Breadcrumb

Leonard M. Neckers, Ph.D.

Leonard M. Neckers, Ph.D.

  • Center for Cancer Research
  • National Cancer Institute
Urologic Oncology Branch

RESEARCH SUMMARY

Dr. Neckers identified the molecular chaperone Hsp90 as a key non-oncogene addiction of cancer, demonstrated that Hsp90 is an anticancer target, and showed that this target is druggable. Dr. Neckers discovered the first inhibitor of Hsp90, geldanamycin, as well as the first-in-human Hsp90 inhibitor, 17-AAG. His basic and translational research efforts have facilitated the development of a new class of anticancer drugs. Recently, Dr. Neckers has uncovered a fundamental role for the mitochondrial Hsp90 homolog TRAP1 as a key regulator of the balance between oxidative phosphorylation and aerobic glycolysis in cancer cells, expanding our understanding of the Warburg effect in cancer.

Areas of Expertise

1) heat shock protein 90 2) molecular chaperones and cancer 3) molecularly targeted drug development 4) stress response pathways in cancer 5) targeting proteostasis in cancer 6) regulation of cell metabolism by kinase and chaperone networks

Publications

Selected Key Publications

Dynamic Imaging of LDH Inhibition in Tumors Reveals Rapid In Vivo Metabolic Rewiring and Vulnerability to Combination Therapy

Oshima N, Ishida R, Kishimoto S, Beebe K, Brender JR, Yamamoto K, Urban D, Rai G, Johnson MS, Benavides G, Squadrito GL, Crooks D, Jackson J, Joshi A, Mott BT, Shrimp JH, Moses MA, Lee MJ, Yuno A, Lee TD, Hu X, Anderson T, Kusewitt D, Hathaway HH, Jadhav A, Picard D, Trepel JB, Mitchell JB, Stott GM, Moore W, Simeonov A, Sklar LA, Norenberg JP, Linehan WM, Maloney DJ, Dang CV, Waterson AG, Hall M, Darley-Usmar VM, Krishna MC, Neckers LM.
Cell Rep. 30(6): 1798-1810, 2020. [ Journal Article ]

Targeting Glycolysis through Inhibition of Lactate Dehydrogenase Impairs Tumor Growth in Preclinical Models of Ewing Sarcoma

Yeung C, Gibson AE, Issaq SH, Oshima N, Baumgart JT, Edessa LD, Rai G, Urban DJ, Johnson MS, Benavides GA, Squadrito GL, Yohe ME, Lei H, Eldridge S, Hamre J 3rd, Dowdy T, Ruiz-Rodado V, Lita A, Mendoza A, Shern JF, Larion M, Helman LJ, Stott GM, Krishna MC, Hall MD, Darley-Usmar V, Neckers LM, Heske CM.
Cancer Res. 79(19): 5060-73, 2019. [ Journal Article ]

Targeting the Hsp40/Hsp70 Chaperone Axis as a Novel Strategy to Treat Castration-Resistant Prostate Cancer

Moses MA, Kim YS, Rivera-Marquez GM, Oshima N, Watson MJ, Beebe KE, Wells C, Lee S, Zuehlke AD, Shao H, Bingman WE 3rd, Kumar V, Malhotra SV, Weigel NL, Gestwicki JE, Trepel JB, Neckers LM.
Cancer Res. 78(14): 4022-35, 2018. [ Journal Article ]

An Hsp90 co-chaperone protein in yeast is functionally replaced by site-specific posttranslational modification in humans

Zuehlke AD, Reidy M, Lin C, LaPointe P, Alsomairy S, Lee DJ, Rivera-Marquez GM, Beebe K, Prince T, Lee S, Trepel JB, Xu W, Johnson J, Masison D, Neckers L.
Nat Commun. 8: 15328, 2017. [ Journal Article ]

Asymmetric Hsp90 N domain SUMOylation recruits Aha1 and ATP-competitive inhibitors

Mollapour M, Bourboulia D, Beebe K, Woodford MR, Polier S, Hoang A, Chelluri R, Li Y, Guo A, Lee MJ, Fotooh-Abadi E, Khan S, Prince T, Miyajima N, Yoshida S, Tsutsumi S, Xu W, Panaretou B, Stetler-Stevenson WG, Bratslavsky G, Trepel JB, Prodromou C, Neckers L.
Mol. Cell. 53: 317-29, 2014. [ Journal Article ]

Job Vacancies

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Team

Biologist
Kristin E. Beebe, Ph.D.
Postdoctoral Fellow (Visiting)
Li (Joyce) Dai, Ph.D.
Postdoctoral Fellow (CRTA)
Frank Echtenkamp, Ph.D.
Postdoctoral Fellow (Visiting)
Ryo Ishida, Ph.D.
Postdoctoral Fellow (Visiting)
Abhinav Joshi , Ph.D.
Postbaccalaureate Fellow (CRTA)
Maris Maisiak
Biologist
Marianne Poruchynsky, Ph.D.
Postbaccalaureate Fellow (CRTA)
Genesis Rivera-Marquez
Postbaccalaureate Fellow
Megan Tigue