VANDERBILT CHEMISTRY

2014 CONTENTS Greetings from the Chair 3 Research Highlights 4 Faculty 17 Graduate Students 30 0 Undergraduate Students 38 8 Colloquium Speakers 43 3 • Vanderbilt Chemistry 2014 elcome to the 2014/2015 Department of Chemistry newsletter. It has been has It Chemistry of the Department 2014/2015 to newsletter. elcome students. and staff, faculty, its the department, for year outstanding another university with the Vanderbilt at reflection time of also exciting is an It

- a snap with you provide will pages following in the stories The We are proud of all of our students who come from across the U.S. and around around and the U.S. across from who come students our all of of proud are We A hallmark of our faculty is their dedication to research, teaching, and service. and teaching, research, to their faculty dedication is our of A hallmark One of the constants in life is change. Last year, the department saw quite a bit a bit quite saw the department Last year, change. is in life the constants of One David Wright David Chair and Professor Stevenson Chemistry of Department University Vanderbilt shot of what researchers are doing, the changing faces of the depart- faces of the changing doing, are researchers what of shot insights some and garner, to continue we that the recognition ment, to efforts our redoubling are We alumni. and students our into will take the time you that hope and alumni, our you, with connect it. about hear to love would We doing. are you what know let us to the world. This past year, we graduated twenty students with ACS-certified bachelor’s ACS-certified bachelor’s with students twenty we graduated year, This past the world. studies. professional or graduate will whom pursue of most in chemistry, degrees and degree the master’s with students three also graduated We the Our were trainees in chemistry. the Ph.D. with students eleven grant NIH training from ranging awards of a number of recipients Eli Lilly an to Fellowship Research Graduate the NSF to positions Fellowship. Postdoctoral Innovation This faculty excellence is seen in the national awards that we earn. Examples include: include: we earn. Examples that awards is seen facultynational in excellence This the for ACS Cope Scholars named were Armstrong and Richard Johnston Jeff Professors Thought Agilent an named was McLean John Professor research. in organic excellence US-Israel The Innovation. of Center a Waters recognized as was lab Leader his and the Bergmann with Memorial Macdonald recognized Janet Foundation Binational for Award Achievement Faculty the 2014 SEC won Rosenthal Sandra Professor Award. Larry Professor I wish Finally, scholarship. and in teaching recognized excellence her VUMC. at research of vice chancellor the associate as the best new in his role Marnett of it with the retirements from teaching of Professors Ned Porter, Joel Tellinghuisen Tellinghuisen Joel Porter, Ned Professors of teaching from the retirements with it of Steven professor, new a assistant also hired department The Lukehart. Chuck and looking are we Currently, Verberne-Sutton. Susan lecturer, a new senior and Townsend, catalysis. of in the area professor chemistry assistant a new inorganic hire to implementing its new strategic plan. As one of the biggest teachers of undergraduates and and undergraduates of teachers the biggest of one As plan. new strategic its implementing of heartthisat the itself finds the department campus, on program graduate the largest decade, the coming for plan strategic departmental own our develop we While process. experiences, and immersion imagining initiatives, new trans-institutional forging are we the campus. across teach to new ways exploring W 0 8 3 4 43 38 30 17 Students Undergraduate Speakers Colloquium CONTENTS the Chair from Greetings Highlights Research Faculty Students Graduate RESEARCHHIGHLIGHTS

Micro-BrainBy Jennifer McKenzie, Ph.D., Cliffel Group on a Chip

Take a millionth of a human brain and squeeze it into a special chamber the size of a mustard seed. Link it to a second chamber filled with cerebral spinal fluid and thread both of them with artificial blood vessels in order to create a microenvironment that makes the neurons and other brain cells behave as if they were in a living brain. Then, surround the chambers with a battery of sensors that monitor how the cells respond when exposed to minute quantities of dietary toxins, disease organisms, or new drugs under development.

reating such a “microbrain bioreactor” is the challenge of new drugs—cell cultures and animal and human testing. These a new $2.1 million research grant awarded to an interdis- gaps not only add substantially to the difficulty and expense of ciplinary team of researchers from Vanderbilt University, developing new drugs, but also contribute to the large number of CVanderbilt University Medical Center, the Cleveland Clinic and experimental drugs that aren’t effective or have unacceptable side Meharry Medical College. The grant is one of seventeen that are effects when they are finally tested on people. being issued by the National Center for Advancing Translational “Given the differences in cellular biology in the brains of Sciences at the National Institutes of Health as part of a $70 rodents and humans, development of a neurovascular model that million “Tissue Chip for Drug Testing” program. The five-year contains neurons and all three barriers between blood, brain, and program is a cooperative effort on the part of NIH, the Defense cerebral spinal fluid, using entirely human cells, will represent Advanced Research Projects Agency, and the FDA. a fundamental advance in and of itself,” said John Wikswo, the The reason for microfabricating organ simulators containing Gordon A. Cain University Professor and Director of the Vander- small populations of human cells—generally known as “organ- bilt Institute for Integrative Biosystems Research and Education on-a-chip” technology—is to bridge the formidable gaps that exist (VIIBRE), who is orchestrating the multidisciplinary effort. between the models that researchers currently use to develop Vanderbilt Professors of Chemistry David Cliffel and John

Artist’s conception of the microbrain bioreactor. The upper chamber contains the neurons and an artificial capillary that carries blood to the brain surrounded by the cells that make up the blood-brain barrier. The lower layer is filled with cerebral spinal fluid (CSF) and contains an artificial choroid plexus (red) that makes CSF and a venule (blue) that carries blood away from the brain, along with a collection of cells that form the blood-CSF and CSF-brain barriers. Collectively, all these cells will reproduce the microenvironment found in the brain. The entire device will be about the size of a grain of rice. (Dominic Doyle and Frank Block / Vanderbilt) 5 • Vanderbilt Chemistry 2014 - - - John McLeanJohn David Cliffel Wikswo and his collaborators agree that this new type that agree collaborators his and Wikswo been has and developed bioreactor the microbrain Once - Medi of Professor Associate headed by group, Another This research is supported by the NIH National Center for Advancing Advancing for Center National NIH the by supported is research This UH3TR000491. UH2TR000491 and Sciences, Grants Translational the how into new insights provide model should brain of disease and by drugs affected is and modifies, receives, brain communication chemical of the forms replicating By agents. brain, human place inthe take that trafficking molecular and various of the devicethe effectiveness will test them to allow both acute prevent designed to therapies nutritional drug and diseases and obesity like chronic and strokes like injuries of effects adverse the potential uncovering as well as epilepsy, experimental drugs. of professor assistant Daniels, Scott headed by a team tested, - pharma drug and metabolism of director pharmacology and Drug Neuroscience for Center the Vanderbilt at cokinetics - Clinic Founda the Cleveland with will collaborate Discovery, a with it testing technology by the chip validate to group tion experimental compounds and approved clinically of number nervous the central penetrate to varythat in their ability technology brain-on-a-chip “the that noted Daniels system. penetra- brain human of prediction the accurate enable could a bridge therefore, and, small molecule therapeutics by tion in the drug discovery gap arena.” critical translational the new device to will be applying Niswender, Kevin cine in plays the brain that the role and stroke the biology of study ask fundamental to will his group system The allow obesity. - inflam and dietary how macronutrients about questions in present components various the signals influence matory and Physiology Molecular of Professor Assistant the brain. under to the system Ellacot will employ Kate Biophysics of in the context neurons with glial interact cells how stand Clinic the Cleveland In addition, obesity. in inflammation these with and patients from samples collection of a large has selected cells patients Theyfrom put will conditions. other differ to they respond how quantify and in the bioreactors samples precious these apply to “Theability treatments. ent liter can we where a platform to patients by us to entrusted true,” come a dream is parameters of hundreds ally measure professor BethAnn assistant member team said McLaughlin, Center. Kennedy the Vanderbilt of member and neurology of to therapeutics in developing challenges enormous have “We unmet this a profound is and injury from the brain protect protect to approval drug a single passed has FDA need. Not up breaks that one have only we and stroke, from the brain do better.” need to We clots. - While the Cliffel lab focuses on small metabolites focuseswhich on small metabolites lab the Cliffel While Professor David Cliffel and his group have build- been have his group and Cliffel David Professor instru- previous on basedare electrochemical The sensors The sensors designed in the Cliffel lab can be integrated downstream of the Neurovascular Unit-on-a-Chip, allowing for online analysis. Pumps and valve developed by VIIBRE allow for automation of fluid handling. of Professor Stevenson electrochemistry, using detectable are to been has the effort leading group McLean’s Chemistry John that spectrometers mass sophisticated to theseconnect organs differ of thousands of identify time the in real presence can ent proteins and other molecules that the cells produce. “It’s “It’s the produce. cells molecules that other and proteins ent decipher to analytics real-time apply to challenge exciting an in the takes brain,” place that the communication molecular instrumental high-powered with coupled When said. McLean discern to able is group McLean’s techniques, analysis data and how focus signals in on to of the thousands within patterns over changing certain small of molecules are concentrations a drug treatment. of the course McLean are leading the efforts to enable online analytical online enable to the efforts leading are McLean component key a the organs, developed from measurements and health before organ of monitoring automated for allow to investigation. drugs with undergoing treatment after cellular measure that electrochemical sensors miniature ing glucose and of the consumption tracking by metabolism in acidity, changes and lactate of the production and oxygen monitoring energy moleculeskey By in the cycle. cellular insight will gain it be to time, possible over these analytes specific drugsmay how track as well health, as cellular into own energy. their produce to organs of the ability the affect by developed instrumentation the novel with coupled When - moni automated and real-time enable these VIIBRE, sensors key“Our contribution Cliffel, health. Says cellular of toring of components the major of measurement the continuous is all to organs: common bioenergetics and physiology cellular a study we Thus, acidification. and lactate, oxygen, glucose, and liver, lung, the brain, including organs wide of variety nodes.” even the lymph with collaboration the but lab, the Cliffel by developed ments of development into further sparked research has VIIBRE - research Student be could employed. that sensors additional - undergradu including levels, education all different from ers develop to together working are students, graduate and ate be can used monitor to that sensors new metabolic test and Unit-on-a-Chip. the Neurovascular to changes RESEARCHHIGHLIGHTS

Vanderbilt Awarded $16.5 Million Agreement to Determine How Toxic Agents Affect Human Cells Adapted from an article by Bill Snyder

anderbilt University has been awarded a Cooperative The Vanderbilt Agreement governs research that will be con- Agreement with the Defense Advanced Research Projects ducted in up to four phases. At the end of each one, the mile- VAgency (DARPA) and the Army Research Office (ARO) stones and the metrics “get tougher and tougher,” said Caprioli, a that is worth up to $16.5 million over five years. pioneer in mass spectrometry techniques. The Vanderbilt Agreement is led by Richard Caprioli, Ph.D., A transinstitutional effort, the Vanderbilt project consists of Stanford Moore Professor of Biochemistry, Professor of Chem- three teams: istry, and director of the Mass Spectrometry Research Center The analytics team—co-led by John McLean, Ph.D., Steven- (MSRC), and principal investigator of a National Institutes of son Professor of Chemistry, and Jeremy Norris, Ph.D., research Health grant (GM103391) that in 2011 established a National assistant professor of biochemistry, who also serves as project Resource in Imaging Mass Spectrometry at Vanderbilt University. manager. Other faculty team members include Brian Bachmann, “In the second half of my career, I want to take some of the … Ph.D., associate professor of chemistry and biochemistry, and really extraordinary things that can be done in research labs, and … Kevin Schey, Ph.D., professor of biochemistry and director of the bring them into the public domain on problems that can directly help MSRC Proteomics Lab. (people),” said Caprioli, who joined the Vanderbilt faculty in 1998. The biology team—led by Eric Skaar, Ph.D., MPH, Ernest W.

Richard Caprioli, Ph.D., leads the Vanderbilt Agreement for the Rapid Threat Assessment Program with DARPA and ARO to develop mass spectrometry methods for quickly determining how potentially toxic agents, including drugs, affect human cells. 7 • Vanderbilt Chemistry 2014 - Jeremy Norris is project manager transinstitutional the effort.of Norris received his Ph.D. in chemistry from Vanderbilt in 2002, in the Caprioli lab. Instrumentation that that Instrumentation - amaz is “Theopportunity bilt that is being used to study how changing used to study how changing bilt that is being affects production of proteins gene expression important in cellular function and metabolites and regulation. of Institutes National the from by a wassupported grant research This (GM103391). Health using a hydrogel containing proteases (protein “scissors”). The approaches, reported in the August 6 issue of Analytical Chemistry will enable further MALDI IMS studies of trans- membrane protein distribution. “We’re going to grow human cells on slides … slides cells on human to grow going “We’re the toxins to be exposed going to they’re and laser- our scanning, be analyzed using and will … to technologies spectrometry based mass on going of what’s rapid assessment get a very the molecular level,” he said. in those cells at IMS, an imaging mass These include MALDI developed at Vander spectrometry technology will- these be stud used for a new 15.5 tesla ies includes that spectrometer mass FTICR lab installedwas in Caprioli’s of MRB III floor the ninth on roughly fall is last (15.5 tesla of 200,000 times the strength and field), magnetic the earth’s instrument. a 9.4 tesla makes “It said. Caprioli ing,” in the morning up get you say, and enthusiasm great with do this. and there get ‘Let’s worth doing.’” is This By Leigh MacMillan By

—led by John Wikswo, Ph.D., Ph.D., Wikswo, John team —led by automation The cell Mapping Brain Membrane Proteins The study also includes new processes for assessing fatty acid modifications and for on-tissue protein identification Richard Caprioli, Ph.D., and colleagues have now developed a novel sample preparation procedure for MALDI IMS of transmembrane proteins directly from tissue. They used the method to assess the spatial distribution of myelin proteolipid protein and DM-20, two highly abundant transmembrane proteins within central nervous system myelin, throughout various regions of the rat brain. MALDI imaging mass spectrometry (IMS) is a powerful tool for studying the spatial distribution of molecules directly within tissues. It has been applied to many different pharmaceuticals, metabolites, and small, soluble proteins. Large membrane- have not been well studied by spanning proteins, however, MALDI IMS because of analytical challenges related to their size and solubility. Professor of Chemistry John McLean, Ph.D., is co-leader of the analytics team. Goodpasture Professor of Pathology, director of the Division the Division of director Pathology, of Professor Goodpasture the Program of director and Interactions Host-Pathogen of Pathology, of in the Department Pathogenesis in Microbial associate Ph.D., Immunology; Lacy, Borden and Microbiology of and immunology and microbiology, pathology, of professor this team. of a faculty member is biochemistry, the of director and Professor University Cain A. the Gordon and Research Biosystems Integrative for Institute Vanderbilt methods willteam develop automation cell The Education. “very fifty fast…in agents exposed cells freezing toxic to for said. Caprioli experiments,” milliseconds in some RESEARCHHIGHLIGHTS

