- Note: Search PubMed for the most up-to-date list of publications from the lab.
- Klinke DJ 2nd and Broadbelt LJ, Mechanism Reduction during Computer Generation of Compact Reaction Models, AIChE J 1997; 43:1828-1837.
- Klinke DJ 2nd, Wilke S, and Broadbelt LJ, A Theoretical Study of Carbon Chemisorption on Ni(111) and Co(0001) Surfaces, J Catal 1998; 178:540-554.
- Klinke DJ 2nd and Broadbelt LJ, Construction of a Mechanistic Model of Fischer-Tropsch Synthesis on Ni(111) and Co(0001) Surfaces, Chem Eng Sci 1999; 54:3379-3389.
The first application of a rule-based reaction network generation algorithm to heterogeneous catalytic chemistry.
- Klinke DJ 2nd, Dooling DJ, and Broadbelt LJ, A Theoretical Study of Methylidyne Chemisorption on Ni(111) and Co(0001) Surfaces; Surf Sci 1999; 425:334-342.
- Klinke DJ 2nd and Broadbelt LJ, A Theoretical Study of Hydrogen Chemisorption on Ni(111) and Co(0001) Surfaces, Surf Sci 1999; 429:169-177.
- Broadbelt LJ and Klinke DJ 2nd, Kinetics of Catalyzed Reactions – D (Heterogeneous) in Encyclopedia of Catalysis, Istvan T. Horvath (Editor-in-Chief), ISBN 0-471-24183-0, pp. 4772, December 2002.
- Klinke DJ 2nd, The ratio of P40 monomer to dimer is an important determinant of IL-12 bioactivity, J Theor Biol 2006; 240:323-35. PMID 16448670
- Klinke DJ 2nd, An age-structured model of dendritic cell trafficking in the lung, Am J Physiol Lung Cell Mol Physiol 2006; 291:L1038-49. PMID 17030902
- Klinke DJ 2nd, A multi-scale model of dendritic cell education and trafficking in the lung: implications for T cell polarization, Ann Biomed Eng 2007; 35:937-55. PMID 17457675
- Klinke DJ 2nd, Integrating epidemiological data into a mechanistic model of type 2 diabetes: validating the prevalence of virtual patients, Ann Biomed Eng 2008; 36:321-34. PMID 18046647
Provides a glimpse of the size and complexity of the proprietary PhysioLab models developed by Entelos, Inc.
- Klinke DJ 2nd, Extent of Beta Cell Destruction is Important but Insufficient to Predict the Onset of Type 1 Diabetes Mellitus, PLoS ONE 2008; 3:e1374. PMID 18167535
In a review by Mark Atkinson (Curr Opin Endo Diab Obesity (2009) 16:279-285 PMID 19502978), this is highlighted as a paper of special interest with the comment: "An interesting meta-analysis that draws to the forefront, the question of, `what percentage of b cells are destroyed at the symptomatic onset of T1D?'."
- Klinke DJ 2nd, Ustyugova IV, Brundage K, Barnett JB, Modulating Temporal Control of NF-kappaB Activation: Implications for Therapeutic and Assay Selection, Biophys J 2008; 94:4249-4259. PMID 18281385
Finds that our ability to observe significant biological events is limited by the signal-to-noise characteristics of the assays that we use to observe cellular responses.
- Klinke DJ 2nd, Validating a Dimensionless Number for Glucose Homeostasis in Humans, Ann Biomed Eng 2009; 37:1886-1896. PMID 19513847
Develops and validates a dimensionless number for the ratio of insulin production and insulin-dependent glucose metabolism in humans.
- Klinke DJ 2nd, Brundage KM, Scalable analysis of flow cytometry data using R/Bioconductor, Cytometry A 2009; 75:699-706. PMID 19582872
Provides a tutorial for using R/Bioconductor to process flow cytometry data.
