Lynch Candace, Vu Don, Ngo Kim A, Basak Soumen, Ghosh Gourisankar, Hoffmann Alexander IκBβ enhances the generation of the low-affinity NFκB/RelA homodimer. Nature communications. 2015; 6(21): 7068.
Spreafico Roberto, Mitchell Simon, Hoffmann Alexander Training the 21st Century Immunologist. Trends in immunology. 2015; 36(5): 283-5.
Shokhirev Maxim N, Almaden Jonathan, Davis-Turak Jeremy, Birnbaum Harry A, Russell Theresa M, Vargas Jesse A D, Hoffmann Alexander A multi-scale approach reveals that NF-κB cRel enforces a B-cell decision to divide. Molecular systems biology. 2015; 11(1): 783.
Jiang Miao, Österlund Pamela, Fagerlund Riku, Rios Diana N, Hoffmann Alexander, Poranen Minna M, Bamford Dennis H, Julkunen Ilkka MAP kinase p38α regulates type III interferon (IFN-λ1) gene expression in human monocyte-derived dendritic cells in response to RNA stimulation. Journal of leukocyte biology. 2015; 97(2): 307-20.
Davis-Turak Jeremy C, Allison Karmel, Shokhirev Maxim N, Ponomarenko Petr, Tsimring Lev S, Glass Christopher K, Johnson Tracy L, Hoffmann Alexander Considering the kinetics of mRNA synthesis in the analysis of the genome and epigenome reveals determinants of co-transcriptional splicing. Nucleic acids research. 2015; 43(2): 699-707.
Mitchell Simon, Tsui Rachel, Hoffmann Alexander Studying NF-κB signaling with mathematical models. Methods in molecular biology (Clifton, N.J.). 2015; 1280(4-5): 647-61.
Almaden Jonathan V, Tsui Rachel, Liu Yi C, Birnbaum Harry, Shokhirev Maxim N, Ngo Kim A, Davis-Turak Jeremy C, Otero Dennis, Basak Soumen, Rickert Robert C, Hoffmann Alexander A pathway switch directs BAFF signaling to distinct NFκB transcription factors in maturing and proliferating B cells. Cell reports. 2014; 9(6): 2098-111.
Selimkhanov Jangir, Taylor Brooks, Yao Jason, Pilko Anna, Albeck John, Hoffmann Alexander, Tsimring Lev, Wollman Roy Systems biology. Accurate information transmission through dynamic biochemical signaling networks. Science (New York, N.Y.). 2014; 346(6215): 1370-3.
Caldwell Andrew B, Cheng Zhang, Vargas Jesse D, Birnbaum Harry A, Hoffmann Alexander Network dynamics determine the autocrine and paracrine signaling functions of TNF. Genes & development. 2014; 28(19): 2120-33.
Shinohara Hisaaki, Behar Marcelo, Inoue Kentaro, Hiroshima Michio, Yasuda Tomoharu, Nagashima Takeshi, Kimura Shuhei, Sanjo Hideki, Maeda Shiori, Yumoto Noriko, Ki Sewon, Akira Shizuo, Sako Yasushi, Hoffmann Alexander, Kurosaki Tomohiro, Okada-Hatakeyama Mariko Positive feedback within a kinase signaling complex functions as a switch mechanism for NF-κB activation. Science (New York, N.Y.). 2014; 344(6185): 760-4.
Alves Bryce N, Tsui Rachel, Almaden Jonathan, Shokhirev Maxim N, Davis-Turak Jeremy, Fujimoto Jessica, Birnbaum Harry, Ponomarenko Julia, Hoffmann Alexander IκBε is a key regulator of B cell expansion by providing negative feedback on cRel and RelA in a stimulus-specific manner. Journal of immunology (Baltimore, Md. : 1950). 2014; 192(7): 3121-32.
