Introducing Our Authors pubs.acs.org/acschemicalbiology
■
ABHINAV DHALL
Education: University of Pavia/National Council of Research (IGM-CNR), B.S. Biology, 2010, and M.S. Molecular Biology, 2012, Advisor: Prof. Giovanni Maga; Institute for Advanced Study of Pavia (IUSS), Diploma in Biomedical Sciences, 2012, Advisor: Prof. Andrea Mattevi; University of Pavia/Austrian Centre of Industrial Biotechnology (ACIB), Ph.D. Molecular Biology and Biotechnology, 2015, Advisor: Prof. Andrea Mattevi Current Position: Postdoctoral research assistant at University of Pavia, Structural Biology, Advisor: Prof. Andrea Mattevi Nonscientific Interests: Traveling, reading, hiking, cooking pasta, and tasting red wine My current research interests (funded by ACIB and Fondazione Cariplo) focus on enzymes that combine substrate versatility with the capability to catalyze chemically demanding reactions. In this study, we investigated the role of human flavin-containing monooxygenase 5 (hFMO5), a highly expressed hepatic enzyme recently shown to feature an atypical activity as a Baeyer−Villiger monooxygenase. Here, we were able to demonstrate the strong oxygenation activity of hFMO5 on two approved and widespread drugs bearing a carbonyl moiety on an aliphatic chain, nabumetone and pentoxifylline. This finding unfolds a new pathway by which these two drugs can be metabolized in humans and highlights how the Baeyer−Villiger reactions catalyzed by FMO5 may represent a so far neglected entry point in drug metabolism. (Read Fiorentini’s article DOI: 10.1021/ acschembio.7b00470.)
Image courtesy of Benoit Laurent.
Education: Indian Institute of Technology Bombay, Integrated M.Sc. in Chemistry, 2009; University of Washington, Seattle, Ph.D. in Chemistry, 2016, Advisor: Dr. Champak Chatterjee Current Position: Postdoctoral Fellow under Dr. Yang Shi in the department of Newborn Medicine and Cell Biology at Boston Children’s Hospital and Harvard Medical School Nonscientific Interests: Weightlifting, music, traveling, theology, and baking The epigenetic landscape of a genome influences several key biological processes such as DNA transcription, replication, and repair. Histone post-translational modifications (PTMs) are an integral part of this landscape and are known to play important regulatory roles in these processes. In this study, we focused on the biochemical roles of histone sumoylation, a poorly understood histone PTM. We developed new chemical biology tools that allowed us to synthesize nucleosomes containing sumoylated and methylated histone proteins. These “designer” nucleosomes revealed a novel crosstalk between these two PTMs and shed light on the direct role of histone sumoylation on transcriptional repression. Our results reported in ACS Chemical Biology have set the stage for further characterization of the role played by sumoylation in the histone code. (Read Dhall’s article DOI: 10.1021/acschembio.7b00716.)
■
■
CHANDRIMA MAJUMDAR
FILIPPO FIORENTINI
Image courtesy of Aveek Das.
Education: B.Sc. Chemistry, St. Stephen’s College, University of Delhi, India; M.Sc. in Chemistry from University of Hyderabad, India, Advisor: Dr. Rengarajan Balamurugan Current Position: Ph.D. student at the University of California Davis, Advisor: Dr. Sheila David Nonscientific Interests: Drawing and painting, paper crafts, cooking, and traveling Published: September 15, 2017
Image courtesy of Valentina Speranzini.
© 2017 American Chemical Society
2225
DOI: 10.1021/acschembio.7b00782 ACS Chem. Biol. 2017, 12, 2225−2226
ACS Chemical Biology
■
My project is focused on using substrate analogs of the DNA glycosylase MutY to understand the structural features it employs in recognizing its target base pair. MutY is specifically tuned to locate and cleave adenines (A) that are accidentally incorporated opposite the oxidatively damaged base 8-oxoguanine (OG) in OG:A mispairs and thus stalls the accumulation of G:C to T:A mutations in the genome. These OG:A mispairs are insidious due to both their miscoding potential and their resemblance to undamaged DNA. In this paper, we employed a panoply of OG analogs that helped us discern the structural features of the OG base that allow the enzyme to detect this elusive mispair and initiate the process of repair. (Read Majumdar’s article DOI: 10.1021/acschembio.7b00389.)
■
Introducing Our Authors
JOHN SANTA MARIA
Photo courtesy of John Santa Maria.
Education: Muhlenberg College, B.S. Biochemistry and Mathematics, 2008; Harvard University, Ph.D. Chemical Biology, 2014 Current Position: Postdoctoral Fellow in Modeling and Informatics at Merck Research Laboratories, Advisor: Peter Kutchukian Nonscientific Interests: Volleyball, running, climbing, undergraduate advising, and traveling I have a longstanding interest in the discovery of novel antibiotic targets and approaches to combat resistant bacteria. My doctoral research identified genetic interactions within the cell wall of the deadly pathogen Staphylococcus aureus. Genes we uncovered were not only functionally coupled to physiology surrounding cell wall glycopolymer biosynthesis but were also viable targets for subsequent successful inhibitor discovery. Our current work leverages the power of machine learning and cheminformatic modeling to combine diverse high-throughput screening data and elucidate mechanisms of action for antibiotic hits. The methodology we developed uncovered novel inhibitors of mycobacterial dihydrofolate reductase and is applicable across therapeutic areas for future drug discovery endeavors. (Read Santa Maria’s article DOI: 10.1021/acschembio.7b00468.)
AMELIA MANLOVE
Photo courtesy of Sheila David.
Education: University of California at Berkeley, B.A. Anthropology, 2002; California State University Easy Bay, M.S. Chemistry, 2010, Advisor: Michael Groziak; University of California Davis, Ph.D. Chemistry, 2017, Advisor: Dr. Sheila David Current Position: Working in local politics and seeking a position in Biotechnology Nonscientific Interests: Politics and policy, graphic design, and needlework Enzymes that initiate the repair of damaged DNA, such as the BER glycosylases that excise damaged bases, play a crucial role in maintaining cell viability by intercepting damaged DNA prior to replication. The difficulty of their task is compounded by the relative rarity of their damaged base substrates in comparison to the pool of normal DNA. How these enzymes find their targets to begin the repair process is thus an important research question and, as this paper demonstrates, one that does not often have a simple answer. Here, we report on the results of our investigation into the molecular requirements of E. coli MutY for recognition of substrate bases using a variety of prepared substrate analogs to compare enzyme behavior in vitro with successful repair inside living bacterial cells. (Read Manlove’s article DOI: 10.1021/acschembio.7b00389.) 2226
DOI: 10.1021/acschembio.7b00782 ACS Chem. Biol. 2017, 12, 2225−2226
