Department of Pharmaceutical Sciences

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Shugeng Cao, Ph.D.
Shugeng Cao

Associate Professor

Biologically active compounds from natural sources:
(i) The distribution and biologically active compounds of marine fungi have not been well studied compared with their counterparts in freshwater and terrestrial ecosystems. Few studies have addressed the occurrence of fungi in deep-sea sediments. Studies also showed that taxonomic and functional annotation of the transcriptome demonstrated that coral-associated fungi in Hawaii represent a diverse and metabolically active community, indicating that there is much to learn about fungi in corals.
(ii) A total of 23,680 Hawaiian species have been documented, including 18,607 native Hawaiian species (9,151 indigenous species and 9,456 endemic species), and 5,073 human-introduced (non-native) species. Among the formally recognized species of native Hawaiian flowering plants, 88.9% are endemic to the Hawaiian islands. Research in the past ten years reveals that endophytic fungi are a rich source of biologically active secondary metabolites, but endophytic fungi are much underexplored.
(iii) Bacteria, particularly actinimycetes, were traditionally a rich source for drug discovery, especially for antibiotic. Many efforts have been focusing on discovering new drugs from old sources (for example, streptomyces), but it usually leads to the discovery of known natural products.  More recently, efforts have been taken to reveal the cryptic natural products based on their unique genomic signatures New technology enables scientists to study bacteria from new sources (for example, cyanobacteria, myxobacteria, uncultured bacteria, bacteria in lower animals, insects-associated bacteria, and bacteria from marine etc); and these adventures have resulted in the discovery of novel bioactive compounds with unique structural skeletons. Also, globally and locally remote, as well as physically and chemically diverse, Hawaiian aquatic habitats provide unique niches for the evolution of novel communities and microorganisms. Cao Lab is interested in finding new anticancer (& antibacterial, etc.) natural products from marine and terrestrial fungi and bacteria collected in Hawaii, manipulating silent genes for the production of secondary metabolites, understanding how they are biosynthetically synthesized, and elucidating their mechanisms of action. Other research areas of interest are herbal medicine used for diseases related to cancer and diabetes etc., and small molecules with various biological functions in bacteria.

Education

  • Ph.D., National University of Singapore
  • Postdoctoral Fellow, Virginia Polytechnic Institute & State University
  • Postdoctoral Fellow, Harvard Medical School

