Berl R Oakley


Berl R. Oakley
  • Irving S. Johnson Distinguished Professor of Molecular Biology

Biography

I have a long-term interest in mitosis, microtubules and the cell cycle. More recently, molecular genetic tools we have developed for the fungus Aspergillus nidulans have led to an interest in fungal secondary metabolites, bioactive compounds that include important toxins as well as many medically important compounds such as antibiotics, cholesterol reducing compounds (statins), immune suppressors, and antifungals.

I received my B. S. degree from Duke University (1971) where I was an Angier B. Duke Memorial Scholar. I was fortunate enough to win a Marshall Scholarship to study at Birkbeck College, University of London where I received my Ph. D. (1974) working on the structure of mitotic apparatuses in unicellular algae. After a brief postdoc at the University of British Columbia, I moved to York University in Toronto to work with Brent Heath on the implications of the arrangement of microtubules in mitotic apparatuses for the mechanisms of chromosomal movement. I next joined the lab of Ron Morris at Rutgers Medical School who was pioneering the use of genetics to study mitosis and microtubules. Working with the filamentous fungus Aspergillus nidulans, we were able to use genetics in combination with electron and light microscopy, and we were able to make a number of contributions that were published in Cell and the Journal of Cell Biology. These include the demonstration that nuclear migration in A. nidulans is microtubule-mediated, that microtubule disassembly is required for mitosis and that the nimA gene is required for the G2 to M transition. NimA was later shown to be a kinase, the founding member of the NimA kinase family.

I joined the faculty of Ohio State University in 1982 and was a faculty member there for 26 years. In that time, my lab made a number of significant discoveries. Most notably, we discovered gamma-tubulin, showed that it is essential for mitotic apparatus formation in A. nidulans, showed that it is present in flies and humans, and showed that it is located at microtubule organizing centers such as centrosomes. We also mapped the two human gamma-tubulin genes within the human genome. These results led to several honors. Our paper reporting the discovery of gamma-tubulin was selected as a Nature Milestone in Cytoskeleton research; our paper demonstrating that gamma-tubulin localizes to microtubule organizing centers and is required for mitotic apparatus formation was selected as a Landmark Paper in Cell Biology; I won the Harlan Hatcher Memorial Award for Excellence, awarded by the Colleges of the Arts and Sciences at OSU; I was elected a Fellow of the American Association for the Advancement of Science and I was subsequently selected as an Ohio State University Research and Creative Expression Innovator, a recognition of 150 Ohio State innovators and their contributions in all fields over the first 150 years of Ohio State's existence.

I joined the faculty of the University of Kansas in 2008 as the first Irving S. Johnson Distinguished Professor. Working in collaboration with Dr. Clay Wang at the University of Southern California, Dr. Nancy Keller at the University of Wisconsin and others, we have applied molecular genetic methods we have developed to elicit the production of scores of novel fungal secondary metabolites and thereby helped to reinvigorate an important field. In 2021 I was elected a Fellow of the American Society for Cell Biology.

Education

Postdoc, Rutgers Medical School, 1981, Piscataway, New Jersey
Postdoc, York University, 1977, Toronto, Ontario, Canada
Postdoc, University of British Columbia, 1975, Vancouver, British Columbia, Canada
Ph.D. in Algal Mitosis, Birkbeck College, University of London, 1974, London, England
Marshall Scholar
B.S. in Botany, Duke University, 1971, Durham, NC
Angier B. Duke Scholar

Research

The main focus of my lab's current work is fungal secondary metabolism, and we use the filamentous fungus Aspergillus nidulans for much of our work. Secondary metabolites are bioactive compounds produced by fungi, bacteria, plants and algae that are not strictly required for viability or growth, but they convey a selective advantage to the producers, often by inhibiting the growth of their competitors. The biological activities of these compounds often make them medically useful, penicillin being the archetypal example. Genome sequencing projects have revealed that in fungi the genes responsible for production of a particular secondary metabolite are clustered in the genome and that there are many more secondary metabolite biosynthetic gene clusters than there are known secondary metabolites. The reason is that when fungi are grown under standard laboratory conditions, most secondary metabolite biosynthetic gene clusters are not expressed. We have developed, and continue to develop, approaches to activate expression of A. nidulans secondary metabolite gene clusters and to express secondary metabolite gene clusters from other fungi. Working with colleagues, we have expressed and identified nearly 200 new secondary metabolites. Relatedly, we are facilitating recycling of plastics and carbon fiber composites by developing strains of A. nidulans that can produce useful and potentially valuable compounds when grown on organic acids produced by catalytic cleavage of plastics and matrices of carbon fiber and fiberglass composites.