- Leski TA, Caswell CC, Pawlowski M, Bujnicki JM, Hart SJ, Klinke DJ 2nd, Lukomski S, Identification and Classification of bcl Genes and Proteins of Bacillus cereus Group Organisms and Their Application in Bacillus anthracis Detection and Fingerprinting, Appl Environ Microbiol 2009; 75:7163-7172. PMID 19767469.
Describes an approach to distinguish with confidence among B. anthracis strains using variability in collagen-like proteins. This addresses one of the problems with finding the perpetrators of the B. anthracis attacks on the U.S. Capital in 2001.
- Klinke DJ 2nd, An empirical Bayesian approach for model-based inference of cellular signaling networks, BMC Bioinformatics 2009; 10:371. PMID 19900289
In a paper from Peter Sorger's group at Harvard (Chen et al. Genes Dev (2010) 24:1861-75. PMID 20810646), it is stated that Bayesian methods are at the forefront for using mathematical models to reason about biological systems. This highly accessed publication in BMC Bioinformatics is one of two citations provided for this statement and, according to ImpactStory, has received more citations that 94% of all papers indexed in Web of Science that were published in 2009.
- Klinke DJ 2nd, Signal Transduction Networks in Cancer: Quantitative Parameters Influence Network Topology, Cancer Res 2010; 70:1773-1782. PMID 20179207
This publication was highlighted as Research News on the Physical Sciences in Oncology website hosted by the National Cancer Institute.
- Finley SD, Gupta D, Cheng N, Klinke DJ 2nd, Inferring Relevant Control Mechanisms for Interleukin-12 Signaling in Naive CD4+ T Cells, Immunol Cell Biol 2011; 89:100-110. PMID 20479776
This publication uses an empirical Bayesian approach to infer the contributions of different mechanisms that regulate IL-12 signaling in naïve CD4+ T cells derived from Balb/c mice.
- Kulkarni Y, Suarez V, Klinke DJ 2nd, Inferring Predominant Pathways in Cellular Models of Breast Cancer Using Limited-Sample Proteomic Profiling, BMC Cancer 2010; 10:291. PMID 20550684
This publication uses a proteomics workflow that includes 2D-gel electrophoresis and MALDI-TOF MS peptide mass fingerprinting to identify predominant pathways in two breast cancer cell models.
- Klinke DJ 2nd, A multiscale systems perspective on cancer, immunotherapy, and Interleukin-12, Molecular Cancer 2010; 9:242. PMID 20843320
This is a highly accessed paper in Molecular Cancer.
- Klinke DJ 2nd, Finley SD, Timescale analysis of rule-based biochemical reaction networks, Biotechnol Prog 2012; 28(1):33-44. PMID 21954150
This publication describes a new approach for timescale analysis, where timescales are obtained for reaction rules (edges) rather than for reaction species (nodes).
- Klinke DJ 2nd, Age-corrected beta cell mass following onset of type 1 diabetes mellitus correlates with plasma C-peptide in humans, PLoS ONE 2011; 6(11):e26873. PMID 22073210
- Kulkarni YM, Klinke DJ 2nd, Protein-based identification of quantitative trait loci associated with malignant transformation in two HER2+ cellular models of breast cancer, Proteome Sci 2012; 10(1):11. PMID 22357162
This publication uses a proteomics workflow that includes 2D-gel electrophoresis and MALDI-TOF MS peptide mass fingerprinting to contrast the predominant pathways in two HER2+ breast cancer cell models against predominant pathways inferred from a normal human mammary epithelial cell line.
