We are a multidisciplinary group of scientists in the Department of Chemistry and ChEM-H Institute interested in mitigating bacterial multidrug resistance. We elucidate and exploit the trafficking mechanisms of natural products, as well as perform chemoenzymatic syntheses of bioactive natural products.
Rm. 177 Seeley G. Mudd Chemistry Bldg., Stanford University
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Laura M. K. Dassama, Ph.D.
Laura obtained her Bachelor of Science in Biochemistry from Temple University in 2007. She completed graduate studies at The Pennsylvania State University in 2013 under the mentorship of Profs. Marty Bollinger and Carsten Krebs, where she used transient state kinetics and spectroscopy to elucidate reaction mechanisms of metalloenzymes. Following receipt of her Ph.D., Laura performed postdoctoral training in the laboratory of Prof. Amy Rosenzweig at Northwestern University. At Northwestern, her research focused on elucidating the transport and biosynthetic mechanisms of peptidic natural products. In 2017, Laura moved to the laboratory of Dr. Stuart Orkin at Boston Children's Hospital, Harvard Medical School, and Dana-Farber Cancer Institute, where she worked to biochemically characterize regulators of hemoglobin relevant to sickle cell disease. In 2018, Laura began her tenure as Assistant Professor of Chemistry and ChEM-H Institute Scholar at Stanford University. Her work has been funded by the Alfred P. Sloan Foundation, the National Institutes of Health, and the Burroughs Wellcome Fund.
Laura is a beer aficionado who has visited 6 of 12 Trappist breweries and routinely brews Belgian IPAs. She considers the process of brewing a perfect representation of her interests in microbiology and chemistry.
Esteffanie received her B.A. in Molecular and Cell Biology from UC Berkeley in 2018, where she performed undergraduate research in the laboratory of Prof. Kathleen Ryan in the Department of Plant and Microbial Biology. Esteffanie’s work focused on understanding the fitness cost of protein degradation in Caulobacter crescentus. Her research interests include microbial biology, genetics, and organic chemistry. At Stanford, Esteffanie will work on genetic manipulations of bacteria drug resistance machinery and on natural product biosynthesis.
The Dassama laboratory at Stanford performs research directed at understanding and mitigating bacterial multidrug resistance (MDR). Described as an emerging crisis, MDR often results from the misuse of antibiotics and the genetic transfer of resistance mechanisms by microbes. Efforts to combat MDR involve two broad strategies: understanding how resistance is acquired in hopes of mitigating it, and identifying new compounds that could serve as potent antibiotics. The successful implementation of both strategies relies heavily on an interdisciplinary approach, as resistance mechanisms must be elucidated on a molecular level, and formation of new drugs must be developed with precision before they can be used. The laboratory will use these strategies to contribute to current MDR mitigation efforts.
One area of research involves integral membrane proteins called multidrug and toxin efflux (MATE) pumps that have emerged as key players in MDR because their presence enables bacteria to secrete multiple drugs. The genes encoding these proteins are present in many bacterial genomes. However, the broad substrate range and challenges associated with membrane protein handling have hindered efforts to elucidate and exploit transport mechanisms of MATE proteins. Many of the substrates identified for MATE proteins are small and ionic drugs, but recent reports have implicated these proteins in efflux of novel natural product substrates. The group’s approach will focus on identifying the natural product substrates of some of these new MATE proteins, as well as obtaining static and dynamic structures of the proteins during efflux. These efforts will define the range of molecules that can be recognized and effluxed by MATE proteins and reveal how their transport mechanisms can be exploited to curtail drug efflux.
Another research direction involves the biosynthesis of biologically active natural products. Natural products are known for their therapeutic potential, and those that derive from modified ribosomal peptides are an important emerging class. These ribosomally produced and post-translationally modified peptidic (RiPP) natural products have the potential to substantially diversify the chemical composition of known molecules because the peptides they derive from can tolerate sequence variance, and modifying enzymes can be selected to install specific functional groups. With an interest in producing new antimicrobial and anticancer compounds, the laboratory will exploit the versatility of RiPP natural product biosynthesis. Specifically, efforts in the laboratory will revolve around elucidating the reaction mechanisms of particular biosynthetic enzymes and leveraging that understanding to design and engineer new natural products with desired biological activities.
12) Grace E. Kenney, Laura M. K. Dassama, Maria-Eirini Pandelia, Anthony S. Gizzi, Ryan J. Martinie, Peng Gao, Caroline J. DeHart, Luis F. Schachner, Owen S. Skinner, Soo Y. Ro, Xiao Zhu, Monica Sadek, Paul M. Thomas, Steven C. Almo, J. Martin Bollinger Jr., Carsten Krebs, Neil L. Kelleher, Amy C. Rosenzweig. The Biosynthesis of Methanobactin. Science 2018, 359, 1411-1416.
