Biographical Information

Education

Honors and Awards

Research Interests

Research in the Linderman group focuses on understanding the binding of extracellular ligands to cell surface receptors and the signal transduction events involved in the generation of a cellular response. Current work includes: (1) multi-scale and multi-system approaches to understanding the immune response to Mycobacterium tuberculosis, focusing especially on the role of TNF and IL-10, and (2) mathematical models of signal transduction, particularly for G-protein coupled receptors, and including complex membrane geometries.

Recent Publications

Books and Book Chapters

Jovic, A, Takayama S, Linderman JJ.  “Using microfluidics, real-time imaging and mathematical modeling to study GPCR signaling”, G protein-coupled receptors:  From Structure to Function (J. Giraldo and J-P Pin, eds.), The Royal Society of Chemistry, in press.

Woolf, P.J., and Linderman, J.J., “From the Static to the Dynamic: Three Models of Signal Transduction in G-protein Coupled Receptors”, in Biomedical Applications of Computer Modeling, A. Christopoulos, ed., pp. 87-108, 2000.

Linderman, J.J., “Kinetic Modeling Approaches to Understanding Ligand Efficacy”, The Pharmacology of Functional, Biochemical, and Recombinant Receptor Systems, Handbook of Experimental Pharmacology Volume 148, T. Kenakin and J. A. Angus, eds., Springer-Verlag, pp. 119-146, 2000.

Lauffenburger, D.A. and J.J. Linderman, Receptors: Models for Binding, Trafficking, and Signaling, Oxford University Press, 365 pp., 1993. Reprinted in paperback, 1996.

Linderman, J.J. and D.A. Lauffenburger, "Receptor/Ligand Sorting Along the Endocytic Pathway", Lecture Notes in Biomathematics, Vol. 78. Springer-Verlag, 165 pp., 1989.

Journal Publications

Fallahi-Sichani M, El-Kebir M, Marino S, Kirschner DE, Linderman JJ.  “Multi-scale computational modeling reveals a critical role for TNF receptor dynamics in tuberculosis granuloma formation”, J. Immunology, 2011, in press.

Marino S, Linderman JJ, Kirschner DE.  “A multi-faceted approach to modeling the immune response in tuberculosis”, Wiley Interdisciplinary Reviews:  Systems Biology and Medicine, in press.

Comisar WA, Mooney DJ, Linderman JJ.  “Integrin organization:  Linking adhesion ligand nanopatterns with altered cell responses”, J. Theor. Biol., 274:  120-130, 2011.

Jovic A, Howell B, Cote M, Wade SM, Mehta K, Miyawaki A, Neubig RR, Linderman JJ, Takayama S.  “Phase-locked signals elucidate circuit architecture of an oscillatory pathway”, PLoS Computational Biology 6(12) e1001040, 2010.

Fallahi-Sichani M, Schaller MA, Kirschner DE, Kunkel SL, Linderman JJ.  “Identification of key processes that control tumor necrosis factor availability in a tuberculosis granuloma”, PLoS Computational Biology 6(5):  e1000778, 2010.

Linderman JJ, Riggs T, Pande M, Miller M, Marino S, Kirschner DE.  “Characterizing the dynamics of CD4+ T cell priming within a lymph node”, J. Immunology 184:  2873-2885, 2010.

Mehta, K., Mehta, G., Takayama, S., Linderman, J., “Quantitative inference of cellular parameters from microfluidic cell culture systems”, Biotechnology and Bioengineering 103: 966-974, 2009.

Mehta, G., Lee, J., Cha, W., Tung, Y., Linderman, J.J., Takayama, S., “Hard top soft bottom microfluidic devices for cell culture and chemical analysis”, Analytical Chemistry 81:  3714-3722, 2009.

Fallahi-Sichani, M., Linderman, J.J., “Lipid raft-mediated regulation of G-protein coupled receptorsignaling by ligands which influence receptor dimerization:  A computational study”, PLOS One 4:  e6604, 2009.

Mehta, K., Hoppe, A.D., Kainkaryam, R., Woolf, P.J., Linderman, J.J., “A computational approach to inferring cellular protein binding affinities from quantitative fluorescence resonance energy transfer imaging”, Proteomics 9:  5371-5385, 2009.

