Introducing Our Authors pubs.acs.org/acschemicalbiology
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KAI CAI
The Pennsylvania State University, Ph.D. Candidate in Bioengineering and Biomedical Engineering, Research Advisor: William O. Hancock Current Position: The Pennsylvania State University, Ph.D. Candidate in Bioengineering and Biomedical Engineering Nonscientific Interests: Travel, baseball, rafting/kayaking, snowboarding, Frisbee, BBQ, and other outdoor activities The current focus of my research is understanding the link between the mechanochemical mechanisms and the physiological functions of kinesin motor proteins and their associated cytoskeletal tracks. One thread of my research is to apply single-molecule enzymology, high-resolution particle tracking, and stochastic kinetics simulations to illuminate enzymatic state transitions in kinesins. The second thread is to understand how kinesins cooperate with other factors, including posttranslational modifications of tubulin and microtubule-associated proteins, particularly in relation to mitosis and microtubule dynamics. The third thread is to design high-throughput screening methods for motor proteins using fluorescence microscopy and micro/nanofabrication tools. My investigations into kinesin mechanochemistry involve single-molecule and ensemble experiments integrated extensively with theory and computational modeling, which may help to understand and develop anticancer therapeutics. (Read Chen’s article DOI: 10.1021/acschembio.6b01040.)
Image courtesy of Robert Davies.
Education: Nanjing University, Nanjing, China, B.S. in Chemistry; University of WisconsinMadison, Ph.D. in Biochemistry, Advisor: John Markley Current Position: University of WisconsinMadison, Department of Biochemistry, Postdoctoral Research Associate Nonscientific Interests: Movies, music, books, and sports My research is focused on the investigation of mitochondrial iron−sulfur cluster biosynthesis and regulation. Iron−sulfur clusters are among the most ancient and ubiquitous protein cofactors. The biosynthesis of iron−sulfur clusters in human mitochondria is a highly regulated process and involves many protein partners. Among them is cysteine desulfurase, which catalyzes the transformation of L-cysteine to L-analine and mobilizes sulfur for cluster formation. It is known that cysteine desulfurase consists of two proteins: NFS1 and ISD11. In this work, we reported that E. coli acyl carrier protein (Acp) is an also essential component of recombinant-made human cysteine desulfurase complex from E. coli cells. (Read Cai’s article DOI: 10.1021/acschembio.6b01005.)
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LAUREN BURIANEK CROWE
GENG-YUAN CHEN
Image courtesy of Lauren Burianek Crowe
Education: B.S. Chemistry, 2010, University of North Carolina at Chapel Hill, Advisor: Prof. Ken Harden; Ph.D. Cell Biology, 2016, Duke University, Advisor: Prof. Timothy Haystead Current Position: TEACRS Postdoctoral Fellow at Tufts University in the Department of Neuroscience; Advisor: Prof. Rob Jackson Nonscientific Interests: Hiking, cooking, and board games
Image courtesy of Geng-Yuan Chen.
Education: National Taiwan University, B.S. Biochemical Science and Technology and B.S. Chemical Engineering, 2010; © 2017 American Chemical Society
Published: April 21, 2017 878
DOI: 10.1021/acschembio.7b00278 ACS Chem. Biol. 2017, 12, 878−881
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My graduate work focused on bringing cell biological and imaging techniques to a very biochemistry- and pharmacologyheavy project in the lab. We were interested in exploring and investigating new in vivo methods for validating the tumorspecificity of fluorescent compounds for therapeutic and diagnostic purposes. We were excited to see that fluorescent cell impermeable Hsp90 inhibitors were actively trafficked in cells after binding to eHsp90 and that three-dimensional cryo-slicing and -imaging of tumor-bearing mice injected with our compound showed that this process was tumor cell specific. Although most studies of trafficked proteins use antibodies or genetic tags, this research highlights the ability to use small molecules with fluorescent dyes as an inexpensive and simple method to achieve the same goal with little steric hindrance. (Read Crowe’s article DOI: 10.1021/acschembio.7b00006.)
