C. Anthony Hunt, PhD
Professor
Bioengineering
School of Pharmacy
My research is motivated by this question. What are the causal mechanisms that link induced changes in molecular level events to emergent changes in phenotype at the organism level? We need new ways to explore and challenge plausible answers.
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So doing will facilitate moving away from empirical approaches to biomedical research and reliance on correlational methods toward new approaches based on improving mechanistic knowledge and insight. We need ways to build and challenge experimentally (falsify) many alternative, nested, networked mechanistic hypotheses. Doing so using established, bottom-up, computational mathematical models is problematic at best. New methods and new approaches are needed. My search started in earnest circa 1997. We have now developed and demonstrated the scientific power of a novel, fundamentally new class biomedical simulation models along with methods to challenge and iteratively improve plausible, explanatory mechanisms. We adapted concepts and advanced methods from several domains. I call the process the synthetic method of modeling and simulation (SM). I say synthetic because standalone biomimetic components are plugged together in specific ways to form hierarchical, multiscale biomimetic mechanisms in software. I refer to the models as analogues because even though they exist only in silico, their phenotypes can be made to increasingly overlap more of the referent, biological phenotype. They are designed to evolve to become embodiments of most of what we know (or think we know) about aspects of specific organisms and their components.
Awards
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- American Association for the Advancement of Science, 1984
- BS in Chemistry with Highest Honors, Georgia Institute of Technology, 1970
Publications (88)
Top publication keywords:
Computer SimulationChemical and Drug Induced Liver InjurySaquinavirModels, BiologicalComputational BiologyHepatocytesPharmaceutical PreparationsSystems BiologyLiverTechnology, PharmaceuticalNecrosisBiomimeticsPharmacokineticsAcetaminophenDrug Interactions
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An exploration of knowledge-organizing technologies to advance transdisciplinary back pain research.
JOR spine 2023 Lotz JC, Ropella G, Anderson P, Yang Q, Hedderich MA, Bailey J, Hunt CA -
Theoretical Schemas to Guide Back Pain Consortium (BACPAC) Chronic Low Back Pain Clinical Research.
Pain medicine (Malden, Mass.) 2023 Chau A, Steib S, Whitaker E, Kohns D, Quinter A, Craig A, Chiodo A, Chandran S, Laidlaw A, Schott Z, Farlow N, Yarjanian J, Omwanghe A, Wasserman R, O'Neill C, Clauw D, Bowden A, Marras W, Carey T, … -
Utilizing virtual experiments to increase understanding of discrepancies involving in vitro-to-in vivo predictions of hepatic clearance.
PloS one 2022 Krishnan P, Smith AK, Ropella GEP, Dutta L, Kennedy RC, Hunt CA -
Contrasting model mechanisms of alanine aminotransferase (ALT) release from damaged and necrotic hepatocytes as an example of general biomarker mechanisms.
PLoS computational biology 2020 Smith AK, Ropella GEP, McGill MR, Krishnan P, Dutta L, Kennedy RC, Jaeschke H, Hunt CA -
Propagation of Pericentral Necrosis During Acetaminophen-Induced Liver Injury: Evidence for Early Interhepatocyte Communication and Information Exchange.
Toxicological sciences : an official journal of the Society of Toxicology 2019 Kennedy RC, Smith AK, Ropella GEP, McGill MR, Jaeschke H, Hunt CA
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The Spectrum of Mechanism-Oriented Models and Methods for Explanations of Biological Phenomena.
Processes (Basel, Switzerland) 2018 Hunt CA, Erdemir A, Lytton WW, Gabhann FM, Sander EA, Transtrum MK, Mulugeta L -
A Model Mechanism-Based Explanation of an In Vitro-In Vivo Disconnect for Improving Extrapolation and Translation.
The Journal of pharmacology and experimental therapeutics 2018 Smith AK, Xu Y, Ropella GEP, Hunt CA -
Simulation enabled search for explanatory mechanisms of the fracture healing process.
PLoS computational biology 2018 Kennedy RC, Marmor M, Marcucio R, Hunt CA -
Competing Mechanistic Hypotheses of Acetaminophen-Induced Hepatotoxicity Challenged by Virtual Experiments.
PLoS computational biology 2016 Smith AK, Petersen BK, Ropella GE, Kennedy RC, Kaplowitz N, Ookhtens M, Hunt CA -
Virtual Experiments Enable Exploring and Challenging Explanatory Mechanisms of Immune-Mediated P450 Down-Regulation.
PloS one 2016 Petersen BK, Ropella GE, Hunt CA -
A cell-centered, agent-based framework that enables flexible environment granularities.
Theoretical biology & medical modelling 2016 Kennedy RC, Ropella GE, Hunt CA -
In silico, experimental, mechanistic model for extended-release felodipine disposition exhibiting complex absorption and a highly variable food interaction.