Linderman, J.J., “Modeling of G-protein coupled receptor signaling pathways”, J. Biological Chemistry 284:  5427-5431, 2009.

Kirschner, D.E., Linderman, J.J., “Mathematical and computational approaches can complement experimental studies of host-pathogen interactions”, Cellular Microbiology 11:  531-539, 2009.

Brinkerhoff CJ, Traynor JR, Linderman JJ. Collision coupling, crosstalk, and compartmentalization in G-protein coupled receptor systems: Can a single model explain disparate results? J Theor Biol 255: 278-286, 2008.

Chang ST, Linderman JJ, Kirschner DE. The effect of multiple polymorphisms on antigen presentation and susceptibility to M. Tuberculosis infection. Infection Immunity 76:  3221-3232, 2008.

Clark MJ, Linderman JJ, Traynor JR. Endogenous RGS proteins differentially modulate full and partial mu-opioid agonists at adenylyl cyclase as predicted by a collision coupling model. Molec Pharmacol 73: 1538-1548, 2008.

Brinkerhoff CJ, Choi JS, Linderman JJ. Diffusion-limited reactions in G-protein activation:  Unexpected consequences of agonist and antagonist competition. J Theor Biol 251:  561-569, 2008.

Riggs T, Walts A, Perry N, Bickle L, Lynch JN, Myers A, Flynn J, Linderman JJ, Miller MJ, Kirschner DE. A comparison of random vs. chemotaxis driven contacts of T cells with dendritic cells during repertoire scanning. J Theor Biol 250:  732-751, 2008.

Thwar P, Linderman JJ, Burns MA. Electrode-less DC dielectrophoresis using reconfigurable field-shaping oil barriers. Electrophoresis 28:  4572-4581, 2007.

Comisar W, Kazmers NH, Mooney DJ and Linderman JJ.  Engineering RGD nanopatterned hydrogels to control preosteoblast behavior:  A combined computational and experimental approach.  Biomaterials 28:  4409-4417, 2007.

Mehta G, Kiel MJ, Lee JW, Kotov N, Linderman JJ, Takayama S.  Polyelectrolyte-clay-protein layer films on microfluidic PDMS bioreactor surfaces for primary murine bone marrow culture.  Adv Functional Materials 17:  2701-2709, 2007.

Kirschner DE, Chang ST, Riggs T, Perry N, Linderman JJ. Toward a multi-scale model of antigen presentation in immunity. Immunological Rev 216:  93-118, 2007.

Mehta G, Mehta K, Sud D, Song J, Bersano-Begey T, Futai N, Mycek M, Linderman JJ, Takayama S.  Quantitiative oxygen measurements and analysis of cellular oxygen uptake in microfluidic poly(dimethylsiloxane) bioreactors. Biomedical Microdevices 9:  123-134, 2007.

Kinzer-Ursem TL, Linderman JJ.  Both ligand- and cell-specific parameters control ligand agonism in a kinetic model of G protein coupled receptor signaling. PLOS Computational Biol 3:  e6, 2007.

Thwar PK, Guptaroy B, Gnegy ME, Burns MA, Linderman JJ.  A simple transporter trafficking model for amphetamine-induced dopamine efflux. Synapse 61:  500-514, 2007.

Brinkerhoff, C, and Linderman, JJ, “Integrin dimerization and ligand arrangement: Key components in integrin clustering for cell adhesion”, Tissue Engineering 11: 865-876, 2005.

Chang, ST, Linderman, JJ, and Kirshner, DE, “Multiple mechanisms allow Mycobacterium tuberculosis to continuously inhibit MHC class II-mediated antigen presentation by macrophages”, PNAS 102: 4530-4535, 2005. This paper was highlighted in the “Research Roundup” feature of the Journal of Cell Biology (“TB bug inhibits any which way”, J. Cell Biol. 168: 896, 2005).

Chang, PS, Axelrod, D, Omann, GM, and Linderman, JJ, “G-protein threshold behavior in the human neutrophil oxidant response: Measurement of G-proteins available for signaling in responding and nonresponding subpopulations”, Cellular Signalling 17: 605-614, 2005.