Fundamental Discovery of New Form of Crystalline Order By Sandra Ford, with Janet Macdonald, Ph.D., Assistant Professor of Chemistry

ince the 1850s, scientists have known thin films or bulk samples, but it has appar- that crystalline materials are orga- ently gone unnoticed.” They also predict nized into fourteen different basic interlaced crystals are present naturally in a latticeS structures. However, a collaborative much broader class of materials. team of researchers from three different Assistant Professor of Chemistry Janet backgrounds and from Vanderbilt University Macdonald, Ph.D., explains, “In CIS, the and Oak Ridge National Laboratory (ORNL) sulfurs make these perfectly packed 2-D now reports that it has discovered an entirely layers and the Cu and In ions lie in between, new form of crystalline order. They saw crys- like jam in a sandwich. My postdoctoral tals that simultaneously exhibit both crystal student, Emil Hernandez-Pagan, was making and polycrystalline properties, which they nanoparticles of this material in the lab, but describe as “interlaced crystals” and hold didn’t know if the Cu and In were ordered, promise for thermoelectric applications. or just randomly distributed in the “jam” In the Nov. 14, 2014, issue of the journal, layers. This is really important for the optical Scanning Transmission Electron Microscope Nature Communications, the researchers properties as disordered structures would image showing the interlaced crystalline structure. describe finding this unusual arrangement have poor properties.” (Wu Zhou/ORNL) of atoms while studying nanoparticles made She continues: “There was no easy way you have poly crystalline samples, there is from the semiconductor copper-indium to tell if they were cation ordered or not strain or breaks at the edges between areas of sulfide (CIS), which is being actively studied using our usual tools for nanocrystals, as crystalline order. However, there seemed to “This was really very fundamental and beautiful: discovering a be no strain or breaks at the edges. Despite all of the little crystallites, the sulfur layers whole new way that nature packs atoms together in crystals. It’s and the broader lattice of the crystal are com- always been there but no one has noticed before. We’re not sure pletely ordered and needn’t shift or twist or break at all to accommodate all these changes of the full implications ourselves yet.”—Janet Macdonald in the cation layers. Without strain or defects in the interlaced for use in solar cells. The interlaced crystal they just can’t “see” details down to the crystals, interlaced crystals should be great arrangement has properties that make it atomic level. We asked Dr. Pantelides and conductors of electricity, despite all these ideal for thermoelectric applications that Dr. Xiao Shen to do some modeling calcula- different regions of cation ordering. As Mac- turn heat into electricity. The discovery of tions to see if ordering was reasonable. Xiao donald summarized the discovery, she said, materials with improved thermoelectric came up with multiple possible ways the Cu “Electrons will have a smooth path. But, heat efficiency could increase the efficiency of and In could be ordered. He calculated they travels through atomic vibrations, and all of electrical power generation, improve auto- were very similar in energy. Since there was the grain boundaries in the cation layers will mobile mileage, and no clear winner, we sent some particles to scatter these vibrations and hinder heat from reduce the cost of air Dr. Wu Zhou and Dr. Steve Pennycock at flowing easily through the material. This is conditioning. ORNL. Wu got these amazing images that exactly what you want for a thermoelectric. “We discovered this not only told us the cations were ordered, I’m excited to see what comes out of thermo- new form while study- but all of Xiao’s predicted structures were electric studies.” ing nanoparticles,” said there, all in one particle. Turns out they Sokrates Pantelides, were all winners!” Research was funded by National Science Foundation Ph.D., University Dis- Then, things got even more interesting grants DMR-0938330, EPS-1004083 and CHE- Janet Macdonald 1253105; U.S. Department of Energy grant DE-FG02- tinguished Professor of for the researchers. When the images were and a postdoctoral 0946554; Office of Science contract DE-AC02- student synthesized Physics and Engineer- analyzed even more closely, they discovered 05CH11231; and by ORNL’s Basic Energy Sciences/ the nanoparticles ing at Vanderbilt, who it was really hard to decide exactly where Materials Science and Engineering Directorate and that revealed coordinated the study. the edges were between the areas of different Center for Nanophase Materials Sciences, sponsored the new form of crystalline order. “It most likely exists in ordering. Usually, it is clear because when by US DOE. 9 • Vanderbilt Chemistry 2014 That’s just the tip of the iceberg, of course. “One of the “One of course. of iceberg, the the tip just That’s by Babbitt’s provided bioinformatics the is This where - previ not had that enzymes in eighty-two activity cytGST-like of known number increased been This the characterized. ously 50 percent. about by in thisenzymes superfamily - illus it that is aspects the bioinformatics of important most challenge The said. Babbitt know,” don’t we much how trates through structure protein determining or sequencing not is lab, which, in Almo’s crystallography, X-ray like techniques operation. high-throughput automated, a heavily become has and expensive difficult the the function, most which is “It’s said. Armstrong in the lab,” elucidate to thing for structuralcontext provided lab crucial. was Almo’s team his and while Armstrong group, her of out coming the data the proteins. of functional annotations provided colleagues - sup Initiative, FunctionEnzyme the was through research funded The also NIH by and GM093342, grant Health of Institutes ported National by GM103311. GM060595 and grants of Enzymes of - - - - Once function has been function has Once deter “We don’t know what most of these of most what know don’t “We Babbitt, Ph.D., from the University of of the University from Ph.D., Babbitt, Francisco. California, San proteins actually do. That’s the major major the That’s actually do. proteins professor Armstrong, said challenge,” who chemistry biochemistry, of and Steven with in thepartnered research College Albert of Einstein Ph.D., Almo, Patricia and York, New in Medicine of them and their three-dimensional their three-dimensional them and structures.

anderbilt University’s Richard Armstrong, Ph.D., is is Ph.D., Armstrong, Richard University’s anderbilt has that team research a multi-institutional part of of a “super-family” interrogate to a new way found

The scientists focused super on the The scientists in enzymes known from information Using Their approach, published in the current issue of the jour issue in the current published approach, Their

By Bill Snyder Snyder Bill By V mined, it may be possible to alter it in a way to in a way it alter be to possible may it mined, - anti to resistant becoming bacteria from prevent - microorgan other of boost or the ability biotics, pollutants, environmental down break to isms bioremediation. as known a process transfer cytosolic glutathione of family these means Cytosolic ases (cytGSTs). a cellular to bound not are enzymes They act the with in concert membrane. protect to primarily glutathione antioxidant detoxify stress,” “oxidative the cell from key other play and harmful chemicals, 13,000 non- From in metabolism. roles sequences, cytGST genetic redundant “clusters” generated the researchers structures. and sequences similar of They crystalizedrepresentative clusters, various from samples thirty- identified in so doing and seven new structures, molecular in proteins twenty-seven of snapshots, or states. different system assay a high-throughput and the clusters, confirm to able they were others, analyzing for , provides a “roadmap” for determining the determining for a “roadmap” , provides Biology nal PLOS encode that sequences the genetic from enzymes function of enzymes involved in detoxification, cellular metabolism, and and metabolism, cellular in detoxification, involved enzymes - as-yet-undis other many which have resistance, antibiotic functions. covered Richard ArmstrongRichard

SUPER FAMILY SUPER Team Finds Way to Explore to Way Finds Team RESEARCHHIGHLIGHTS Research by Michael Stone and Co-Workers Illuminates the Replication Bypass of Aflatoxin Adducts in Mammalian Cells

flatoxin B 1 (AFB1) is a fungal toxin which is a known which either an AFB1–N7-Gua- carcinogen associated with early-onset hepatocellular carci- or AFB1–FAPY-containing DNA Anoma. Two new reports by Professor Michael Stone, Ph.D., substrate was introduced. and his collaborator, Professor R. Stephen Lloyd at the Oregon This work has been high- Health & Science University, confirm that both AFB1–N7-Gua and lighted in the Spotlight section of AFB1–FAPY are, in fact, highly mutagenic in primate cells into the American Chemical Society journal Chemical Research in Toxicology http://pubs.ac s.org/doi/ abs/10.1021/tx500300x]. Liang Li, a Ph.D. student in Stone’s laboratory, synthesized a series of site-specific AFB1 lesions that were inserted into Liang Li, a Ph.D. did his dissertation describing DNA adducts of AFB1 in primate cells and replicated. The the Stone Lab. He will recieve his results of this research revealed Ph.D., in fall 2014. that these AFB1 lesions were highly mutagenic, yielding repli- cation error frequencies of 97 percent, with the predominant base substitutions being G to T transversions. These transversions are consistent with mutational data derived from aflatoxin-associated HCCs. The original research articles were published in the Journal of Biological Chemistry and in Carcinogenesis. This research was supported by a grant from the NIH, National Cancer Institute, Grant R01-CA-55678

Chemistry Ph.D. student, Liang Li (center), was presented with an achievement award from the American Chemical Society Division of Chemical Toxicology by Dr. Griff Humphries (left) and Professor Trevor Penning (right), recognizing his dissertation work describing DNA Adducts of Aflatoxin B1. Michael P. Stone, Ph.D., Stevenson Professor of Chemistry, led the research on the Aflatoxin B 1 (AFB1). 11 • Vanderbilt Chemistry 2014 -

These and related studies also set the stage for translation to translation for also studies stage set the related and These - understand for a newprovided framework These findings ent functions with human DNA, and when it repairs damaged damaged repairs when it and DNA, human with functions ent XPA. factor the critical with repair DNA of fac- laboratory the with effort a joint In clinical applications. involved already Chazin is Ph.D., Fesik, Stephen member ulty - inhibit of value therapeutic in trying the potential evaluate to cancer current to small adjuvant with molecules, an as RPA ing chemotherapies. initially binds ssDNA in a condensed state and becomes and state in a condensed ssDNA binds initially alsowork The the substrate. fully engages it as extended more binds it as transitions three) (not two undergoes revealed RPA state. intermediate an evidence no for with ssDNA, DNA stimulate to able is it how and works RPA both how ing into new insights provides it Further, machines. processing others. be can selected over pathway processing DNA one how to developed use the to new they strategy have are steps Next differ it itself performs when configures RPA how characterize The RPA research was supported by NIH RO1 GM65484, RO1 CA092584,RO1 GM65484, by NIH supported was research RPA The Molecular in T32 GM80320; Center grant: EH1065561; training RO1 and Center Cancer Vanderbilt-Ingram P30 ES00267; and no. grant Toxicology P30 CA068485. grant . RPA functions by serving by functions a platform as RPA tendency to become tangled and is also is tangled and become tendency to nuclease numerous by up cut readily evolved has Every organism enzymes. the protect to proteins binding ssDNA untangled.” it keep and ssDNA - multi-pro highly dynamic, the many, for these perform essential that machines tein manages only not It processes. genetic also orchestrates but the ssDNA, to access - pro the other of going and the coming e now know that many serious diseases have diseases serious have many that know e now individual’s in an present are links that genetic our where helix double DNA genome—the

Nucleic Acids Research Acids Nucleic The results altered the long-standing views of RPA. They of RPA. views long-standing the altered results The Researchers know too that a protein protects our DNA, DNA, our protects a protein too that know Researchers A (RPA). Protein is called Replication protein precious This is RPA in humans, protein binding the primary ssDNA As its from be needs to unwound the DNA be read, “To how about known is little importance, central its Despite

Walter Chazin Walter W Works and How It Stimulates the DNA Processing Machines the DNA Processing and How It Stimulates Works Leigh MacMillan By New Study Provides a Framework for Understanding How Protein for Understanding How Provides a Framework New Study that Protects Our DNAOur Protects that New Light on Critical Protein’s Activity Protein’s Critical on Light New contrast with previous models that had proposed that RPA RPA that proposed had that models previous with contrast hereditary information is encoded. is hereditary information unwound when it’s entangled becoming to vulnerable which is by also being attacked to and be to read, the helix from the making code thereby the strands, damage that enzymes indecipherable. makes protein in a book, then the RPA the words was DNA If that when the in place book and open is kept are the pages sure order. in correct the words reads the reader and maintain virtually that to all essential processes absolutely genomes. our propagate strands,” separate into state helical double-stranded familiar, Chazin, Walter lead investigator and facultymember explains a strong has (ssDNA) DNA stranded single “But Ph.D. machines. processing the DNA up make that teins study, a recent In roles. molecules these perform complex RPA new approach used a fundamentally collaborators Chazin and engages which RPA by process the multi-stage investigating to - com studies The biosystems. other to be can applied that DNA Source Light the Advanced at scattering X-ray from data bined scattering neutron Laboratory, Berkeley National Lawrence at at supercomputers and Laboratory, Oak National Ridge at article featured as a published was study The facilities. national in RESEARCHHIGHLIGHTS From R&D to Academia and Industry Pool Their Efforts to Speed Discovery of Potent and Personalized New Drugs

By Bill Snyder

anderbilt scientists have discovered a series of small mol- Schizophrenia affects an estimated one of every 100 adults. Cur- ecules that may help unlock the mystery of schizophrenia, rent medications can keep hallucinations and delusions at bay but Va severe mental disorder that can cause disabling halluci- do little to address other symptoms, including cognitive difficulties nations, delusions, and disorganized thinking. and a tendency to withdraw from others. The drugs also cause side If they can refine the molecules into drug-like compounds, and effects that can be devastating for patients and family members, pass the baton to a drug company for further development, the result including metabolic disorders and significant weight gain. could be a new class of drugs significantly more effective than cur- rent therapy and with fewer side effects. The work is slow going, and FREEDOM OF PURSUIT the risk of failure is high. Even if a candidate compound passes the “Clearly, there are huge unmet clinical needs,” says Mark Duggan, rigorous safety and efficacy testing required of a potential new drug, vice president for neuroscience at AstraZeneca. “That’s why we it may be 2016 before it can be tested extensively in patients, and 2020 are continuing to invest in neuroscience but via external scien- before it reaches the market. tific partnerships with some of the best groups around the world, But the project, conducted in collaboration with the global bio- including Vanderbilt,” adds John Dunlop, also a vice president of pharmaceutical company AstraZeneca, represents a paradigm shift neuroscience at AstraZeneca. “Together we are aiming at getting a in the way novel drugs are discovered and developed. The hope is compound that could advance into clinical testing.” that such partnerships will significantly improve treatment of a host The target of the collaboration is the M4 muscarinic acetylcho- of disorders, from serious infections to cancer and diabetes. line receptor, which in the brain binds the neurotransmitter ace- That research is supported by the university, the National Insti- tylcholine. In animal models the Vanderbilt scientists have shown tutes of Health (NIH), philanthropy and, increasingly, revenues that “allosteric modulators” of M4 can “ramp up” the receptor’s from licensing agreements negotiated by the Vanderbilt Center for activity without affecting other signaling pathways. The result is Technology Transfer and Commercialization (CTTC). an improvement in cognitive impairments and behavioral distur- “If we don’t invest in the basic science, we’re not going to be suc- bances that, in humans, are associated with Alzheimer’s disease as cessful,” says Craig Lindsley, professor of chemistry and director of well as schizophrenia. medicinal chemistry in the Vanderbilt Center for Neuroscience Drug Craig Lindsley, along with P. Jeffrey Conn, Ph.D.—the Lee E. Discovery; the William K. Warren Jr. Professor of Medicine; and professor of pharmacology. “I feel schizophrenia is the scourge of all illnesses because of its devastating, vulnerable symptoms,” says William K. Warren Jr., chairman emeritus of the Oklahoma-based foundation named for his father. “Other illnesses receive a lot more attention, but we must support ‘deep biology’ research to better understand and treat this horrific illness.”

“What distinguishes Vanderbilt,” says Craig Lindsley, Ph.D., who leads the schizophrenia project, “is that drug discovery is run in parallel with basic research – ‘deep biology’ – in an effort to understand the pathophysiology of the disease down to the molecular level.”

