Introducing Our Authors - ACS Publications - American Chemical Society

Introducing Our Authors pubs.acs.org/acschemicalbiology

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RAPHAEL ISAAC BENHAMOU

Image courtesy of Yael Benhamou.

MARCEL BERMUDEZ

Image courtesy of Trung Ngoc Nguyen.

Education: Tel Aviv University, Israel, B.Sc. in Chemistry and

Education: Technische Universität Braunschweig, Institute of

Biology, 2013 Current Position: Ph.D. student, Tel Aviv University, Israel,

Pharmacy; State examination, 2009; licensed pharmacist, 2010; Freie Universität Berlin, Doctorate in Pharmaceutical Chemistry,

School of Chemistry, Raymond & Beverly Sackler Faculty of

2015; visiting scientist at the lab of Prof. Masha Niv, Hebrew

Exact Sciences, Advisor: Prof. Micha Fridman Nonscientific Interests: Sports, football, cinema, politics, and

University of Jerusalem, 2016 Current Position: Postdoctoral researcher in the Computer-

traveling My Ph.D. research focuses on the development of new

Aided Drug Design group of Prof. Gerhard Wolber, Freie

antimicrobial compounds and of novel molecular tools to be

Universität Berlin Nonscientific Interests: Traveling, books, and movies My research focuses on in silico pharmacology, following the

used as probes to study the mechanism of antifungal drugs. Fungal infections present an increasing medical challenge in the world, and Candida albicans is the most common opportunistic

interdisciplinary approach to connect computational methods

fungal pathogen. The goal of this manuscript was to develop inherently fluorescent antifungal azoles and to systematically

and molecular pharmacology. I am particularly interested in

evaluate and validate their suitability. This manuscript describes

mechanistic investigations of G protein-coupled receptors

the development process of two probes and shows that both

(GPCRs) as an important class of drug targets. This includes

inhibit Erg11, the primary target of the azole class of antifungals.

the investigation of multidimensional receptor functions like

To demonstrate one of the utilities of the probes, we showed

selectivity profiles, partial agonism, allosteric modulation,

that both localize primarily to mitochondria during the first

dimerization, and functional selectivity. I believe that a deeper

hours after uptake into fungal cells. Hence, we report, for the first time, information about the subcellular localization of

understanding of specific receptor mechanisms can allow

azole antifungals, which is valuable for the design of future

drug design to be more rational and goal-oriented. Besides my

generations of azoles. The reported probes will have a broad

research on GPCRs, I am also studying other protein classes

range of applications to study the metabolism, pharmacokinetics,

like bacterial toxins, toll-like receptors, and ion channels. (Read

dynamics, uptake, efflux, and localization of the azole family, one

Bermudez’s article DOI: 10.1021/acschembio.7b00275.)

of the most important antifungal drugs. (Read Benhamou’s article DOI: 10.1021/acschembio.7b00339.) © 2017 American Chemical Society

Published: July 21, 2017 1711

DOI: 10.1021/acschembio.7b00575 ACS Chem. Biol. 2017, 12, 1711−1714

ACS Chemical Biology

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Introducing Our Authors

MAAYAN BIBI

Doctorate in Pharmacology and Toxicology, 2013; postdoctoral fellow of Prof. Martin J. Lohse, University of Würzburg, Germany Current Position: Postdoctoral fellow of Prof. Martin J. Lohse, Max Delbrück Center for Molecular Medicine, Berlin, Germany Nonscientific Interests: Food, friends, and traveling My research focuses on the dynamics of G protein-coupled receptors (GPCRs), specifically on the molecular and structural details of ligand binding, activation, and signaling specificity of class A GPCRs. We have shown that bitopic orthosteric/ allosteric agonists have multiple binding modes (“dynamic ligand binding”) that produce active as well as inactive receptors in the same receptor ensemble. This results in altered functional properties of the receptors, e.g., partial agonism and biased signaling. The second focus of my research deals with the compartmentalization of GPCR signaling. This research is done in collaboration with Prof. Martin J. Lohse at the Max Delbrück Center in Berlin. We are aiming at understanding the molecular mechanisms of cAMP compartmentalization in living cells using a combination of biochemistry and advanced microscopy methods. Together, both research avenues should help elucidate the complexity of GPCR dynamics. (Read Bock’s article DOI: 10.1021/acschembio.7b00275.) ALEKSANDRA MARŠAVELSKI

Image courtesy of Alex Rosenberg.

