Introducing Our Authors pubs.acs.org/acschemicalbiology
■
HARALD M. H. G. ALBERS
Education: University of Pavia, Italy, B.A. in Biotechnology, 2005 and MA in Industrial Biotechnology & Biomolecular Research, 2007. University of Cambridge, U.K., Ph.D. in Chemistry, 2011. Advisor: Prof. Chris Dobson. Nonscientific interests: Trekking, traveling, photography My graduate research aimed at understanding the physicochemical determinants of protein aggregation. Over the course of my Ph.D. I employed numerous techniques in order to describe the relationship between the primary amino acid sequence of the Amyloid-Beta peptide and the toxic properties of the aggregates that it forms. In this study I compare two variants of the peptide and I show how single amino acid substitutions can alter dramatically the microscopic mechanism that drives aggregation of the peptide and the structure of the species that are formed and ultimately macroscopically affect the in vivo pathogenicity of such variants. (Read Bolognesi’s article, DOI: 10.1021/cb400616y)
Image courtesy of Harald Albers.
■
Current position: Senior Scientist Medicinal Chemistry at MercaChem in The Netherlands Education: Eindhoven University of Technology, The Netherlands, Master in Chemical Engineering and Chemistry, 2007, Advisor: Bert Meijer; Leiden University, The Netherlands, Ph.D. in Chemistry, with professor Huib Ovaa, 2012. The Netherlands Cancer Institute, The Netherlands, Postdoc in chemical biology with professor Huib Ovaa and professor Jacques Neefjes, 2012−2013. Nonscientific interests: Movies, hiking, and traveling One of our interests is to understand bacterial infection on a molecular level. In this pursue we aim to find general mechanisms that we can exploit to control infection. Our paper describes a novel strategy that integrates a chemical and genetic screen to identify essential proteins required for bacterial infection, in this case dual specificity phosphatases (DUSPs), and in parallel find inhibitors that target these DUSPs to control infection. The unique thing about our approach is that we target the proteins of the infected host cell and not that of the bacterium, in contrast to classic antibiotics. These host-targeted inhibitors could be a useful addition to classical antibiotics and thereby lower the pressure of multidrug resistant bacterial infection. (Read Albers’ article, DOI: 10.1021/cb400421a)
■
Image courtesy of Joseph H. Parker.
Current position: Postdoctoral Research Fellow at Washington University School of Medicine in the Department of Internal Medicine; Advisor: Dr. J. P. Henderson. Education: University of New Mexico, B.S. in Chemistry, 2007; Washington University in Saint Louis School of Medicine, Ph.D. in Biochemistry, 2012. Nonscientific interests: Music, reading, baking, traveling During infection, pathogenic bacteria secrete thousands of small molecules with largely unknown function. My research efforts are aimed at understanding the biochemical mechanisms by which these natural products lend pathogens a competitive advantage against the infected host. Here, we chemically characterize yersiniabactin, a virulence-associated siderophore expressed by several Gram-negative pathogens, including Yersinia pestis and Escherichia coli. Combining biochemical and microbiological techniques with density function theory, we show a previously unappreciated superoxide dismutase (SOD) property associated with yersiniabactin−copper complexes. This study lends insight into the chemistry by which yersiniabactinexpressing organisms maintain niche specificity and survive
BENEDETTA BOLOGNESI
Image courtesy of Edoardo Palmieri.