11) Spencer C. Peck, Chen Wang, Laura M. K. Dassama, Bo Zhang, Yisong Guo, Lauren J. Rajakovich, J. Martin Bollinger, Jr., Carsten Krebs, and Wilfred A. van der Donk. O-H Activation by an Unexpected Ferryl Intermediate during Catalysis by 2-Hydroxyethylphosphonate Dioxygenase. J. Am. Chem. Soc. 2017, 139, 20145-2052.
10) Laura M. K. Dassama*, Grace E. Kenney*, and Amy C. Rosenzweig. Methanobactins: From Genome to Function. Metallomics 2017, 9, 7-20.
9) Laura M. K. Dassama, Grace E. Kenney, Soo Y. Ro, Eliza L. Zielanzinski, and Amy C. Rosenzweig. The Methanobactin Transport Machinery. Proc. Natl. Acad. Sci. USA 2016, 113, 13027-13032.
8) Jovan Livada*, Ryan J. Martinie*, Laura M. K. Dassama, Carsten Krebs, J. Martin Bollinger, Jr., Alexey Silakov. Direct Measurement of the Radical Translocation Distance in the Class I Ribonucleotide Reductase from Chlamydia trachomatis. J. Phys. Chem. B. 2015, 119, 13777-13784.
7) Yeonju Kwak, Wei Jiang, Laura M. K. Dassama, Kiyoung Park, Caleb B. Bell, Lei V. Liu, Shaun D. Wong, Makina Saito, Yasuhiro Kobayashi, Shinji Kitao, Makoto Seto, Yoshitaka Yoda, Esen E. Alp, Jiyong Zhao, J. Martin Bollinger, Jr., Carsten Krebs, and Edward I. Solomon. Geometric and Electronic Structure of the Mn(IV)/Fe(III) Cofactor in Class Ic Ribonucleotide Reductase: Correlation to the Class Ia Binuclear Non-Heme Iron Enzyme. J. Am. Chem. Soc. 2013, 135, 17573-17584.
6) Laura M. K. Dassama, Alexey Silakov, Courtney M. Krest, Julio C. Calixto, Carsten Krebs, J. Martin Bollinger, Jr., and Michael T. Green. A 2.8 Å Fe−Fe Separation in the Fe2III/IV Intermediate (X) from Escherichia coli Ribonucleotide Reductase. J. Am. Chem. Soc. 2013, 135, 16758-16761.
5) Laura M. K. Dassama, Carsten Krebs, Amy C. Rosenzweig, J. Martin Bollinger, Jr., and Amie K. Boal. Structural Basis for Assembly of the MnIV/FeIII Cofactor in the Class Ic Ribonucleotide Reductase from Chlamydia trachomatis. Biochemistry 2013, 52, 6424-6436.
4) Carsten Krebs, Laura M. K. Dassama, Megan L. Matthews, Wei Jiang, John C. Price, Victoria Korboukh, Ning Li, and J. Martin Bollinger, Jr. Novel Approaches for the Accumulation of Oxygenated Intermediates to Multi-Millimolar Concentrations. Coord. Chem. Rev. 2013, 257, 234-253.
3) Laura M. K. Dassama*, Wei Jiang*, Paul T. Varano, Maria-Eirini Pandelia, Denise A. Conner, Jiajia Xie, J. Martin Bollinger, Jr., and Carsten Krebs. Radical-Translocation Intermediates and Hurdling of Pathway Defects in “Super-oxidized” (MnIV/FeIV) Chlamydia trachomatis Ribonucleotide Reductase. J. Am. Chem. Soc. 2012, 134, 20498-20506.
2) Laura M. K. Dassama, Timothy H. Yosca, Denise A. Conner, Michael H. Lee, Béatrice Blanc, Bennett R. Streit, Michael T. Green, Jennifer L. DuBois, Carsten Krebs, and J. Martin Bollinger, Jr. O2-Evolving Chlorite Dismutase as a Tool for Studying O2-Utilizing Enzymes. Biochemistry 2012, 51, 1607-1616.
1) Laura M. K. Dassama*, Amie K. Boal*, Carsten Krebs, Amy C. Rosenzweig, and J. Martin Bollinger, Jr. Evidence That the β Subunit of Chlamydia trachomatis Ribonucleotide Reductase Is Active with the Manganese Ion of Its Manganese(IV)/Iron(III) Cofactor in Site 1. J. Am. Chem. Soc. 2012, 134, 2520-2523.
LAB: Seeley G. Mudd Chemistry Building
333 Campus Drive, Room 177
LAB OFFICE: Seeley G. Mudd Chemistry Building
333 Campus Drive, Room 281
Stanford, CA 94305-4401
Dr. Dassama: Seeley G. Mudd Chemistry Building
333 Campus Drive, Room 283
Chemistry Receiving - Stanford University
337 Campus Drive
Stanford, CA 94305-4401