Cao Lab

Cao Lab
Cao Lab
Cao Lab
Cao Lab
Cao Lab
Cao Lab

Principal Investigator

Research Topic Areas
  1. Biologically active compounds from natural sources including fungi, bacteria, marine organisms and plants;
  2. Herbal medicine

Contact Information

Contact information

Lab Location: Waiakea Research Station, Building F
Lab Phone: (808) 981-8017

For UHH undergraduate students, if you are interested in research at Cao Lab, please feel free to contact Dr. Cao directly.

Lab Members

Lab Members

Senior lab members:
•       Xiaohua Wu, Research Associate and Lab Manager
•       Hyung Sik Kim, visiting Professor from Sungkyunkwan University, Korea

Postdoctoral researchers:
•       Yun Kwon, Ph.D., Postdoc
•       Helong Bai, Ph.D., Visiting scholar

Graduate students:
•       Kh Ahammad Uz Zaman

Undergraduate students:
•       Jasmine Hicking
•       Ellen Hauschild
•       Michelle Biete
•       Julian Huang

High school students:
•       Lela DeVine

If you are interested in the research at Cao Lab, please contact Dr. Cao directly.  All undergraduate students are welcome to apply.

Detailed Research Description

Detailed Research Description
  1. Biologically active compounds from natural sources: Natural products were and are still a rich source for drug discovery. One challenge is the rediscovery of known compounds. To avoid replication, Cao Lab is interested in studying the under-explored microorganisms in Hawaii. (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 the main 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 and anti-fungal, 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. Since the end of 2013, Cao Lab has published more than ten papers about anti-proliferative compounds, p53 reactivator, STAT3 & NF-kB inhibitors, and antibacterial & anti-fungal agents from Hawaiian fungi in "Org. Lett.", "Sci. Rep.", "Phytochemistry", "Bioorg. Med. Chem. Lett.", "Tetrahedron Lett.", "Molecules", and "Cancer Biol." etc.
  2. Herbal medicine: Herbal medicine has a long history, which is still used in many countries. Although herbal medicine is not part of the mainstream medical care in the USA, FDA has approved two botanic drugs, and will likely approve more. One challenge to study herbal medicine is the identification of biologically active molecules that account for the claimed therapeutic effects and mechanisms of action. Cao Lab is interested in studying traditional medicine used in the Asia-Pacific Region. In the past few years, Cao Lab has been studying some medicinal plants including Barleria lupulina and Morinda citrifolia. From these plants, Cao Lab has isolated many new compounds, identified a few previously unknown Nrf2 activators, and published some papers in "PLoS ONE", "J. Ethnopharmacol.", "J. Nat. Prod.", "Tetrahedron Lett.", "Bioorg. Med. Chem. Lett.", and "J. Nat. Sci." etc.

Current Funding

Current Funding
  • JBRI, Biological activity of minor herbal products, 2019 - 2021 
  • INBRE-IV Seed Funding, Antibacterial screening of Hawaiian endophytic fungi, 2019 – 2020 
  • HCF, Natural products from Hawaiian endophytic fungi targeting mtp53 for TNBC & other cancers, 2017-2018 (NCE to 2019)

