Summary

The Rosania lab studies the microscopic transport properties of small drug-like molecules inside cells. Our overarching hypothesis is that a drug's microscopic distribution within organelles is as important as its macroscopic distribution in organs in determining efficacy and toxicity. We use microscopic imaging instruments to capture the local distribution and dynamics of small molecules inside cells and analyze image data with innovative computational tools and statistical strategies, combining cheminformatics and machine vision to relate the chemical structure of small molecules to their subcellular distribution. We also develop biochemical analysis methods to study the microdistribution and cellular pharmacokinetics of small drug-like molecules. Lastly, we build mathematical models to simulate drug transport and distribution in single cells and higher order cellular organizations, based on biophysical principles governing molecular transport phenomena at the cellular level.

We envision a day when drugs are designed, optimized, and approved based on their site of action, much as drugs today are designed, optimized, and approved based on their molecular mechanism of action. 

Research Interests

  • Exploring the application of in silico models, such as the cell-based molecular transport simulations we use in our experiments, to pharmaceutical discovery and development
  • Exploring cell-based molecular transport simulations as a way to probe the role of microscopic drug transport as a determinant of drug absorption, distribution, metabolism, and excretion
  • Using mathematical and experimental approaches to explore how specific chemical moieties can be used to massively target small-molecule drugs to specific cell types in animals and humans
  • Dissemination of free modeling and simulation tools to help educate the next generation of pharmaceutical scientists and medicinal chemists and to facilitate the development of drugs neglected by the pharmaceutical industry

Awards

  • 2004 Exterior Colombia Award for Excellence in the USA
  • 2007 Presidential Early Career Award for Scientists and Engineers

Recent Publications

  • Kyoung Ah Min; Arjang Talattof; Yasuhiro Tsume; Kathleen A. Stringer; Jing-Yu Yu; Dong Hyun Lim; Gus R. Rosania The extracellular microenvironment explains variations in passive drug transport across different airway epithelial cell types. Pharmaceutical Research. 2013;30(8):2118-2132
  • Kyoung Ah Min; Meong Cheol Shin; Faquan Yu; Meizhu Yang; Allan E. David; Victor C. Yang; Gus R. Rosania Pulsed magnetic field improves the transport of iron oxide nanoparticles through cell barriers. ACS Nano. 2013;7(3):2161-2171
  • Jason Baik; Kathleen A. Stringer; Gerta Mane; Gus R. Rosania Multiscale distribution and bioaccumulation analysis of clofazimine reveals a massive immune system-mediated xenobiotic sequestration response. Antimicrobial Agents and Chemotherapy. 2013;57(3):1218-1230
  • X. Chu; K. Korzekwa; R. Elsby; K. Fenner; A. Galetin; Y. Lai; P. Matsson; A. Moss; S. Nagar; G.R. Rosania; J.P.F. Bai; J.W. Polli; Y. Sugiyama; K.L.R. Brouwer Intracellular drug concentrations and transporters: Measurement, modeling, and implications for the liver. Clinical Pharmacology and Therapeutics. 2013;94(1):126-141
  • Jing-yu Yu; Nan Zheng; Gerta Mane; Kyoung Ah Min; Juan P. Hinestroza; Huaning Zhu; Kathleen A. Stringer; Gus R. Rosania A cell-based computational modeling approach for developing site-directed molecular probes. PLoS Computational Biology. 2012;8(2):