- Klinke DJ 2nd, Cheng N, Chambers E, Quantifying cross-talk among Interferon-γ, Interleukin-12 and Tumor Necrosis Factor signaling pathways within a TH1 cell model, Sci Signal 2012; 5:ra32. PMID 22510470
According to ImpactStory, this publication has received more citations that 93% of all papers indexed in Web of Science that were published in 2012. Editor's summary: The fate of T cells involved in an immune response is determined in part by the cytokine milieu. Despite our extensive knowledge of the receptors, signaling proteins, and cytokines involved, how downstream signaling pathways interact to determine T cell fate is unclear. Klinke et al. measured receptor abundance, signaling protein activation, cytokine production, and cell population changes and used these parameters to construct mathematical models to gain insights into the signaling pathways in a mouse T cell line that were stimulated by the cytokine interleukin-12 (IL-12). This combined approach uncovered previously unappreciated aspects of IL-12 signaling that determined the T cell response and serves as an example of how mathematical modeling can refine our understanding of signaling pathways.
- Kulkarni YM, Chambers E, McGray AJR, Ware JS, Bramson JL, Klinke DJ 2nd, A quantitative systems approach to identify paracrine mechanisms that locally suppress immune response to Interleukin-12 in the B16 melanoma model, Integr Biol (Camb) 2012; 4(8):925-936. PMID 22777646
This study describes an in vitro phenotypic assay that recreates closed-loop behavior between an immune cell model and the B16F0 melanoma model. Proteomics and in silico model-based inference are used to identify novel mechanisms of immunosuppression.
- Klinke DJ 2nd, Wang Q, Understanding Immunology via Engineering Design: The Role of Mathematical Prototyping, Comput Math Methods Med 2012; 676015. PMID 22973412.
- Klinke DJ 2nd, An evolutionary perspective on anti-tumor immunity, Front Oncol 2013; 2:202. PMID 23336100.
Reviews evidence to support cancer as an evolutionary process and how advances in technology have strengthened this viewpoint. Compared to all 373 articles published in this journal, it ranks 24th in Altmetric score - a measure of the quality and quantity of online attention that an article receives.
- Kulkarni YM, Qi Q, Zhu Y, Liu C, Klinke DJ 2nd, Liu J, Differential proteomic analysis of caveolin-1 KO cells reveals Sh2b3 and Clec12b as novel interaction partners of caveolin-1 and capns1 as potential mediator of caveolin-1-induced apoptosis, Analyst 2013; 138(22):6986-96. PMID 24091439.
- Klinke DJ 2nd, Induction of Wnt-inducible signaling protein-1 correlates with invasive breast cancer oncogenesis and reduced type 1 cell-mediated cytotoxic immunity: a retrospective study, PLoS Comput Biol 2014; 10(1): e1003409. PMID 24426833 DOI: 10.1371/journal.pcbi.1003409.
- Klinke DJ 2nd, Kulkarni YM, Wu Y, Byrne-Hoffman C, Inferring alterations in cell-to-cell communication in HER2+ breast cancer using secretome profiling of three cell models, Biotech and Bioeng 2014; 111(9):1853-63. PMID 24752654.
Spotlight: Cancer = (Mutation x Selection)^n Biotech and Bioeng 2014; 111(9):vi.
- Klinke DJ 2nd, In silico model-based inference: a contemporary approach for hypothesis testing in network biology, Biotechnol Prog 2014; 30(6):1247-61. PMID 25139179.
- Klinke DJ 2nd, Is immune checkpoint modulation a potential therapeutic option in triple negative breast cancer?, Breast Cancer Res 2014; 16:457. PMID 25927347.
- Klinke DJ 2nd, Eavesdropping on altered cell-to-cell signaling in cancer by secretome profiling, Mol Cell Oncol 2015; 3(1): e1029061. PMID 27308541. DOI: 10.1080/23723556.2015.1029061
- Byrne-Hoffman C, Klinke DJ 2nd, "A Quantitative Systems Pharmacology Perspective on Cancer Immunotherapy", Processes 2015; 3(2):235-256.
- Wang Q, Klinke DJ 2nd*, Wang Z, "CD8+ T cell response to adenovirus vaccination and subsequent suppression of tumor growth: modeling, simulation and analysis", BMC Systems Biology 2015; 9:27. PMID 26048402. *corresponding author
- Klinke DJ 2nd, "Enhancing the discovery and development of immunotherapies for cancer using quantitative and systems pharmacology: Interleukin-12 as a case study", J ImmunoTher Cancer 2015; 3:27. PMID 26082838.
