Clay C.C. Wang, PhD Headshot
Faculty Directory

Clay C.C. WangPhD

Clay C.C. WangPhD

Chair & Professor of the Department of Pharmacology and Pharmaceutical Sciences

Department of Pharmacology and Pharmaceutical Sciences

Clay Wang is a professor at USC Mann and chair of the Department of Pharmacology and Pharmaceutical Sciences. He also holds a joint appointment in the Department of Chemistry of the Dornsife College of Letters, Arts and Sciences.

Wang received his BA in chemistry from Harvard University in 1996 and a PhD in chemistry from the California Institute of Technology in 2001. After completing a two-year postdoctoral fellowship in chemistry and chemical engineering at Stanford University, he joined the faculty in the Department of Pharmaceutical Sciences at USC School of Pharmacy as an assistant professor in 2003.

His research program focuses on the interface of chemistry and biological sciences. Specifically, he is exploring the mechanism of natural product biosynthesis in bacteria and fungi. His lab has been studying the use of Aspergillus nidulans as a general host for the production of fungal natural products. The lab is exploring using the fungal host as a platform for upcycling of plastics into high value natural products.

Areas of Expertise

  • Natural Products Drug Discovery
  • Gene Regulation of Fungal Secondary Metabolism
  • Sustainability
  • Fungal and Bacterial Genomes
  • Space Biology
  • Metabolic Engineering
  • Education

    Stanford University

    Postdoctoral Research Fellowship

    California Institute of Technology


    Harvard University


  • Links
  • Selected Articles

    Overexpression of an LaeA-like Methyltransferase Upregulates Secondary Metabolite Production in Aspergillus nidulans.

    ACS Chem Biol.
    CC Wang et al.

    2019 Fungal secondary metabolites (SMs) include medically valuable compounds as well as compounds that are toxic, carcinogenic, and/or contributors to fungal pathogenesis. It is consequently important to understand the regulation of fungal secondary metabolism. McrA is a recently discovered transcription factor that negatively regulates fungal secondary metabolism. Deletion of mcrA ( mcrAΔ), the gene encoding McrA, results in upregulation of many SMs and alters the expression of more than 1000 genes. One gene strongly upregulated by the deletion of mcrA is llmG, a putative methyl transferase related to LaeA, a major regulator of secondary metabolism. We artificially upregulated llmG by replacing its promoter with strong constitutive promoters in strains carrying either wild-type mcrA or mcrAΔ. Upregulation of llmG on various media resulted in increased production of the important toxin sterigmatocystin and compounds from at least six major SM pathways. llmG is, thus, a master SM regulator. mcrAΔ generally resulted in greater upregulation of SMs than upregulation of llmG, indicating that the full effects of mcrA on secondary metabolism involve genes in addition to llmG. However, the combination of mcrAΔ and upregulation of llmG generally resulted in greater compound production than mcrAΔ alone (in one case more than 460 times greater than the control). This result indicates that deletion of mcrA and/or upregulation of llmG can likely be combined with other strategies for eliciting SM production to greater levels than can be obtained with any single strategy.

    Read More

    Proteomic and Metabolomic Characteristics of Extremophilic Fungi Under Simulated Mars Conditions.

    Frontiers in Microbiology
    CC. Wang

    2019 Filamentous fungi have been associated with extreme habitats, including nuclear power plant accident sites and the International Space Station (ISS). Due to their immense adaptation and phenotypic plasticity capacities, fungi may thrive in what seems like uninhabitable niches. This study is the first report of fungal survival after exposure of monolayers of conidia to simulated Mars conditions (SMC). Conidia of several Chernobyl nuclear accident-associated and ISS-isolated strains were tested for UV-C and SMC sensitivity, which resulted in strain-dependent survival. Strains surviving exposure to SMC for 30 min, ISSFT-021-30 and IMV 00236-30, were further characterized for proteomic, and metabolomic changes. Differential expression of proteins involved in ribosome biogenesis, translation, and carbohydrate metabolic processes was observed. No significant metabolome alterations were revealed. Lastly, ISSFT-021-30 conidia re-exposed to UV-C exhibited enhanced UV-C resistance when compared to the conidia of unexposed ISSFT-021.

    Read More

    International Space Station conditions alter genomics, proteomics, and metabolomics in Aspergillus nidulans.

    Applied Microbiology and Biotechnology
    CC. Wang et al.

    2019 The first global genomic, proteomic, and secondary metabolomic characterization of the filamentous fungus Aspergillus nidulans following growth onboard the International Space Station (ISS) is reported. The investigation included the A. nidulans wild-type and three mutant strains, two of which were genetically engineered to enhance secondary metabolite production. Whole genome sequencing revealed that ISS conditions altered the A. nidulans genome in specific regions. In strain CW12001, which features overexpression of the secondary metabolite global regulator laeA, ISS conditions induced the loss of the laeA stop codon. Differential expression of proteins involved in stress response, carbohydrate metabolic processes, and secondary metabolite biosynthesis was also observed. ISS conditions significantly decreased prenyl xanthone production in the wild-type strain and increased asperthecin production in LO1362 and CW12001, which are deficient in a major DNA repair mechanism. These data provide valuable insights into the adaptation mechanism of A. nidulans to spacecraft environments.