Vogel Christoph F A, Khan Elaine M, Leung Patrick S C, Gershwin M Eric, Chang W L William, Wu Dalei, Haarmann-Stemmann Thomas, Hoffmann Alexander, Denison Michael S Cross-talk between aryl hydrocarbon receptor and the inflammatory response: a role for nuclear factor-κB. The Journal of biological chemistry. 2014; 289(3): 1866-75.
Feldman Kristyn E, Loriaux Paul M, Saito Mayuko, Tuero Iskra, Villaverde Homarh, Siva Tenaya, Gotuzzo Eduardo, Gilman Robert H, Hoffmann Alexander, Vinetz Joseph M Ex vivo innate immune cytokine signature of enhanced risk of relapsing brucellosis. PLoS neglected tropical diseases. 2013; 7(9): e2424.
Behar Marcelo, Barken Derren, Werner Shannon L, Hoffmann Alexander The dynamics of signaling as a pharmacological target. Cell. 2013; 155(2): 448-61.
Mukherjee Sulakshana P, Behar Marcelo, Birnbaum Harry A, Hoffmann Alexander, Wright Peter E, Ghosh Gourisankar Analysis of the RelA:CBP/p300 interaction reveals its involvement in NF-κB-driven transcription. PLoS biology. 2013; 11(9): e1001647.
Mulero María Carmen, Ferres-Marco Dolors, Islam Abul, Margalef Pol, Pecoraro Matteo, Toll Agustí, Drechsel Nils, Charneco Cristina, Davis Shelly, Bellora Nicolás, Gallardo Fernando, López-Arribillaga Erika, Asensio-Juan Elena, Rodilla Verónica, González Jessica, Iglesias Mar, Shih Vincent, Mar Albà M, Di Croce Luciano, Hoffmann Alexander, Miyamoto Shigeki, Villà-Freixa Jordi, López-Bigas Nuria, Keyes William M, Domínguez María, Bigas Anna, Espinosa Lluís Chromatin-bound IκBα regulates a subset of polycomb target genes in differentiation and cancer. Cancer cell. 2013; 24(2): 151-66.
Shokhirev Maxim Nikolaievich, Hoffmann Alexander FlowMax: A Computational Tool for Maximum Likelihood Deconvolution of CFSE Time Courses. PloS one. 2013; 8(6): e67620.
Behar Marcelo, Hoffmann Alexander Tunable signal processing through a kinase control cycle: the IKK signaling node. Biophysical journal. 2013; 105(1): 231-41.
Loriaux Paul Michael, Hoffmann Alexander A protein turnover signaling motif controls the stimulus-sensitivity of stress response pathways. PLoS computational biology. 2013; 9(2): e1002932.
Polley Smarajit, Huang De-Bin, Hauenstein Arthur V, Fusco Amanda J, Zhong Xiangyang, Vu Don, Schröfelbauer Bärbel, Kim Youngchang, Hoffmann Alexander, Verma Inder M, Ghosh Gourisankar, Huxford Tom A structural basis for IκB kinase 2 activation via oligomerization-dependent trans auto-phosphorylation. PLoS biology. 2013; 11(6): e1001581.
Loriaux Paul Michael, Tesler Glenn, Hoffmann Alexander Characterizing the relationship between steady state and response using analytical expressions for the steady states of mass action models. PLoS computational biology. 2013; 9(2): e1002901.
Longo Diane M, Selimkhanov Jangir, Kearns Jeffrey D, Hasty Jeff, Hoffmann Alexander, Tsimring Lev S Dual delayed feedback provides sensitivity and robustness to the NF-κB signaling module. PLoS computational biology. 2013; 9(6): e1003112.
Shih Vincent F-S, Davis-Turak Jeremy, Macal Monica, Huang Jenny Q, Ponomarenko Julia, Kearns Jeffrey D, Yu Tony, Fagerlund Riku, Asagiri Masataka, Zuniga Elina I, Hoffmann Alexander Control of RelB during dendritic cell activation integrates canonical and noncanonical NF-κB pathways. Nature immunology. 2012; 13(12): 1162-70.