Current position: INTERPOD Post-Doctoral fellow at the Centre for Genomic Regulation, Barcelona, Spain. © 2014 American Chemical Society
KAVERI S. CHATURVEDI
Published: February 21, 2014 311
dx.doi.org/10.1021/cb5000828 | ACS Chem. Biol. 2014, 9, 311−314
ACS Chemical Biology
Introducing Our Authors
Bangalore, India, M.S. in Chemical Sciences with Prof. G. Mugesh, 2008; University of Michigan, Ann Arbor, USA, Ph.D. in Chemistry with Prof. Neil Marsh, 2013. Nonscientific interests: Cooking, watching games, and leaning about planets Fascinating enzymes of biofuel-research have always inspired me. My graduate work has been focused on investigating a key enzyme from the alkane-biosynthetic pathway found in cyanobacteria, aldehyde deformylating oxygenase (cADO), that holds potential for future biofuels applications. This enzyme catalyzes the conversion of aldehydes to the corresponding alka(e)nes, which is mechanistically a very challenging reaction. We have investigated the mechanism of C1−C2 bond cleavage of the aldehyde by cADO using strategically designed oxiranyl aldehydes that work as slow “radical clocks”. The enzyme catalyzes conversion of oxiranyl aldehydes to the corresponding oxiranes. Surprisingly, the enzyme also catalyzes a side reaction of tandem deformylation of the oxiranyl aldehydes to produce alkanes two carbons shorter. This study provides evidence for a homolytic cleavage of C1−C2 bond of the aldehyde by cADO and allowed the lifetime of the intermediate radical to be estimated. (Read Das‘ article, DOI: 10.1021/cb400772q)
despite a robust host inflammatory response. (Read Chaturvedi’s article, DOI: 10.1021/cb400658k)
■
FABRIZIO CHIODO
Image courtesy of Fabrizio Chiodo.
Current position: Postdoctoral Researcher at the Parasitology Glyco Immunology Group, Leiden Medical Center, The Netherlands. Education: Master’s degree in Chemistry and Pharmaceutical Technology (2008), University of Palermo, Italy; Advisor: Prof. L. I. Giannola. Ph.D. in Applied Chemistry (2013) with Dr. Soledad Penadés and Dr. Marco Marradi, at CIC biomaGUNE, San Sebastian, Spain. Nonscientific interests: Geopolitics, Italian soccer, athletics From my Master’s studies (classic galenic formulations and liposomes preparation) I always tried to have a real multidisciplinary background. During my Ph.D. I learned about carbohydrate organic chemistry, carbohydrate multivalent systems preparation, nanotechnology, and glyco-immunology. The role of carbohydrates in triggering innate immune responses was one of the projects developed during my Ph.D. The unique technology (GlycoNanoTechnology) I learned during my studies allowed me to design and prepare different glyconanoparticles to study adaptive and innate immune responses to carbohydrates. Exploring galactofuranose-coated gold nanoparticles, we were able to induce a carbohydrate-mediated signaling in human dendritic cells, which could be really useful to better understand the interactions between pathogens and host. (Read Chiodo’s article DOI: 10.1021/cb4008265)
■
■
BRENT KUENZI
Image courtesy of Brent Kuenzi.
Education: University of Wisconsin−Madison, B.S. Biology, 2012; University of South Florida and H. Lee Moffitt Cancer Center & Research Institute, Ph.D. Candidate in Cancer Biology, Mentor: Uwe Rix Nonscientific interests: Sailing, guitar, cooking, brewing My graduate research focuses on identifying and characterizing cellular target profiles of clinically relevant kinase inhibitors using integrated chemical biology approaches focusing on chemical proteomics. Through this we aim to identify mechanism-based biomarkers and design rational drug combinations. As described in our manuscript, we recently synthesized a tethered tivantinib analog for use in drug affinity chromatography experiments. Using this probe, we identified two novel targets of the drug tivantinib, which had previously been labeled as a specific c-MET inhibitor. Subsequently, we demonstrated the functional relevance of these targets using pharmacological tool compounds and siRNA-mediated knockdowns. I am very excited that we were able to elucidate these targets of tivantinib. Hopefully, these results will lead to further clinical development of tivantinib and guide better patient stratification. (Read Kuenzi’s article, DOI: 10.1021/cb400660a)
DEBASIS DAS
Image courtesy of Debasis Das.