    Read More

    Genomic Characterization and Virulence Potential of Two Fusarium oxysporum Isolates Cultured from the International Space Station.

    M. Systems
    CC. Wang et al.

    2019 Two isolates of Fusarium oxysporum, ISS-F3 and ISS-F4, were cultured from the dining table on the International Space Station (ISS). Genomic analyses using EF-1α sequences, presence/absence of effector proteins, k-mer comparisons, and single nucleotide polymorphisms indicate that these two strains are genomically different from 65 known sequenced strains. Functional analysis revealed that ISS-F3/F4 had higher relative abundances of polyketide synthase domains than a non-plant-pathogenic soil isolate, used for biocontrol properties (Fo47), and a clinical isolate (FOSC-3a). Putative secondary metabolite analysis indicates that ISS-F3/F4 may produce yet-unreported polyketides and nonribosomal peptides. While genomic analysis showed that these ISS strains are unlikely to be plant pathogens, a virulence assay using an immunocompromised Caenorhabditis elegans model of fusariosis revealed that they were virulent and may represent opportunistic pathogens in animals, including humans. However, its effects on the health of immunocompromised humans warrant further study. IMPORTANCE This is the first study to isolate and characterize F. oxysporum isolates from a built environment, as well as one that has been exposed to space. The characterization and analysis of these two genomes may have important implications for the medical, agricultural, and food industries as well as for the health of the crew who coinhabit the ISS with these strains.

    Read More

    Proteomic characterization of Aspergillus fumigatus isolated from air and surfaces of the International Space Station.

    Fungal Genet Biol.
    CC. Wang et al.

    2019 The on-going Microbial Observatory Experiments on the International Space Station (ISS) revealed the presence of various microorganisms that may be affected by the distinct environment of the ISS. The low-nutrient environment combined with enhanced irradiation and microgravity may trigger changes in the molecular suite of microorganisms leading to increased virulence and resistance of microbes. Proteomic characterization of two Aspergillus fumigatus strains, ISSFT-021 and IF1SW-F4, isolated from HEPA filter debris and cupola surface of the ISS, respectively, is presented, along with a comparison to well-studied clinical isolates Af293 and CEA10. In-depth analysis highlights variations in the proteome of both ISS-isolated strains when compared to the clinical strains. Proteins that showed increased abundance in ISS isolates were overall involved in stress responses, and carbohydrate and secondary metabolism. Among the most abundant proteins were Pst2 and ArtA involved in oxidative stress response, PdcA and AcuE responsible for ethanol fermentation and glyoxylate cycle, respectively, TpcA, TpcF, and TpcK that are part of trypacidin biosynthetic pathway, and a toxin Asp-hemolysin. This report provides insight into possible molecular adaptation of filamentous fungi to the unique ISS environment.

    Read More

  • Affiliations
    • USC Academic Senate : Executive Board

  • Patents

    Dereplication strain of aspergillus nidulans

    15338696 | 2017

    Modified fungal strains having deleted gene clusters are provided. The modified fungal strains include A. nidulans. The deleted gene clusters are selected from the group of gene clusters responsible for the biosynthesis of sterigmatocystin, emericellamides, asperfuranone, monodictyphenone, terrequinone, F9775A, F9775B, asperthecin, and both portions of the split cluster that makes austinol and dehydroaustinol. Methods for making compounds by culturing the fungus in a growth media and separating the compound from the fungus and/or separating the compound from the growth media are included, as are the compounds and compositions comprising them.

    Read More

    System for managing transitions between media content items

    10101960 | 2018

    A system for playing media content items operates to provide smooth transitions between the media content items to continuously support a user's repetitive motion activity. The system can generate crossfade data containing information for transitions between media content items. The mix-in and mix-out points for the transitions are calculated to eliminate one or more portions of media content items that have lower musical energy than a majority portion of the items, and to maintain substantially consistent and/or stable musical energy (eg, audio power or sound power) throughout the media content items including transitions there between.

    Read More

  • Multimedia
    • Clay C.C. Wang, PhD
    • Clay C.C. Wang, PhD
    • Clay C.C. Wang, PhD
  • Selected Media Appearances

    Scientists are sending fungi into space in the hope of developing new medicines

    Los Angeles Times | 03/29/2016

    Scientists are sending four strains of fungi to the International Space Station to see what happens when the tiny organisms contend with the stress of microgravity and space radiation. The work is one of the first to look at the intersection of pharmaceutical science and space exploration said principal investigator Clay Wang, a professor of pharmacology at USC.

    Read More

    USC, JPL to launch fungi in quest to develop space meds

    USC News | 03/28/2016

    The stressful environment of the International Space Station (ISS) could trigger changes in physiological responses (such as gene expression) and metabolism of a well-studied fungus called Aspergillus nidulans, said Clay Wang, a professor of pharmacology and pharmaceutical sciences and chemistry at USC Mann and the USC Dornsife College of Letters, Arts and Sciences.

    Read More

    NASA backs biology in space project

    USC News | 10/13/2014

    USC Mann is launching its research into outer space, thanks to Associate Professor Clay Wang’s three-year, $600,000 grant from the national Space Biology Program — the first time the school has received grant support from NASA.

    Read More