Teaching

  • Biology 752--Graduate Cell Biology (Fall alternate years)
  • Biology 416--Undergraduate Cell Biology (Spring)

Over my career, my classroom teaching has included General Biology, Cell Biology, Graduate Cell Biology, Graduate Molecular Biology, Graduate and Student Seminar Courses. In addition, I have been fortunate enough to train and mentor 17 graduate students and 15 postdocs many of whom have gone on to prestigious positions in academia, research administration and corporate research.

Selected Publications

See all papers by Berl R Oakley on PubMed

  • Olivar C, Yu Z, Miller B, Tangalos M, Jenkinson CB, Nutt SR, Oakley BR, Wang CCC, Williams TJ. (2024) Composite Recycling with Biocatalytic Thermoset Reforming. J Am Chem Soc. 2024 Oct 24. Epub ahead of print. 
  • Rabot C, Grau MF, Entwistle R, Chiang YM, Zamora de Roberts Y, Ahuja M, Oakley CE, Wang CCC, Todd RB, Oakley BR. (2024) Transcription Factor Engineering in Aspergillus nidulans Leads to the Discovery of an Orsellinaldehyde Derivative Produced via an Unlinked Polyketide Synthase Gene. J Nat Prod.Epub ahead of print. 
  • Oakley, C. E., Barton, T. S. and Oakley, B. R. (2024) Identification of the chaA and fwA Spore Color Genes of Aspergillus nidulans. J Fungi 10, 104
  • Jenkinson, C. B., Podgorny, A. R., Zhong, C. and Oakley, B. R. (2023) Computer-aided, Resistance Gene-Guided Genome Mining for Proteasome and HMG-CoA Reductase Inhibitors. J Ind Microbiol Biotechnol 50, kuad045
  • Lin, S. Y. et al. (2023) A Heterologous Expression Platform in Aspergillus nidulans for the Elucidation of Cryptic Secondary Metabolism Biosynthetic Gene Clusters: Discovery of the Aspergillus fumigatus Sartorypyrone Biosynthetic Pathway. Chem Sci 14, 11022-11032
  • Rabot, C., Chen, Y., Lin, S. Y., Miller, B., Chiang, Y. M., Oakley, C. E., Oakley, B. R., Wang, C. C. C. and Williams, T. J. (2023) Polystyrene Upcycling into Fungal Natural Products and a Biocontrol Agent. J Am Chem Soc 145, 5222-5230
  • Zhang, J., Qiu, R., Bieger, B. D., Oakley, C. E., Oakley, B. R., Egan, M. J. and Xiang, X. (2023) Aspergillus SUMOylation Mutants Exhibit Chromosome-Segregation Defects Including Chromatin Bridges. Genetics 225, iyad169
  • Rabot, C., Chen, Y., Bijlani, S., Chiang, Y. M., Oakley, C. E., Oakley, B. R., Williams, T. J. and Wang, C. C. C. (2022) Conversion of Polyethylenes into Fungal Secondary Metabolites. Angew Chem Int Ed Engl e202214609
  • Yuan, B., Keller, N. P., Oakley, B. R., Stajich, J. E. and Wang, C. C. C. (2022) Manipulation of the Global Regulator mcrA Upregulates Secondary Metabolite Production in Aspergillus wentii Using CRISPR-Cas9 with In Vitro Assembled Ribonucleoproteins. ACS Chem Biol 17, 2828-2835
  • Ingham, D. J., Blankenfeld, B. R., Chacko, S., Perera, C., Oakley, B. R. and Gamblin, T. C. (2021) Fungally Derived Isoquinoline Demonstrates Inducer-Specific Tau Aggregation Inhibition. Biochemistry 60, 1658-1669
  • Lan, L., Liu, J., Xing, M., Smith, A. R., Wang, J., Wu, X., Appelman, C., Li, K., Roy, A., Gowthaman, R., Karanicolas, J., Somoza, A. D., Wang, C. C. C., Miao, Y., De Guzman, R., Oakley, B. R., Neufeld, K. L. and Xu, L. (2020) Identification and Validation of an Aspergillus nidulans Secondary Metabolite Derivative as an Inhibitor of the Musashi-RNA Interaction. Cancers (Basel) 12, 2221
  • Grau, M. F., Entwistle, R., Oakley, C. E., Wang, C. C. C. and Oakley, B. R. (2019) Overexpression of an LaeA-like Methyltransferase Upregulates Secondary Metabolite Production in Aspergillus nidulans. ACS Chem Biol 14, 1643-1651