Craig Lindsley 13 • Vanderbilt Chemistry 2014 - Brian Bachmann, associate Bachmann, Brian professor of chemistry, was attracted to Vanderbilt in 2003 from industry, and is one of about sixteen faculty investigators in VICB who have primary appointments in the Department of Chemistry. – Chemical & Engineering News, December 9, 2013 – Chemical & Engineering News, December “One of my basic assumptions is that I don’t understand too understand I don’t that is basic assumptions my of “One - Poten course. of enough, aren’t techniques screening Fancy would-be drug for at least with schizophrenia, problem The That’s why some drugs work in some patients but not innot but patients in some drugswork some why That’s in the mechanisms the right need molecules the right for “We into these advances translate to positioned well is Vanderbilt Marnett. says very a “is progress fragile scientific thing,” But “Chemistry is at the heart of translating basic basic of translating heart is at the “Chemistry in clinical into advances discoveries research Marnett, Ph.D. – Lawrence medicine.” accelerated dramatically in recent years through advances in advances through years in recent dramatically accelerated HTS facility, (HTS). screening Vanderbilt’s high-throughput 190,000 a “library” of in 2005, has Weaver David by established compounds and the ability to test tens of thousands of samples samples of thousands of tens test to the ability and compounds per day. - pro assistant Weaver, says works,” the system how about much “open-minded” tries he develop to So, pharmacology. of fessor of effects a detect unanticipated let scientists designed to assays, example. for a drug drug target, on potential animal models before in efficacysafety and show tial drugs must failed has agent a promising many and in humans, being tested the clinical trial. to got when it many. disease one but not is it cancer, like that, is discoverers, impair cognitive and behaviors, symptoms, of constellation Its ments probably results from more than one genetic mutation mutation genetic one than more from results probably ments signaling pathways and receptors, proteins, multiple affecting the brain. throughout research with new drugs be could potential “matched” If others. - them based their to “geno on respond to likely most subjects clinical trials would for rate the success makeup, genetic or type” Lindsley says. higher, be much to advances Thanks Dunlop. AstraZeneca’s agrees patients,” right within arrive may and coming, is day that genetics, in psychiatric says. decade, he the next new in to invest it continues if patients, for benefits tangible people. and facilities, technologies, exciting really some doing people of a lot got we’ve though “Even quickly.” pretty unravels it tended, isn’t … if thethings garden - Lawrence Marnett When it comes to translating basic research discoveries into into discoveries basic research translating to comes it When are which compounds chemistry at the stage is Medicinal beencompounds—has drug-like stage—identifying first The “We do really good basic science on novel targets and novel novel and targets good novel do really basic science on “We first her or his gotten has student every graduate So far, a Ph.D., Bridges, Thomas says here,” spot in a sweet “We’re - com early its of in drug discovery strength grew out Vanderbilt’s drugs work how of the study clinical pharmacology, to mitment Medi- of tothe School limited weren’t These efforts in the body. of - Chemi Institute Vanderbilt of the establishment The cine. Lawrence of cal the direction in 2002 under Biology (VICB) Biochemistry Chemistry, of and Professor University Marnett, Research, Cancer of the Mary Geddes Professor and Stahlman cross-campus, of encouragement the university’s demonstrated collaborations. multidisciplinary it,” the heart of at is “chemistry in clinical medicine, advances become new molecules make that “Chemists Marnett. says the heart at are methods analytical that drugs. develop Chemists development.” biomarker of and to, bind to ability their for tested and made, identified, mo- by followed That’s M4. like a of, target activity the affect - pharmacokinet drug and metabolism, lecular pharmacology, their potential test to pharmacology, then behavioral ics, and drugs. become to drug-discovery programs in the country. in the country. drug-discovery programs PROGRESS IS FRAGILE 33rd place in 2010 to 12th place in 2011. Today Vanderbilt has one of the top Vanderbilt place in 2011. Today 33rd place in 2010 to 12th ” catapulted from ranking in total spending on “chemical R&D Vanderbilt’s Limbird Professor of Pharmacology, who Pharmacology, of Professor Limbird neuroscience the university’s launched in 2003—and drug-discovery program the use of pioneered their have colleagues, theactivity adjust to allosteric modulators in the brain. receptors neurotransmitter of activity receptor activating Rather than dim- like work these compounds directly, induce in electrical and switches circuits mer function in receptor changes subtle more agonists. receptor seen traditional with are than says journals,” in high-profile publish we and mechanisms, 300 nearly published “we’ve During six years, the past Lindsley. program The he says. 290 patents,” filedabout we’ve and papers - in trans postdoctoral fellows and students graduate also trains the universities: most at find that can’t “You research. lational scientists.” industry-knowledgeable … be to by trained ability into go to they wanted “If a postdoc position. of choice have don’t Lindsley “We adds. jobs,” all gotten they’ve industry, work.” for looking anyone postdoc who now is and student graduate Vanderbilt former full assigned the time scientists to of team a dedicated part of … a deep under pursue can “We AstraZeneca collaboration. standing of our targets. There’s a lot of freedom in it.” in of freedom a lot There’s targets. our of standing RESEARCHHIGHLIGHTS Controversial Info Release Aids VUMC Bird Flu Research Computational Models Prove Accurate By Carole Bartoo 15 • Vanderbilt Chemistry 2014 - Some of the new computer-driven, virtual test models used virtual models test the new computer-driven, of Some of accu- a high degree have models the shown has team The the of director M.D., Jr., E. Crowe James Senior author transmissible droplet respiratory use not the did team The David Nannemann, Ph.D., earned his doctorate in 2011 work- He then ing with Professor Brian Bachmann at Vanderbilt. completed postdoctoral training with Professor Jens Meiler doing computational modeling. Nannemann at Vanderbilt is now at EMD Serono, which is a division of the German chemical and pharmaceutical group Merck KGaA (distinct from Merck & Co., USA). The Merck KGaA US research site is in Billerica, Massachusetts, outside of Boston. Nannemann is responsible for protein modeling and computational protein - design in the Protein Engineering and Antibody Technolo gies group of the New Biological Entities department, with primary focus on discovery of therapeutic antibodies. Nannemann, Ph.D., left, and Natalie Thornburg, Ph.D., are investigating left, are Ph.D., Ph.D., Thornburg, Natalie Nannemann, and the human antibodyresponse to H5N1 bird flu. This work was supported by NIH grant R01 AI106002, NIAID contract contract R01 AI106002, NIAID by NIH This wassupported work grant UL1 RR024975, NIH CTSA grant Vanderbilt the HHSN272200900047C, HDTRA1-10-1-0067. DoD grant the and in this study provide virus/antibody interaction snapshots that snapshots interaction virus/antibody provide in this study method the classical than capture easier to and be quicker may complexes. protein natural of crystallography of will it be- useful that com to out pointed he However, racy so far. as crystallography traditional with results the Vanderbilt pare with Spiller, Ben pursuing is team which the progresses, the field team. his and pharmacology, of professor assistant Ph.D., - pediatrics pathol of professor and Center Vaccine Vanderbilt of the combination said immunology, and microbiology, ogy, and the 2010 research, from critical information of the release - used labora in his highlybiotechnology the developed use of and vaccine inform to continue can this work typetory of shows exist. yet not do that pandemics even for development, treatment protein synthetic viruses they used themselves; a noninfectious the sur to sequences viral mutation added the controversial and study to laboratory Crowe the This allowed the protein. face of through in viralstructures safely mutations of the the effect tuned experiments. finely . and Nature

anderbilt University Medical Center research has has research Center Medical University anderbilt some address that results reassuring produced - influ avian of power the pandemic about fears

- antibod human that , shows Investigation Clinical of Journal “The work we did was only made possible by the publication publication by the made only possible we did was “Thework Institutes National to a home is Vanderbilt Then, because isolated we the antibodies discovered we “Fortunately, David with in collaboration team, his and Crowe sets diverse together bring approaches modeling “Hybrid down reach to able are the antibodies that show images “Our

H5N1 avian influenza virus essentially does not yet seem virus doesnot essentially influenza H5N1 avian Sept.2013, in 3, online published work, the Vanderbilt Now, - poten of community in the fears scientific stirred work The V of the controversial sequences. The publications identified the identified publications The sequences. the controversial of them engineer and back go to then able were we and mutations, antibodies if our determine to protein recombinant our into viruses,” transmissible aerosol such against be effective might Vanderbilt in the a scientist Ph.D., Thornburg, J. Natalie said Professor, Carell Scott Ann M.D., E. Crowe, James of laboratory and microbiology, pathology, of pediatrics, professor of professor the publication. of author corresponding and immunology, - Evalua and Treatment and (NIH)-funded Vaccine Health of Research Vaccine (VTEU), Vanderbilt within housed Unit tion previously participants ask to able was team Crowe’s Program, blood supply and trial H5N1 vaccine return in an to involved - they pro antibodies had of isolation for the laboratory to cells the vaccine. to in response duced also vaccine the existing with immunized subjects from - these had muta specificnew that strains neutralize would said. Thornburg tions,” in the Department a postdoctoral student Ph.D., Nannemann, of professor associate Ph.D., Meiler, Jens and Chemistry, of - Structural Biol for in the Center chemistry pharmacology, and describe to the viral/antibody approach” utilized a “hybrid ogy, interactions. tell a smallof part alone fields, which of a number from data of global a more upon inform which can a picture into the story, said. Nannemann hypothesis,” it, neutralize and to the virus bind of to area a protected into are the virus of that structure in its made the changes despite - informa important provide These findings area. adjacent in an these to new viruses, in this case the and immunity about tion said. Crowe also is reassuring,” information enza viruses (commonly referred to as “bird flu”) created in created flu”) “bird as to referred enza viruses (commonly labs. research directly only in nature, person to person from transmit to in the in 2010, scientists However, people. to birds from that found Wisconsin of the University at and Netherlands in intentionally was passaged influenza when H5N1 avian the deadly virus could ferret, to ferret from the laboratory transmissibility. aerosol acquire the during in volunteers H5N1, induced of strain thenatural ies to kill to - the poten able are testing, experimental vaccine H5N1 flu. the avian of strain laboratory-created dangerous tially more purposes led to and bioterrorist for tial this information use of publication withholding temporarily journals of step the unusual viruses - even of the transmissible The sequences the research. of in the Science journals published were tually VUMC Bird Flu Research Flu Bird VUMC Controversial RESEARCHHIGHLIGHTS

New Insights into Steroid Biosynthesis

he research of Vanderbilt Chemistry Professors B. Andes Professor Lidia Smentek received her Ph.D. in physics from N. Hess, Jr., and Lidia Smentek provides fundamental new Copernicus University, Toruń, Poland. She completed her Habili- T insight into a long-standing controversy regarding the tation in 1993 and was awarded the National Title of Professor of mechanism of one of the most intriguing biological reactions, the Physical Sciences in 2009 by the president of Poland. Professor conversion of the acyclic polyene, squalene, to an intermediate Smentek’s association with Vanderbilt goes back to 1982 when she with four fused rings, which is the backbone of all steroids. spent a year as a postdoctoral fellow in computer sciences with Previously, Hess had shown how the last ring of the four was Professor Charlotte Frose Fischer. She has held the title of adjoint formed in an unusual concerted manner starting from a three-ring professor of chemistry since 1994. She is an atomic physicist and intermediate [Hess, B.A.Jr., J.Am.Chem.Soc. 2002, 124, 10286- quantum chemist. 10287]. His was the first theoretical description of a type of reaction that has since been found by others to occur widely in nature. In the new work [Hess, B.A. Jr., & Smentek, L., 2013, Ange- wandte Chemie Int. Ed. 2013, 52, 11029-11033.], Profs. Hess and Smentek demonstrate that the first three rings are formed in a completely concerted reaction, much like closing a zipper, that leads to an intermediate, which then undergoes the reaction to form the fourth ring. Their results suggest that the major role of the enzyme in this biosynthesis is to “cradle” the squalene mol- ecule in the appropriate shape (conformation), which allows the reaction to occur. Understanding of this key biosynthetic reaction may allow the design of better drugs to thwart the biosynthesis of the steroid cholesterol in humans. Professor B. Andres Hess, Jr., received his Ph.D. from Yale Uni- versity in 1966 and joined the Chemistry Department at Vander- bilt in 1968. He served as chairman of the department from 1982 to 1994. In addition to his research, he was deeply involved in the realization, planning, and construction of the new Chemistry Building from 1992 to 1995. FACULTY

Marnett Named Associate Vice Chancellor for Research By John Howser

awrence J. “Larry” Marnett, Ph.D., support cross-institutional collaboration for Vanderbilt in 1989. the Mary Geddes Stahlman Pro- shared institutes and centers. Among the leadership positions he has fessor of Cancer Research, and He will work closely with other held since joining Vanderbilt include asso- UniversityL Professor of Biochemistry and institutional leaders on the university’s ciate director for Basic Research Programs Chemistry, has been named Vanderbilt newly unveiled strategic plan and how it for the Vanderbilt-Ingram Cancer Center University Medical Center’s next associ- will strengthen basic sciences across the from 1993 to 2002. In 2002, Marnett was ate vice chancellor for research and senior institution. named the founding director for the Insti- associate dean for biomedical sciences, “I want to welcome Dr. Marnett into this tute of Chemical Biology and has held this effective September 1, 2014. new role. Larry possesses both a distin- position since. Marnett will succeed Susan Wente, guished career as an investigator and a rich Marnett’s research focuses on the role of Ph.D., who held the position for the past tradition as someone with a passion for the enzyme cyclooxygenase-2 in cancer and five years, and was named provost and nurturing young scientists. He also brings inflammation, as well as on the contribution vice chancellor for academic affairs for a wealth of institutional knowledge and of oxidative metabolism to the generation of Vanderbilt University. proven leadership experience, essential for DNA damage and mutation. His laboratory has used structure- based approaches in conjunction with medicinal chemistry to design selective cyclooxygenase-2 inhibitors as potential anti-inflammatory, cancer preventive, and anti-anxiety agents. Marnett is a Fellow of the Ameri- can Association for the Advancement of Science and the American Chemical Society and is the author of more than 450 research publications and fourteen patents. He is the founding editor-in-chief of the American Chemical Society journal, Chemical Research in Toxicology. He has trained fourty-two Ph.D.s and fourty-nine postdoctoral fellows. “I am grateful to Jeff Balser and his senior leadership team for this opportunity,” Marnett said. “Vanderbilt is one of the top academic medical centers in the world Marnett, who is also director of the A.B. this critical role at a time that is so pivotal in comprising exceptional investigators, depart- Hancock Jr. Memorial Laboratory for Cancer our future,” said Jeff Balser, M.D., Ph.D., vice ments and centers. We are also part of a great Research, director of the Vanderbilt Institute chancellor for health affairs and dean of the university that is committed to integration of for Chemical Biology, and professor of phar- Vanderbilt University School of Medicine. basic research and education across campus. macology, has been a member of Vanderbilt’s Marnett received a Bachelor of Science The recent strategic plan establishes fostering faculty since 1989. from Rockhurst College, and a Ph.D. in transinstitutional initiatives as one of its top In his new role Marnett will support chemistry from Duke University with Ned four goals. the operations and strategic development Porter. He did his postdoctoral work at the “The opportunity to participate in of basic sciences throughout the Medical Karolinska Institute and Wayne State Univer- that effort at an institutional level and to Center, including its many programs in basic sity. He began his academic career at Wayne help build a sustainable and robust model sciences education. And in coordination State University where he rose to the position for basic biomedical research is exciting,” with the Provost’s Office, Marnett will also of professor of chemistry, before joining he said. FACULTY

Richard N. Armstrong and Jeffrey N. Johnston Receive Cope Scholar Award for Research Excellence in Organic Chemistry

Two organic chemists at Vanderbilt University are among the ten recipients of the 2014 Arthur C. Cope Scholars Award that recognizes and encourages excellence in the field of organic chemistry. The Arthur C. Cope Scholar Awards were established in 1984 by the American Chemical Society Board of Directors, under the terms of the will of Arthur C. Cope.

anderbilt’s Cope Scholar award winners are Richard N. to the erosion of efficacy of antibiotics that has become a major Armstrong, professor of biochemistry and chemistry, and public health problem. VJeffrey N. Johnston, Stevenson Professor of Chemistry. Johnston specializes in building complex organic molecules Armstrong is being recognized for his significant contribu- from scratch using purely chemical means. He has led the devel- tions to understanding detoxification enzymes that are essential opment of a novel method for chemically synthesizing peptides components in organisms’ ability to resist toxic chemicals. He that promises to lower the cost and increase the availability of has applied cutting-edge technology and chemistry to identify drugs based on natural compounds. In addition, he has developed the molecular mechanisms that several of these enzymes use to other chemical short-cuts that allow more efficient methods for metabolize foreign molecules. He has also investigated the man- synthesizing a promising new drug for Chagas disease and a novel ner in which disease organisms adapt detoxification enzymes to therapeutic being tested for its anti-cancer properties. protect themselves from antibiotics—a process that contributes

JEFFREY N. JOHNSTON Natural products with underexplored biological activity are the The Johnston laboratory specializes in reaction development and destinations, including alkaloids ((+)-serratezomine A and the target-oriented synthesis. At Vanderbilt University, his group ambiguines) and peptides. In their development of new reac- develops innovative methods for enantioselective synthesis by tions, the Johnston lab often uses the opportunity to discover and employing novel organocatalysts. These developments are tools leverage unusual reactivity. They discovered that aryl and vinyl that enable concise routes to natural products and therapeutic radicals could add to azomethine with regioselectivity opposite molecules. Collaborating with a diverse set to that observed in most every case. The resulting functionality of colleagues in biochemistry, cancer biol- was perfectly positioned to enable a highly convergent synthesis ogy, and drug development, the Johnston of indoline α-amino acids and several complex alkaloid natural lab advances the field of chemical biology by products. providing access to small molecules used to Similarly, an unprecedented amide–forming reaction was illuminate our understanding of the pathol- discovered in the Johnston lab and incorporated into a short ogy of disease, and ultimately treatments to sequence that allows the convergent preparation of amides and improve human health. peptides from non-carboxylic acid substrates. The significance of New reaction development is not unlike this development is illustrated by the enantioselective preparation paving roads through undeveloped land. of α-aryl gylcinamides, amides that normally suffer from stereo- chemical isomerization when prepared using traditional pre- chromatography. The Johnston lab developed an efficient syn- paratory techniques. Mechanistically, this reaction uniquely thesis to enantiopure (–)-Nutlin-3 employing a unique BAM 19 • achieves the reversal of polarity (German, “umpolung”) for organocatalyst. The key step involves an aza-Henry reaction Vanderbilt Chemistry 2014 the critical carbon-nitrogen bond forming step. Chemists can developed in the Johnston lab utilizing the BAM organocata- now synthesize peptides as single diasteriomers. This new lyst for the first highly diastereo- and enantioselective addi- reaction, dubbed Umpolung Amide Synthesis or UmAS, has tion of aryl nitromethanes to aryl aldimines, granting access been used to synthesize peptide candidate drugs that contain to the more potent enantiomer of Nutlin-3. non-natural amino acids which pose a problem for tradi- An Ohio native, Jeffrey Johnston received his B.S. degree tional peptide coupling methods. in chemistry (summa cum laude) from Xavier University and Stereoselective synthesis has been led by the development his Ph.D. with Leo Paquette at The Ohio State University in of a class of Bis(AMidine) [BAM] organocatalysts to achieve 1997. He was an NIH Postdoctoral Fellow at Harvard with the synthesis of stereochemically complex small molecules. David Evans prior to his independent career at Indiana Uni- The Johnston group has completed the only stereoselective versity, where he began in 1999 and was ultimately promoted synthesis of (–)-Nutlin-3, the first potent small molecule to professor of chemistry with tenure. In 2006, he moved with inhibitor of p53/MDM2 protein-protein binding. In 2004 his research group to Vanderbilt University where he is cur- Hoffmann-La Roche patented the first route to (–)-Nutlin-3 rently Stevenson Professor of Chemistry and a member of the but furnished the compound as a racemate, which was later Vanderbilt Institute of Chemical Biology. separated into the pure (–)-Nutlin-3 using supercritical chiral

