B.S. Biology and B.S. Molecular and Microbiology
University of Central Florida 2007
I am examining the effects of different bacterial pathogens on the dynamics and kinetics of the NF-kappaB signaling network. Through these investigations I hope to learn more about how pathogens might alter or disrupt host cell signaling and how different pathogens might elicit different immune responses.
Cheng CS, Feldman KE, et al. The Specificity of Innate Immune Responses Is Enforced by Repression of Interferon Response Elements by NF-B p50. 22 February 2011. Science Signaling. 4 (161), ra11.
B.A. in Molecular Biology, Princeton University 2004
Fellow, National Science Foundation Graduate Research Program
I am interested in the coupling between transcriptional elongation and splicing. In addition to modeling, I am pursuing a high-throughput assay of splicing events in pathogen response genes.
|Control of RelB during dendritic cell activation integrates canonical and noncanonical NF-κB pathways.
Shih VF, Davis-Turak J, Macal M, Huang JQ, Ponomarenko J, Kearns JD, Yu T, Fagerlund R, Asagiri M, Zuniga EI, Hoffmann A.
Nat Immunol. 2012 Dec;13(12):1162-70.
|Human-specific transcriptional networks in the brain.
Konopka G, Friedrich T, Davis-Turak J, Winden K, Oldham MC, Gao F, Chen L, Wang GZ, Luo R, Preuss TM, Geschwind DH.
Neuron. 2012 Aug 23;75(4):601-17
|Transcriptional architecture of the primate neocortex.
Bernard A, Lubbers LS, Tanis KQ, Luo R, Podtelezhnikov AA, Finney EM, McWhorter MM, Serikawa K, Lemon T, Morgan R, Copeland C, Smith K, Cullen V, Davis-Turak J, Lee CK, Sunkin SM, Loboda AP, Levine DM, Stone DJ, Hawrylycz MJ, Roberts CJ, Jones AR, Geschwind DH, Lein ES.
Neuron. 2012 Mar 22;73(6):1083-99
|A multiplex RNA-seq strategy to profile poly(A+) RNA: application to analysis of transcription response and 3′ end formation.
Fox-Walsh K, Davis-Turak J, Zhou Y, Li H, Fu XD.
Genomics. 2011 Oct;98(4):266-71
|Tauopathy with paired helical filaments in an aged chimpanzee.
Rosen RF, Farberg AS, Gearing M, Dooyema J, Long PM, Anderson DC, Davis-Turak J, Coppola G, Geschwind DH, Par JF, Duong TQ, Hopkins WD, Preuss TM, Walker LC.
J Comp Neurol. 2008 Jul 20;509(3):259-70.
B.S. Chemistry, Biochemistry,Seattle Pacific University, 2008
I am interested in the mechanisms of IKK activation and regulation in NFκB signaling.
B.S. Biochemistry and Cell Biology, UCSD
B-cells undergo dramatic expansion during immune response, which involves one of the most rapid proliferation rates known for mammalian cells. B-cell survival and death is highly regulated, and the proliferative program is limited to about 12 divisions.
The NF-kB signaling system plays a critical role in B-cell biology. Two distinct NF-kB activation pathways have been described to induce overlapping sets of NF-kB transcription factors containing the three activation domain containing NF-kB proteins, RelA, RelB, and cRel. My research is focused on understanding which NF-kB dimers control B-cell survival and proliferation. This study is complicated by the overlap of these two B-cell processes, as well as the interdependencies of NF-kB dimers produced by the NF-kB signaling system in response to B-cell activating signals. Using a combination of in depth experimental analysis and mathematical modeling, at both the cellular and molecular levels, I hope to elucidate the homeostatic and dynamic regulation of the NF-kB signaling system in B-cell physiology.
Sun, S., J. Almaden, et al. (2005). “Assay development and data analysis of receptor-ligand binding based on scintillation proximity assay.” Metab Eng 7(1): 38-44.
Humphries, P. S., J. V. Almaden, et al. (2006). “Pyridine-2-propanoic acids: Discovery of dual PPARalpha/gamma agonists as antidiabetic agents.” Bioorg Med Chem Lett 16(23): 6116-9.
Humphries, P. S., S. Bailey, et al. (2006). “Pyridine-3-propanoic acids: Discovery of dual PPARalpha/gamma agonists as antidiabetic agents.” Bioorg Med Chem Lett 16(23): 6120-3.
Ralph, E. C., J. Almaden, et al. (2008). “Glucose modulation of glucokinase activation by small molecules.” Biochemistry 47(17): 5028-36.
Ph.D. Molecular Biology, Univ of Life Sciences (Austria) 2007
Ph.D. student, Salk Institute 2003-2006
M.S. Biotechnology, Univ of Life Sciences (Austria) 2002
Ph.D. General Microbiology, University of Helsinki (2008)
M.S. General Microbiology, University of Helsinki (2003)
Ph.D Physics (Biophysics) (2008)
The University of North Carolina. Chapel Hill, NC
Department of Physics and Astronomy
Program in Cellular and Molecular Biophysics (T. Elston Lab, Dept. of Pharmacology)
Dissertation topic: “Dynamic regulation and information transfer in intracellular-signaling pathways”
M.S. Physics (2005)
The University of North Carolina. Chapel Hill, NC
Department of Physics and Astronomy (Y. Wu Lab)
Masters Topic: “NMR study of Anomalous spin relaxation in carbon nanotubes”
Licentiate Physical Sciences (1999)
University of Buenos Aires. Buenos Aires, Argentina
Check out more about me and my research at CellularCrossroads.org
I am interested in dynamical aspects of intracellular signaling events and the mechanisms that impart signal specificity.