Education: Ramakrishna Mission Residential College, Narendrapur, India, B.Sc. in Chemistry, 2005; Indian Institute of Science, 312
dx.doi.org/10.1021/cb5000828 | ACS Chem. Biol. 2014, 9, 311−314
ACS Chemical Biology
■
Introducing Our Authors
COEN KUIJL
My current research focuses on the development of novel peptide mimics based on our γ-AA peptide backbone reported in 2011. By putting the amphipathic building blocks together, we made a series of cyclic compounds which have a long lipid tail in the structure and named them as lipidated cyclic γ-AA peptides. This class of compounds shows potent antibacterial activities against various multiple drug resistant pathogens such as methicillin-resistant Staphylococcus epidermidis (MRSE) and methicillin-resistant Staphylococcus aureus (MRSA). Besides, they antagonize the lipopolysaccharide (LPS) activated NF-κB signaling pathways and suppress the release of pro-inflammatory cytokines such as tumor-necrosis factor-α (TNF-α). As a result, these γ-AA peptides provide a promising approach to treat bacterial infection by dual functions: directly killing pathogens as antibiotic agents and harnessing immune responses as anti-inflammatory agents. (Read Li’s article, DOI: 10.1021/ cb4006613)
Image courtesy of Coen Kuijl.
Current position: Postdoctoral researcher at Genentech, South San Francisco, California; Research advisor: Jagath Junutula. Education: M.S. in Immunology and Oncology, Free University of Amsterdam, 2000; Ph.D. in Cell Biology at The Netherlands Cancer Institute with professor Jacques Neefjes, 2008; Postdoc in immunology at The Netherlands Cancer Institute with professor Jacques Neefjes, 2009−2010. Nonscientific interests: Mountain biking, snowboarding My primary research interest is to study the role of host proteins in infectious disease and develop novel therapeutic approaches. The focus of my graduate studies is the identification of these host proteins and concomitant small molecules that act upon them to combat infectious disease. Here we present a strategy that integrates chemical (compound) and genetic (siRNA) inhibition screens to define host target-inhibitor combinations in controlling bacterial infections. This yielded host target-inhibitor combinations for dual specificity phosphatases (DUSPs) involved in the control in bacterial infections. This study provides evidence that targeting the host proteins with small molecules instead of the pathogen can potentially treat bacterial infections. (Read Kuijl’s article, DOI: 10.1021/ cb400421a)
■
■
YING (BEVERLY) LU
Image courtesy of Ying Lu.
Current position: Harvard University, School of Engineering and Applied Sciences, Postdoctoral Fellow in Prof. David Mooney’s laboratory. Education: University of California, Berkeley, B.S. in Chemical Biology, 2006 with Prof. Matthew Francis; California Institute of Technology, Ph.D. in Chemistry, 2013 with Prof. David Tirrell Nonscientific interests: Badminton, photography, culinary art, interior design My Ph.D. work focused on the development and application of the bio-orthogonal noncanonical amino acid tagging (BONCAT) method for analysis of cellular protein synthesis. In this manuscript, we combined BONCAT and SILAC to acquire quantitative, time-resolved information on the response of human breast cancer cells to overexpression of tumor suppressor mircroRNA-126. We discovered a new direct target of miR-126: CD97, a G-protein-coupled receptor that has been previously reported to play dual roles in metastasis by promoting tumor cell invasion and recruiting endothelial cells for angiogenesis. This discovery establishes a link between two well-documented observations in cancer biology: the down-regulation of tumor suppressor miR-126 and the overexpression of pro-metastatic factor CD97, and provides new mechanistic insight into the role of miR-126 in inhibiting both cell-autonomous and noncellautonomous cancer progression. (Read Lu’s article, DOI: 10.1021/cb400704n)
YAQIONG LI
Image courtesy of Haifan Wu.