RICHARD N. ARMSTRONG investiation of glutathione transferase enzymes known as Armstrong has long been interested in detoxification Membrane-Associated Proteins in Eicosanoid and Glutathi- enzymes. “I actually became interested in the detoxification one Metabolism (MAPEG). Kristin Droege is a third-year of toxic compounds from my days at NIH when I worked Chemistry graduate student investigating the chemical with Don Jerina on epoxide hydrolases. That was basically interaction and dynamics of the MAPEG protein 5-lipoxy- what got me into the detoxification chemistry. Then when I genase activation protein (FLAP) and how it allows the moved to Maryland as an assistant professor, I continued to enzyme, 5-lipoxygenase (5-LOX) to catalyze the conversion do work in the field, mostly focusing on glutathione transfer- of the fatty acid, arachidonic acid, to its product 5-hydroper- ases,” says Armstrong. oxyeicosatetraenoic acid (5-HpETE). Hydrogen-Deuterium In the laboratory, cutting-edge technology and chemistry Exchange Mass Spectrometry (HDX-MS) is a highly sensitive are utilized to identify and understand method that investigates the exchange rates of hydrogens on the molecular mechanisms of glutathione the amide backbone of an enzyme for the purpose of detect- transferases and how they interact with ing conformational changes and interactions with substrates foreign compounds. Methods include the and other proteins. These studies aim to provide a more use of three-dimensional crystal X-ray dynamic overview of how this complex interacts, leading to structures, kinetic assays utilizing NMR, novel therapeutics specific for the 5-LOX/FLAP complex. HPLC, and UV spectroscopy, as well as One other ongoing project in the Armstrong lab involves Hydrogen-Deuterium Exchange Mass the investigation of the chemical mechanism and inhibi- Spectrometry to observe conformational tion of another MAPEG enzyme, microsomal prostaglandin changes and ligand binding. E2 synthase 1 (MPGES1). MPGES1 is the most prominent One of the projects in the Armstrong prostaglandin synthase expressed during inflammation laboratory investigates FosB, a detoxification enzyme in bac- and catalyzes the conversion of PGH2 to the prostaglandin teria that results in bacterial resistance to the antibiotic fos- PGE2. It is a promising therapeutic target for the treatment fomycin. In the Armstrong lab, postdoctoral researcher Dr. of chronic inflammation and potential drug candidates have Matthew Thompson and Chemistry graduate students Mary been pursued by the pharmaceutical industry. Little is known Keithly and Michael Goodman as well as other Vanderbilt about the chemical mechanism of the enzyme, with no researchers have been investigating the structure and func- physical evidence to support it. However, glutathione (GSH) tion of the FosB enzyme from the Gram-positive pathogen appears to participate as a cofactor in the reaction. Michael S. aureus and how it interacts with fosfomycin, a broad-spec- Goodman, a second-year Chemistry graduate student, is cur- trum antibiotic. In the study, the three-dimensional X-ray rently synthesizing the serine analog of GSH, γ-L-glutamyl- crystal structure of FosB from S. aureus was determined to a L-serylglycine (GOH). This compound will be used with resolution of 1.15 Å. Along with various kinetic studies, sig- MPGES1 to investigate the kinetics of the enzyme, giving nificant insights were revealed as to how the enzyme operates further evidence to the chemical mechanism of the enzyme in the presence of particular metal ions and thiol substrates. through spectroscopic techniques. Another project in the Armstrong lab involves the FACULTY

John McLean Named Agilent Thought Leader; McLean Lab Named Waters Center of Innovation By Andrew Cognata Graduate Student, Cliffel and McLean Group

he pace of scientific innovation is ever-increasing as the A major goal of medical research in recent years has been the methodologies and instruments available to researchers identification of biological molecules that indicate otherwise obscure T continue to improve. The early adopters of new investi- disease states in patients. These molecules, called biomarkers, could gative technology are modern-day pioneers of science, finding be proteins, lipids, carbohydrates, or oligonucleotides that are all applications for these new tools that even their inventors could naturally present within a potential patient. A change in the health of not have foreseen. John McLean’s laboratory is at the forefront of the patient should be matched by a change in the concentrations of one of these wild frontiers of scientific inquiry where new meth- the many biomolecules present in the patient. If appropriate biomark- odologies, instrumentation, and applications are explored in the ers are identified, they could be used for early detection of condi- application of mass spectroscopy to biology and medicine. tions such as various cancers, infections, and toxin exposures before symptoms are presented. Aided by emerging analytical techniques, the medical community stands at the edge of potential significant breakthroughs in diagnostic science. The McLean laboratory takes a systems approach to biology. Systems biology is an attempt to understand living organisms by observing as much of the organism as possible. By monitoring many aspects simultaneously, it becomes possible to see how the diverse mechanisms of a living organism fit together and interact with one another. By developing instruments, methods, and analysis tech- niques capable of monitoring many biological molecules at once, scientists are provided with a big picture view of an organism without losing finer details. This approach requires investigators to be able to analyze samples and process data very quickly. The McLean group uses ion mobility-mass spectrometry, or IM-MS, to identify potential biomarkers in biological samples. The field of ion mobility experiments, developed in the late 1800s, is itself experiencing something of a renaissance in recent years, as improvements in technology have enhanced the technique’s power and compatibility with other devices. Because of the vast range of diseases investigated and the staggering number of unique biologi- cal molecules that must be observed for each disease, one of the Professor of Chemistry John McLean, Ph.D., and his colleagues major challenges faced by biomarker investigators is how to improve have made quite an impact with their work at Vanderbilt. Their experimental throughput to handle the huge number of samples work in the field of mass spectroscopy has led Waters Corporation, and amount of experimental data involved in the research. McLean’s a three-billion dollar developer and manufacturer of analytical research proceeds on several instruments, to name his lab a Waters Center of Innovation, indi- fronts: the development of more cating their recognition of the research group as one of the leaders versatile IM-MS instruments, in the field of health and life science research. exploration and refinement of Agilent Technologies, formerly the scientific development arm of IM-MS techniques, and stream- Hewlett-Packard, has granted McLean the Agilent Thought Leader lining the interpretation of Award in recognition of his contributions to ion mobility mass IM-MS experimental data. spectrometry (IM-MS) focused on advanced applications, includ- The use of IM-MS has advan- ing comprehensive biomolecular systems analysis and synthetic and tages over more traditional mass chemical biology. spectrometry approaches when it Vanderbilt University is also proud to recognize the achievements comes to handling large pools of of one of their own and have recently granted McLean the position samples. An IM-MS instrument of Stevenson Professor of Chemistry, one of the university’s distin- can run a sample in fractions of guished endowed chairs. a second whereas other related a single experiment. The development of new approaches

to process and understand this data is an important part of 21 •

the McLean lab’s work. Members of the lab have developed Vanderbilt Chemistry 2014 and continue to work on a wide variety of approaches to this problem. Approaches include algorithms for the classification and eventual identification of the many unknown molecules in biological samples, as well as the application of tools borrowed from astronomy and Internet data mining to allow quick visual interpretation of vast quantities of data. These techniques allow the rapid comparison of samples, for example, by highlighting which of the many analyzed molecules are more or less prevalent techniques such as liquid chromatography-mass spectrometry in a cancer patient compared to a healthy patient. require minutes to hours to complete their analysis. Reducing Computer modeling is another tool utilized by the group to the time required to analyze a sample is essential to systems biol- improve understanding of molecular structure. By comparing ogy investigations. In some cases even a few seconds per sample ion-mobility data to theoretically generated molecular struc- may still be too slow to tackle the problem of biomarker identi- tures, the lab helps determine a more comprehensive knowl- fication as the IM-MS step is often a bottleneck in multiplexed edge of how and why molecules take certain confirmations and studies in which multiple samples are prepared simultaneously. consequently why those molecules interact with other mol- This problem is being addressed through the development of ecules the way they do. an eight-channel IM-MS instrument capable of conducting The ability to replicate real-world observations is a key multiple experiments simultaneously and potentially speeding test for scientific models. An emerging application of systems up research by nearly an order of magnitude. This device will biology is the development of synthetic biological systems. The streamline investigations involving large numbers of samples, McLean group, in collaboration with Professors David Cliffel in such as in high-throughput screening of drug libraries. Chemistry and John Wikswo in Biomedical Engineering, as well The group is also preparing a variable temperature ion- as investigators at Harvard University and Los Alamos National mobility device to improve the scientific understanding of the Labs, are developing replicas of human biology for medical relationship between temperature and molecular structure. This testing. It is hoped that these “organ-on-a-chip” platforms will knowledge is expected to be extremely useful in understanding provide realistic test environments for the efficacy of medi- the interactions of various molecule classes such as the protein- cal treatments and the effects of toxic compounds. The ability ligand interactions which are responsible for the efficacy of the to build and model complex systems of multiple organs will majority of pharmaceutical compounds. be a profound milestone in human understanding of complex Development of new instruments is by no means the only biological systems. way to accelerate research. The McLean lab also excels in finding The new techniques and discoveries the lab and its many new ways to use the existing resources available to the field. In collaborators are responsible for are important advance- order to explore the theory that not only the concentration but ments in systems biology. The McLean laboratory is making also the location of potential biomarkers in the tissues is impor- significant contributions to the omics fields involved in the tant, techniques for spatial resolution of tissues have been devel- search for new biomarkers and to the process of drug discov- oped. In collaboration with Professors Richard Caprioli, Sharon ery. There can be no doubt that future developments in the Weiss, and Donna Webb and the National Research Resource research group will continue to excite the curiosity of and be for Imaging Mass Spectrometry at Vanderbilt University, the of service to the research community. McLean group is using a technique called matrix-assisted laser desorption/ionization in conjunction with a moving sample This work was supported by NIH grant R01 AI106002, NAID contract platform to perform rapid IM-MS analysis across surfaces of HHSN272200900047C, the Vanderbilt NIH CTSA grant UL1 RR024975, and the DoD grant HDTRA1-10-1-0067. entire organs or even organisms. This technique generates an atlas revealing the locations and identities of the many biomol- ecules in a sample and allows investigators to determine whether a given disease state causes unusual enrichments or depletion of potential biomarkers in specific organs with spatial resolu- tion as small as a few micrometers. The research group has also developed an application of IM-MS to analyze the surfaces of metal nanoparticles too small for microscopy studies. These particles have broad application in both medical diagnostics and treatment strategies. The final bottleneck in biomarker studies is data analysis. A single IM-MS analysis may reveal thousands to hundreds of thousands of different molecules at various concentrations and experiments may range from having dozens to thousands of samples, leading to the production of terabytes of data from FACULTY

Steven Townsend Joins Vanderbilt Department of Chemistry as Assistant Professor Although He Is Lactose Intolerant, Steven Townsend Has More than a Passing Interest in Mother’s Milk

By Alexander Geanes Graduate Student, Meiler and Lindsley Lab

s of July 1, 2014, Steve Townsend joined the faculty of also synthesized the tumor-associated antigen GM2 for use in a Vanderbilt University as assistant professor of chemistry. vaccine against ovarian cancer that recently finished first-phase A Townsend earned his Ph.D. at Vanderbilt in 2010, clinical trials. where he was a UNCF/Merck Predoctoral Fellow, under the At Vanderbilt, Townsend’s research will focus on the synthesis advisement of Gary Sulikowski. His Ph.D. thesis was entitled and evaluation of carbohydrates, proteins, and other compounds “Studies Toward the Total Synthesis of Bielschowskysin,” and found in human milk. “Our global goal is to synthesize compounds focused on the total synthesis of a member of the important that will allow us to take advantage of the benefits of human furanocembrane class of natural products, which has known milk for use in infant formula and possibly adult supplements,” anti-cancer and anti-malarial properties. He concluded his time says Townsend. When his wife became pregnant, Townsend was at Vanderbilt by spending six months in Craig Lindsley’s lab appalled when he looked into the current practice in baby feeding. synthesizing potassium channel activators and glutamate receptor “Only in the United States do the big pharmaceutical companies allosteric ligands. dominate public opinion so thoroughly that they have convinced In 2011, he began his postdoctoral work as a National Cancer most Americans that infant formula is just as good as breast milk. Institute Postdoctoral Fellow under Samuel Danishefsky at the That simply isn’t the case,” he said. “Breast milk is a complete nutri- Memorial Sloan-Kettering Cancer Center and Columbia Univer- tional source for babies that can’t be adequately replaced by any sity in New York City, where he was involved in the total synthesis other food, including infant formula.” of erythropoetin and para-thyroid hormone related protein. He The current major project in the Townsend group focuses on components of human breast milk, known as human milk oligosac- charides (HMOs), which fall under the broader term “glycocon- 23 Susan Verberne-Sutton Joins •

jugates.” HMOs are the third-largest component of human breast Vanderbilt Chemistry 2014 milk and are made up of long chains of individual sugar molecules. Vanderbilt Chemistry Faculty as Even though HMOs make up a large percentage of human milk, Senior Lecturer they are largely indigestible by humans. This interesting fact has led to research indicating that HMOs are both useful as probiotics for Susan Verberne-Sutton has joined the faculty in beneficial bacteria in the human gut and as decoys to deter harmful the Department of Chemistry as a senior lecturer. bacteria from attaching to the intestinal wall. Since these discover- In addition to general chemistry courses, she will ies, companies such as Abbott Laboratories have sought to take teach analytical chemistry as well. advantage of these biological benefits by including HMO analogs, Verberne-Sutton earned her bachelor of science known as galactooligosaccharides (GOs) in baby formulas. degree in chemistry from Southeastern Louisiana “Because human milk features some pretty complex glycans, University in Hammond, Louisiana, in 2000 and pharma attempts to mimic those structures in infant formula by a master’s degree in chemistry, with an emphasis utilizing GOs, which are easy to prepare. As you can imagine, these in inorganic chemistry, from the University of compounds are nothing like the complex compounds actually California, Davis, in 2004. While at UC-Davis, present in human milk,” says Townsend. Not only is human milk she completed a semester-long internship with chemically complex, it also differs from woman to woman, and its a start-up electronics company, Kovio, Inc., in chemical makeup varies over the course of breastfeeding an infant. Sunnyvale, California. He has begun developing novel ways for synthesizing HMOs and exploring their pro- and antibiotic properties. Verberne-Sutton taught general chemistry courses There are currently few ways to artificially prepare specific at Southeastern Louisiana University before mov- oligosaccharides, and HMOs have a highly complicated composi- ing to Nashville, Tennessee, where she worked tion. The combination of these two factors makes it difficult to as an analytical chemist for study the behavior and biological properties of specific components Environmental Science, Inc. in Mount Juliet, Tennessee, of HMO mixtures. Townsend’s group aims to help counteract this where she operated ICP-OES methodological deficiency by developing state-of-the-art methods instruments for ultra-low for assembling oligosaccharides like HMOs. “What [we want] to do detection of trace metals. is synthesize small HMOs and design methods to polymerize them, She became an instructor of in order to make better GOs,” says Townsend. The synthesized gly- chemistry and undergradu- coconjugates could then be used to study the specific effects of each ate laboratory coordinator at substance in living beings. These techniques could ultimately be Tennessee State University, used to make glycoconjugates to help control biological phenom- where she coordinated all ena such as the type and amount of gut flora in babies, and to help undergraduate teaching improve human health in general. His ultimate goal is to develop laboratories and wrote new laboratory manuals a new kind of infant formula that contains multiple HMOs that with Web enhancement for four undergraduate duplicate some of human milk’s nutritional and protective qualities. chemistry classes, in addition to teaching general The Townsend lab will also pursue projects concentrated on the chemistry courses. Verberne-Sutton joined the development of techniques for site-specific protein modifications. Division of Research and Sponsored Programs at Most of the chemical processes that occur in our bodies are per- TSU, where she purchased, installed, and trained formed by proteins. Major factors influencing how a protein does researchers on analytical equipment in the Nano- its job are post-translational modifications—modifications made to science and Biotechnology Core Facility. the proteins after they have been synthesized by our bodies. These Upon deciding to complete her Ph.D. in 2012, post-translational modifications play direct roles in many meta- she joined the Garno research group at Louisi- bolic processes; for example, modification of extracellular proteins ana State University. Verberne-Sutton’s research with sugars is necessary for cellular recognition by the immune focused on the development of a new sample stage system. Despite the impact that these modifications can have on for photocurrent measurements using scanning protein function, there are relatively few known ways to post- probe microscopy. translationally modify proteins in the lab, and these techniques are mostly restricted to specific amino acids such as lysine or cysteine. The Townsend group aims to expand these techniques to include additional amino acids. These developments will help enable site- specific amino acid modifications that could be leveraged to alter the structure and function of both natural and man-made proteins. Currently, his research team consists of John Hayes and Dorothy Ackerman, both second-year graduate students. FACULTY