Recent Publications

Recent publications
  • Wang Q, Hu Z, Luo X, Liu J, Li* G, Cao* S, Liu* Q. “Clavukoellians A-G, Highly Rearranged Nardosinane Sesquiterpenoids  with Anti-angiogenic Activity from Clavularia koellikeri” J. Nat. Prod. 2019, revision
  • Li C, Sarotti AM, Wu X, Yang B, Turkson J, Chen Y, Liu Q, Cao* S. “An Unusual Benzoisoquinoline-9-one Derivative and Other Related Compounds with Antiproliferative Activity from Hawaiian Endophytic Fungus Peyronellaea sp. FT431.” Molecules. 2019 Jan 7;24(1). pii: E196. doi: 10.3390/molecules24010196.
  • Wang Q, Hu Z, Li X, Wang A, Wu H, Liu J, Cao* S, Liu* Q. “Salviachinensines A-F, New Anti-leukemic Phenolic Acids from  Chinese Herbal Medicine Salvia chinensis Benth” J. Nat. Prod. 2018, 81(11), 2531-2538. doi: 10.1021/acs.jnatprod.8b00638.
  • Zhou SY, Zhou TL, Qiu G, Huan X, Miao ZH, Yang SP, Cao* S, Fan* F, Cai* Y-S. “Three New Cytotoxic Monoterpenoid Bisindole Alkaloids from Tabernaemontana bufalina.” Planta Med. 2018, 84(15), 1127-1133. doi: 10.1055/a-0608-4988.
  • Li C, Hu Z, Liu Q, Wu X, Cao* S. “Two new tricycloalternarenes from Hawaiian endophytic fungus Didymella sp. FT433” Tetrahedron Lett. 2018, 59(36), 3381-3383.
  • Cai* Y-S, Sarotti AM, Zhou T-L, Huang R, Qiu Q, Tian C, Miao Z-H, Mándi A, Kurtán T, Cao* S, Yang* S-P. “Flabellipparicine, a Flabelliformide-Apparicine-Type Bisindole Alkaloids from Tabernaemontana divaricata.” J. Nat. Prod. 2018, 81(9), 1976-1983.
  • Nilubol N, Yuan Z-Q, Paciott GP, Tamarkin L, Sanchez C, Gaskins K, Freedman EM, Cao S, Zhao J, Kingston DGI, Libutti SK, Kebebew E. “A Novel Dual-Action Targeted Nanomedicine Effective in Mouse Models of Endocrine Cancers” J Natl Cancer Inst. 2018, 110(9), 1019-1029. doi: 10.1093/jnci/djy003
  • Li C, Sarotti AM, Wesley Y, Cao S. “Two new polyketides from Hawaiian endophytic fungus Pestalotiopsis sp. FT172” Tetrahedron Lett. 2018, 58, 42-45. 
  • Cai Y-S, Sarotti AM, Gündisch D,. Kondratyuk TP, Pezzuto JM, Turkson J, Cao*, S. “Heliotropiumides A and B, new  phenolamides with N-carbamoyl putrescine moiety from Heliotropium foertherianum collected in Hawaii and their biological activities” Bioorg. Med. Chem. Lett. 2017, 27, 4630-4634.
  • Li C-S, Sarotti AM, Huang P, Dang UT, Hurdle J, Kondratyuk TP, Pezzuto JM, Turkson J, Cao, S. “NF-κB inhibitors, unique γ-pyranol-γ-lactams with sulfide and sulfoxide moieties from Hawaiian plant Lycopodiella cernua derived fungus Paraphaeosphaeria neglecta FT462” Sci. Rep. 2017, 7(1):10424.
  • Li C, Sarotti AM, Yang B, Turkson J, Cao S. “A New N-methoxypyridone from the Co-Cultivation of Hawaiian Endophytic Fungi Camporesia sambuci FT1061 and Epicoccum sorghinum FT1062” Molecules 2017, 22(7), 1166. 
  • Li C, Sarotti AM, Turkson J, Cao S. “Verbenanone, an octahydro-5H-chromen-5-one from a Hawaiian-Plant Associated Fungus FT431” Tetrahedron Lett., 2017, 58, 2290–2293. 
  • Li C, Yang B, Turkson J, Cao* S. Anti-proliferative ambuic acid derivatives from Hawaiian endophytic fungus Pestalotiopsis   sp. FT172 Phytochem. 2017, 140, 77–82.
  • Wyche TP, Ruzzini AC, Beemelmanns C, Kim KH, Klassen JL, Cao S, Poulsen M, Bugni TS, Currie CR, Clardy J. “Linear peptides are the major products of a biosynthetic pathway that encodes for cyclic depsipeptides” Org Lett. 2017, 19(7), 1772–1775.