PloS one 2014 Kim SH, Jackson AJ, Hunt CA -
Toward modular biological models: defining analog modules based on referent physiological mechanisms.
BMC systems biology 2014 Petersen BK, Ropella GE, Hunt CA -
Tuneable resolution as a systems biology approach for multi-scale, multi-compartment computational models.
Wiley interdisciplinary reviews. Systems biology and medicine 2014 Kirschner DE, Hunt CA, Marino S, Fallahi-Sichani M, Linderman JJ -
Agent-based modeling: a systematic assessment of use cases and requirements for enhancing pharmaceutical research and development productivity.
Wiley interdisciplinary reviews. Systems biology and medicine 2013 Hunt CA, Kennedy RC, Kim SH, Ropella GE -
Individualized, discrete event, simulations provide insight into inter- and intra-subject variability of extended-release, drug products.
Theoretical biology & medical modelling 2012 Kim SH, Jackson AJ, Hur R, Hunt CA -
Relational grounding facilitates development of scientifically useful multiscale models.
Theoretical biology & medical modelling 2011 Hunt CA, Ropella GE, Lam Tn, Gewitz AD -
Enabling clearance predictions to emerge from in silico actions of quasi-autonomous hepatocyte components.
Drug metabolism and disposition: the biological fate of chemicals 2011 Sheikh-Bahaei S, Hunt CA -
MDCK cystogenesis driven by cell stabilization within computational analogues.
PLoS computational biology 2011 Engelberg JA, Datta A, Mostov KE, Hunt CA -
Cloud computing and validation of expandable in silico livers.
BMC systems biology 2010 Ropella GE, Hunt CA -
Tracing multiscale mechanisms of drug disposition in normal and diseased livers.
The Journal of pharmacology and experimental therapeutics 2010 Park S, Kim SH, Ropella GE, Roberts MS, Hunt CA -
Simulation of lung alveolar epithelial wound healing in vitro.
Journal of the Royal Society, Interface 2010 Kim SH, Matthay MA, Mostov K, Hunt CA -
Identifying the rules of engagement enabling leukocyte rolling, activation, and adhesion.
PLoS computational biology 2010 Tang J, Hunt CA -
A computational approach to resolve cell level contributions to early glandular epithelial cancer progression.
BMC systems biology 2009 Kim SH, Debnath J, Mostov K, Park S, Hunt CA -
Mechanistic insight from in silico pharmacokinetic experiments: roles of P-glycoprotein, Cyp3A4 enzymes, and microenvironments.
The Journal of pharmacology and experimental therapeutics 2009 Lam TN, Hunt CA -
At the biological modeling and simulation frontier.
Pharmaceutical research 2009 Hunt CA, Ropella GE, Lam TN, Tang J, Kim SH, Engelberg JA, Sheikh-Bahaei S -
Computational investigation of epithelial cell dynamic phenotype in vitro.
Theoretical biology & medical modelling 2009 Kim SH, Park S, Mostov K, Debnath J, Hunt CA -
A computational approach to understand in vitro alveolar morphogenesis.
PloS one 2009 Kim SH, Yu W, Mostov K, Matthay MA, Hunt CA -
Essential operating principles for tumor spheroid growth.
BMC systems biology 2008 Engelberg JA, Ropella GE, Hunt CA -
Computational strategies unravel and trace how liver disease changes hepatic drug disposition.
The Journal of pharmacology and experimental therapeutics 2008 Park S, Ropella GE, Kim SH, Roberts MS, Hunt CA -
Discovering plausible mechanistic details of hepatic drug interactions.
Drug metabolism and disposition: the biological fate of chemicals 2008 Lam TN, Hunt CA -
Dichotomies between computational and mathematical models.
Nature biotechnology 2008 Hunt CA, Ropella GE, Park S, Engelberg J -
In silico methods for unraveling the mechanistic complexities of intestinal absorption: metabolism-efflux transport interactions.
Drug metabolism and disposition: the biological fate of chemicals 2008 Garmire LX, Hunt CA -
A framework and mechanistically focused, in silico method for enabling rational translational research.
Summit on translational bioinformatics 2008 Hunt CA, Baranzini S, Matthay MA, Park S -
Predictions of hepatic disposition properties using a mechanistically realistic, physiologically based model.
Drug metabolism and disposition: the biological fate of chemicals 2008 Yan L, Sheihk-Bahaei S, Park S, Ropella GE, Hunt CA -
In silico simulation of epithelial cell tubulogenesis.
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference 2008 Engelberg JA, Kim M, Mostov KE, Hunt CA -
Mechanistic simulations explain paradoxical saquinavir metabolism during in vitro vectorial transport study.
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference 2008 Lam TN, Hunt CA -
Using an in silico liver to evaluate a hepatic enzyme induction mechanism.