Ned Porter Retires from Teaching Continues Research on Mechanisms of Free Radical Reactions and SLOS

ed Porter has been a member of the Vanderbilt Chemistry Arthur C. Cope Scholar and a Norris Award winner of the American Department since 1998, when he joined the department as Chemical Society; a C. K. Ingold Prize winner of the Royal Society N Stevenson Professor. While at Vanderbilt, he served as the (Great Britain); an NIH Career Awardee; a Humboldt Senior Fellow chairman of the Department of Chemistry from 2003 to 2009, and (Germany); and an NIH MERIT Awardee. He is a Fellow of AAAS was associate director of the Vander- and the American Chemical Society. bilt Institute of Chemical Biology Over the years, Porter spent sab- from 2003 to 2012. baticals at Cal Tech, the University In fall 2013, Porter retired from of Nijmegen (the Netherlands), the teaching, and now maintains an University of Freiburg (Germany), active research program in the The Technische Hochschule at department as research profes- Darmstadt (Germany), The Univer- sor, and gives occasional lectures sity of New South Wales (Sydney), in various graduate courses. He and The Australian National Univer- continues his research efforts with sity (Canberra). the support of grants from the His main research interests NIH and NSF and is a member of evolved from studies of mechanisms the Vanderbilt Center for Molecu- of free radical reactions, including lar Toxicology and the Vanderbilt the oxidation of lipids, to investiga-

Kennedy Center. Ned Porter has mentored more than 150 graduate students and tions of cholesterol biosynthesis Porter received his B.S. from postdoctoral associates during his career. Larry Marnett (left) was his disorders. These recent studies have Princeton University in 1965, where first graduate student, and Connor Lamberson (right) will likely be his focused on a human genetic condi- he majored in chemical engineer- last graduate student. tion called Smith-Lemli-Opitz Syn- ing; his Ph.D. in chemistry was drome (SLOS), an inborn error of from Harvard University. He joined the faculty of the Department of cholesterol synthesis. It is an autosomal recessive, multiple malforma- Chemistry at Duke University in 1969, and rose through the ranks to tion syndrome caused by a mutation in the enzyme 7-Dehydrocho- James B. Duke Professor of Chemistry. lesterol reductase, or DHCR7. It causes a broad spectrum of effects, Over the years, Porter developed and maintains active research ranging from mild intellectual disability and behavioral problems collaborations with colleagues from Vanderbilt, as well as at institu- to lethal malformations. His discoveries have identified SLOS as an tions around the world. He is the author of more than 280 publica- oxidative stress disorder and they forge a direct connection between tions and a book, Control of Stereochemistry in Free Radical Reactions; a highly oxidizable cholesterol biosynthetic precursor, 7-dehydrocho- Concepts, Guidelines, and Synthetic Applications. He has been an lesterol, and SLOS pathology.

From First to Last, Ned Porter Nurtures Scientific Excellence

Among the many accomplishments of Ned Porter in the field of in 1989. He is the Mary Geddes Stahlman Professor of Cancer chemistry research, including studies of mechanisms of free radical Research, director of the A.B. Hancock Jr. Memorial Laboratory for reactions and SLOS, Porter mentored more than 150 graduate stu- Cancer Research, director of the Vanderbilt Institute of Chemical dents and postdoctoral associates from 1969, when he joined the Biology, and professor of chemistry. As of September 1, 2014, Mar- faculty at Duke University, to present, at Vanderbilt University. nett was named associate vice chancellor for research and senior associate dean for biomedical sciences. After Porter joined the faculty at Duke, his first graduate student was Lawrence J. (Larry) Marnett. Marnett graduated from Rock- Porter’s last graduate student will likely be Connor Lamberson. hurst College in 1969, entered Duke University graduate program Lamberson came to Vanderbilt initially as a rising junior at Augus- to pursue a Ph.D. in chemistry, and chose as his mentor Ned Porter, tana College in South Dakota, through the VICB Research Experi- who had just joined the faculty at Duke as associate professor of ence for Undergraduates in the summer of 2009, and again in 2010. chemistry. Marnett received his Ph.D. in 1973. The first summer (2009), he worked with Ned Porter and Libin Xu, a research associate professor in Porter’s lab. The project involved Since then, Marnett completed postdoctoral training at the Karolin- synthesis of a specific product that was isolated from free radical ska Institute with Bengt Samuelson and joined the faculty at Wayne oxidation of the 7-dehydrocholesterol, thought to be involved in the State in 1975. He subsequently joined the faculty at Vanderbilt 25 • Vanderbilt Chemistry 2014 - Professor Tellinghuisen came to Vanderbilt University in University Vanderbilt to came Tellinghuisen Professor - ultra emphasized research early Tellinghuisen’s Professor different seventeen taught has Tellinghuisen Professor Joel B. Tellinghuisen Retires B. Tellinghuisen Joel Emeritus of Chemistry, Professor Joel Tellinghuisen earned his A.B. from Cornell University Cornell University from earned A.B. his Tellinghuisen Joel of in chemistry the University from Ph.D. his in 1965 and in did postdoctoral research 1969. He in California, Berkeley, Can- of the University at physics chemical and spectroscopy Laureate Nobel (with Chicago of terbury (NZ), the University Research a National of the support with and, Robert Mulliken) Atmospheric Oceanic and the National at Council Fellowship, Colorado. in Boulder, Laboratory Aeronomy Administration’s Chem - of in the Department professor assistant an 1975 as and in 1980 professor associate to promoted was He istry. in 1983. professor the understanding to relevant spectroscopy visible and violet widely those lasers, like now excimer of development and recently More usedlasik in surgery. eye - analy data focused statistical has he on experimental to interest methodssis of used in the life commonly methods more calorimetry titration sciences, and like chain polymerase real-time quantitative - profes his With procedures. reaction has he collaborators, student and sional papers 200 refereed than more published more given has and book chapters and work. his on presentations contributed and 200 invited than supervised in chemistry has courses and undergraduate parents appreciative The thirty by students. projects research an endowing by Tellinghuisen honored student such one of - a graduat 2003 to since each year given name, his in award outstanding of in recognition BetaPhi in senior ing Kappa research. in undergraduate performance under my belt, I see why his students have done so well for leadership and the wonderful themselves. Between Ned’s postdocs and research professors he recruits, I have rarely be solved with some critical encountered an issue that couldn’t thinking and a few well-placed questions.” He continues, “I have learned through experience that Ned has a fatherly style of teaching—all he has to do is give you ‘the look’ (which is almost perfectly replicated by Larry Mar nett during committee meetings), and you know that your even after However, attempt at science has failed miserably. my failures he continues supportive of my endeavors which truly speaks to his excellence as both an educator and a man. I am truly grateful to work with Ned for these reasons, and hope to carry on his passion for science and mentoring after leaving Vanderbilt.” of graduate studies studies graduate of years twenty-one for assistant or chair and Chemistry of chair years; sixteen for helped the found Interdisciplinary Program Graduate Science; in Materials elected the to and ScienceArts and Council and Faculty Senate. the Faculty also has servedHe the chemistry- com chairman as munity pathology of SLOS. When it came time for Lamberson to attend graduate school in 2009, Porter agreed to take Connor into his group, as his last graduate student. Connor recently published a paper in JACS (see “Graduate Student” section of this edition for more information about the of the Chemistry newsletter, research in this publication). Porter when I came to As Lamberson tells it, “I first met Dr. campus for the NSF Research Experience for Undergradu- ates. The atmosphere of his lab and the overall experience of that summer led me to pursue the next steps in my career at lab As fate would have it, I was able to join Ned’s Vanderbilt. as his last graduate student, an opportunity that I would have been hard pressed to pass up. At first it was both daunting and exciting to look at his long list of former students who have accomplished so much; now with a few years of experience Lukehart has served Vanderbilt in many different roles roles different in many served has Vanderbilt Lukehart Lukehart’s students remember him fondly, having having him fondly, remember students Lukehart’s Chuck Lukehart retired this year at the age of sixty-seven of the age at this year retired Lukehart Chuck of in the Department position professorship his from at career long His University. Chemistry Vanderbilt at - receiv after in 1973, ago years started forty-one Vanderbilt - Technol of Institute the Massachusetts from Ph.D. his ing in interested was Lukehart A. Cotton. F. ogy Dr. under metals. Since chemistry the transition of organometallic peer- 200 nearly published has he Vanderbilt, at arriving and books, three reviewed articles, edited filed six patents, students. Ph.D. M.S. and mentored Chemistry of the Department was director He career. in his of the Nashville Section of the American Chemical Society. Section Chemical the American Society. of the Nashville of Fund Endowment M. Lukehart the Charles established in 1995. He in Chemistry honor in his Study Graduate for for Science Arts Award the and 2009 College of received a three-time was he and Mentoring, in Graduate Excellence Affili- Chemical the American Society of Student recipient Award. in Teaching Excellence ates Charles (Chuck) M. Lukehart (Chuck) Charles Retires FACULTY

David W. Wright Appointed Chairman of the Department of Chemistry and Stevenson Professor of Chemistry

rofessor David W. Wright has been named chairman of the diagnostics. The other area of his research is focused on the amaz- Department of Chemistry, effective July 1, 2014. He will ing structural processing of biomaterials in nature. He is interested Psucceed Michael P. Stone, who served as chair from 2009 to in why beetle shells and butterfly wings are so iridescent, how 2014. Wright was also named a Stevenson Professor of Chemistry diatoms make their intricate glass houses, and how these lessons this spring. can lead to new and revolutionary materials for applications such as Professor Wright completed his doctoral dissertation at the biomedical sensors and next-generation batteries. Massachusetts Institute of Technology under the late Prof. Orme- Wright has received a number of awards, including the Young Johnson, where he made significant contributions toward eluci- Investigator Award from the Society of Infectious Diseases; a dating the structure of the co-factor of the enzyme nitrogenase. National Science Foundation CAREER award; and in 2011 was Subsequently, he moved to Boston College for his postdoctoral selected by the National Academy of Sciences and the Kavli Foun- research with Prof. William H. Armstrong on the structure and dation as a Kavli Fellow at the Frontiers of Science. reactivity of the oxygen-evolving complex of Photosystem II. The Stevenson Chair honors Eldon Stevenson Jr. (1893–1972), a In 2001, Wright was recruited to Vanderbilt University as assis- member of the Vanderbilt Board of Trust and president of National tant professor of chemistry. At Vanderbilt, his work is focused on Life and Accident Insurance Co. in Nashville. Generous gifts from the role of heme detoxification in the malaria parasite, leading to Stevenson helped make possible the original construction of the new approaches to drug discovery and low resource point-of-care Vanderbilt University natural science complex in the early 1960s. 27 • Vanderbilt Chemistry 2014 Cliffel currently serves standing as a currently Cliffel monolayer protected clusters. He received received He clusters. protected monolayer the Society Electroanalytical of Chemistry in 2005, Award Investigator Young (SEAC) Chemistry Committee Younger ACS an and in 2004. Award Development Leadership for the NIH Review of member Panel Medicine in Biology and Nanotechnology Board 2014, the SEAC of the end until steering two 2016, and until Directors of the Electrochemical Society for committees - electrochemis analytical and in physical - electro biological and try in organic and research current chemistry 2015. His until the electrochemistry on and concentrates and chemistryanalytical nanoparticles of has group his and proteins, photosynthetic - microphysiom the multianalyte invented toxicology. and profiling metabolic for eter Austin, working with Professor Allen J. Bard. He did his postdoc did his - He Bard. Allen J. Professor with working Austin, of the University at Murray W. Royce Professor with work toral the electrochemistry on of working Hill, Chapel Carolin, North His group applies these strategies to forefront translational translational forefront to these strategies applies group His the including awards, of a number received has McLean (1893– Jr. Stevenson Eldon honors Chair Stevenson The Chemistry and the Vanderbilt Institute of Chemical Biology. At At Chemical Biology. of Institute Chemistry the Vanderbilt and - the conceptualiza focus colleagues on and McLean Vanderbilt, structural spectrometers, mass of construction design, and tion, and synthetic, in systems, samples complex specifically targeting nanotechnology. as biologychemical well as and personalized medicine, in drug discovery, areas research his and McLean biology platforms. synthetic “human-on-chip” Vanderbilt, those with across these strengths leverage group - govern and industry, in academe, internationally and nationally, collaborations. interdisciplinary cutting-edge through ment Award Teaching in Excellence Award, Leader Thought Agilent a Chemical the American Society, of members the student from Ameri- an Award, Agency Research Reduction Threat Defense - a Spectros Spectrometry Award, Research Society Mass can for the and R&D 100 Award, an Award, Society Pittsburgh of copy GDChthe Prize from (German Chemical Bunsen–Kirchhoff others. Society), among president and Trust Board of the Vanderbilt of 1972), a member in Nashville. Co. Insurance Accident and Life National of avid Cliffel has been promoted to professor of chemistryof professor to promoted has been Cliffel avid recognizes his promotion Cliffel’s University. Vanderbilt at in the scholarship and recognized research internationally

- Steven to beenhas promoted A. McLean John rofessor University. Chemistry Vanderbilt of at Professor son the George at doctoral dissertation his completed McLean

In addition to his primary appointment in primary his to appointment addition In in chemistry a and a B.S. received He Working with David Russell from 2001 from Russell David with Working as University Vanderbilt to recruited was 2006, McLean In

field of analytical chemistry, as well as his as his well as analyticalchemistry, of field graduate and undergraduate outstanding teaching. secondary has he appointments Chemistry, with and Pediatrics of in the Department Center Training and Research the Diabetes in the a faculty is fellow He VUMC. within Biosystems Integrative for Institute Vanderbilt the of a member and Education, and Research - Insti in the Vanderbilt Committee Steering Engineering Science and Nanoscale of tute - Nano the Biomolecular oversees he where Facility. Laboratory structures Electrical of Bachelor from Engineering in 1992. Cliffel Dayton of the University - Fel Graduate Predoctoral NSF an received in chemistry earned Ph.D. his and lowship at Texas of the University in 1998 from

Washington University with Prof. Akbar Montaser, where he where Montaser, Akbar Prof. with University Washington spectrochemistry plasma in in contributions significant made complex of the analysis for new technologies of the development biological and radionuclide limited and performed post- he Subsequently, samples. Forschungszentrum at doctoral research Sabine J. Prof. with in Germany Jülich Texas a postdoctoral at then as and Becker, - H. Rus David Prof. with A&M University spectrometry. sell mass in biological mobility-mass ion constructed 2006, he to broad-scale of capable spectrometers biological complex extremely of analyses the basis on termed “panomics,” samples, - mobil ion Sophisticated mass. and both structure molecular of by released subsequently were spectrometryity-mass platforms manufacturers. global leading instrument scientific multiple both of the Department through chemistry, of professor assistant Promoted to Professor of Chemistry David E. Cliffel Promoted to Professor

Professor of Chemistry Chemistry of Professor Promoted to Stevenson Stevenson to Promoted A. McLean John

D P FACULTY

Craig Lindsley Wins John J. Abel Award in Pharmacology Vanderbilt University’s Craig Lindsley, Ph.D., has won the 2014 Lindsley’s award lecture, entitled “Exploiting Allosteric Sites for John J. Abel Award in Pharmacology for young investigators from Target Modulation,” was given April 28. the American Society for Pharmacology and Experimental Thera- He is the third Vanderbilt scientist to receive the award, which has peutics (ASPET). been given sixty-seven times since 1947. F. Peter (Fred) Guengerich, Lindsley, director of Medicinal Chemistry and co-director of Ph.D., won the award in 1984, and Lee Limbird, Ph.D., in 1987. the Vanderbilt Center for Neuroscience Drug “Receiving this award is a great honor and a continued testa- Discovery (VCNDD), and William K. Warren ment to the science, environment, and amazing colleagues here Jr. Professor of Medicine, was honored for at Vanderbilt that made this possible,” said Lindsley, who is also “his fundamental and transforming impact on professor of pharmacology and chemistry. Lindsley is widely rec- pharmacology, medicinal chemistry, and drug ognized as a pioneer who brought technology-enabled synthesis discovery in the fields of neuroscience and to the forefront of drug discovery chemistry. Using the technol- cancer biology.” ogy platform he developed, he has discovered and developed The award, named for ASPET’s founder, high-quality novel compounds in multiple therapeutic areas, from was presented to Lindsley on April 26, 2014, cancer to neuroscience, and pioneered the medicinal chemistry of during ASPET’s annual meeting in San Diego. allosteric modulation.