  • Dohn, J. W., Grubbs, A. W., Elizabeth Oakley, C. and Oakley, B. R. (2018) New Multi-Marker Strains and Complementing Genes for Aspergillus nidulans Molecular Biology. Fungal Genet Biol 111, 1-6
  • Grau, M. F., Entwistle, R., Chiang, Y. M., Ahuja, M., Oakley, C. E., Akashi, T., Wang, C. C. C., Todd, R. B. and Oakley, B. R. (2018) Hybrid Transcription Factor Engineering Activates the Silent Secondary Metabolite Gene Cluster for (+)-Asperlin in Aspergillus nidulans. ACS Chem Biol 13, 3193-3205
  • Paolillo, V., Jenkinson, C. B., Horio, T. and Oakley, B. R. (2018) Cyclins in aspergilli: Phylogenetic and functional analyses of group I cyclins. Stud Mycol 91, 1-22
  • Oakley, C. E., Ahuja, M., Sun, W. W., Entwistle, R., Akashi, T., Yaegashi, J., Guo, C. J., Cerqueira, G. C., Russo Wortman, J., Wang, C. C., Chiang, Y. M. and Oakley, B. R. (2017) Discovery of McrA, a master regulator of Aspergillus secondary metabolism. Mol Microbiol 103, 347-365
  • Kaur, K., Wu, X., Fields, J. K., Johnson, D. K., Lan, L., Pratt, M., Somoza, A. D., Wang, C. C. C., Karanicolas, J., Oakley, B. R., Xu, L. and De Guzman, R. N. (2017) The fungal natural product azaphilone-9 binds to HuR and inhibits HuR-RNA interaction in vitro. PLoS One 12, e0175471
  • Yeh, H. H., Ahuja, M., Chiang, Y. M., Oakley, C. E., Moore, S., Yoon, O., Hajovsky, H., Bok, J. W., Keller, N. P., Wang, C. C. and Oakley, B. R. (2016) Resistance Gene-Guided Genome Mining: Serial Promoter Exchanges in Aspergillus nidulans Reveal the Biosynthetic Pathway for Fellutamide B, a Proteasome Inhibitor. ACS Chem Biol 11, 2275-2284
  • Chiang, Y. M., Ahuja, M., Oakley, C. E., Entwistle, R., Asokan, A., Zutz, C., Wang, C. C. and Oakley, B. R. (2016) Development of Genetic Dereplication Strains in Aspergillus nidulans Results in the Discovery of Aspercryptin. Angew Chem Int Ed Engl 55, 1662-1665
  • Oakley, B. R., Paolillo, V. and Zheng, Y. (2015) γ-Tubulin complexes in microtubule nucleation and beyond. Mol Biol Cell 26, 2957-2962
  • Wang, B., Li, K., Jin, M., Qiu, R., Liu, B., Oakley, B. R. and Xiang, X. (2015) The Aspergillus nidulans bimC4 mutation provides an excellent tool for identification of kinesin-14 inhibitors. Fungal Genet Biol 82, 51-55
  • Paranjape, S. R., Riley, A. P., Somoza, A. D., Oakley, C. E., Wang, C. C., Prisinzano, T. E., Oakley, B. R. and Gamblin, T. C. (2015) Azaphilones inhibit tau aggregation and dissolve tau aggregates in vitro. ACS Chem Neurosci 6, 751-760
  • Edgerton, H., Paolillo, V. and Oakley, B. R. (2015) Spatial regulation of the spindle assembly checkpoint and anaphase-promoting complex in Aspergillus nidulans. Mol Microbiol 95, 442-457
  • Chiang, Y. M., Oakley, C. E., Ahuja, M., Entwistle, R., Schultz, A., Chang, S. L., Sung, C. T., Wang, C. C. C. and Oakley, B. R. (2013) An efficient system for heterologous expression of secondary metabolite genes in Aspergillus nidulans. J Am Chem Soc 135, 7720-7731
  • Edgerton-Morgan, H. and Oakley, B. R. (2012) γ-Tubulin plays a key role in inactivating APC/CCdh1 at the G1-S boundary. J Cell Biol 198, 785-791
  • Taheri-Talesh, N., Xiong, Y. and Oakley, B. R. (2012) The Functions of Myosin II and Myosin V Homologs in Tip Growth and Septation in Aspergillus nidulans. PLoS One 7, e31218
  • Somoza, A. D., Lee, K. H., Chiang, Y. M., Oakley, B. R. and Wang, C. C. C. (2012) Reengineering an azaphilone biosynthesis pathway in Aspergillus nidulans to create lipoxygenase inhibitors. Org Lett 14, 972-975
