The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases

 Gerald F. Bills, Ph.D.

Gerald F. Bills, Ph.D.

Professor, Texas Therapeutics Institute

Gerald.F.Bills@uth.tmc.edu

(713) 486-2344

Dr. Bills received his B.S. in Plant Sciences and M.S. in Plant Pathology from West Virginia University, and his Ph.D. in botany and mycology from Virginia Polytechnic University and State University with the late Prof. Orson K. Miller, Jr. After post-docs at the U.S.D.A. Agriculture Research Service and University of Wyoming, he was recruited by Merck Research Laboratories (MRL) to establish strategies for generating fungal and other microbial metabolites for discovery of novel and structurally diverse therapeutic agents. Over a course of 20 years, Dr. Bills was key member of MRL teams that discovered some of the most significant m fungal natural products of the past two decades, including molecules that were the objective of major medicinal chemistry programs. He recognized the novelty of and characterized the organism producing Merck’s first-in-class antifungal drug, CANCIDAS. At Merck, Dr. Bills pioneered a modern industrial bioprospecting program, and was a principal investigator in Merck’s historic and highly publicized drug discovery project with the National Biodiversity Institute of Costa Rica (INBio), and subsequently set up and led similar projects in Mexico, Puerto Rico, New Zealand, South Africa, and elsewhere. His group implemented creative high-throughput methods for separating novel microorganisms from nature and applied improved methods for testing them for new antibiotics. At the same, his group also initiated an innovative project that mapped the data of antibiotic screening of human pathogens and analytical chemistry onto microbial rDNA phylogenies, thus accelerating novel antibiotic discovery by predicting the location of specific metabolite pathways. In 2005, he was recognized with MRL’s Basic Research Award for these efforts. He was named a Fellow of the Mycological Society of America in 2003.

More recently, he was the Area Head for Microbiology at the Foundation MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Granada, Spain, a not-for-profit research institute devoted to the discovery of antiinfective and therapeutic agents from microbial metabolites. Dr. Bills helped set up the Foundation’s infrastructure, was part of the Foundation’s management team and contributed directly to developing and implementing the Foundation’s overall scientific, technology and business strategies and activities.

His current work interprets genomes to predict genetically encoded chemical diversity of microorganisms using filamentous fungi as model organisms, especially those biosynthetic families relevant for pharmaceutical intervention in human diseases. For example, he and Prof. Zhiqiang An have recently characterized the polyketide synthase-non-ribosomsal synthase pathway that synthesizes pneumocandin B0, the starting molecule for the antifungal drug CANCIDAS. A long-term goal is to develop methods to reprogram pneumocandin biosynthesis and produce new chemical derivatives that that have improved potency, spectrum and pharmacokinetics, while reducing fermentation production costs. Characterization of related lipopeptide pathways will enable us to recombine genes from these pathways to produce hybrid natural products with improved therapeutic properties.

The group continues to seek new genetic and physiological methods for expressing and un-regulating unexpressed biosynthetic pathways using filamentous fungi as model organisms with the goal of building a microbial chemical collection focused on metabolites appropriate for intervention in cancer biology, modulation of human molecular signaling pathways, and in other human therapies. 

RESEARCH PROJECTS:

    • Biosynthesis and pathway engineering of the pneumocandin lipopeptides for improved antifungals.
    • Methods for inducing and reprogramming transcription of biosynthetic genes of fungi to discover new natural products useful to treat human diseases
    • Development of a natural products ‘chemical resource platform’ for drug discovery for other investigators within the UT System, Texas and elsewhere.

    SELECTED PUBLICATIONS

    Chen, L., Q. Yue, X. Zhang, M. Xiang, C. Wang, S. Li, Y. Che, F.J. Ortiz-López, G.F. Bills, X. Liu & Z. An. 2013. Genomics-driven discovery of the pneumocandin biosynthetic gene cluster in the fungus Glarea lozoyensis. BMC Genomics 14:339.

    Bills, G.F., González-Menéndez, J. Martín, G. Platas, J. Fournier, D. Peršoh & M. Stadler. 2012. Hypoxylon pulicicidum sp. nov. (Ascomycota, Xylariales), a pantropical insecticide-producing endophyte. PLoS One 7: e46687. doi:10.1371/journal.pone.0046687.

    de la Cruz, M., J. Martín, V. González-Menéndez, I. Pérez-Victoria, C. Moreno, J.R. Tormo, N. El Aouad, J. Guarro, F. Vicente, F. Reyes & G.F. Bills. 2012. Chemical and physical modulation of antibiotic activity in Emericella species. Chemistry & Biodiversity 9:1095-1113.

    Bills, G.F., A.W. Dombrowski & M.A. Goetz. 2012. The “FERMEX” method for metabolite-enriched fungal extracts. Methods in Molecular Biology. Fungal Secondary Metabolism. N.P. Keller & G. Turner. Eds. 944:79-96.

    Sánchez-Hidalgo, M., J. Pascual, M. de la Cruz, J. Martín, G.S. Kath, J.M. Sigmund, P. Masurekar, F. Vicente, O. Genilloud & G.F. Bills. 2012. Prescreening bacteria colonies for bioactive molecules with Janus plates, a SBS standard double-faced microbial culturing system. Antonie van Leeuwenhoek 102:361–374.

    Cueva, C., A. Garcia Ruiz, E. González-Rompinelli, B. Bartolomé, P.J. Martín-Álvarez, O. Salazar, M.F. Vicente, G. Bills & V. Moreno-Arribas. 2012. Degradation of biogenic amines by vineyard ecosystem fungi. Potential use in winemaking. Journal of Applied Microbiology 112:672-682.

    Xu, D, J. Ondeyka, G.H. Harris, D. Zink, J. Nielsen-Kahn, H. Wang, G. Bills, G. Platas, W. Wang, A.A. Szewczak, P. Liberator, T. Roemer & S.B Singh. 2011. Isolation, structure and biological activities of fellutamides C and D from an undescribed Metulocladosporiella (Chaetothyriales) using the genome-wide Candida albicans fitness test. Journal of Natural Products 74:1721-1730.

    Roemer, T., D. Xu, S.B. Singh, C.A. Parish, G. Harris, H. Wang, J.E. Davies & G.F. Bills. 2011. Confronting the challenge of natural product-based antifungal discovery. Chemistry & Biology 18:148-164.

    Peláez, F., J. Collado, G. Platas, D.P. Overy, J. Martín, F. Vicente, A. González del Val, A. Basilio, M. de la Cruz, J.R. Tormo, A. Fillola, F. Arenal, M. Villareal, V. Rubio, H.O. Baral, R. Galán & G.F. Bills. 2011. The phylogeny and intercontinental distribution of the pneumocandin-producing anamorphic fungus Glarea lozoyensis. Mycology: An International Journal of Fungal Biology 2:1-17.

    See link to Google Scholar for more complete bibliography (http://scholar.google.com/citations?hl=en&user=jwkLPtAAAAAJ&view_op=list_works&cstart=20 ).

    BOOKS

    Mueller, G.M., G.F. Bills & M.S. Foster. (Editors). 2004. Biodiversity of Fungi. Inventory and Monitoring Methods. Elsevier Academic Press. 777 pp.