American Society for Mass Spectrometry Sandra Rosenthal Named Winner of Recognizes Richard Caprioli for 2014 SEC Faculty Achievement Award Distinguished Contributions Sandra J. Rosenthal, Jack and Pamela Egan Professor of Chemistry at Vanderbilt, is a recipient of the 2014 SEC Faculty Achievement Richard M. Caprioli was awarded the 2014 ASMS Award for a Award. These annual awards recognize a faculty member from Distinguished Contribution in Mass Spectrometry for the develop- every Southeastern Conference university who demonstrates ment of MALDI Imaging Mass Spectrometry and its application to outstanding records of teaching, research, molecular mapping of tissues in biology and medicine. and scholarship. Caprioli’s work led to a new paradigm for molecular imaging To be eligible for the SEC Faculty of tissues, founded on the development of matrix assisted laser Achievement Award, a professor must be desorption ionization (MALDI) imaging mass spectrometry. This a teacher or scholar at an SEC university; is now a burgeoning application of mass spectrometry whereby have achieved the rank of full professor molecular measurements can be made directly from tissues, add- at an SEC university; have a record of ing significantly to the information that can extraordinary teaching; and have a record be obtained from these specimens. of scholarship that is recognized nationally This work has made significant contribu- and/or internationally. tions to the study of proteins, lipids, metabo- “The 2014 SEC Faculty Achievement lites, and pharmaceutical compounds. Since Award winners are some of our nation’s most accomplished publication of Caprioli’s seminal 1997 paper instructors, researchers, and scholars,” Jay Gogue, president of (Anal. Chem. 69(23), 4751-4760) showing the Auburn University and president of the Southeastern Confer- power of MALDI imaging mass spectrometry ence, said. “It is my great pleasure to preside over an intercollegiate for tissue analysis, he has pioneered advance- athletics conference that not only recognizes their work, but strives ments in sample preparation, instrumenta- to support it as well.” tion, and informatics approaches that have “These…professors positively represent the breadth and depth considerably advanced the technology and made it accessible to of education in the Southeastern Conference, and I want to con- hundreds of laboratories worldwide. gratulate each of them,” SEC Commissioner Mike Slive said. “The The impact of his work is evident in the numerous commercial commitment to their students, universities, and communities is platforms that employ this technology. Approximately 2,500 papers truly commendable.” have been published to date on the subject of MALDI imaging Selected by a committee of SEC provosts, the SEC Faculty mass spectrometry. Achievement Awards and the SEC Professor of the Year Award are Caprioli is the Stanford Moore Chair in Biochemistry, profes- part of SECU, the academic initiative of the Southeastern Con- sor of chemistry, and director of the Mass Spectrometry Research ference, which sponsors, supports, and promotes collaborative Center at Vanderbilt University. higher education programs and activities involving administrators, faculty, and students at its fourteen member universities. 29 • Vanderbilt Chemistry 2014

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While working on her postdoc Uri Banin at in Israel with Dr. Hebrew University of Jerusalem, Macdonald and Banin discovered a new type of hexagon-shaped nanoparticle that, when photo- graphed from above, resembled the six-pointed Star of David, a centuries-old Jewish symbol. “It made quite a sensation in the scientific world at the time,” Macdonald said with a chuckle. “Many had a lot of fun that a laboratory in Israel made this discovery.” - the Alice Interdis Leach of student Ph.D. and Macdonald Her research group has been synthesizing nanoparticles of a of nanoparticles been has synthesizing group research Her Nano Star of David absorbs sunlight very strongly. The vision is that by addingby is that vision The very sunlight strongly. absorbs be can used metal the sunlight as particle, to of pieces reactive fuels. green make that reactions chemical energy drive to Vander Science at in Materials Program Graduate ciplinary Their in May. laboratory Banin’s to Jerusalem to travelled bilt the new how the of details will there discover experiments energy. that to happens what and light absorb nanoparticles of atoms large. Her aim is to solve problems in solar energy in solar problems solve to is aim Her large. atoms of different more or two have that nanoparticles with capture particle. the same on connected materials types of Disulfide which Copper Indium callednew material Wurtzite ticles, tiny bits of solids that are only hundreds or thousands or hundreds only are that solids of bits tiny ticles, - to conduct collaborative collaborative conduct to

previous winner of the Berg of winner - previous

Memorial Award from the United the United from Award Memorial

ssistant Professor Janet Macdonald recently travelled travelled recently Macdonald Janet Professor ssistant accept to D.C., in Washington, Embassy the Israeli to the Bergmann

Macdonald’s research focuses on the synthesis of nanopar of the focuses synthesis on research Macdonald’s - col promotes that institution is a grant-awarding BSF The a grant with comes award The

research on hybrid nanoparticles with Professor Uri Banin Uri Professor with nanoparticles hybrid on research a University, the Hebrew from mann Award in 1997. Macdonald worked with him previously him previously with worked in 1997. Macdonald Award mann in Jerusalem. postdoctoral position two-year her during

States-Israel Binational Science Foundation (BSF). Said Yair Yair Said (BSF). Science Foundation Binational States-Israel give annually “We the BSF, of director executive Rotstein, scientist a young to Award the Bergmann Memorial out proposal…[Macdonald’s] research an exceptional who offers energy use in clean is its and nanotechnology into research very exciting.” scien- applied basic and of in a wide range research laborative between agreement an by in 1972 established tific disciplines, BSF’s The Israel. and States the United of the governments $100 of endowment an on interest from derived is income the United in equal parts by established which was million governed is organization The governments. Israeli and States five and American five of consisting Governors a Board of by governments. their respective by appointed members, Israeli The Israel. Jerusalem, is in operations of base BSF’s The promising for young the award Award, Bergmann Memorial - Profes honor 1976 to in February established , was scientists one and chemistry researcher organic Bergmann, an E.D. sor the BSF. the who leaders established of A Janet Macdonald with BSF board members Shlomo Dr. Wald (left) and Michael Dr. Crosby (right) at Award Ceremony Award for Young Scientists from the BSF from Scientists Young for Award Receives Bergmann Memorial Memorial Bergmann Receives Macdonald Janet GRADUATESTUDENTS

Alternative Methods of Drug Delivery By Benjamin Spears, Graduate Student, Harth Lab

he realm of medical research is inundated with individ- exceedingly hydrophobic. The underlying issue which prevents uals whose sole goal is to formulate a single novel idea these cures from being readily utilized today lies in the inher- T that may somehow shape the way future generations ent desire of the human immune system to destroy any entity relate to the diseases that plague the human race. However, it deemed foreign to the body. This dynamic system, which has has been seen time and again that nature has a way of creating evolved as a defense mechanism against disease, can wreak therapeutics so robust and effective that they easily outstrip havoc on the therapeutics which have been found efficacious as most synthetic medical remedies. Furthermore, many of the treatments for many serious ailments that attack one’s health. most effective synthetic and natural product molecules are Whether this limitation arises from the rapid removal of the 31 • Vanderbilt Chemistry 2014 From the treatment of chronic hepatitis and types of types of and hepatitis chronic of the treatment From Ben Spears expects to receive his Ph.D. in 2015. He is from Pearl, Mississippi. poly(glycidol) polymers, protein polymer conjugates were were conjugates polymer protein polymers, poly(glycidol) serum.resulting bovine The from albumin using formed - attach confirm polymer to characterized were conjugates species, polymer and the attached size of as well as ment validate performed to were measurements dichroism circular structure. three-dimensional the protein’s of the retention their bioactivity. for tested species were the conjugate Finally, done studies to similar comparable were obtained results The the at aimed is research PEG-basedwith Future structures. - conju glycidol-protein relevant biologically of formulation and pharmacokinetics their in vivo of the study and gates time. circulation of the production of stimulation to leukemia lymphocytic a dramatic had have proteins blood PEGylated cells, white devastating the most of some of the treatment on impact increased with system, analogous an of diseases. advent The to lead even can that avenue an is potential, modification is done being research The options. beneficial treatment more the most combating new methods of towards step exciting an today. world deadly our diseases plaguing Caitlin; McQuade, Julian; R.; Waksal, Benjamin Spears, - polyg of branching M. Controlled Eva Harth, Laura; Lanier, via a bioconjugates protein-glycidol of formation and lycidol arms. Chem. Commun. “PEG-like” with approach -from graft 2013, 49, 2394. - can a viable time as some been for has studied Glycidol methodfor notable the first of discuss the formulation We of newof class this the effect study to order In - physi in in solution remain to inability an or therapeutics alternative the same: is the solution ological conditions, be created. deliverymethods must of analogous Its systems. small molecule convoy form to didate glycol) poly(ethylene implemented the currently to structure secondary primary and of abundance its as well as (PEG), and oxidatively is that a system provides groups hydroxyl exceedingly and biocompatible, nontoxic, thermally stable, dendrimer-like of single-step formation The hydrophilic. dendrimers of the abilities maintain that macromolecules, growth, dendrimer of process the painstaking without those interested from the attention of much garnered have - mono AB2 latent The poly(glycidol). of in the formation control additional for allows glycidol of characteristic mer a rampant than rather polymerization a step-wise through mechanism the usual reaction which is polycondensation, of capability The seen type AB2 other monomers. with this AB2 characteristic suppress to monomer the glycidol success to the contributed has opens the ring after until the allows added This control polymers. glycidol-based of other of the benefits maintain to poly(glycidol) synthesized with macromolecules while affording systems hyperbranched more much lower, 1.5 and of (PDIs) indices polydispersity observed other greater with 5 or of the PDIs than manageable has in thissuccessfulbeen field Work AB2 type monomers. in varying systems, poly(glycidol) hyperbranched in forming controlled and (PDIs) indices polydispersity low sizes, with very could These systems (DP). polymerization of degrees den- multistep to alternatives as advantageous become well drimer species. Thesenovel poly(glycidol). semibranched of the formation unachievable hitherto motion of a range afford architectures branched a exhibit structures species. the dendritic The by - applica biological for be to advantageous shown backbone, possess. Although do not systems which the linear tions, the through formed previously systems the hyperbranched the applicability, some shown have glycidol of polymerization - branch of degree a controlled with polymers form to ability will systems branching These lower advantageous. is ing “fuzziness” system’s hyperbranched of the the benefits retain reactions. subsequent of a wider range while for allowing will this secondary ability that reaction hypothesized is It robust the already to versatility of degree a greater impart in increase post-modifica This - architecture. poly(glycidol) the synthesized of will the viability increase capability tion macromolecules. novel for allow and systems polymer GRADUATESTUDENTS Using Deuterated Fatty Acids to Combat Oxidative Stress 33 • Vanderbilt Chemistry 2014

- in the oxida role a key play been to has TMP suggested - hydro the reactive of one of the removal radical through lipid molecular thisradical Once formed, is the PUFA. on atoms gen radical. These a peroxyl form add in to rapidly can oxygen another abstracting by the reaction radicals propagate peroxyl a lipid generating PUFA, a neighboring from hydrogen reactive of radical. Buildup lipid centered a new carbon and peroxide with associated is health and to detrimental is these peroxides α-tocopherol as such Antioxidants above. listed the pathologies inhib- radical, effectively the peroxyl to atom a hydrogen donate the propagating eliminating by reaction the peroxidation iting lipid of levels the overall time reducing species the same while at tocopheryl onformed newly go The radicals formed. peroxides another or tocopherol moleculeof another with terminate to radicalchainthe halting free effectively radical in solution, in human as such certain under conditions, However, reaction. used in our the conditions and (LDL) lipoprotein low-density ini- to tocopheryl enough experiments, survive radicals can long acting a pro-oxidant. as oxidation, chain of round another tiate TMP. or peroxidation is called tocopherol-mediated process This lead eventually can which LDL, human of modification tive core a lipid itself contains particle LDL The atherosclerosis. to - phos various and linoleate cholesterol of mainly consisting When α-tocopherol. of levels appreciable with along pholipids, oxidative of external source some by particle hit is the LDL radicals peroxyl As initiated. is process the peroxidation stress, atoms hydrogen donate begins to α-tocopherol form, start to LDL, In the peroxidation. halt to theseto attempt species in an periods the tocopheryl long of radical survive can for however, even- radical terminate, to another encountering time without - mol lipid another from atom a hydrogen abstracting tually the free propagates and α-tocopherol regenerates ecule. This modifica - furthering the thus oxidative reaction, radical chain only not indicate high The particle. KIE values the LDL of tion their than oxidizable less much are PUFAs the deuterated that powerful forces molecular also that but counterparts, natural tocopheryl by abstraction atom hydrogen during work at are an the theory plays TMP that radicals, further reinforcing and the of LDL modification in the oxidative role important atherosclerosis. of onset eventual - Founda Science National the from by a supported was grant research The CHE-1057500). (NSF NAP tion to Rafael Montenegro-Burke, graduate student in the McLean Lab that is being is that trong scientific attention has has to been the directed free attention scientific trong polyunsaturated of peroxidation) (or radical oxidation has the process since years in recent (PUFAs) acids fatty Ned Porter’s lab has looked into the perceived “protective” “protective” the perceived into looked has lab Porter’s Ned above the results abundant, naturally is α-tocopherol Since a carbon-centered generate reactions peroxidation Typical Due to the limited success of antioxidant therapies, a new therapies, antioxidant of success the Due limited to Fatty Acids in Tocopherol-Mediated Free Radical Chain Oxidations Fatty Acids in Tocopherol-Mediated Shchepinov, McLean, J. A.; Clarke, C. F.; Bekish, A. V.; V.; Lamberson, C. R.; Xu, L.; Muchalski, H.; Montenegro-Burke, J. R.; Shmanai, V. N. A, J. Am. Chem. Soc. 2014, 136, 838. M. S.; Porter, Effects of Deuterium Reinforced Polyunsaturated Unusual Kinetic Isotope Effects of Deuterium Reinforced Polyunsaturated by mea- done is This PUFAs. bythese deuterated afforded effects deuterated and natural for peroxidation of constants rate suring kinetic calculate isotope to able are these we values Using PUFAs. oxidizability the relative us gives (KIE), which ultimately effects Values PUFA. the deuterated to compared PUFA the natural of with 7. Our initial experiments than less typically KIE are for 10, around KIEs of in measured resulted PUFAs the deuterated less ten-fold some were these compounds that demonstrating antioxidants when no counterparts their natural than reactive present. were in the presence oxidations to the study broaden to us spurred as these reached experiments for KIE values α-tocopherol. of in the KIEs measured the previous higher than high 36, far as are what this is the case, and Why antioxidant! an of absence the implications? pursued by our collaborators is to replace the reactive hydrogen hydrogen the reactive replace to is collaborators our by pursued a heavy is Deuterium atoms. deuterium with PUFAs of atom freevia remove to difficult more much and hydrogen, of isotope strategyhas The peroxidation. during radical species generated a with yeast of treatment example, in one success: seen recent the of resistance increases PUFAs deuterated of small percentage these that shown has report Another stress. oxidative to yeast model in a mouse also neurodegeneration diminish compounds disease. Parkinson’s of been associated with a variety of human pathologies, such as such pathologies, human been of a variety with associated neurodegenerative and exposures, heart disease, environmental disease. disease Parkinson’s and Alzheimer’s as such disorders being the E (α-tocopherol Vitamin as such antioxidants Natural these peroxidation of inhibitors excellent are component) main of consisting clinical therapies However, in solution. reactions diseases with with associated in patients treatment antioxidant been underwhelming. have peroxidation in vivo peroxidation lipid diminish to strategy By Connor R. Lamberson, Graduate Student, Porter Lab Student, R. Graduate Lamberson, Connor By S Oxidative Stress Oxidative GRADUATESTUDENTS

Norie Sugitani Unravels New Details about DNA Repair in Skin Cancer NA molecules are constantly exposed to endogenous and XPA mutations located at the putative DNA binding region lead exogenous toxins. These toxins can give rise to about a to accelerated aging and neurological disorders, suggesting the Dmillion molecular lesions per cell per day in humans. importance of XPA-DNA interaction in human NER. Although DNA repair mechanisms are thus important for maintaining ge- XPA has been extensively studied for more than twenty-five years, nomic health. Nucleotide excision repair (NER) is a type of DNA the structural basis for its binding to DNA is not well understood. repair mechanism specialized to remove bulky DNA lesions from A putative DNA-binding domain (DBD) was initially assigned the genome. Defects in NER result in Xeroderma pigmentosum to residues 98–219 of XPA (XPA98-219) (Kuraoka et al. Mutat Res (XP), a spectrum of disorders characterized by hypersensitivity to 1996). Subsequently, the solution NMR structures of a globular sunlight and dramatically increased rate of skin cancer. There is domain within XPA98-219 were determined (Ikegami et al. Nat currently no cure for XP. Understanding of the molecular details Struct Biol 1998 and Buchko et al. Nucleic Acids Res 1998) and of human NER can potentially aid in the development of treat- chemical shift perturbations induced by binding of a 9-nt ssDNA ment for XP. However, the process of dissecting details of human oligomer were measured (Buchko et al. Nucleic Acids Res 2001).