Classes and Courses

  • Medicinal Chemistry
  • Drug Action II

Selected Presentations and/or Publications

  • Hiraki,+ M.; Hwang,+ S-Y.; Cao,+ S.; Ramadhar, T. R.; Byun, S.; Yoon, K. W.; Chu, K.; Gurkar, A. U.; Vihren Kolev, V.; Zhang, J.; Namba, T.; Murphy, M. E.; Aaronson, S. A.; Newman, D. J.; Mandinova, A.; Clardy,* J.; Lee,* S. W. Small molecule reactivation of mutant p53 to wt-like p53 through the p53-Hsp40 regulatory axis Chemistry & Biology 2015, online (+Co-first author/Equal contribution)
  • Wei, S.; Kozono, S.; Kats, L.; Nechama, M.; Li, W.; Guarnerio, J.; Luo, M.; You, M-H.; Yao, Y.; Kondo, A.; Hu, H.; Bozkurt, G.; Moerke, N. J.; Cao, S.; Reschke,M.; Chen,C-H.; Rego,E. M.; LoCoco, F.; Cantley, L.; Lee, T. H.; Wu, H.; Zhang,Y.; Pandolfi,P. P.; Zhou, Z. Z.; Kun Ping Lu, K-P*. Active Pin1 is a key target of all-trans retinoic acid in acute promyelocytic leukemia and breast cancer Nature Medicine 2015, 21(5), 457-466.
  • Kim, K. H.; Park, Y. J.; Chung, K. H.; Yip, M.L. R.; Clardy,J.; Senger, D.; Cao, S.* Iridoid Glycosides from Barleria lupulina J. Nat. Prod. 2015, 78, 320-324.
  • Li, C-S.; Ding, Y.; Yang, B-J.; Miklossy, G.; Yin, H-Q.; Walker, L. A.; Turkson,T.; Cao, S*. A Novel Metabolite with a Unique 4-pyranone-γ-lactam-1,4-thiazine moiety from a Hawaiian-Plant Associated Fungus Org. Lett. 2015, 17(14), 3556-3559.
  • Gavrish, E.; Sit, C.S.; Cao, S.; Kandror, O.; Spoering, A.; Peoples, A.; Ling, L.; Fetterman, A.; Hughes, D.; Bissell, A.; Torrey, H.; Akopian, T.; Mueller, A.; Epstein, S.; Goldberg, A.; Clardy, J.; Lewis, K. Lassomycin, a Ribosomally Synthesized Cyclic Peptide, Kills Mycobacterium tuberculosis by Targeting the ATP-Dependent Protease ClpC1P1P2. Chem Biol. 2014, 41(4), 509-518.
  • Cheng, B.; Cao, S.; Vasquez, V.; Annamalai, T.; Tamayo, G.; Clardy, J.; Tse-Dinh, Y-C. “A High Throughput Screening Assay identified a depsode as a New Topoisomerase Poison Inhibitor” PLoS ONE 2013, 8(4):e60770.
  • Alegado, R. A.; Brown, L. W.; Cao, S.; Dermenjian, R. K.; Zuzow, R.; Fairclough, S. R.; Jon Clardy*, J.; King*, N. Bacterial regulation of colony development in the closest living relatives of animals eLife 2012, 1:e00013.
  • Chen+, Y.; Cao+, S.; Chai+, Y.; Clardy, J.; Kolter R.; Guo, J.; Losick*, R. A Bacillus subtilis sensor kinase involved in triggering biofilm formation on the roots of tomato plants. Mol. Microbiol. 2012, 85(3), 418-430. (+Co-first author/equal contribution)
  • Cao, S.; Clardy*, Jon. New naphthoquinones and a new d-lactone produced by endophytic fungi from Costa Rica Tetrahedron Lett. 2011, 52, 2206-2208.
  • Blodgett, J. A. V.; Oh, D-C.; Cao, S.; Currie, C. R.; Kolter, R.; Clardy*, J. Common biosynthetic origins for polycyclic tetramate macrolactams from phylogenetically diverse bacteria. PNAS (Proc. Natl. Acad. Sci., Proceedings of the National Academy of Sciences), 2010, 107(26), 11692-11697.
  • Cao, S.; Ross, L.; Tamayo, G.; Clardy*, J. Asterogynins: secondary metabolites from a Costa Rican endophytic fungus Org. Lett. 2010, 12(20), 4661-4663
  • Cao, S.; Blodgett, J. A. V.; Clardy*, J. Targeted discovery of polycyclic tetramate macrolactams from an environmental Streptomyces strain. Org. Lett. 2010, 12(20), 4652-4654

Selected Patents

  • Watnick, P. I.; Ymele-Leki, P.; Clardy, J.; Cao, S. “Natural Product Antibiotics and Analogs Thereof” US 2013/0245130 Al; Sept. 19, 2013.
  • Sinclair, D. A.; Price, N. L.; Chini, E.; Clardy, J.; Cao, S. “Small Molecule CD38 Inhibitors and Methods of Using Same” (2013) WO2013002879 (A1) - 2013-01-03.
  • Kingston, D. G. I.; Cao, S. G.; Zhao, J. L.; Hodge, M. “Thiolated Paclitaxel for Reaction with Gold Nanoparticles as Drug Delivery Agents” (2009) International Publication Number: WO 2009/062138 A1; International Publication Date: 14 May 2009
  • Kingston, David G. I.; Cao, Shugeng. “Morning glory-derived anticancer agents, and novel ipomoeassin compounds.” U.S. Pat. Appl. Publ. (2006), 35pp. CODEN: USXXCO US 2006264383 A1 20061123 AN 2006:1228618

Active Grants

  • Gordon and Betty Moore Foundation (Co-PI)
  • R01 (Co-Investigator), NCCIH/NIH
  • Victoria S. and Bradley L. Geist Fund of the Hawaii Community Foundation (PI)