My research goal is to understand the functional principles underlying biological networks. To this end, I use mathematical models, single-cell experiments, and multi-scale computational simulations to gain insight about how cells overcome the operational constraints they face when dealing with changing environmental and internal conditions. Many of the most significant advances in the life sciences arose from collaborations that cut across disciplines. My approach to scientific research is multidisciplinary and collaborative. I expect findings to enable novel therapeutic strategies based on the restoration of malfunctioning information pathways or induction of new patterns of information flow to control cellular functions impacted by disease.
14. Shinohara H*, Behar M*, Inoue K, Hiroshima M, Yasuda T, Nagashima T, Kimura S, Sanjo H, Maeda S, Yumoto N, Ki S, Akira S, Sako Y, Hoffmann A, Kurosaki T, Okada-Hatakeyama M (2014). Positive Feedback Within a Kinase Signaling Complex Functions as a Switch Mechanism for NF-κB Activation, Science, 344, pp.760-764. PMID: 24833394. (* equal contribution)
13. Behar, M., B.arken, D., Werner, S.L., Hoffmann, A (2013). The Dynamics of Signaling as a Pharmacological Target. Cell, 155, pp.448-461. PMID: 24120141.
The equilibrium, quasi-equilibrium, and out-of equilibrium parts of a signal can be manipulated through different perturbation strategies and, under some conditions, selectively suppressed (or enhanced)
12. Mukherjee SP, Behar M, Birnbaum HA, Hoffmann A, Wright PE, et al. (2013). Analysis of the RelA:CBP/p300 Interaction Reveals NF-κB-Driven Transcription. PLoS Biol 11(9): e1001647. doi:10.1371/journal.pbio.1001647. PMID: 24019758.
I’m interested in all things concerning T cells. I received my Ph.D. with studies of T cell cytotoxicity and activation. Currently I’m working on how different IkBs influence T cell proliferation and survival.
|Hydrolysis of tumor cell lipids after cytotoxic T lymphocyte (CTL)-mediated death.
Bryce N. Alves, Jeff Leong, David Tamang, Viki Elliott, Mark Lowe, and Dorothy Hudig.
Int Immunol. 2009 May;21(5):543-53.
|Pancreatic lipase-related protein 2 (PLRP2) induction by IL-4 in CTLs and reevaluation of the negative effects of its gene ablation on cytotoxicity.
Bryce N. Alves, Jeff Leong, David Tamang, Viki Elliott, Jillian Edelnant, Doug Redelman, Cherrie A. Singer, Andy R Kuhn, Rita Miller, Mark E Lowe, and Dorothy Hudig.
J Leukoc Biol. 2009 Sep;86(3):701-12.
|Lipid-dependent cytotoxicity by the lipase PLRP2 and by PLRP2-positive cytotoxic T lymphocytes (CTLs).
Bryce N. Alves, Kristen Marshall, David L.Tamang, Jeff Leong, Doug Redelman, Viki Elliott, Mark E. Lowe, and Dorothy Hudig.
Cell Biochem Funct. 2009 Jul;27(5):296-308
Alex’s interests began to focus on biology when undergraduate research on topoisomerases provided the thrill of discovery while studying for a Physics BA at Cambridge. During his graduate research with Dr. Bob Roeder at Rockefeller University, he cloned genes for TBP and some components of the TFIID complex, and developed the now popular His-tag to purify and characterize recombinant proteins. During his postdoctoral training with Dr. David Baltimore at MIT and Caltech, he first focused on HIV and then aimed to understand the dynamic control of the NFκB signaling network and its ability to produce distinct gene expression programs. Reactivating undergraduate math and physics skills, and with the help of really smart students and postdocs, Alex has pursued a Systems Biology approach (iterating between quantitative experimentation and computational modeling) in order to understand how molecular networks generate precise immune responses to pathogens and control development of the immune system. A recurring theme of our research is that it is the kinetic properties of these regulatory networks that provide the explanations for understanding specificity, robustness, diversification, fine-tuning, and other characteristics of biological processes.
Alex is PI of the Signaling Systems Laboratory, first at UCSD (2003-2013) and then at UCLA (since 2014). At UCSD he was Professor of Chemistry and Biochemistry, and Director of the Graduate Program in Bioinformatics and Systems Biology, was PI of the P50 Center of Excellence for Systems Biology (SDCSB) and co-founded the BioCircuits Institute (BCI). At UCLA he is the Asher Professor of Microbiology in the Department of Microbiology, Immunology and Molecular Genetics (MIMG), and the director of the Institute for Quantitative and Computational Biosciences (QCBio).