Current position: Ph.D. candidate at University of South Florida, Chemistry Department; Advisor: Dr. Jianfeng Cai. Education: Bachelor of Medicine, Dalian Medical University, Dalian, China Nonscientific interests: Table tennis, running, reading, and cooking 313
dx.doi.org/10.1021/cb5000828 | ACS Chem. Biol. 2014, 9, 311−314
ACS Chemical Biology
■
Introducing Our Authors
SHUKUN REN
Nonscientific interests: Hockey, Pittsburgh’s sports teams, baking, spending time with family and friends My Ph.D. research was focused on decoding protein arginine methyltransferase I (PRMT1) by studying the catalytic mechanism, regulation, inhibition, and crosstalk of PRMT1dependent methylation. PRMT1 is the predominant member of the PRMT family and is involved in the onset and progression of cancer, heart disease, and ALS, thus making it an intriguing target for investigation. The work presented in this issue of ACS Chemical Biology investigates the relatively unexplored territory of the regulation of PRMT1 by post translational modifications, specifically phosphorylation. Utilizing unnatural amino acid mutagenesis to incorporate p-carboxymethyl-L-phenylalanine (pCmF) and p-benzoyl-L-phenylalanine (pBpF), we discovered that phosphorylation of Tyr291 alters the substrate specificity and protein−protein interactions of PRMT1, thus opening the door to future studies on the regulation of this once thought constitutively active enzyme. (Read Rust’s article, DOI: 10.1021/ cb200171d)
Image courtesy of Shukun Ren.
Current position: Postdoctoral Fellow with Assoc. Prof. Shinji Masuda, in Center for Biological Resources and Informatics, Tokyo Institute of Technology. Education: Heilongjiang Bayi Agricultural University, B.S. in College of Food Science; Hokkaido University, Ph.D. in Agriculture with Prof. Kozo Asano; Nonscientific interests: Music, dancing, cooking, and watching movies Photoreceptor proteins are unique models for understanding signal transduction by protein interaction since the activity could be “switched on” by light excitation. My current research is focused on mechanisms of signal transduction of BLUF (Blue-light using FAD) proteins. We have utilized FT-IR techniques to determine the structural and reactive events in the signal transduction from the photoreceptor proteins to their downstream components. We also developed a novel technique for manipulation the activity of transcription factors with blue light (termed “PICCORO”) using the bacterial BLUF-type photoreceptor protein PixD. It will open a new door in optogenetic research fields to control gene expression by light. (Read Ren‘s article, DOI: 10.1021/cb400174d).
■
■
JUSTIN E. SILPE
Image courtesy of Katie Wood.
Current position: Graduate student (MS) at the University of Michigan in the Department of Macromolecular Science & Engineering; Advisors: Professors Mark Banaszak Holl and Seok Ki Choi Education: University of Michigan, Ann Arbor (BS) in Theoretical Medicine & Bioethics−ICP, 2012. Nonscientific interests: Antibubbles, tennis, travel, and playing cards with friends My primary University-related research is on targeted drug delivery for chemotherapeutic and antibiotic applications. Beginning in 2010 at the Michigan Nanotechnology Institute for Medicine and Biological Sciences (MNIMBS), my particular involvement in this area is in validating some of the kinetic aspects of these systems in binding to their corresponding targets, i.e., receptors. In this paper, we study a dendrimer-based multivalent targeting system, and find that multivalency, and thereby its avidity, is highly dependent on both the number of targeting ligands attached to the dendrimer as well as the number of receptors capable of binding the ligand at the surface. This is interesting because it provides a biophysical basis for exploiting differences in receptor density through multivalent design. (Read Silpe’s article, DOI: 10.1021/cb400258d)
HEATHER L. RUST
Image courtesy of Heather L. Rust.
Current position: University of Pittsburgh School of Medicine, Department of Microbiology & Molecular Genetics, Postdoctoral Associate; Advisor: Dr. Thomas Smithgall. Education: Saint Francis University, B.S. in Chemistry, 2008, Advisor: Dr. Balazs Hargittai; University of South Carolina, Ph.D. in Chemistry and Biochemistry, 2013, Advisor: Dr. Paul Thompson. 314
dx.doi.org/10.1021/cb5000828 | ACS Chem. Biol. 2014, 9, 311−314