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference 2008 Hunt C, Ropella GE -
Modeling and simulation of hepatic drug disposition using a physiologically based, multi-agent in silico liver.
Pharmaceutical research 2007 Yan L, Ropella GE, Park S, Roberts MS, Hunt CA -
Synthetic nano-LDL with paclitaxel oleate as a targeted drug delivery vehicle for glioblastoma multiforme.
Journal of controlled release : official journal of the Controlled Release Society 2007 Nikanjam M, Gibbs AR, Hunt CA, Budinger TF, Forte TM -
An in silico transwell device for the study of drug transport and drug-drug interactions.
Pharmaceutical research 2007 Garmire LX, Garmire DG, Hunt CA -
Formation of cysts by alveolar type II cells in three-dimensional culture reveals a novel mechanism for epithelial morphogenesis.
Molecular biology of the cell 2007 Yu W, Fang X, Ewald A, Wong K, Hunt CA, Werb Z, Matthay MA, Mostov K -
Dynamics of in silico leukocyte rolling, activation, and adhesion.
BMC systems biology 2007 Tang J, Ley KF, Hunt CA -
Physiologically based synthetic models of hepatic disposition.
Journal of pharmacokinetics and pharmacodynamics 2006 Hunt CA, Ropella GE, Yan L, Hung DY, Roberts MS -
Simulating properties of in vitro epithelial cell morphogenesis.
PLoS computational biology 2006 Grant MR, Mostov KE, Tlsty TD, Hunt CA -
Mechanistic study of the cellular interplay of transport and metabolism using the synthetic modeling method.
Pharmaceutical research 2006 Liu Y, Hunt CA -
Simulating in vitro epithelial morphogenesis in multiple environments.
Computational systems bioinformatics. Computational Systems Bioinformatics Conference 2006 Grant MR, Kim SH, Hunt CA -
Studies of intestinal drug transport using an in silico epithelio-mimetic device.
Bio Systems 2005 Liu Y, Hunt CA -
Glucose transport to the brain: a systems model.
Brain research. Brain research reviews 2005 Qutub AA, Hunt CA -
Plasticity of gene expression in injured human dorsal root ganglia revealed by GeneChip oligonucleotide microarrays.
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 2004 Rabert D, Xiao Y, Yiangou Y, Kreder D, Sangameswaran L, Segal MR, Hunt CA, Birch R, Anand P -
An agent-based computational approach for representing aspects of in vitro multi-cellular tumor spheroid growth.
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference 2004 Chen S, Ganguli S, Hunt CA -
Applying models of targeted drug delivery to gene delivery.
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference 2004 Lam TN, Hunt CA -
In silico representation of the liver-connecting function to anatomy, physiology and heterogeneous microenvironments.
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference 2004 Yan L, Hunt CA, Ropella GE, Roberts MS -
Modeling liver physiology: combining fractals, imaging and animation.
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference 2004 Lin DW, Johnson S, Hunt CA -
Modeling mammary gland morphogenesis as a reaction-diffusion process.
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference 2004 Grant MR, Hunt CA, Xia L, Fata JE, Bissell MJ -
Novel stepwise normalization method for two-channel cDNA microarrays.
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference 2004 Xiao Y, Hunt CA, Segal MR, Yang YH -
Representing intestinal drug transport in silico: an agent-oriented approach.
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference 2004 Liu Y, Hunt CA -
The necessity of a theory of biology for tissue engineering: metabolism-repair systems.
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference 2004 Ganguli S, Hunt CA -
Assessment of differential gene expression in human peripheral nerve injury.
BMC genomics 2002 Xiao Y, Segal MR, Rabert D, Ahn AH, Anand P, Sangameswaran L, Hu D, Hunt CA -
A forecasting approach to accelerate drug development.
Statistics in medicine 1998 Hunt CA, Guzy S, Weiner DL -
Bootstrapping for pharmacokinetic models: visualization of predictive and parameter uncertainty.
Pharmaceutical research 1998 Hunt CA, Givens GH, Guzy S -
Validation of a decision support system for use in drug development: pharmacokinetic data.
Pharmaceutical research 1997 Guzy S, Hunt CA -
Sequence-independent inhibition of RNA transcription by DNA dumbbells and other decoys.
Nucleic acids research 1997 Lim CS, Jabrane-Ferrat N, Fontes JD, Okamoto H, Garovoy MR, Peterlin BM, Hunt CA -
Measures of uncertainty of pharmacokinetic and pharmacodynamic parameter estimates: a new computerized algorithm.
Computers and biomedical research, an international journal 1996 Guzy S, Hunt CA -
An oligonucleotide blocks interferon-gamma signal transduction.
Transplantation 1996 Lee PP, Ramanathan M, Hunt CA, Garovoy MR -
Screening and characterization of estrogenic activity from a hydroxystilbene library.
