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Suresh V. Ambudkar, Ph.D.

Suresh V. Ambudkar, Ph.D.

  • Center for Cancer Research
  • National Cancer Institute

RESEARCH SUMMARY

Dr. Ambudkar and colleagues elucidate the role of ABC drug transporters in cancers that develop resistance to anti-cancer drugs. They facilitate the development of new therapeutic strategies to improve the efficiency of chemotherapy for cancer patients. Transition metal ion Forster resonance energy transfer, chemical crosslinking, directed mutagenesis, and molecular modeling techniques are used to understand the molecular mechanisms of polyspecificity, the catalytic cycle and drug transport. Monoclonal antibodies and various mutant variants are used to obtain high-resolution structures of P-glycoprotein (ABCB1). They also characterize the modulatory effect of targeted therapeutic tyrosine kinase inhibitors and non-toxic natural products to overcome ABC transporter-mediated drug resistance.

Areas of Expertise

ABC Transporters
Catalytic Cycle
Multidrug Resistance
Transport Mechanism
Tyrosine Kinase Inhibitors

Publications

Selected Key Publications

Evidence for a requirement for ATP hydrolysis at two distinct steps during a single turnover of the catalytic cycle of human P-glycoprotein

Sauna ZE, Ambudkar SV
Proc. Natl. Acad. Sci. U.S.A.. 97: 2515-20, 2000. [ Journal Article ]

Elucidation of the structural basis of interaction of the BCR-ABL kinase inhibitor, nilotinib (Tasigna) with the human ABC drug transporter P-glycoprotein

Shukla S, Chufan EE, Singh S, Skoumbourdis AP, Kapoor K, Boxer MB, Duveau DY, Thomas CJ, Talele TT, Ambudkar SV.
Leukemia. 28: 961-4, 2014. [ Journal Article ]

Cryo-EM analysis of conformational landscape of human P-glycoprotein (ABCB1) during its catalytic cycle

Frank, G.A., Shukla, S., Rao, P., Borgnia, M.J., Bartesaghi, A., Merk, A., Mobin. A., Esser, L., Earl, L.A., Gottesman, M.M., Xia, D., Ambudkar*, S.V. and Subramaniam*, S (*corresponding authors)
Mol. Pharmacol.. 90: 35-41, 2016. [ Journal Article ]

Reversing the direction of drug transport mediated by the human multidrug transporter P-glycoprotein

Sajid, A., Lusvarghi, L., Murakami, M., Chufan, E.E., Abel, B., Gottesman, M.M., Durell, S.R. and Ambudkar, S.V.
Proc. Natl. Acad. Sci. U.S.A.. 117: 29609-29617, 2020. [ Journal Article ]

Advances in the structure, mechanism and targeting of chemoresistance-linked ABC transporters

Sajid, A., Rahman, H. and Ambudkar, S.V.
Nat. Rev. Cancer. Online ahead of print: doi: 10.1038/s41568-023-00612-3, 2023. [ Journal Article ]

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Team

Staff Scientist
Andaleeb Sajid, Ph.D.
Postdoctoral Fellow (Visiting)
Megumi Murakami, Ph.D.
Predoctoral Fellow (Graduate Student)
Idrisa Rahman
Postdoctoral Fellow (Visiting)
Paula Salazar, Ph.D.
Postdoctoral Fellow (Visiting)
Nandhini Ranganathan, Ph.D.
Biologist
Tapan Maity, Ph.D.
Post-Baccalaureate Fellow
Shafaq Ahmed
Post-baccalaureate Fellow
Conner Jewell

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