NER had been slow as this is a multi-step mechanism involving However, we found that XPA98-219 lacks full DNA-binding activity more than thirty proteins. as compared to full-length (FL) XPA. Detailed sequence analysis XPA is one of the proteins involved in human NER. XPA led us to generate a series of C-terminally extended constructs. serves as a scaffold for NER, interacting with several other NER XPA 98-239, containing twenty extra residues, was identified as most proteins as well as the DNA substrate. The critical importance stable of these and bound DNA substrates with the same affinity of XPA is underscored by its association with the most severe as FL XPA. We also show via NMR analysis that some of the extra clinical phenotypes of the genetic disorder XP. Especially, those C-terminal residues are likely to be directly involved in DNA

binding. Together, we redefine XPA98-239 as XPA DBD which can now be used for structural investigation of XPA-DNA interaction to aid in the understanding of human NER. Sugitani, N., Shell, S. M., Soss, S. E., Chazin, W. J. (2014) “Re-defining the DNA-Binding Domain of Human XPA.” JACS. 136 (31), 10830–3. Grants which supported this research include R01 ES1065561 (NIH); P01 CA092584 (NIH); P30 ES00267 (Vanderbilt Center in Molecular Toxicology); P30 CA068485 (Vanderbilt-Ingram Cancer Center).

Norie Sugitani is a fifth-year graduate student in Walter Chazin’s lab. 35 • Vanderbilt Chemistry 2014 Aspirin and other non-steroidal anti-inflammatory drugs anti-inflammatory non-steroidal other and Aspirin inhibition COX-2 that several years been for has known It knew everything we know to was thought there “We - in Chemis student graduate a former Hermanson, Daniel applications of activating endocannabinoids by substrate- by endocannabinoids activating of applications treating pain, relieving including inhibition, selective COX-2 cancer. colon preventing possibly and disorders, movement either blocking by inflammation and pain relieve (NSAIDs) - which pro enzymes, (COX) the cyclooxygenase both of or prostaglandins. pro-inflammatory duce selec- Because the “substrate endocannabinoids. also activates - endocan increase Vanderbilt at developed inhibitors tive” prostaglandin blocking without in the mouse levels nabinoid - the gastroin think (they) “we have will not production, other side effects that cardiovascular possibly and testinal Mary and Professor University Marnett, said do,” NSAIDs Research. Cancer of Geddes Professor Stahlman we when ago years five about until inhibitors) (COX-2 about The added. he selective inhibition,” the substrate discovered “is powerful a really team the Vanderbilt used by approach drugs.” of design generation the next help to way of the paper. author first was try, The three-year-long study was supported by National Institutes of Health Health of Institutes National by wassupported study three-year-long The HL096967, NS064278, DA031572, CA089450, GM015431, grants MH065215. HL109199, MH063232, NS078291 and - , M.D., Ph.D. , M.D., If the “substrate-selective” COX-2 COX-2 the “substrate-selective” If inhibitors developed at Vanderbilt also Vanderbilt at developed inhibitors side effects, without in humans work to a new approach they represent could disorders, mood anxiety and treating Clinical trials concluded. the researchers drugs these could potential of some of and elsewhere in the body, and there is there and in the elsewhere body, and in a wide a role theyevidence play that - pathologi and physiological of range modulating to in addition cal processes, anxiety. and stress hemically modified inhibitors of the COX-2 enzyme enzyme of the COX-2 hemically modified inhibitors natural activating in mice by behaviors anxiety relieve side gastrointestinal without “endocannabinoids” in August 2013. in August

Endocannabinoids are natural signaling molecules that molecules signaling that natural are Endocannabinoids system in gastrointestinal the found also are receptors These other potential pursuing are scientists Vanderbilt The

effects, Daniel Hermanson, Ph.D., reported in Nature Ph.D., Hermanson, Neuro effects, Daniel , Ph.D., , Ph.D., Marnett begin Lawrence said several in the next years, Chemical Biology of and Institute the Vanderbilt of director Patel Sachin with author co-senior the paper’s science - recep the same in the brain, receptors cannabinoid activate in marijuana. ingredient the active by on turned tors Dan Hermanson,Dan Ph.D. New Way to Treat Anxiety Treat to Way New Vanderbilt Scientists Discover Potential Potential Discover Scientists Vanderbilt C GRADUATESTUDENTS

Christine Markwalter Wins Prestigious NSF Graduate Research Fellowship Christine Markwalter, a second-year graduate student, knew she allowance for tuition and fees, and opportunities for international wanted to devote herself to a medically oriented chemical re- research and professional development. search career when her husband, Daniel, now Markwalter’s project employs aptamers—short, single-strand- a medical student at Vanderbilt School of ed oligonucleotides capable of recognizing nearly any class of Medicine, suffered severe complications from target molecule with high affinity and specificity—as molecular Rocky Mountain spotted fever in 2012. The recognition elements for diagnostic tests. She has proposed a Graduate Program at Vanderbilt caught her novel aptamer selection protocol designed to select two aptamers eye because of its focus on medically relevant with distinct binding sites against a single target. The NSF GRFP chemical research that positively impacts award provides Markwalter the opportunity to develop a fluores- populations around the globe. Particularly cent aptamer sandwich assay on magnetic particles to detect hu- interested in the diagnosis of infectious man secretory immunoglobulin A (h-SIgA), a biomarker for fecal diseases, Markwalter joined Professor David contamination of drinking water. Wright’s laboratory, where her initial research In addition, Markwalter will be working on diagnostic tests focuses on developing a robust and affordable diagnostic test for for complications of pregnancy, including preeclampsia and malaria using Plasmodium lactate dehydrogenase as a biomarker. chorioamnionitis, using protein and microRNA biomarkers. This This year, Markwalter was awarded a National Science Founda- research has the potential to improve outcomes for at-risk preg- tion Graduate Research Fellowship (NSF GRF), a three-year sup- nancies in both developing and developed nations through early port package, which includes a $32,000 annual stipend, education detection and intervention.

Graduate Student Gabriel LeBlanc Steven Combs, Ph.D., Awarded Eli Lilly Participates in SciFinder Future Leaders Innovation Postdoctoral Fellowship in Chemistry Program Steven Combs, Ph.D., working with Associate Professor of Last fall, Gabriel LeBlanc participated in the SciFinder® Future Chemistry Jens Meiler, and Sergey Tsukanov, Ph.D., work- Leaders in Chemistry Program. This competitive travel grant ing with Jeff Johnston, Stevenson Professor of Chemistry, have program included graduate students and postdocs from across received an Eli Lilly Innovation Fellowship. The Lilly Innovation the world. The participants learned about the inner workings Fellowship Award (LIFA) program was created to identify and at Chemical Abstracts Services (CAS) and made recommenda- foster exceptional postdoctoral scientists pursuing ground- tions for future products. They were additionally provided the breaking research projects. The LIFA program pairs postdoctoral opportunity to present their research at scientists with their academic mentors and Lilly scientists, who the national ACS conference in Indianapo- serve as industry mentors, to advance innovative research pro- lis, Indiana. There, LeBlanc presented his posals developed by the fellows. The goal of the LIFA program thesis research conducted under the guid- is to focus on research topics or “Grand ance of Professor David Cliffel. His work Challenges” that will drive innovation focused on an interdisciplinary project that in scientific areas of greatest strategic looks to integrate materials directly from interest to Eli Lilly and Company, while nature into next-generation solar energy remaining general enough to foster dis- technologies. Working with a number of ruptive innovation. Fellowship awardees collaborators, LeBlanc discovered that cou- typically work at both their academic in- pling an efficient protein from photosynthesis with semicon- stitutions and at a Lilly research site, with ductor electrodes provided an incredible boost in the current access to Lilly scientists and technologies, that could be generated from these devices. Other work from to advance their research plans. this same research team has led to faster and less expensive Combs entered the Graduate Program device fabrication methods. in Chemistry in 2008, joining Jens Meiler’s research group. He At the conference, LeBlanc also met his current postdoc- received his Ph.D. in May 2014. toral advisor, Delia Milliron. Now at the University of Texas at Austin, LeBlanc is working with nanostructured materials and composites for battery and smart window applications. 37 • Vanderbilt Chemistry 2014 2013–2014 Master of Science Dain Bridgeon Beezer Holly Marie Carrell Nina Renee Collins 2013–2014 Ph.D. Graduates Ph.D. 2013–2014 Doody Amanda Blane of the Tridecapeptide Synthetic Pursuit Alkaloid and the Manzamine Feglymycin Kauluamine Jay Garrett Forsythe for Imaging Mass Spec- Advanced Strategies Spectrometry trometry and Ion Mobility-Mass Daniel John Hermanson of Cyclooxygen- Substrate-Selective Inhibition Probe Develop- ase-2 Molecular Determinants, Effects ment and In Vivo Kelly Marie Hines of Disease via Ion Biomolecular Signatures Mobility and Mass Spectrometry Techniques Gabriel Adrien LeBlanc I Biohybrid Electrodes Based on Photosystem for Solar Energy Conversion Marta Wieslawa Szulik Oxidation of Cytosine in DNA Steven Combs Identification and Scoring of Partial Covalent Interactions in Proteins and Protein Ligand Complexes Oleg Kovtun - Probing Ensemble and Single-Molecule Behav ior of Cocaine-Sensitive Dopamine Transporter with Antagonist-Conjugated Quantum Dots Ian Roys Olmsted - Investigating Biochemical Interactions Rel evant to Human Health Using Backscattering Interferometry Michael Lawrence Schulte Application of Organocatalysis to the Synthe- sis of Pharmaceutically Relevant Scaffolds: Chiral Aziridines and B-Fluoroamines; Total Synthesis of Stemaphylline and Discovery of Selective Par4 Antagonists Artez Sims Laurant Development and Application of Dendritic Intracellular Delivery Systems for Targeted - - Noah OrfieldNoah The seminar featured eight panels panels eight featured The seminar biomolecular engineering, public policy public engineering, biomolecular society. health, and medicine, and studies, whom of many speakers, nineteen with covered Speakers alumni. Vanderbilt are science U.S. the history as of such topics the federal budget technology policy, and in policy coalitions of the role and process, making. Several also addressed panels of the value as such topics career-oriented - pro societies fellowship and professional Education in the STEM sciences in the STEM Education conference congressional in a mock participated Students a from came workshop Vanderbilt originalthe for ideaThe Darwin Fu bilt University Office of Federal Relations FederalRelations of Office University bilt D.C. October 16-17, 2014, in Washington to explain designed was workshop The policy federal STEM and demonstrate and - the stu introduce and advocacy processes, sector and government potential to dents considered not had many careers related existed. know didn’t or thinking of a methodical way provides complex of the breakdown allows that The solutions. look for to policy questions postdoc to - undergraduates from ranged participants student study, of academic fields twenty represented and scholars toral phar neuroscience, engineering, environmental including and chemical engineering, biomedical chemistry, macology, career and Hill, Capitol on the working experiencegrams, of in science policy advocacy and opportunities - science-relat many funds that bill the spending for committee role-played participants the simulation, part of As ed agencies. set that agreement an produce to legislators senior the part of year. the coming for policy and priorities levels funding Association the American run by and created program similar Science. of the Advancement for Noah Orfield (Rosenthal Group) and Darwin Fu (Meiler and Darwin (Meiler Fu Group) Orfield (Rosenthal Noah with participated both students, Chemistry graduate Group) Federal in the first students Vanderbilt other twenty-four the Vander by organized Program Advocacy and Policy STEM and and Orfield Noah Students Graduate Fu ParticipateDarwin STEM in Federal Workshop and Advocacy Policy UNDERGRADUATESTUDENTS From Vanderbilt Chemistry to Combatting Bioterrorism Around the World

By Sandra Ford

“My job is to design an overall bioengagement ave you considered applying your scientific training to a career with the U.S. government? Well, neither had strategy for a particular country, identify projects Samantha Arnett when she graduated from Vanderbilt or activities that advance BEP’s mission, and then Hwith a B.S. in 2002. Now, at thirty-four years old, she works at the go find the implementation experts.” U.S. State Department in the Biosecurity Engagement Program (BEP), which aims to keep terrorists and/or unstable governments from making or acquiring weapons of mass destruction. Obviously, you don’t instantly go from being an undergrad at Vanderbilt to the BEP Deputy Team Chief and Program Officer for Iraq and South Asia at the State Department. Arnett graduated from Vanderbilt University in 2002, with a B.S. in chemistry, having done undergraduate research in the lab of Michael P. Stone, Ph.D. in physi- cal chemistry, DNA damage and repair. She then entered graduate school at Johns Hopkins University, where she earned a Ph.D. in bio- organic chemistry in 2008 in the laboratory of Dr. Craig Townsend. While working toward her doctorate, she made time to volunteer with a local HIV testing clinic, which brought her to the realiza- tion toward the end of graduate school that she wanted to use her scientific skills to pursue her interest in the HIV field and infectious diseases. Her postdoc was at The Scripps Research Institute in the laboratory of Dr. Dennis Burton, where she integrated her knowledge of bio-organic and protein chemistry with the field of HIV vaccine development. During her postdoc, she began exploring careers outside aca- demia. and applied for the American Association for the Advance- ment of Science and Technology Policy Fellowship, which is a highly competitive program that provides accomplished U.S. scientists and engineers the opportunity to contribute to the federal policymaking process, while learning firsthand about the intersection of science and policy. Arnett explains, “Scientists in the STEM sciences are sought after for the way they think, their stepwise approach to prob- lem solving, and their ability to synthesize large amounts of informa- tion quickly…We need scientists in government positions to ensure that government policymaking and implementation are informed by the best available science. Scientists, and engineers, are imperative to addressing global policy issues such as climate change, national security, and global food security.” The selection process for the fellowship introduced Arnett to a wide range of “alternative” career opportunities in the U.S. govern- ment where she could potentially utilize her scientific knowledge, method of problem solving, and analytical rigor away from the bench and laboratory. She was selected for (and accepted) a Program Officer position in the Department of State’s Bureau of Interna- tional Security and Nonproliferation’s Office of Cooperative Threat Reduction (CTR). CTR programs—the Biosecurity Engagement Program (BEP), Chemical Security Program (CSP), and Partnership for Nuclear Security (PNS)—are aimed at reducing the threat posed 39 • Vanderbilt Chemistry 2014

As for the future, Arnett thinks she has found found thinks has she Arnett the future, for As and personal safety and security are pivotal for for pivotal security and are personal safety and very the State with closely I work in-country. BEP Security Regional well as as Office Department’s working are we ensure to Allied Forces and U.S. possible. securest conditions and the safest under communication open and close coordination My - cre to me allowed securitywith have personnel - the parame within programs our implement atively on security situation changing the constantly of ters to me allowed have relationships These the ground. - imple build-in to programs our tailor proactively our mission to achieve order in flexibility mentation of circumstances.” confining even in the most says, and security sector, in the national niche her - diplo background, scientific my applying enjoy “I national to focused and disposition nature, matic always more than one answer, always more than one answer, Arnett’s expertise in Arnett’s her for it easier makes background scientific her Additionally, satisfying experience been, most has her what asked When identify a number of pos- of identifynumber a - explana approaches, sible solutions. or tions, and biology, chemistry, her disease infectious helps advance and develop to the prevent to efforts - biologi of weaponization Furthermore, cal material. molecular of knowledge her and microbiology biology, in her designvaccine puts help to position a unique dual-use the that risk reduce purposes. nefarious for expertise exploited technology and are partners. scientific trust international build with and to relate to a strong initiate to able was “I examples: the following gave She a helping by Asia in Southeast a laboratory with relationship I gained occasion, another on And plates. Agar pour technician by Asia in South director a laboratory respect of the trust and for had broken been that machine a PCR calibrating and fixing particularly skills these are laboratory of Neither several years. as me credibility they do but give level a scientific on impressive verbally to able especially not scientist, when I am a laboratory barriers.” language to due communicate on the ground built relationships the identifies quickly Arnett zone “is a war continues, she “Afghanistan,” in Afghanistan. science of the intersection at working security I like issues. hands-on, more in gaining interested security am and and technical experience in the field.” - - and this is true beyond the bench as well.”