- Klinke DJ 2nd*, Birtwistle M, In silico model-based inference: an emerging approach for inverse problems in engineering better medicines", Curr Opin Chem Eng 2015; 10:14-24. PMID 26309811. *corresponding author
- Klinke DJ 2nd*, Horvath N, Cuppett V, Wu Y, Deng W, Kanj R, Interlocked positive and negative feedback network motifs regulate beta-catenin activity in the adherens junction pathway", Mol Biol Cell 2015; 26:4135-48. PMID 26224311. *corresponding author
- Wu Y, Deng W, Klinke DJ 2nd, Exosomes: Improved methods to characterize their morphology, RNA content, and surface protein biomarkers", Analyst 2015; 140:6631-42. PMID 26332016. (Reprint)
- Kaiser J, Bland C, Klinke DJ 2nd, Identifying causal networks linking cancer processes and anti-tumor immunity using Bayesian network inference and metagene constructs”, Biotechnol Progress 2016; 32:470-9. PMID 26785356.
- Wang Z, Wang Q, Klinke DJ 2nd, Simulation Study on Effects of Order and Step Size of Runge-Kutta Methods that Solve Contagious Disease and Tumor Models", J Comput Sci Syst Biol 2016; 9:163-172. PMID 28220053.
- Wu Y, Deng W, McGinley-Chambers E, Klinke DJ 2nd, Melanoma exosomes deliver a complex biological payload that upregulates PTPN11 to suppress T lymphocyte function", Pigment Cell Melanoma Res 2017; 30(2):203-218. PMID 27930879.
- Klinke DJ 2nd, Wang Q, Inferring the impact of regulatory mechanisms that underpin CD8+ T cell control of B16 tumor growth in vivo using mechanistic models and simulation", Front Pharmacol 2017; 7:515. PMID 2810155.
- Deng W, McLaughlin SL, Klinke DJ 2nd, Quantifying spontaneous metastasis in a syngeneic mouse melanoma model using real time PCR, Analyst 2017; 142:2945-2953. PMID 28725894.
- Bland CL, Byrne-Hoffman CN, Fernandez A, Rellick SL, Deng W, Klinke DJ 2nd, Exosomes derived from B16F0 melanoma cells alter the transcriptome of cytotoxic T cells that impacts mitochondrial respiration, FEBS J 2018; 285:1033-1050. PMID 29399967. Cover Art and Editor's Choice.
Patents and Patent Applications
- Defranoux, N.A.; Dubnicoff, T.B.; Klinke, D.J.; Lewis, A.K.; Paterson, T.S.; Ramanujan, S.; Shoda, L.K.M.; Soderstrom, K.P.; Struemper, H.K.; "Method and apparatus for computer modeling a joint", US Patent #6,862,561.
- Kelly, S.D.; Klinke, D.J.; Leong, C.; Lewis, A.K.; Okino, M.S.; Paterson, T.S.; Shoda, L.K.M.; Stokes, C.; Struemper, H.K.; "Method and apparatus for computer modeling of an adaptive immune response", US Patent Application #10/154,123.
- Friedrich, C.M.; Kansal, A.; Klinke, D.J.; Michelson, S.G.; Paterson, T.S.; Polidori, D.; Trimmer, J.; Wennerberg, L.G.; "Defining Virtual Patient Populations", US Patent Application #11/346,990.
- Defranoux, N.A.; Dubnicoff, T.B.; Klinke, D.J.; Lewis, A.K.; Paterson, T.S.; Ramanujan, S.; Shoda, L.K.M.; Soderstrom, K.P.; Struemper, H.K.; "Method and apparatus for computer modeling a joint", US Patent #7,472,050.