Education

• BSc, Chemistry, Georgia Institute of Technology
• PhD, Pharmaceutical Sciences, University of Florida

Profile

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.

Research Interest

Computational biology/pharmacology, Bioengineering, Multiscale modeling and simulation, Personalized medicine, Biomedical informatics.

Professional Activities:

Positions and Employment

Other Experience and Professional Memberships

Honors and Awards

Publications

1. Hunt CA, Kennedy RC, Kim SH, Ropella GE. Agent-based modeling: a systematic assessment of use cases and requirements for enhancing pharmaceutical research and development productivity. Wiley Interdiscip Rev Syst Biol Med. 2013 Jul-Aug; 5(4):461-80.
2. Kim SH, Jackson AJ, Hur R, Hunt CA. Individualized, discrete event, simulations provide insight into inter- and intra-subject variability of extended-release, drug products. Theor Biol Med Model. 2012; 9:39.
3. Hunt CA, Ropella GE, Lam Tn, Gewitz AD. Relational grounding facilitates development of scientifically useful multiscale models. Theor Biol Med Model. 2011; 8:35.
4. Engelberg JA, Datta A, Mostov KE, Hunt CA. MDCK cystogenesis driven by cell stabilization within computational analogues. PLoS Comput Biol. 2011 Apr; 7(4):e1002030.
5. Park S, Kim SH, Ropella GE, Roberts MS, Hunt CA. Tracing multiscale mechanisms of drug disposition in normal and diseased livers. J Pharmacol Exp Ther. 2010 Jul; 334(1):124-36.
6. Kim SH, Matthay MA, Mostov K, Hunt CA. Simulation of lung alveolar epithelial wound healing in vitro. J R Soc Interface. 2010 Aug 6; 7(49):1157-70.
7. Tang J, Hunt CA. Identifying the rules of engagement enabling leukocyte rolling, activation, and adhesion. PLoS Comput Biol. 2010 Feb; 6(2):e1000681.
8. Kim SH, Debnath J, Mostov K, Park S, Hunt CA. A computational approach to resolve cell level contributions to early glandular epithelial cancer progression. BMC Syst Biol. 2009; 3:122.
9. Lam TN, Hunt CA. Mechanistic insight from in silico pharmacokinetic experiments: roles of P-glycoprotein, Cyp3A4 enzymes, and microenvironments. J Pharmacol Exp Ther. 2010 Feb; 332(2):398-412.
10. Hunt CA, Ropella GE, Lam TN, Tang J, Kim SH, Engelberg JA, Sheikh-Bahaei S. At the biological modeling and simulation frontier. Pharm Res. 2009 Nov; 26(11):2369-400.
11. Kim SH, Park S, Mostov K, Debnath J, Hunt CA. Computational investigation of epithelial cell dynamic phenotype in vitro. Theor Biol Med Model. 2009; 6:8.
12. Kim SH, Yu W, Mostov K, Matthay MA, Hunt CA. A computational approach to understand in vitro alveolar morphogenesis. PLoS One. 2009; 4(3):e4819.
13. Engelberg JA, Ropella GE, Hunt CA. Essential operating principles for tumor spheroid growth. BMC Syst Biol. 2008; 2:110.
14. Park S, Ropella GE, Kim SH, Roberts MS, Hunt CA. Computational strategies unravel and trace how liver disease changes hepatic drug disposition. J Pharmacol Exp Ther. 2009 Jan; 328(1):294-305.
15. Lam TN, Hunt CA. Discovering plausible mechanistic details of hepatic drug interactions. Drug Metab Dispos. 2009 Jan; 37(1):237-46.
16. Yan L, Sheihk-Bahaei S, Park S, Ropella GE, Hunt CA. Predictions of hepatic disposition properties using a mechanistically realistic, physiologically based model. Drug Metab Dispos. 2008 Apr; 36(4):759-68.
17. Lam TN, Hunt CA. Mechanistic simulations explain paradoxical saquinavir metabolism during in vitro vectorial transport study. Conf Proc IEEE Eng Med Biol Soc. 2008; 2008:5462-5.
18. Engelberg JA, Kim M, Mostov KE, Hunt CA. In silico simulation of epithelial cell tubulogenesis. Conf Proc IEEE Eng Med Biol Soc. 2008; 2008:1036-9.
19. Hunt C, Ropella GE. Using an in silico liver to evaluate a hepatic enzyme induction mechanism. Conf Proc IEEE Eng Med Biol Soc. 2008; 2008:2415-8.
