Brooks Taylor

TITLE: Postdoctoral scholar
EMAIL: b4taylor@nullucla.edu
OFFICE: Boyer 570
EDUCATION:
B.S. (Biomedical Engineering) University of Virginia (2009)
Ph.D. (Bioengineering) University of California San Diego (2015)

Research Interests

NF-κB controls some of the most potent antiviral and antibacterial machinery that mammalian cells possess. It’s activated by hundreds of different signals, be they exogenous, endogenous, or synthetic. Tens of negative feedback regulators of NF-κB have been identified, which all serve to attenuate its activity. And while proper activation of NF-κB is a hallmark of a functional inflammatory response, improper activation is associated with pathologies in conditions ranging from Alzheimer’s to cancer to atherosclerosis.

We’ve seen tantalizing glimpses that NF-κB activates via intricately-controlled dynamics of translocation to and from the nucleus, and it’s been hypothesized that these patterns might convey information, allowing a cell to discriminate between different inputs using this single transcription factor. However, we’re still unclear on what these specific dynamic codes are, and how the information they convey might be decoded by the cell.

Using single-cell microscopy and automated tracking and measurement, I’m hoping to help crack the NF-κB dynamical code. I think it’s likely that NF-κB dynamics can convey information, not just about the nature of a particular stimulus, but about the disease state of a cell. Knowing what healthy and aberrant NF-κB dynamics look like (and even how to modulate one into the other) could afford new windows into both diagnosis and treatment.

 

Publications

Selimkhanov J*, Taylor B*, Yao J, et al. Accurate information transmission through dynamic biochemical signaling networks. Science. 2014; 346(6215):1370-1373.

Cheng Z*, Taylor B*, Ourthiague DR, Hoffmann A. Distinct single-cell signaling characteristics are conferred by the MyD88 and TRIF pathways during TLR4 activation. Sci Signal. 2015; 8(385):1-13.

(* denotes equal contribution)

Karen Fortmann

Chemistry & Biochemistry Graduate Student (2009-)

Office: NSB 3318
Phone: 858-822-4673

 

B.S. Cellular & Molecular Biology, San Diego State University 2009

Research Interests

Coming soon.

Rachel Tsui

Chemistry and Biochemistry Graduate Student (2009-)

Office: NSB 4318
Phone: 858-822-4673

B.S. Chemistry, Boston University 2009

Research Interests

I am interested in the dynamic encoding of stimulus specificity in the canonical NFκB pathway.

Max Shokhirev

max

TITLE: Bioinformatics and Systems Biology Graduate Student (2008-June 2014)
OFFICE: NSB 3209
PHONE: 520-4717076qrcode.19193237
EMAIL: mshokhir at ucsd.edu
EDUCATION:
B.S. Computer Science, Biochemistry and Molecular Biophysics, University of Arizona – 2008
LINKEDIN: http://www.linkedin.com/pub/maxim-shokhirev/19/948/62

Research Interests

CellPopulationModel250nm0126.png_processed_ 126cPARPCurves

 

I am interested in understanding how cell population dynamics are coordinated on the cellular and biochemical levels. A prime example, the mammalian immune response involves seemingly stochastic cellular decisions to respond, divide, and undergo programmed cell death. Understand how immune cells make decisions that result in an effective population response sheds light on the nature of multi-cellular biology and may provide insights into treating immune disorders and cancers. To this end, I have developed computational tools for describing cell population dynamics in terms of stochastic cellular processes, cell tracking software for quantifying time-lapse microscopy movies, performed single-cell RNAseq experiments, ran immunfluorescence studies, and constructed kinetic ODE models which incorporate the cell-cycle, apoptosis, and NFkB signaling. This has allowed me to characterize the responses of primary mouse B cells under diverse conditions in a multi-scale manner.

 

Publications

  1. Shokhirev MN and Alexander Hoffmann (2013) FlowMax: a computational tool for maximum likelihood deconvolution of CFSE time courses. PLoS One.
  2. Jiao B, Ma H, Shokhirev MN, Drung A, Yang Q, et al. (2012) Paternal RLIM/Rnf12 is a survival factor for milk-producing alveolar cells. Cell 149: 630-641.
  3. Grubisic I, Shokhirev MN, Orzechowski M, Miyashita O, Tama F (2010) Biased coarse-grained molecular dynamics simulation approach for flexible fitting of X-ray structure into cryo electron microscopy maps. J Struct Biol 169: 95-105.
  4. Berry RE, Shokhirev MN, Ho AY, Yang F, Shokhireva TK, et al. (2009) Effect of mutation of carboxyl side-chain amino acids near the heme on the midpoint potentials and ligand binding constants of nitrophorin 2 and its NO, histamine, and imidazole complexes. J Am Chem Soc 131: 2313-2327.
  5. Knipp M, Yang F, Berry RE, Zhang H, Shokhirev MN, et al. (2007) Spectroscopic and functional characterization of nitrophorin 7 from the blood-feeding insect Rhodnius prolixus reveals an important role of its isoform-specific N-terminus for proper protein function. Biochemistry 46: 13254-13268.
  6. Berry RE, Shokhireva T, Filippov I, Shokhirev MN, Zhang H, et al. (2007) Effect of the N-terminus on heme cavity structure, ligand equilibrium, rate constants, and reduction potentials of nitrophorin 2 from Rhodnius prolixus. Biochemistry 46: 6830-6843.
  7. Borunda, P.; Brewer, C.; Erten, C.; King, N.; Nation Z.; Shokhirev, M. (2005) GSPIM: Graphical Visualization Tool for MIPS Assembly Programming and Simulation. SIGCSE 2005.