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Introducing Our Authors
KELSEY KEAN
Image courtesy of Andrew Brereton
Education: The University of Tulsa, B.S. Biochemistry, 2012; Oregon State University, Ph.D. Candidate in Biochemistry and Biophysics, Advisor: Dr. Andy Karplus Current Position: Oregon State University, Ph.D. Candidate in Biochemistry and Biophysics Nonscientific Interests: Dogs, donuts, hiking, and reading I got my first taste of structural biology during a summer research internship and followed this interest to graduate school, where I joined a protein crystallography lab. Now, I study the structure−function relationships of a variety of proteins ranging from peroxiredoxins involved in signaling to carbonic anhydrase with applications in carbon sequestration. I also study the sedoheptulose seven-phosphate cyclases (SH7PCs) discussed in our paper. The SH7PCs are interesting because, despite being remarkably alike in terms of active site identity and structure, they use the same substrate to each generate a unique product. Making them even more intriguing is the recent, unexpected discovery of a SH7PC in nonmammalian vertebrates (like the chicken I am shown holding). I want to figure out how these enzymes work and what their function is in these organisms. (Read Kean’s article DOI: 10.1021/acschembio.7b00066.)
REBECCA HANCOCK
Image courtesy of Dr. Adam Hardy
Education: University of Oxford, MChem in Chemistry, 2012 Current Position: DPhil candidate in Cardiovascular Medicinal Chemistry, Department of Chemistry, University of Oxford, supervised by Dr. Emily Flashman, Dr. Akane Kawamura, and Professor Chris Schofield Nonscientific Interests: Yoga, writing, literature, and all things culinary Epigenetic regulation relies on the activity of a diverse collection of enzymes to enable the cell to respond to environmental stimuli. My DPhil research has focused on the histone lysine demethylase KDM4A, an enzyme that catalyzes the removal of methyl groups from specific lysyl residues on the histone tails, thereby modulating transcription. Using biochemical and cellular techniques to probe the reaction of KDM4A, we were excited to find that KDM4A activity is sensitive to oxygen availability. This phenomenon may have significant implications for epigenetic regulation and gene expression in hypoxic disease states, such as cancer and cardiovascular disease. For me, this work represents the potential of chemistry to enhance our fundamental knowledge of biology and to aid in the validation of new therapeutic targets. (Read Hancock’s article DOI: 10.1021/ acschembio.6b00958.)
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SRIKANTH KUDITHIPUDI
Image courtesy of Neelina Kudithipudi
Education: M.Sc. Biochemistry from Sri Krishnadevaraya University, India; Ph.D from Jacobs University Bremen under the supervision of Prof. Dr. Albert Jeltsch, 2011; Postdoctoral Scientist from 2012 to 2014 and Group Leader from 2014 to 2017 at the Institute of Biochemistry, Stuttgart University 879
DOI: 10.1021/acschembio.7b00278 ACS Chem. Biol. 2017, 12, 878−881
ACS Chemical Biology
Introducing Our Authors
disorders, suggesting that AGE formation, due to a glycation process, boosts protein aggregation. My Ph.D. research focuses on the glycation, using three different glycating agents (ribose, methylglyoxal, and glycolaldehyde), of two different proteins: lysozymea globular protein with low aggregation tendency and alpha-synucleinan intrinsically disordered protein with high aggregation tendencythe latter being one of the main components of brain aggregates of patients suffering from Alzheimer’s. To carry out this study, we used a combination of different biophysical techniques (NMR spectroscopy, UV−vis and fluorometric spectroscopies, microscopies, MALDI-TOF, etc.), which provided high-resolution structural information and new insights about the mechanism that links glycation with protein aggregation. (Read Mariño Pérez’s article DOI: 10.1021/ acschembio.6b01103.)
Current Position: Novartis (Kundl, Austria) as Team Leader Down Stream Process-Development, Biologics Technical Development and Manufacturing Nonscientific Interests: Playing cricket, strolling countrysides, and reading biographies My education background is biochemistry; I always had high interest in investigating the enzymatic properties of proteins and understanding their potential role in various diseases. I was introduced to the field of protein lysine methyltransferases by Prof. Albert Jeltsch. My research is focused on the discovery of new substrates and resolving the ambiguity of designated substrates of some PKMTs. Thereby, my aim was to contribute to understanding the cellular role of the PKMTs. In our manuscript, we have studied the substrate specificity of the first identified human PKMT SUV39H1 using peptide array libraries. Our results showed that SUV39H1 catalytic properties are not just limited to histone methylation, but they can also modify other chromatin proteins such as RAG2, SET8, and DOT1L. Methylation of SET8 by SUV39H1 allosterically regulates its catalytic activity and leads to an increase of H4K20me1 levels, which would be further used by SUV4−20H1 proteins to generate higher H4K20 methylation levels. Hence, our results open a new pathway for heterochromatin formation. In summary, we expanded the substrate spectrum of SUV39H1, which hints that the effects function of SUV39H1 should be viewed in a more complex context. (Read Kudithipudi’s article DOI: 10.1021/ acschembio.6b01076.)