Wang Vivien Ya-Fan, Huang Wendy, Asagiri Masataka, Spann Nathanael, Hoffmann Alexander, Glass Christopher, Ghosh Gourisankar The transcriptional specificity of NF-κB dimers is coded within the κB DNA response elements. Cell reports. 2012; 2(4): 824-39.
Schröfelbauer Bärbel, Polley Smarajit, Behar Marcelo, Ghosh Gourisankar, Hoffmann Alexander NEMO ensures signaling specificity of the pleiotropic IKKβ by directing its kinase activity toward IκBα. Molecular cell. 2012; 47(1): 111-21.
Jiao Baowei, Ma Hong, Shokhirev Maxim N, Drung Alexander, Yang Qin, Shin JongDae, Lu Shaolei, Byron Meg, Kalantry Sundeep, Mercurio Arthur M, Lawrence Jeanne B, Hoffmann Alexander, Bach Ingolf Paternal RLIM/Rnf12 is a survival factor for milk-producing alveolar cells. Cell. 2012; 149(3): 630-41.
Loriaux Paul M, Hoffmann Alexander A framework for modeling the relationship between cellular steady-state and stimulus-responsiveness. Methods in cell biology. 2012; 110(1): 81-109.
Tam Arvin B, Mercado Ellen L, Hoffmann Alexander, Niwa Maho ER stress activates NF-κB by integrating functions of basal IKK activity, IRE1 and PERK. PloS one. 2012; 7(10): e45078.
Busino Luca, Millman Scott E, Scotto Luigi, Kyratsous Christos A, Basrur Venkatesha, O'Connor Owen, Hoffmann Alexander, Elenitoba-Johnson Kojo S, Pagano Michele Fbxw7α- and GSK3-mediated degradation of p100 is a pro-survival mechanism in multiple myeloma. Nature cell biology. 2012; 14(4): 375-85.
Basak Soumen, Behar Marcelo, Hoffmann Alexander Lessons from mathematically modeling the NF-κB pathway. Immunological reviews. 2012; 246(1): 221-38.
Escoubet-Lozach Laure, Benner Christopher, Kaikkonen Minna U, Lozach Jean, Heinz Sven, Spann Nathan J, Crotti Andrea, Stender Josh, Ghisletti Serena, Reichart Donna, Cheng Christine S, Luna Rosa, Ludka Colleen, Sasik Roman, Garcia-Bassets Ivan, Hoffmann Alexander, Subramaniam Shankar, Hardiman Gary, Rosenfeld Michael G, Glass Christopher K Mechanisms establishing TLR4-responsive activation states of inflammatory response genes. PLoS genetics. 2011; 7(12): e1002401.
Murray Susan E, Polesso Fanny, Rowe Alexander M, Basak Soumen, Koguchi Yoshinobu, Toren Katelynne Gardner, Hoffmann Alexander, Parker David C NF-κB–inducing kinase plays an essential T cell–intrinsic role in graft-versus-host disease and lethal autoimmunity in mice. The Journal of clinical investigation. 2011; 121(12): 4775-86.
Schröfelbauer Bärbel, Hoffmann Alexander How do pleiotropic kinase hubs mediate specific signaling by TNFR superfamily members?. Immunological reviews. 2011; 244(1): 29-43.
Ho Jessica Q, Asagiri Masataka, Hoffmann Alexander, Ghosh Gourisankar NF-κB potentiates caspase independent hydrogen peroxide induced cell death. PloS one. 2011; 6(2): e16815.
Wuerzberger-Davis Shelly M, Chen Yuhong, Yang David T, Kearns Jeffrey D, Bates Paul W, Lynch Candace, Ladell Nicholas C, Yu Mei, Podd Andrew, Zeng Hu, Huang Tony T, Wen Renren, Hoffmann Alexander, Wang Demin, Miyamoto Shigeki Nuclear export of the NF-κB inhibitor IκBα is required for proper B cell and secondary lymphoid tissue formation. Immunity. 2011; 34(2): 188-200.