Brinkerhoff, CJ, Woolf, PJ, and Linderman, JJ “Monte Carlo Simulations of Receptor Dynamics: Insights into Cell Signaling, J. Molec. Histology 35: 667-677, 2004.

Lee, KY. Alsberg, E, Hsiong, S, Comisar, W, Linderman, J, Ziff, R, and Mooney, D, “Nanoscale adhesion ligand organization regulates osteoblast proliferation and differentiation”, Nano Letters 4: 1501-1506, 2004.

Waller, A, Sutton, KL, Kinzer, TL, Absood, A, Linderman, JJ, and Omann, GM, “Receptor binding kinetics and cellular responses of six N-formyl peptide agonists in human neutrophils”, Biochemistry 43: 8204-8216, 2004.

Woolf, PJ. and Linderman, JJ, “An algebra of dimerization and its physiological implications for G-protein coupled receptor signaling”, J. Theor. Biol. 229: 157-168, 2004.

Chang, PS. Absood, A, Linderman, JJ, and Omann, GM, “Magnetic Bead Isolation of Neutrophil Plasma Membranes and Quantification of Membrane-Associated Guanine Nucleotide Binding Proteins”, Analytical Biochemistry 325: 172-184, 2004.

Woolf, P.J., and Linderman, J.J., “Self organization of membrane proteins via dimerization”, Biophysical Chemistry 104: 217-233, 2003.

Zhong, H., Wade, S.M., Woolf, P.J., Linderman, J.J., Clark, M.J., Traynor, J.R., and Neubig, R.R., “A spatial focusing model for G protein signals: RGS protein-mediated kinetic scaffolding”, J. Biological Chemistry 278: 7278-7284, 2003.

Keil,M.L., Solomon,N.L., Lodhi, I.J., Stone, K.C., Jesaitis, A., Chang,P.S., Linderman, J.J., and Omann, G.M., “Priming-induced localization of Gia2 in high density membrane microdomains”, Biochem. Biophys. Res. Commun. 310: 862-872, 2003.

Shim, J., Bersano-Begey, T.F., Zhu, X., Tkaczyk, A.H., Linderman, J.J., and Takayama, S., “Micro- and nanotechnologies for studying cellular function”, Current Topics in Medicinal Chemistry 3: 339-353, 2003.

Woolf, P.J., and Linderman, J.J., “Untangling ligand induced activation and desensitization of G-protein coupled receptors”, Biophysical J 84: 3-13, 2003.

Cunningham, J.J., Linderman, J.J., and Mooney, D.J., “Externally applied cyclic strain regulates focal contact composition in cultured smooth muscle cells”, Annals of Biomedical Engineering 30: 927-935, 2002.

Cunningham, J.J.. Nikolovski, J., Linderman, J.J., and Mooney, D.J. “Quantification of fibronectin adsorption to silicon rubber substrates”, BioTechniques 32: 876-878, 2002.

Waller, A.W., Pipkorn, D., Sutton, K.L., Linderman, J.J., and Omann, G.M., and Linderman, J.J., “Validation of flow cytometric competitive binding protocols and characterization of fluorescently labeled ligands”, Cytometry 45: 102-114, 2001.

Woolf, P.J., Kenakin, T.P., and Linderman, J.J., “Uncovering biases in high throughput screens of G-protein coupled receptors”, J. Theoretical Biology 208: 403-418, 2001.

Shea, L.D., Neubig, R.R., and Linderman, J.J., “Timing is everything: The role of kinetics in G protein activation”, Life Sciences 68: 647-658, 2000.

Courses Taught at the University of Michigan

Undergraduate ChE Courses

ChE 230, Thermodynamics I
ChE 342, Heat and Mass Transfer
ChE 344, Chemical Reaction Engineering
ChE 490, Directed Study & Research

Graduate ChE Courses

ChE 510, Applied Mathematical Methods in ChE
ChE 518, Engineering Fundamentals in Biological Systems
ChE 607, Mathematical Modeling in ChE
ChE 616, Analysis of Chemical Signaling

ChE Course Descriptions

Other Courses

Micro 505, Cellular Biotechnology
BME 590, Directed Research