Education: Ruppin Academic Center, Michmoret, Israel, B.Sc. Marine Biotechnology, 2014; M.Sc. Molecular Biology and Biotechnology (Life Sciences), 2016, Advisor: Judith Berman Current Position: Ph.D. student, Tel-Aviv University, Israel, Department of Life Sciences; Advisor: Prof. Judith Berman Nonscientific Interests: Surfing, sailing, running, cooking, traveling, and music My Ph.D. research focuses on understanding cellular mechanisms by which pathogenic fungi survive in fungistatic drugs. Using Candida albicans, the most prevalent fungal pathogen, we study the effect of antifungals and potentially therapeutic drug combinations on changes in yeast ploidy and morphology and how they influence the drug responses. Our paper describes the synthesis and cellular localization of two new fluorescent azole probes, one with traits very similar to fluconazole, the most widely used antifungal drug, and one that shares some traits with a larger imidazole antifungal, ketoconazole. Microscopy revealed that both probes localize to the mitochondria within 30 min following probe addition, which was unexpected as the drug targets are thought to localize primarily to the endoplasmic reticulum. The fluorescent probes provide us with a useful tool for understanding mechanisms by which azole drugs affect fungal cells and how the fungal cells respond to the drugs. (Read Bibi’s article DOI: 10.1021/acschembio.7b00339.)

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Image courtesy of Aleksandar Maršavelski.

Education: University of Belgrade, Faculty of Chemistry, Serbia, B.Sc. in Biochemistry, 2010; M.Sc. in Biochemistry, 2011, Advisor: Prof. Natalija Polović Current Position: Ph.D. candidate, University of Zagreb, Faculty of Science, Croatia, Advisor: Dr. Robert Vianello, Computational Organic Chemistry and Biochemistry group, Ruđer Bošković Institute, Zagreb, Croatia. During my Ph.D. research, I spent some time learning empirical valence bond simulations in the group of Prof. Janez Mavri at the National Institute of Chemistry, Ljubljana, Slovenia, and as a FEBS fellow in the group of Prof. Lynn Kamerlin at Uppsala University, Department of Cell and Molecular Biology, Uppsala, Sweden. Nonscientific Interests: Traveling and learning about different cultures, languages, music, and long walks My Ph.D. research is aimed at shedding more light on histamine catabolism using methods of computational enzymology. More precisely, my dissertation work is focused on enzymes monoamine oxidase B and diamine oxidase that catalyze the reaction of oxidative deamination of amines. Mechanistic studies have shown that the degradation of histamine and N-methylhistamine to corresponding aldehydes always occurs via the same catalytic mechanism regardless of histamine catabolic pathway, which is a new insight in studies related to histamine catabolism. Apart from this, I have been involved in research related to the

ANDREAS BOCK

Image courtesy of Verena E. Soemer.

Education: Rheinische Friedrich-Wilhelms-Universität Bonn, Institute of Pharmacy; State examination, 2008; licensed pharmacist, 2009; Rheinische Friedrich-Wilhelms-Universität Bonn, 1712




extracellular lipase from Streptomyces rimosus (SrLip). Our approach, based on the combination of structural and computational analysis, has explained the role of the catalytic dyad of SrLip. It has been demonstrated that the active site catalytic dyad, which involves Ser10 and His216, is essential for the catalysis. (Read Maršavelski’s article DOI: 10.1021/acschembio.6b01140.)

