C. Anthony Hunt, PhD

Professor
Bioengineering

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. 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.

Publications: 

An exploration of knowledge-organizing technologies to advance transdisciplinary back pain research.

JOR spine

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.)

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, Mehling W, Hunt CA, Lotz J

Contrasting model mechanisms of alanine aminotransferase (ALT) release from damaged and necrotic hepatocytes as an example of general biomarker mechanisms.

PLoS computational biology

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

Kennedy RC, Smith AK, Ropella GEP, McGill MR, Jaeschke H, Hunt CA

The Spectrum of Mechanism-Oriented Models and Methods for Explanations of Biological Phenomena.

Processes (Basel, Switzerland)

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

Smith AK, Xu Y, Ropella GEP, Hunt CA

Simulation enabled search for explanatory mechanisms of the fracture healing process.

PLoS computational biology

Kennedy RC, Marmor M, Marcucio R, Hunt CA

Competing Mechanistic Hypotheses of Acetaminophen-Induced Hepatotoxicity Challenged by Virtual Experiments.

PLoS computational biology

Smith AK, Petersen BK, Ropella GE, Kennedy RC, Kaplowitz N, Ookhtens M, Hunt CA

A cell-centered, agent-based framework that enables flexible environment granularities.

Theoretical biology & medical modelling

Kennedy RC, 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

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

Hunt CA, Kennedy RC, Kim SH, Ropella GE

Relational grounding facilitates development of scientifically useful multiscale models.

Theoretical biology & medical modelling

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

Sheikh-Bahaei S, Hunt CA

MDCK cystogenesis driven by cell stabilization within computational analogues.

PLoS computational biology

Engelberg JA, Datta A, Mostov KE, Hunt CA

Tracing multiscale mechanisms of drug disposition in normal and diseased livers.

The Journal of pharmacology and experimental therapeutics

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

Kim SH, Matthay MA, Mostov K, Hunt CA

At the biological modeling and simulation frontier.

Pharmaceutical research

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

Kim SH, Park S, Mostov K, Debnath J, Hunt CA

A computational approach to understand in vitro alveolar morphogenesis.

PloS one

Kim SH, Yu W, Mostov K, Matthay MA, Hunt CA

Essential operating principles for tumor spheroid growth.

BMC systems biology

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

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

Lam TN, Hunt CA

Dichotomies between computational and mathematical models.

Nature biotechnology

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

Garmire LX, Hunt CA

A framework and mechanistically focused, in silico method for enabling rational translational research.

Summit on translational bioinformatics

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

Yan L, Sheihk-Bahaei S, Park S, Ropella GE, Hunt CA

In silico simulation of epithelial cell tubulogenesis.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference

Engelberg JA, Kim M, Mostov KE, Hunt CA

Mechanistic simulations explain paradoxical saquinavir metabolism during in vitro vectorial transport study.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference

Lam TN, Hunt CA

Using an in silico liver to evaluate a hepatic enzyme induction mechanism.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference

Hunt C, Ropella GE

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

Nikanjam M, Gibbs AR, Hunt CA, Budinger TF, Forte TM

Formation of cysts by alveolar type II cells in three-dimensional culture reveals a novel mechanism for epithelial morphogenesis.

Molecular biology of the cell

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

Tang J, Ley KF, Hunt CA

Physiologically based synthetic models of hepatic disposition.

Journal of pharmacokinetics and pharmacodynamics

Hunt CA, Ropella GE, Yan L, Hung DY, Roberts MS

Simulating properties of in vitro epithelial cell morphogenesis.

PLoS computational biology

Grant MR, Mostov KE, Tlsty TD, Hunt CA

Simulating in vitro epithelial morphogenesis in multiple environments.

Computational systems bioinformatics. Computational Systems Bioinformatics Conference

Grant MR, Kim SH, Hunt CA

Glucose transport to the brain: a systems model.

Brain research. Brain research reviews

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

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

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

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

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

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

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

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

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

Ganguli S, Hunt CA

Assessment of differential gene expression in human peripheral nerve injury.

BMC genomics

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

Hunt CA, Guzy S, Weiner DL

Sequence-independent inhibition of RNA transcription by DNA dumbbells and other decoys.

Nucleic acids research

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

Guzy S, Hunt CA

An oligonucleotide blocks interferon-gamma signal transduction.

Transplantation

Lee PP, Ramanathan M, Hunt CA, Garovoy MR

Screening and characterization of estrogenic activity from a hydroxystilbene library.

Chemistry & biology

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

Tam S, Huey B, Li Y, Lui GM, Hwang DG, Lantz M, Weiss TL, Hunt CA, Garovoy MR

Paradoxical production of target protein using antisense RNA expression vectors.

Gene

Williard R, Benz CC, Baxter JD, Kushner P, Hunt CA

Characterization of apocytochrome C binding to human erythrocytes.

American journal of hematology

Krishnan G, MacGregor RD, Shohet SB, Hunt CA

Calcium dependent cellular uptake of a c-myc antisense oligonucleotide.

Cellular and molecular biology (Noisy-le-Grand, France)

Wu-Pong S, Weiss TL, Hunt CA

Detection of triplex-forming RNA oligonucleotides by triplex blotting.

BioTechniques

Noonberg SB, Scott GK, Hunt CA, Benz CC

Inhibition of interferon-gamma-induced major histocompatibility complex class I expression by certain oligodeoxynucleotides.

Transplantation

Ramanathan M, Lantz M, MacGregor RD, Huey B, Tam S, Li Y, Garovoy MR, Hunt CA

Antisense c-myc oligonucleotide cellular uptake and activity.

Antisense research and development

Wu-Pong S, Weiss TL, Hunt CA

Characteristics of oligonucleotide uptake in human keratinocyte cultures.

The Journal of investigative dermatology

Noonberg SB, Garovoy MR, Hunt CA

Predictions of effect for intracellular antisense oligodeoxyribonucleotides from a kinetic model.

Antisense research and development

Ramanathan M, MacGregor RD, Hunt CA

Antisense c-myc oligodeoxyribonucleotide cellular uptake.

Pharmaceutical research

Wu-Pong S, Weiss TL, Hunt CA

Buffer effects on swelling kinetics in polybasic gels.

Pharmaceutical research

Siegel RA, Johannes I, Hunt CA, Firestone BA

Comparison and critique of two models for regional drug delivery.

Journal of pharmacokinetics and biopharmaceutics

Siegel RA, MacGregor RD, Hunt CA

Artificial red cells. A link between the membrane skeleton and RES detectability?

Biomaterials, artificial cells, and artificial organs

MacGregor RD, Hunt CA