20. Yan L, Ropella GE, Park S, Roberts MS, Hunt CA. Modeling and simulation of hepatic drug disposition using a physiologically based, multi-agent in silico liver. Pharm Res. 2008 May; 25(5):1023-36.
21. Yu W, Fang X, Ewald A, Wong K, Hunt CA, Werb Z, Matthay MA, Mostov K. Formation of cysts by alveolar type II cells in three-dimensional culture reveals a novel mechanism for epithelial morphogenesis. Mol Biol Cell. 2007 May; 18(5):1693-700.
22. Tang J, Ley KF, Hunt CA. Dynamics of in silico leukocyte rolling, activation, and adhesion. BMC Syst Biol. 2007; 1:14.
23. Hunt CA, Ropella GE, Yan L, Hung DY, Roberts MS. Physiologically based synthetic models of hepatic disposition. J Pharmacokinet Pharmacodyn. 2006 Dec; 33(6):737-72.
24. Grant MR, Mostov KE, Tlsty TD, Hunt CA. Simulating properties of in vitro epithelial cell morphogenesis. PLoS Comput Biol. 2006 Oct 6; 2(10):e129.
25. Liu Y, Hunt CA. Mechanistic study of the cellular interplay of transport and metabolism using the synthetic modeling method. Pharm Res. 2006 Mar; 23(3):493-505.
26. Grant MR, Kim SH, Hunt CA. Simulating in vitro epithelial morphogenesis in multiple environments. Comput Syst Bioinformatics Conf. 2006; 381-4.
27. Liu Y, Hunt CA. Studies of intestinal drug transport using an in silico epithelio-mimetic device. Biosystems. 2005 Nov; 82(2):154-67.
28. Qutub AA, Hunt CA. Glucose transport to the brain: a systems model. Brain Res Brain Res Rev. 2005 Nov; 49(3):595-617.
29. Lam TN, Hunt CA. Applying models of targeted drug delivery to gene delivery. Conf Proc IEEE Eng Med Biol Soc. 2004; 5:3535-8.
30. Grant MR, Hunt CA, Xia L, Fata JE, Bissell MJ. Modeling mammary gland morphogenesis as a reaction-diffusion process. Conf Proc IEEE Eng Med Biol Soc. 2004; 1:679-82.
31. Ganguli S, Hunt CA. The necessity of a theory of biology for tissue engineering: metabolism-repair systems. Conf Proc IEEE Eng Med Biol Soc. 2004; 7:5031-4.
32. Lin DW, Johnson S, Hunt CA. Modeling liver physiology: combining fractals, imaging and animation. Conf Proc IEEE Eng Med Biol Soc. 2004; 5:3120-3.
33. Liu Y, Hunt CA. Representing intestinal drug transport in silico: an agent-oriented approach. Conf Proc IEEE Eng Med Biol Soc. 2004; 1:770-3.
34. Xiao Y, Segal MR, Rabert D, Ahn AH, Anand P, Sangameswaran L, Hu D, Hunt CA. Assessment of differential gene expression in human peripheral nerve injury. BMC Genomics. 2002 Sep 27; 3(1):28.
35. Hunt CA, Guzy S, Weiner DL. A forecasting approach to accelerate drug development. Stat Med. 1998 Aug 15-30; 17(15-16):1725-40; discussion 1741-3.
36. Hunt CA, Givens GH, Guzy S. Bootstrapping for pharmacokinetic models: visualization of predictive and parameter uncertainty. Pharm Res. 1998 May; 15(5):690-7.
37. Guzy S, Hunt CA. Validation of a decision support system for use in drug development: pharmacokinetic data. Pharm Res. 1997 Oct; 14(10):1287-97.
38. Lim CS, Jabrane-Ferrat N, Fontes JD, Okamoto H, Garovoy MR, Peterlin BM, Hunt CA. Sequence-independent inhibition of RNA transcription by DNA dumbbells and other decoys. Nucleic Acids Res. 1997 Feb 1; 25(3):575-81.
39. Guzy S, Hunt CA. Measures of uncertainty of pharmacokinetic and pharmacodynamic parameter estimates: a new computerized algorithm. Comput Biomed Res. 1996 Dec; 29(6):466-81.
40. Lee PP, Ramanathan M, Hunt CA, Garovoy MR. An oligonucleotide blocks interferon-gamma signal transduction. Transplantation. 1996 Nov 15; 62(9):1297-301.
41. Williard R, Jammalamadaka V, Zava D, Benz CC, Hunt CA, Kushner PJ, Scanlan TS. Screening and characterization of estrogenic activity from a hydroxystilbene library. Chem Biol. 1995 Jan; 2(1):45-51.
42. Tam S, Huey B, Li Y, Lui GM, Hwang DG, Lantz M, Weiss TL, Hunt CA, Garovoy MR. Suppression of interferon-gamma induction of MHC class II and ICAM-1 by a 26-base oligonucleotide composed of deoxyguanosine and deoxythymidine. Transpl Immunol. 1994 Dec; 2(4):285-92.