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Education: University of Manchester, U.K., B.Sc. in Biochemistry, 1997; M.Res. in Biological Sciences, 1998, Advisors: Prof. A. Dickson and Prof. C. Stirling; University of Glasgow, Beatson Institute for Cancer Research, U.K., Ph.D., Checkpoint signaling pathways in cancer formation and therapy, 2004, Advisor: Prof. D. A. F. Gillespie; St. Jude Children’s Research Hospital, Memphis, TN, USA, Postdoctoral Fellow, Molecular Therapeutics, 2008, Advisor: Prof. M. B. Kastan Current Position: Senior Postdoctoral Researcher and Honorary Research Lecturer, National University of Ireland, Galway, Republic of Ireland, Biomedical Sciences, Advisor: Prof. C. Santocanale Nonscientific Interests: Badminton, swimming, reading, family walks, picnics, and camping My research interests are in CDC7 kinase and the role it plays in DNA replication and its potential as a target for anticancer therapy. As such, small molecule inhibitors have been developed and are widely used as tools to probe CDC7 function in different cellular processes. In our current publication, we dissect the mechanism of action of current ATP competitive inhibitors that inhibit the kinase in vitro but have strikingly different effects on cells. Our study provides valuable insight on what to expect from selective inhibitors and how off-target effects contribute to their cellular activity, and it outlines a need for identification of more potent selective inhibitors and more predictive biomarkers. My current research goal is to identify relevant pathways involving CDC7 by exploiting the CDC7 analog-sensitive cell line created in this study. (Read Rainey’s article DOI: 10.1021/acschembio.7b00117.)

SEAN PIDGEON

Image courtesy of Marcos M. Pires.

Education: Wilkes University, B.S. in Biochemistry, Advisor: Dr. Amy L. Bradley Current Position: Ph.D. candidate at Lehigh University, Advisor: Dr. Marcos M. Pires Nonscientific Interests: Running, golfing, attending Penn State football games, and spending time with my nieces and nephews Our research is focused on the development of unnatural D-amino acid derivatives for metabolic remodeling of bacterial cell surfaces. Many antibiotics, such as beta-lactams and vancomycin, act to disrupt cell wall synthesis to inhibit bacterial growth. Bacteria that have evolved to alter their cell walls to become drug-resistant have emerged as a major medical concern. In this article, we showcase the ability to hijack cell wall biosynthesis of vancomycin-resistant enterococci (VRE) through an enzyme responsible for vancomycin resistance. A probe was synthesized to mimic D-lactic acid, one of the building blocks necessary for bacteria to convert to glycopeptide resistance. We show that such a probe can be leveraged to visually detect realtime induction and kinetics of antibiotic resistance. This simple platform can pave the way for high-throughput analysis of drug leads that may evade activation of resistance machinery. (Read Pidgeon’s article DOI: 10.1021/acschembio.7b00412.)

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BENYIN ZHANG

Image courtesy of Xudong Qu.

MICHAEL DAVID RAINEY

Education: B.Sc. in Biotechnology at Qinghai Normal University, China, 2007; Ph.D. in Natural Product Chemistry at Northwest Institute of Plateau Biology, Chinese Academy of Sciences, China, 2012, Advisor: Prof. Xiaofeng Zhang; postdoctoral fellow at Wuhan University, China, 2015, Advisor: Prof. Xudong Qu Current Position: Associate professor (since 2016) at the State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, China Nonscientific Interests: Reading, swimming, playing basketball, traveling, and music My current research focuses on mining new natural products from Actinomycetes, especially Streptomyces, by modifying the crucial biosynthesis carrier proteins in bacteria to activate the cryptic gene clusters. The method is simple, so the microbial genome is not necessary to sequence, and cutting-edge

Image courtesy of Michael David Rainey.

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instruments are not necessary. More importantly, the method is highly universal and efficient; over 70% of tested strains produce new compounds or promote production of known compounds. Currently, we are also trying to expand the application ranges, e.g., fungi. The new method would provide a novel way to efficiently discover bioactive natural products. We also investigate bioactive polyketides and polypeptides from the Actinomycetes surviving in extreme environments of the Qinghai-Tibetan Plateau (QTP) through a combination of next-generation sequencing and molecular phylogenetic analysis, from which we expect to understand the biogeographic distributions of biosynthesis capacity of polyketides and polypeptides. The results will provide a roadmap for mining new polyketides and polypeptides from extreme environments and also benefit new microbial drug discovery. (Read Zhang’s article DOI: 10.1021/ acschembio.7b00225.)

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Introducing Our Authors - ACS Publications - American Chemical Society

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