Cheng Christine S, Feldman Kristyn E, Lee James, Verma Shilpi, Huang De-Bin, Huynh Kim, Chang Mikyoung, Ponomarenko Julia V, Sun Shao-Cong, Benedict Chris A, Ghosh Gourisankar, Hoffmann Alexander The specificity of innate immune responses is enforced by repression of interferon response elements by NF-κB p50. Science signaling. 2011; 4(161): ra11.
Shih Vincent Feng-Sheng, Tsui Rachel, Caldwell Andrew, Hoffmann Alexander A single NFκB system for both canonical and non-canonical signaling. Cell research. 2011; 21(1): 86-102.
Huxford Tom, Hoffmann Alexander, Ghosh Gourisankar Understanding the logic of IκB:NF-κB regulation in structural terms. Current topics in microbiology and immunology. 2011; 349(1): 1-24.
Hasty Jeff, Hoffmann Alexander, Golden Susan Systems biology of cellular rhythms: from cacophony to symphony. Current opinion in genetics & development. 2010; 20(6): 571-3.
Behar Marcelo, Hoffmann Alexander Understanding the temporal codes of intra-cellular signals. Current opinion in genetics & development. 2010; 20(6): 684-93.
Rao Ping, Hayden Mathew S, Long Meixiao, Scott Martin L, West A Philip, Zhang Dekai, Oeckinghaus Andrea, Lynch Candace, Hoffmann Alexander, Baltimore David, Ghosh Sankar IkappaBbeta acts to inhibit and activate gene expression during the inflammatory response. Nature. 2010; 466(7310): 1115-9.
von Vietinghoff Sibylle, Asagiri Masataka, Azar David, Hoffmann Alexander, Ley Klaus Defective regulation of CXCR2 facilitates neutrophil release from bone marrow causing spontaneous inflammation in severely NF-kappa B-deficient mice. Journal of immunology (Baltimore, Md. : 1950). 2010; 185(1): 670-8.
Longo Diane M, Hoffmann Alexander, Tsimring Lev S, Hasty Jeff Coherent activation of a synthetic mammalian gene network. Systems and synthetic biology. 2010; 4(1): 15-23.
Takeda Norihiko, O'Dea Ellen L, Doedens Andrew, Kim Jung-whan, Weidemann Alexander, Stockmann Christian, Asagiri Masataka, Simon M Celeste, Hoffmann Alexander, Johnson Randall S Differential activation and antagonistic function of HIF-{alpha} isoforms in macrophages are essential for NO homeostasis. Genes & development. 2010; 24(5): 491-501.
Brunner Alexander, Horisberger Monika, Ulmar Benjamin, Hoffmann Alexander, Babst Reto Classification systems for tibial plateau fractures; does computed tomography scanning improve their reliability?. Injury. 2010; 41(2): 173-8.
O'Dea Ellen, Hoffmann Alexander The regulatory logic of the NF-kappaB signaling system. Cold Spring Harbor perspectives in biology. 2010; 2(1): a000216.
Bergqvist Simon, Alverdi Vera, Mengel Benedicte, Hoffmann Alexander, Ghosh Gourisankar, Komives Elizabeth A Kinetic enhancement of NF-kappaBxDNA dissociation by IkappaBalpha. Proceedings of the National Academy of Sciences of the United States of America. 2009; 106(46): 19328-33.
Ramirez-Carrozzi Vladimir R, Braas Daniel, Bhatt Dev M, Cheng Christine S, Hong Christine, Doty Kevin R, Black Joshua C, Hoffmann Alexander, Carey Michael, Smale Stephen T A unifying model for the selective regulation of inducible transcription by CpG islands and nucleosome remodeling. Cell. 2009; 138(1): 114-28.