  • Huang P, Li C, Sarotti AM, Turkson J, Cao S. “Sphaerialactonam, a γ-lactam-isochromanone from the Hawaiian endophytic  fungus Paraphaeosphaeria sp. FT462” Tetrahedron Lett., 2017, 58, 1330–1333.
  • Beemelmanns C, Ramadhar TR, Kim KH, Klassen JL, Cao S, Wyche TP, Hou Y, Poulsen M, Bugni TS, Currie CR, Clardy J.“Macrotermycins A-D, Glycosylated Macrolactams from a Termite-Associated Amycolatopsis sp. M39.” Org Lett. 2017,  19(5), 1000–1003.
  • Paciotti GF, Zhao J, Cao S, Brodie PJ, Tamarkin L, Huhta M, Myer LD, Friedman J, Kingston* DGI. “Synthesis and Evaluation of Paclitaxel-Loaded Gold Nanoparticles for Tumor-Targeted Drug Delivery” Bioconj. Chem. 2016, 27 (11), 2646–2657
  • Senger DR, Cao S. “Diabetic Wound Healing and Activation of Nrf2 by Herbal Medicine” J. Nat. Sci. 2016, 2(11):e247
  • Briggs KJ, Koivunen P, Cao S, Backus KM, Olenchock BA, Patel H, Zhang Q, Signoretti S, Gerfen GJ, Richardson AL, Witkiewicz AK, Cravatt BF, Clardy, Kaelin* WG. Jr. “Paracrine Induction of HIF by Glutamate in Breast Cancer: EglN1 Senses  Cysteine” Cell 2016, 166(1), 126-139.
  • Senger DR, Hoang MV, Kim KH, Li C, Cao* S. “Anti-inflammatory activity of Barleria lupulina: Identification of active compounds that activate the Nrf2 cell defense pathway, organize cortical actin, reduce stress fibers, and improve cell junctions in microvascular endothelial cells” J. Ethnopharmacology 2016, 193, 397-407.
  • Fei-Zhang DJ, Li C, Cao* S. “Hawaii Natural Compounds are Promising to Reduce Ovarian Cancer Deaths” Cancer Biology  and Therapy 2016, May 4:1-4.
  • Li C, Ren G, Yang B, Miklossy G, Turkson J, Fei P, Ding Y, Walker LA, Cao* S. “Meroterpenoids with anti-proliferative activity from a Hawaiian-Plant Associated Fungus Peyronellaea coffeae-arabicae FT238” Org. Lett. 2016, 18(10), 2335-2338.
  • Lee SR, Clardy J, Senger DR, Cao* S, Kim* KH. “Phytochemical constituents from the aerial part of Barleria lupulina” Revista Brasileira de Farmacognosia 2016, 26, 281-284.
  • Lee SR, Beemelmanns C, Tsuma LM, Clardy J, Cao* S, Kim* KH. “A New Diketopiperazine, Cyclo(D-trans-Hyp-L-Leu) from  a Kenyan Bacteria Bacillus licheniformis LB 8CT” Nat. Prod. Comm.  2016, 11(4), 461-463.
  • Lee S, Clardy J, Cao* S, Kim* KH. “Diketopiperazines from a Costa Rican funus Colpoma sp. CR1465A” Bioorg. Med. Chem. Lett.  2016, 26, 2438-2441.
  • Li C, Ding Y, Yang B, Yin H-Q, Turkson J, Cao* S. “Antiproliferative sesquiterpenes from Hawaiian endophytic fungus Chaetoconis sp. FT087” Phytochem. 2016, 126, 41-46.
  • Senger DR, Li D, Jaminet SC, Cao S.  “Activation of the Nrf2 cell defense pathway by ancient foods: Disease prevention by important molecules and microbes lost from the modern Western diet” PLoS ONE 2016, e0148042; DOI:10.1371.
  • Wang Y, Qi S, Zhan Y, Zhang N, Wu A, Gui F, Guo K, Yang Y, Cao S, Hu Z, Zheng Z, Song S, Xu Q, Shen Y, Deng X. “Aspertetranones A-D, Meroterpenoids from the Marine Algal-associated Fungus Aspergillus sp.” J. Nat. Prod. 2015, 78(10), 2405-2410.