43. Noonberg SB, Scott GK, Hunt CA, Hogan ME, Benz CC. Inhibition of transcription factor binding to the HER2 promoter by triplex-forming oligodeoxyribonucleotides. Gene. 1994 Nov 4; 149(1):123-6.
44. Williard R, Benz CC, Baxter JD, Kushner P, Hunt CA. Paradoxical production of target protein using antisense RNA expression vectors. Gene. 1994 Nov 4; 149(1):21-4.
45. Ramanathan M, Lantz M, MacGregor RD, Garovoy MR, Hunt CA. Characterization of the oligodeoxynucleotide-mediated inhibition of interferon-gamma-induced major histocompatibility complex class I and intercellular adhesion molecule-1. J Biol Chem. 1994 Oct 7; 269(40):24564-74.
46. Krishnan G, MacGregor RD, Shohet SB, Hunt CA. Characterization of apocytochrome C binding to human erythrocytes. Am J Hematol. 1994 Oct; 47(2):132-4.
47. Lim CS, Hunt CA. Sequential staining of short oligonucleotides in polyacrylamide gels with ethidium bromide and methylene blue. Biotechniques. 1994 Oct; 17(4):626, 628.
48. Wu-Pong S, Weiss TL, Hunt CA. Calcium dependent cellular uptake of a c-myc antisense oligonucleotide. Cell Mol Biol (Noisy-le-grand). 1994 Sep; 40(6):843-50.
49. Noonberg SB, Scott GK, Garovoy MR, Benz CC, Hunt CA. In vivo generation of highly abundant sequence-specific oligonucleotides for antisense and triplex gene regulation. Nucleic Acids Res. 1994 Jul 25; 22(14):2830-6.
50. Noonberg SB, Scott GK, Hunt CA, Benz CC. Detection of triplex-forming RNA oligonucleotides by triplex blotting. Biotechniques. 1994 Jun; 16(6):1070-2, 1074.
51. Tam RC, Li Y, Noonberg S, Hwang DG, Lui G, Hunt CA, Garovoy MR. Biological availability and nuclease resistance extend the in vitro activity of a phosphorothioate-3'hydroxypropylamine oligonucleotide. Nucleic Acids Res. 1994 Mar 25; 22(6):977-86.
52. Ramanathan M, Lantz M, MacGregor RD, Huey B, Tam S, Li Y, Garovoy MR, Hunt CA. Inhibition of interferon-gamma-induced major histocompatibility complex class I expression by certain oligodeoxynucleotides. Transplantation. 1994 Feb 27; 57(4):612-5.
53. Fedoseyeva EV, Li Y, Huey B, Tam S, Hunt CA, Benichou G, Garovoy MR. 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 Feb 27; 57(4):606-12.
54. Wu-Pong S, Weiss TL, Hunt CA. Antisense c-myc oligonucleotide cellular uptake and activity. Antisense Res Dev. 1994; 4(3):155-63.
55. Noonberg SB, Garovoy MR, Hunt CA. Characteristics of oligonucleotide uptake in human keratinocyte cultures. J Invest Dermatol. 1993 Nov; 101(5):727-31.
56. Ramanathan M, MacGregor RD, Hunt CA. Predictions of effect for intracellular antisense oligodeoxyribonucleotides from a kinetic model. Antisense Res Dev. 1993; 3(1):3-18.
57. Wu-Pong S, Weiss TL, Hunt CA. Antisense c-myc oligodeoxyribonucleotide cellular uptake. Pharm Res. 1992 Aug; 9(8):1010-7.
58. Siegel RA, Johannes I, Hunt CA, Firestone BA. Buffer effects on swelling kinetics in polybasic gels. Pharm Res. 1992 Jan; 9(1):76-81.
59. Noonberg SB, Weiss TL, Garovoy MR, Hunt CA. Characterization and minimization of cellular autofluorescence in the study of oligonucleotide uptake using confocal microscopy. Antisense Res Dev. 1992; 2(4):303-13.
60. Woodruff AE, Hunt CA. Involvement in medical informatics may enable pharmacists to expand their consultation potential and improve the quality of healthcare. Ann Pharmacother. 1992 Jan; 26(1):100-4.
61. Siegel RA, MacGregor RD, Hunt CA. Comparison and critique of two models for regional drug delivery. J Pharmacokinet Biopharm. 1991 Jun; 19(3):363-73; discussion 373-4.
62. MacGregor RD, Hunt CA. Artificial red cells. A link between the membrane skeleton and RES detectability? Biomater Artif Cells Artif Organs. 1990; 18(2):329-43.
63. Hunt CA, Macgregor RD, Siegel RA. Engineering targeted in vivo drug delivery. I. The physiological and physicochemical principles governing opportunities and limitations. Pharm Res. 1986 Dec; 3(6):333-44.