 

Diana Rios

Chemistry and Biochemistry Graduate Student (2008-)

dnrios@nullucsd.edu
Office: 858-822-4673

 

B.S. Biochemistry, California Polytechnic State University San Luis Obispo, 2008

 

Research Interests

I am interested in the dynamics of interferon beta production in response to TLR stimulation. I plan to examine, through experimental and computational techniques, the coordination of NF-kappaB and ISGF3 in mounting an innate immune response.

Paul Loriaux

Bioinformatics Graduate Student (1967-)

ploriaux@nullbioinf.ucsd.edu
Office: NSB 4318
Phone: 858-822-4673

B.S. Bioengineering, Univ. of Washington 2001
M.S. Computer Science & Engineering, Univ. of California San Diego, 2011

Research Interests

My current research interests are in understanding the molecular mechanisms that process information in living cells. Cell systems represent a particular challenge in this regard in that their machinery is capable of operating over many orders of magnitude in both space and time. Computational modeling is particularly suited to making conjectures about how systems operate over a high dynamic range in these domains, and these conjectures can then be verified or refuted in the laboratory. Presently I am constructing a model of concurrent activation of the JNK and NF-kappa B signaling pathways, with the goal of understanding how the basal state of the system biases the cellular response towards one or the other of these two contradictory signals. The results could have implications to our basic understanding of why different cell types respond differently to the same set of inflammatory and apoptotic signals.

Publications

Citation Link
Of elections and cell-death decisions.
Loriaux P, Hoffmann A.
Mol Cell. 2009 May 15;34(3):257-8.		 PubMed
A framework for modeling the relationship between cellular steady-state and stimulus-responsiveness.
Loriaux PM, Hoffmann A.
Methods Cell Biol. 2012;110:81-109.		 PubMed
Characterizing the Relationship between Steady State and Response Using Analytical Expressions for the Steady States of Mass Action Models.
Loriaux PM, Tesler G, Hoffmann A.
PLoS Comput Biol. 2013 Feb;9(2):e1002901.		 PubMed
A protein turnover signaling motif controls the stimulus-sensitivity of stress response pathways.
Loriaux PM, Hoffmann A.
PLoS Comput Biol. 2013 Feb;9(2):e1002932.		 PubMed

Jenny Huang

Biomedical Sciences Graduate Student (2011-2013)

j0huang@nullucsd.edu
Office: NSB 3320
Phone: 858-822-4673

B.S. Chemistry, Cornell, 2007

Research Interests

My research interests are to study the pleiotropic effects of drugs on the dynamic regulation of NFkB signaling system using both biochemical assays and single cell experiments. Using a systems pharmacology approach, the goal is to determine a combination of chemical perturbations which could yield specific target effects on gene expression.

Publications

Citation Link
Control of self-assembly of lithographically patternable block copolymer films.
Bosworth JK, Paik MY, Ruiz R, Schwartz EL, Huang JQ, et al
ACS Nano. 2008 Jul;2(7):1396-402.		 PubMed

Kristyn Feldman


Biomedical Sciences Graduate Student (2007-)
kfeldman@nullucsd.edu
Office: NSB 3320
Phone: 858-822-4673

 

B.S. Biology and B.S. Molecular and Microbiology
University of Central Florida 2007

Research Interests

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.

 

Publications

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.

http://www.ncbi.nlm.nih.gov/pubmed/21343618

Jeremy Davis-Turak

Bioinformatics Graduate Student (2009-)
Office: NSB 4418
Phone: 858-822-4673

 

B.A. in Molecular Biology, Princeton University 2004
Fellow, National Science Foundation Graduate Research Program

 

Research Interests

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.

 

 

Publications

Citation Link
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.		 PubMed
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		 PubMed
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		 PubMed
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		 PubMed
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.		 PubMed

Andrew Caldwell

Chemistry and Biochemistry Graduate Student (2008-)
abcaldwe@nullucsd.edu
Office: 858-822-4673

 

B.S. Chemistry, Biochemistry,Seattle Pacific University, 2008

 

Research Interests

I am interested in the mechanisms of IKK activation and regulation in NFκB signaling.

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