Chemistry & biology 1995 Williard R, Jammalamadaka V, Zava D, Benz CC, Hunt CA, Kushner PJ, Scanlan TS -
Suppression of interferon-gamma induction of MHC class II and ICAM-1 by a 26-base oligonucleotide composed of deoxyguanosine and deoxythymidine.
Transplant immunology 1994 Tam S, Huey B, Li Y, Lui GM, Hwang DG, Lantz M, Weiss TL, Hunt CA, Garovoy MR -
Inhibition of transcription factor binding to the HER2 promoter by triplex-forming oligodeoxyribonucleotides.
Gene 1994 Noonberg SB, Scott GK, Hunt CA, Hogan ME, Benz CC -
Paradoxical production of target protein using antisense RNA expression vectors.
Gene 1994 Williard R, Benz CC, Baxter JD, Kushner P, Hunt CA -
Characterization of the oligodeoxynucleotide-mediated inhibition of interferon-gamma-induced major histocompatibility complex class I and intercellular adhesion molecule-1.
The Journal of biological chemistry 1994 Ramanathan M, Lantz M, MacGregor RD, Garovoy MR, Hunt CA -
Characterization of apocytochrome C binding to human erythrocytes.
American journal of hematology 1994 Krishnan G, MacGregor RD, Shohet SB, Hunt CA -
Sequential staining of short oligonucleotides in polyacrylamide gels with ethidium bromide and methylene blue.
BioTechniques 1994 Lim CS, Hunt CA -
Calcium dependent cellular uptake of a c-myc antisense oligonucleotide.
Cellular and molecular biology (Noisy-le-Grand, France) 1994 Wu-Pong S, Weiss TL, Hunt CA -
In vivo generation of highly abundant sequence-specific oligonucleotides for antisense and triplex gene regulation.
Nucleic acids research 1994 Noonberg SB, Scott GK, Garovoy MR, Benz CC, Hunt CA -
Detection of triplex-forming RNA oligonucleotides by triplex blotting.
BioTechniques 1994 Noonberg SB, Scott GK, Hunt CA, Benz CC -
Biological availability and nuclease resistance extend the in vitro activity of a phosphorothioate-3'hydroxypropylamine oligonucleotide.
Nucleic acids research 1994 Tam RC, Li Y, Noonberg S, Hwang DG, Lui G, Hunt CA, Garovoy MR -
Inhibition of interferon-gamma-induced major histocompatibility complex class I expression by certain oligodeoxynucleotides.
Transplantation 1994 Ramanathan M, Lantz M, MacGregor RD, Huey B, Tam S, Li Y, Garovoy MR, Hunt CA -
Inhibition of interferon-gamma-mediated immune functions by oligonucleotides. Suppression of human T cell proliferation by downregulation of IFN-gamma-induced ICAM-1 and Fc-receptor on accessory cells.
Transplantation 1994 Fedoseyeva EV, Li Y, Huey B, Tam S, Hunt CA, Benichou G, Garovoy MR -
Antisense c-myc oligonucleotide cellular uptake and activity.
Antisense research and development 1994 Wu-Pong S, Weiss TL, Hunt CA -
Characteristics of oligonucleotide uptake in human keratinocyte cultures.
The Journal of investigative dermatology 1993 Noonberg SB, Garovoy MR, Hunt CA -
Predictions of effect for intracellular antisense oligodeoxyribonucleotides from a kinetic model.
Antisense research and development 1993 Ramanathan M, MacGregor RD, Hunt CA -
Antisense c-myc oligodeoxyribonucleotide cellular uptake.
Pharmaceutical research 1992 Wu-Pong S, Weiss TL, Hunt CA -
Buffer effects on swelling kinetics in polybasic gels.
Pharmaceutical research 1992 Siegel RA, Johannes I, Hunt CA, Firestone BA -
Characterization and minimization of cellular autofluorescence in the study of oligonucleotide uptake using confocal microscopy.
Antisense research and development 1992 Noonberg SB, Weiss TL, Garovoy MR, Hunt CA -
Involvement in medical informatics may enable pharmacists to expand their consultation potential and improve the quality of healthcare.
The Annals of pharmacotherapy 1992 Woodruff AE, Hunt CA -
Comparison and critique of two models for regional drug delivery.
Journal of pharmacokinetics and biopharmaceutics 1991 Siegel RA, MacGregor RD, Hunt CA -
Artificial red cells. A link between the membrane skeleton and RES detectability?
Biomaterials, artificial cells, and artificial organs 1990 MacGregor RD, Hunt CA -
Engineering targeted in vivo drug delivery. I. The physiological and physicochemical principles governing opportunities and limitations.
Pharmaceutical research 1986 Hunt CA, Macgregor RD, Siegel RA