Shih Vincent F-S, Kearns Jeffrey D, Basak Soumen, Savinova Olga V, Ghosh Gourisankar, Hoffmann Alexander Kinetic control of negative feedback regulators of NF-kappaB/RelA determines their pathogen- and cytokine-receptor signaling specificity. Proceedings of the National Academy of Sciences of the United States of America. 2009; 106(24): 9619-24.
Savinova Olga V, Hoffmann Alexander, Ghosh Gourisankar The Nfkb1 and Nfkb2 proteins p105 and p100 function as the core of high-molecular-weight heterogeneous complexes. Molecular cell. 2009; 34(5): 591-602.
Loriaux Paul, Hoffmann Alexander Of elections and cell-death decisions. Molecular cell. 2009; 34(3): 257-8.
Kearns Jeffrey D, Hoffmann Alexander Integrating computational and biochemical studies to explore mechanisms in NF-{kappa}B signaling. The Journal of biological chemistry. 2009; 284(9): 5439-43.
O'Dea Ellen, Hoffmann Alexander NF-κB signaling. Wiley interdisciplinary reviews. Systems biology and medicine. 2009; 1(1): 107-15.
Ch'en Irene L, Beisner Daniel R, Degterev Alexei, Lynch Candace, Yuan Junying, Hoffmann Alexander, Hedrick Stephen M Antigen-mediated T cell expansion regulated by parallel pathways of death. Proceedings of the National Academy of Sciences of the United States of America. 2008; 105(45): 17463-8.
Werner Shannon L, Kearns Jeffrey D, Zadorozhnaya Victoria, Lynch Candace, O'Dea Ellen, Boldin Mark P, Ma Averil, Baltimore David, Hoffmann Alexander Encoding NF-kappaB temporal control in response to TNF: distinct roles for the negative regulators IkappaBalpha and A20. Genes & development. 2008; 22(15): 2093-101.
O'Dea Ellen L, Kearns Jeffrey D, Hoffmann Alexander UV as an amplifier rather than inducer of NF-kappaB activity. Molecular cell. 2008; 30(5): 632-41.
Basak Soumen, Hoffmann Alexander Crosstalk via the NF-kappaB signaling system. Cytokine & growth factor reviews. 2008; 19(3-4): 187-97.
Cheng Christine S, Johnson Tracy L, Hoffmann Alexander Epigenetic control: slow and global, nimble and local. Genes & development. 2008; 22(9): 1110-4.
Basak Soumen, Shih Vincent Feng-Sheng, Hoffmann Alexander Generation and activation of multiple dimeric transcription factors within the NF-kappaB signaling system. Molecular and cellular biology. 2008; 28(10): 3139-50.
Ch'en Irene L, Hedrick Stephen M, Hoffmann Alexander NF-kappaB as a determinant of distinct cell death pathways. Methods in enzymology. 2008; 446(3-4): 175-87.
Mathes Erika, O'Dea Ellen L, Hoffmann Alexander, Ghosh Gourisankar NF-kappaB dictates the degradation pathway of IkappaBalpha. The EMBO journal. 2008; 27(9): 1357-67.
Kato Tomohisa, Gotoh Yusuke, Hoffmann Alexander, Ono Yoshitaka Negative regulation of constitutive NF-kappaB and JNK signaling by PKN1-mediated phosphorylation of TRAF1. Genes to cells : devoted to molecular & cellular mechanisms. 2008; 13(5): 509-20.
Fusco Amanda J, Savinova Olga V, Talwar Rashmi, Kearns Jeffrey D, Hoffmann Alexander, Ghosh Gourisankar Stabilization of RelB requires multidomain interactions with p100/p52. The Journal of biological chemistry. 2008; 283(18): 12324-32.
Cheong Raymond, Hoffmann Alexander, Levchenko Andre Understanding NF-kappaB signaling via mathematical modeling. Molecular systems biology. 2008; 4(3-4): 192.
Hoffmann Alexander, Xia Yifeng, Verma Inder M Inflammatory tales of liver cancer. Cancer cell. 2007; 11(2): 99-101.