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RYAN S. NETT
LAURA MARIÑ O PÉREZ
Image courtesy of David Stevens
Education: Gustavus Adolphus College, Bachelor of Arts in Biology and Chemistry, Advisors: John Lammert and Brandy Russell; Iowa State University, Ph.D. candidate in Molecular, Cellular, and Developmental Biology, Research Advisor: Reuben J. Peters Current Position: Iowa State University, Ph.D. candidate in Molecular, Cellular, and Developmental Biology Nonscientific Interests: Basketball, guitar (mostly Neil Young and Lindsey Buckingham), and brewing kombucha My graduate research is focused on the biosynthesis of gibberellin (GA) phytohormones by rhizobia, the nitrogenfixing, bacterial symbionts of legumes like soybeans. We have previously been able to describe GA biosynthesis for the majority of rhizobia, but this revealed that many of these rhizobia cease GA biosynthesis at a nonbioactive precursor, GA9. In our manuscript, we describe the characterization of an additional biosynthetic enzyme, a cytochrome P450 (CYP115) that is only present in a small subset of rhizobia, that catalyzes the crucial biochemical transformation of GA9 into bioactive GA4. Interestingly, the scattered and limited distribution of CYP115 suggests that most rhizobia have selectively lost this enzyme, which may provide insight into selective pressures associated with rhizobial production of this plant hormone. (Read Nett’s article DOI: 10.1021/acschembio.6b01038.)
Image courtesy of Sofia Mariño Pérez
Education: Degree in Chemistry at the University of the Balearic Islands, 2013; Master in Chemical Science and Technology in the Department of Chemistry of the University of the Balearic Islands, 2014, Advisor: Dr. Miquel Adrover Estelrich; Master in Teacher Training at the University of the Balearic Islands, 2014 Current Position: Ph.D. student at the University of the Balearic Islands, Department of Chemistry, Advisors: Dr. Josefa Donoso Pardo and Dr. Miquel Adrover Estelrich Nonscientific Interests: Hiking, traveling, cooking, adventure sports, dancing, and playing the clarinet My current aim is to understand the mechanism that links protein glycation with protein aggregation since the latter process is directly related to the development of neurodegenerative pathologies, such as Parkinson’s and Alzheimer’s diseases. Some studies have shown that people suffering from diabetes have a higher prevalence to develop neurodegenerative 880
DOI: 10.1021/acschembio.7b00278 ACS Chem. Biol. 2017, 12, 878−881
ACS Chemical Biology
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Introducing Our Authors
ZHENHUA SHEN
Image courtesy of Bijeta Prasai
Education: Zhengzhou University, P. R. China, B.S. in Chemistry, 2010; M.S. in Organic Chemistry, 2013, Advisor: Prof. Junbiao Chang; Louisiana State University, Ph.D. candidate, Advisor: Prof. Robin L. McCarley Current Position: Louisiana State University, Ph.D. candidate Nonscientific Interests: Hiking, running, traveling, movies, and reading My Ph.D. research is focused on the detection and imaging of disease-associated biomarkers using novel activity-based small organic molecules. Human NAD(P)H:quinone oxidoreductase isozyme I (hNQO1) is a two-electron reductase overexpressed in a multitude of cancer cell lines. In this manuscript, we described a near-infrared (NIR), wavelength-shiftable, turn-on fluorescent probe Q3STCy, and its biological evaluation using cells with different hNQO1 expression levels. Upon selective hNQO1 catalysis, the low-emissive precursor probe yields an intense NIR fluorescent reporter. It successfully reported hNQO1 activities in human tumor cell monolayers, three-dimensional multicellular tumor spheroids (MCTSs), and micrometastases from a xenograft mouse model, making it a promising tool for scientists to unravel the roles of hNQO1 in cancer onset and progression. (Read Shen’s article DOI: 10.1021/acschembio.6b01094.)
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DOI: 10.1021/acschembio.7b00278 ACS Chem. Biol. 2017, 12, 878−881
