Department of Pharmaceutical Sciences

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Ghee T. Tan, Ph.D.

Associate Professor

Malaria is one of the major public health challenges undermining development in the poorest countries of the world. Disease control is hampered by the lack of an efficacious vaccine, and the occurrence of multidrug resistant (mdr) strains of Plasmodium falciparum. A significant number of plant species have been identified by various cultures as having antimalarial properties, and current antimalarial therapy consists substantially of natural products and related derivatives. Artemisinin (ART) is a key ingredient in combination drug therapies recommended by the World Health Organization (WHO) for the treatment of drug resistant strains of falciparum malaria, and the last effective drug available against mdr malaria in the perpetually limited antimalarial armamentarium. Unfortunaterly, the number of stereogenic centers present in the ART molecule makes total synthesis difficult and unadaptable to industrial production at costs that will ensure maximum accessibility in resource-poor countries.

With a view to tackling global health challenges, my lab aims to discover and develop natural product antimalarial agents that are not only clinically efficacious, but also economical to synthesize in large-scale making the drug affordable to low-income countries. To that end, foliar endophytic fungi and the medicinal plants of various cultures around the world are being explored as potential sources of novel antimalarial agents. Established antimalarial lead compounds identified from these natural sources will then be synthesized and structurally modified to improve their antimalarial selectivity and potency against the erythrocytic, hepatic and gametocyte stages of P. falciparum. Studies will also be conducted to elucidate the mechanism(s) of action of these lead compounds as therapeutic and transmission blocking agents. Such efforts may ultimately lead to the identification of new molecular targets for malaria.

In addition to the drug discovery and development effort described above, a project under development proposes to exploit parasite nutrient transporters as novel drug targets and potential routes for the selective delivery of antimalarial agents into infected red blood cells. Recent and emerging literature strongly suggests that this “Trojan Horse” chemotherapeutic approach is applicable to human cancer as well. Driven by a 2-pronged approach, cytotoxic molecules emanating from the malaria screening program will be funneled into a parallel scheme aiming to identify new anticancer compounds and their associated cellular targets, in addition to novel drug targeting and delivery strategies.

Education

  • Ph.D., Molecular Pharmacology, University of Illinois at Chicago
  • Postdoctoral Fellow, Public Health Research Institute/New York University

Classes and Courses

  • PHPS 555 – Geographic Medicine & Global Health
  • PHPS 502/752 – Biochemistry-Metabolism
  • PHPS 702 - Bioassay Development: Principles and Practices in Drug Discovery

Selected Presentations and/or Publications

  • N. Q. Chien, N. V. Hung, B. D. Santarsiero, A. D. Mesecar, N. M. Cuong, D. D. Soejarto, J. M. Pezzuto, H. H. S. Fong, and G. T. Tan (2004) New 3-O-acyl betulinic acids from Strychnos vanprukii Craib. J. Nat. Prod. 67(6), 994-998
  • H.-J. Zhang, N. V. Hung, N. M. Cuong, D. D. Soejarto, J. M. Pezzuto, H. H. S. Fong, and G. T. Tan (2005) Sesquiterpenes and butenolides, natural anti-HIV constituents from Litsea verticillata. Planta Med. 71, 446-451
  • C.-Y. Ma, H.-J. Zhang, G. T. Tan, N. V. Hung, N. M. Cuong, D. D. Soejarto, and H. H. S. Fong (2006) Antimalarial compounds from Grewia bilamellata. J. Nat. Prod., 69, 346-350
  • G. T. Tan, C. Gyllenhaal and D. Soejarto (2006) Biodiversity as a Source of Anticancer Agents. Curr. Drug Targets, 7(3), 265-277
  • S. F. Musoke, O. Odyek, W. W. Anokbonggo, J. Ogwal-Okeng, E. J. Carcache-Blanco, C.-Y. Ma, J. Orjala, and G. T. Tan (2010) Antimalarial activity of Aspilia pruliseta, a medicinal plant from Uganda. Planta Med., 76: 1–3
  • F. M. Sebisubi and G.T. Tan (2010) Natural Products with Promising Antimalarial Activity, in Natural Products, edited by J.M. Pezzuto and M.J. Kato, in Encyclopedia of Life Support Systems (EOLSS), Developed under the Auspices of the UNESCO, Eolss Publishers, Oxford, UK
  • M. Pieroni, S. Girmay, D.-Q. Sun, R. Sahu, B.L. Tekwani, and G.T. Tan (2012) Synthesis and structure–activity relationships of unique lansine analogs as antileishmanial agents. Chem.Med.Chem., 7, 1895-1900.

Awards and Honors

  • Kilmer Prize for meritorious work on natural products, American Pharmaceutical Association and American Society for Pharmacognosy