  • Cheng KCC,+ Cao S,+ Raveh A,+ MacArthur R, Dranchak P, Chipala G, Okoneski M, Guha R, Eastman R, Yuan J, SchultzP, Su X-Z, Tamayo-Castillo G, Matainaho T, Clardy J, Sherman D,* Inglese J.* "Actinoramide A stereoisomer identified as potent anti-malarial from titration-based screening of marine natural product extracts" J. Nat. Prod. 2015, 78(10), 2411-2422. (+ Co-first author/Equal contribution) 
  • Hiraki M,+ Hwang S-Y,+ Cao S,+ Ramadhar TR, T. Byun S, Yoon KW, K. Chu K, Gurkar AU, A. Vihren Kolev V, Zhang J, Namba T, Murphy ME, Aaronson SA, Newman DJ, Mandinova A, Clardy J,* Lee SW.*  “Small molecule reactivation of mutant p53 to wt-like p53 through the p53-Hsp40 regulatory axis”  Chemistry & Biology 2015, 22(9), 1206-1216. (+Co-first author/Equal contribution)
  • Li C, Ding Y, Yang B, Miklossy G, Yin H-Q, Walker LA, Turkson J, Cao S*. “A Novel Metabolite with a Unique 4-pyranone–γ- lactam–1,4-thiazine moiety from a Hawaiian-Plant Associated Fungus (FT462)” Org. Lett. 2015, 17(14), 3556-3559.
  • Kim KH, Beemelmanns C, Clardy J, Cao* S. “A new antimicrobial octaketide and cytotoxic phenylethanoid glycosides from Pogostemon cablin (Blanco) Benth” Bioorg. Med. Chem. Lett. 2015, 25, 2834-2836.
  • Kim KH, Clardy J, Senger DR, Cao* S. “Chakyunglupulins A and B, two novel 4,8,8-trimethylcyclooct-2-enone derivatives from Barleria lupulina” Tetrahedron Lett. 2015, 56, 2732-2734.
  • 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 NJ, Cao S, Reschke M, Chen C-H, Rego EM, LoCoco F, Cantley L, Lee TH, Wu H, Zhang Y, Pandolfi PP, Zhou ZZ, Z. 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.
  • Li C, Yang B, Fenstemacher R, Turkson J, Cao S.* “Lycopodiellactone, an unusual δ-lactone-isochromanone from a Hawaiian plant-associated fungus Paraphaeosphaeria neglecta FT462” Tetrahedron Lett. 2015, 56, 1724-1727.
  • Kim KH, Park YJ, Chung KH, Yip MLR, Clardy J, Senger DR, Cao S.* “Iridoid Glycosides from Barleria lupulina” J. Nat.Prod.  2015, 78, 320-324.
  • Kim KH, Beemelmanns C, Murillo C, Guillén A, Umaña L, Tamayo-Castillo G, Clardy J, Cao S. “Naphthalenones and isocoumarins from the Costa Rican fungus Xylariaceae sp. CR1546C” J. Chem. Res. 2014, 38, 722-725.
  • Schmull M, Dal-Forno M, Lücking R, Cao S, Clardy J, Lawrey JD. “Dictyonema huaorani (Agaricales: Hygrophoraceae), a new lichenized basidiomycete from Amazonian Ecuador with presumed hallucinogenic properties” Bryologist, 2014, 117(4), 386-394.
  • Raveh A, Schultz PJ, Aschermann L, Carpenter C, Tamayo-Castillo G, Cao S, Clardy J, Neubig RR, Sherman DH, Sjögren B. “Identification of PKC activation as a novel mechanism for RGS2 protein up-regulation through phenotypic screening of natural product extracts”  Mol Pharm. 2014, 86(4), 406-416.
  • Kim KH, Ramadhar TR, Beemelmanns C, Cao S, Poulsen M, Currie CR, Clardy J. “Natalamycin A, an Ansamycin from a Termite-Associated Streptomyces sp.” Chem Sci. 2014, 5(11), 4333-4338.
  • Gavrish E, Sit CS, 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 depside as a New Topoisomerase Poison Inhibitor” PLoS ONE 2013, 8(4):e60770.
  • Cryan LM, Bazinet L, Habeshian, KA, Cao S, Clardy J, Christensen KA, Rogers MS. “A polyphenol Inhibits Angiogenesis via Inhibition of CMG2” J. Med. Chem. 2013, 56(5), 1940-1945.