  • Ahuja, M., Chiang, Y. M., Chang, S. L., Praseuth, M. B., Entwistle, R., Sanchez, J. F., Lo, H. C., Yeh, H. H., Oakley, B. R. and Wang, C. C. C. (2012) Illuminating the diversity of aromatic polyketide synthases in Aspergillus nidulans. J Am Chem Soc 134, 8212-8221
  • Nayak, T., Edgerton-Morgan, H., Horio, T., Xiong, Y., De Souza, C. P., Osmani, S. A. and Oakley, B. R. (2010) γ-Tubulin regulates the anaphase-promoting complex/cyclosome during interphase. J. Cell Biol. 190, 317-330
  • Xiong, Y. and Oakley, B. R. (2009) In vivo analysis of the functions of γ-tubulin-complex proteins. J. Cell Sci. 122, 4218-4227
  • Taheri-Talesh, N., Horio, T., Araujo-Bazan, L., Dou, X., Espeso, E. A., Penalva, M. A., Osmani, S. A. and Oakley, B. R. (2008) The tip growth apparatus of Aspergillus nidulans. Mol Biol Cell 19, 1439-1449
  • Nayak, T., Szewczyk, E., Oakley, C. E., Osmani, A., Ukil, L., Murray, S. L., Hynes, M. J., Osmani, S. A. and Oakley, B. R. (2006) A versatile and efficient gene-targeting system for Aspergillus nidulans. Genetics 172, 1557-1566
  • Prigozhina, N. L., Oakley, C. E., Lewis, A., Nayak, T., Osmani, S. A. and Oakley, B. R. (2004) γ-Tubulin plays an essential role in the coordination of mitotic events. Mol Biol Cell 15, 1374-1386
  • Ovechkina, Y., Maddox, P., Oakley, C. E., Xiang, X., Osmani, S. A., Salmon, E. D. and Oakley, B. R. (2003) Spindle formation in Aspergillus is coupled to tubulin movement into the nucleus. Mol Biol Cell 14, 2192-2200
  • Jung, M. K., Prigozhina, N., Oakley, C. E., Nogales, E. and Oakley, B. R. (2001) Alanine-scanning mutagenesis of Aspergillus γ-tubulin yields diverse and novel phenotypes. Mol Biol Cell 12, 2119-2136
  • Wise, D. O., Krahe, R. and Oakley, B. R. (2000) The γ-tubulin gene family in humans. Genomics 67, 164-170
  • Khodjakov, A., Cole, R. W., Oakley, B. R. and Rieder, C. L. (2000) Centrosome-independent mitotic spindle formation in vertebrates. Curr Biol 10, 59-67
  • Wilson, P. G., Zheng, Y., Oakley, C. E., Oakley, B. R., Borisy, G. G. and Fuller, M. T. (1997) Differential expression of two γ-tubulin isoforms during gametogenesis and development in Drosophila. Develop Bio 184, 207-221
  • Horio, T. and Oakley, B. R. (1994) Human γ-tubulin functions in fission yeast. J Cell Biol 126, 1465-1473
  • Zheng, Y., Jung, M. K. and Oakley, B. R. (1991) γ-tubulin is present in Drosophila melanogaster and Homo sapiens and is associated with the centrosome. Cell 65, 817-823
  • Oakley, B. R., Oakley, C. E., Yoon, Y. and Jung, M. K. (1990) γ-Tubulin is a component of the spindle pole body that is essential for microtubule function in Aspergillus nidulans. Cell 61, 1289-1301
  • Oakley, C. E. and Oakley, B. R. (1989) Identification of γ-tubulin, a new member of the tubulin superfamily encoded by mipA gene of Aspergillus nidulans. Nature 338, 662-664
  • Oakley, B. R. and Morris, N. R. (1983) A mutation in Aspergillus nidulans that blocks the transition from interphase to prophase. J Cell Biol 96, 1155-1158
  • Oakley, B. R. and Morris, N. R. (1981) A β-tubulin mutation in Aspergillus nidulans that blocks microtubule function without blocking assembly. Cell 24, 837-845
  • Oakley, Berl R. and Morris, N. R. (1980) Nuclear movement is β-tubulin-dependent in Aspergillus nidulans. Cell 19, 255-262
  • Oakley, B. R., Kirsch, D. R. and Morris, N. R. (1980) A simplified ultrasensitive silver stain for detecting proteins in polyacrylamide gels. Anal Biochem 105, 361-363
  • Oakley, B. R. and Dodge, J. D. (1974) Kinetochores associated with the nuclear envelope in the mitosis of a dinoflagellate. J Cell Biol 63, 322-325
  • Oakley, B. R. and Dodge, J. D. (1973) Mitosis in the Cryptophyceae. Nature 244, 521-522