“As scientists, we are taught that there is “I have worked on both biological and chemical security chemical and both biological on worked have “I As you might expect, no two days, two weeks, two months, months, two weeks, two expect, days, might two no you As split usually are abroad travels “My - politi and a diplomatic From by terrorist organizations or proliferant states seeking to acquire acquire seeking to states proliferant or organizations terrorist by destruction expertise, (WMD) mass and of material, weapons Arnett fellowship, two-year her of theconclusion At equipment. continues she a full-time in CTR where position offered was that programs of the implementation overseeing and developing fruition. to a WMD comes the that risk reduce I am “but, Arnett, continues time in CTR,” my during issues bioterror of the threat reduces BEP team. the BEP on formally - bio dangerous potentially to access terrorist preventing by ism expertise, dual-use infrastructure and logical while materials, disease enhance infectious and to combat efforts supporting I Officer, a Program As health worldwide. animal and public - design country-specificpro to partner with countries work enhance practices, management biorisk strengthen that grams coopera- support and disease control, infectious and detection other and terrorist prevent to development and research tive dangerous potentially to access gaining from actors non-state is approach our and Each country different, is agents. biological - politi and diplomatic culture, unique each country’s by shaped science capacity.” biological and the U.S., with cal relationship one remember “I Arnett. been for the same have years two or bal to - in D.C. suit a business from me took that year last week She says. she a headscarf in Afghanistan,” and bodylistic armor a bud- to fix day working all after evening Friday on a D.C. left officials. After for senior material briefing draft and issue get one flight, wing fixed contract one flights, commercial two military with convoy, movement a ground and ride, helicopter Afghanistan, Kandahar, of province in the southern arrived she afternoon. Tuesday on - the implementa between overseeing activity reduction threat a BEP of tion country part host - with meeting and and design of identification The ners. efforts collaborative activities are BEP liter We partner countries. our with Ministry with down officials,ally sit technicians, field scientists, laboratory law health officials, public and animal - biologi and personnel, enforcement of identify areas to cal professionals our co-develop and interest mutual activities.” bioengagement in some works BEP cal standpoint, her forces world which inthe countries difficult the most of her credits She solving. problem creative of do a lot to team and situation any analyze to ability her with training scientific UNDERGRADUATESTUDENTS

Research Is Shaping the Undergraduate Experience By Sandra Ford s college-bound students interested in a career in the CalTech in August 2014, which will be submitted for publication as STEM sciences or medicine look at institutions they part of a larger study in the Macdonald lab. Mast graduated in May Amight attend, an important factor has become the pros- 2014, and is now a graduate student at Georgia Tech. pect of working in a scientific and/or medical laboratory as part of their undergraduate experience. Those who choose Vanderbilt SUMMER RESEARCH EXPERIENCE often do so on the strength of the research programs and the pos- FOR UNDERGRADUATES sibility of getting hands-on experience in a lab. Such experiences Each summer, undergraduates from across the country come enhance their graduate school or medical school applications, and to Vanderbilt to work in one of the numerous REU (Research teach them to work independently in a lab and to have owner- Experience for Undergraduates) programs. Programs include the ship in their projects. One thing Vanderbilt does particularly well Vanderbilt Institute of Chemical Biology (VICB) REU Program, is enable students to engage in research that crosses traditional Summer Science Academy, Vanderbilt Undergraduate Summer disciplinary lines. Research Program, Vanderbilt Institute of Nanoscale Science and Chemistry majors work alongside fellow undergraduates, Engineering Program REU, as well as Summer Internships in graduate students, and postdocs in the labs of Chemistry faculty. faculty labs. At the conclusion of the ten-week program, a poster With access to state-of-the-art research facilities, they are able to session is held with all programs participating. carry out their own independent research projects, while getting VICB REU hands-on experience in the lab. Doing research bridges the gap During the summer of 2014, students from outside Vanderbilt partic- between something being very theoretical and academic, and ipated in the Vanderbilt Institute of Chemical Biology REU program: something more practical and real. Vanderbilt provides them with an intersection between those two experiences. Vanderbilt is both a top 25 research university and a top 25 undergraduate institution: with Vanderbilt Chemistry ranking twelfth in R&D funds from national research foundations. In addition to working in a chemistry research lab during the school year, Vanderbilt also offers summer research experiences for Vanderbilt undergraduate students, as well as undergrads from other colleges and universities. Some of the programs are described below.

BECKMAN SCHOLARS PROGRAM Arnold O. Beckman, founder and chairman emeritus of Beck- man Instruments, Inc., represents nearly a century of outstanding scientific achievements. Considered one of the top five inventors VICB REU students (l to r) Gabriel Pajares-Hurtado, Corey Hayford, (l to r) Lidalee Silva, Amanda Clark, and Kari Stratton. of scientific instruments, Dr. Beckman cre- ated devices that revolutionized the study and understanding of human biology, ultimately • Amanda Clark from the University of Central Michigan saving countless lives around the world. worked with Gary Sulikowski on the synthesis of oxidative The Beckman Scholars Program, funded by metabolites of curcumin. the Arnold and Mabel Beckman Foundation, • Corey Hayford from the University of Texas at Austin worked provides scholarships that contribute signifi- with Carlos Lopez on mathematical modeling of progressing cantly in advancing the education, research through the mammalian cell cycle. training, and personal development of select • Gabriel Pajares-Hurtado from Georgia Tech worked on oxida- students in chemistry, biochemistry, and the tive stress propagates methylglyoxal generation via inhibition of Beckman Scholar, biological and medical sciences. The sustained, Laura Mast glyoxylase in the lab of Larry Marnett. in-depth undergraduate research experiences 1 and comprehensive faculty mentoring are unique in terms of pro- • Lidalee Silva worked on the development of a catch and gram scope, content, and level of scholarship awards ($17,600 for two release diagnostic platform for the malarial biomarker PfLDH summers and one academic year). in David Wright’s lab; she came from the University of Puerto This past year, Laura Mast participated in the Beckman Scholars Rico at Aguadilla. Program in Chemistry, doing research with Professor Janet Macdon- • Kari Stratton worked with Ned Porter’s research group on ald. One of her projects involved synthesizing CuInS2 nanocrystals. determining the propagation rate constants of biosynthetic She presented her research at the Beckman Scholars Conference at precursors to cholesterol. She attends Texas A&M. TN SCORE REU and materials lab, where she observed the antioxidant properties As part of the grant awarded through the National Science of tea by using nanoparticles. In the summer of 2013, she con- 41 •

Foundation’s Experimental Program to Stimulate Competitive ducted research for Marcelo Sousa’s structural biochemistry lab Vanderbilt Chemistry 2014 Research (EPSCoR) Research Infrastructure Improvement at the University of Colorado Boulder. She investigated the inter- Program of Fall 2010, the TN SCORE (Tennessee Solar Con- action of proteins within the beta-barrel machinery complex to version and Storage Using Outreach, Research, and Education) better understand fundamental cellular processes. grant includes funding for Summer Research Experiences for This summer at Vanderbilt University, Castillo worked Undergraduates. The research focus of TN SCORE is specifi- with a group of undergraduates in Janet Macdonald’s materi- cally advanced solar conversion and innovation, components als science lab. Their role was to understand the electronic and devices for energy storage and con- properties of the new surface chemistry of quantum dots. version, and nanostructures for enhancing “I really enjoyed my summer here at Vanderbilt,” said energy efficiency. Castillo. “Not only is the campus beautiful, but also Nashville Lucas “Louie” Thal began his foray itself is so beautiful. I was impressed with their attentiveness into the field of science with a passion and the sense of community within my lab and the chemistry for the search for renewable energy. He is department… Researching at Vanderbilt opened my eyes to now an undergraduate senior at the Uni- what it would be like as a grad student at their school. Get- versity of Tennessee, Knoxville, working ting that inside look from the grad students and my mentor towards a dual chemistry and BCMB reassured my decision to apply to grad school to pursue a degree. This summer, Thal was invited Ph.D. in chemistry. I am looking forward to hopefully calling Lucas Thal to do research with David Cliffel as a Vanderbilt my new home.” TN-SCORE REU student. Thal’s project focused on a new solar energy concept in which solar cells ENHANCING DIVERSITY IN are being integrated with the ever-abundant plant protein GRADUATE EDUCATION (EDGE) Photosystem I. More specifically, Thal worked to improve the Vanderbilt’s goal of recruiting and retaining talented young photosystem I film orientation in biohybrid solar cells. This scholars in the STEM sciences from underrepresented groups research project could not have been a better fit, as he was is charged to the EDGE office, and Assistant Dean Don C. able to employ techniques and knowledge gained from his Brunson, Ph.D. These efforts are based experience as a research assistant under biologist Barry Bruce on the university’s sincere desire to at UTK, whose research is also centered around Photosystem provide underrepresented students with I applications in solar conversion. This interdisciplinary expe- access to the tools necessary to reach rience enabled him to tackle problems in his summer project their professional goals, while creating a from both biological and chemical angles. In his final year diverse learning community for all of our at UTK, Thal will return to the Bruce Lab where he hopes to students. begin research on Photosystem I crosslinking. Afterwards, One of the programs that EDGE Thal plans to attend graduate school in a chemical biology Jordan Rhodes sponsors is the VU-EDGE PhD Pre- visited Vanderbilt Ph.D. program geared towards renewable energy. VU Recruitment Event. In fall 2013, last fall as part the Graduate Program in Chemistry of the VU-EDGE LEADERSHIP ALLIANCE Recruitment Event; was introduced to Since 1992, the Leadership Alliance has encouraged students he chose to join the seniors Jade Bing from groups traditionally underrepresented in the sci- Graduate Program and Jordan Rhodes, ences, engineering, social sciences, and in Chemistry for both from Rider graduate school in humanities to pursue research careers in fall 2014. University. Both the academic, public, and private sectors. applied to the Grad- SR-EIP is a rigorous ten-week summer uate Program in Chemistry, were offered research experience designed specifically admission to the program, traveled to for undergraduates interested in apply- Nashville for a second look at Vanderbilt Jade Bing is now a ing to Ph.D. or M.D.-Ph.D. programs. It in the spring of 2014, and ultimately first-year graduate student in the provides undergraduates with training accepted our offer and matriculated. Graduate Program and mentoring in the principles underly- Bing is interested in organic synthesis, in Chemistry, after ing the conduct of research and prepares while Rhodes is interested in alternative visiting Vanderbilt The Leadership them to present competitive applications energy and solar cells. as part of the Pre-VU Alliance brought Recruitment Event. Stephanie Castillo to graduate schools. to Vanderbilt for the Vanderbilt University and the Depart- “I have broadened and deepened my skills as a summer of 2014. ment of Chemistry were host to Stephanie scientist … Additionally, I learned how to adapt Castillo during the summer of 2014. She is currently working toward a B.A. in chemistry at the University to a new environment, and personally grew of Central Florida. During the school year, she had the opportu- through the experience of being immersed in a nity to work under Florencio Hernandez in his nonlinear optics new place …”— VICB REU Participant Amanda Clark UNDERGRADUATESTUDENTS

Amanda Clark Undergraduate Awards in Chemistry One of the participants in the fall 2013 Pre- VU Recruitment Event was Amanda Clark. Donald E. Pearson Award for outstanding graduat- As a junior at the time at Central Michigan ing senior majoring in chemistry, planning graduate University, she learned about the VICB NSF work in chemistry — Jennifer M. Ruddock REU internship at Vanderbilt, applied, and was accepted into the program for the sum- Merck Index Award to the outstanding graduating mer of 2014. She worked in the lab of Gary senior going on to medical school — Jennifer Sun Sulikowski on the synthesis of oxidative metabolites of curcumin. In addition to new Distinguished Undergraduate Chemistry Research research skills, this gave her an expanded opportunity to explore all Award — Alec J. Pawlukiewicz of the opportunities at Vanderbilt and the Department of Chemistry.

After her summer in the VICB REU program, Clark explained D. Stanley and Ann T. Tarbell Prize in Organic Chem- the significance that this research experience had on her life istry awarded to the graduating senior who has as a budding scientist: “In addition to conducting research, the excelled in organic chemistry, either having earned program exposed me to research in other fields, and professional the highest grades in the courses taken and/or hav- development topics during a variety of weekly seminars. I have ing done outstanding research in organic chemistry broadened and deepened my skills as a scientist by performing — Alexander J. Levonyak research outside of my home institution. Additionally, I learned how to adapt to a new environment, and personally grew through Thomas W. Martin Award for the outstanding the experience of being immersed in a new place with new peo- ple. After my time at Vanderbilt, I truly think I am more prepared graduating senior excelling in physical chemistry to enter graduate school.” — Ruidan Ma Clark became involved in research at Central Michigan during Robert V. Dilts Award for the outstanding graduating her freshman year when she joined Choon Lee’s organic syn- senior excelling in analytical chemistry — Virginia thesis lab. As a first-generation college student, she developed Ann Smith Liau strong interests in research and pursuing higher education, which led her to become a McNair Scholar at CMU. After joining Mark M. Jones Award for undergraduate achieve- the McNair Scholars Program, she completed her first summer research project on the organic synthesis of a second generation ment in inorganic chemistry — Laura G. Mast antioxidant dendrimer.

Clark’s long-term goals are to pursue doctoral training in chemistry or chemical biology at Vanderbilt. After obtaining her Ph.D., Clark Honors Thesis and Adviser: would like to pursue a tenure-track faculty position and conduct research in the area of chemistry, applied to cancer biology topics. Alexander Levonyak — Ned A. Porter, Ph.D.

Virginia Liau — David E. Cliffel, Ph.D.

Ruidan Ma — Michael P. Stone, Ph.D. Class of 2014

Laura Mast — Janet Macdonald, Ph.D. Ankerholz, Kevin Martin, Justin Donald John Mast, Laura Guilia Alec Pawlukiewicz — David W. Wright, Ph.D. Beiter, Eric Christopher Pawlukiewicz, Alec James Chandler, Dustin Pillai, Arjun Suresh Jennifer Ruddock — David E. Cliffel, Ph.D. Couch, Andrew Lanier Ruddock, Jennifer Marie Jennifer Sun — Walter J. Chazin, Ph.D. Franklyn, Lindsey Anne Sun, Jennifer Kang, June Woo Tang, Schuyler George Schuyler Tang — Lawrence J. Marnett, Ph.D. Kee, John David Wong, Jason Paul Eugene Yap — Sandra J. Rosenthal, Ph.D. Levonyak, Alexander Joel Yap, Eugene (fall 2013) Liau, Virginia Ann Smith Young, Rebecca Adair Ma, Ruidan 2013–2014 Colloquium Speakers 43 • Dr. Charles Chusuei, Middle Tennessee Dr. Joseph Parello, Vanderbilt University, “A Vanderbilt Chemistry 2014 The Chemistry Colloquium State University, “Increasing Amperometric Chemist’s Journey in Structural Biology with a

Series is a mainstay of VU Detection of H2O2 via Controlling ZnO Special Emphasis on Chromatin Structure and Chemistry, broadening Nanosized Morphology” Function, and Pharmacology” knowledge of emerging Dr. David Cliffel, Vanderbilt University, Dr. Michael Pollastri, Northeastern University, science and deepening con- “Electrochemical Nanobiotechnology: Future “Target Repurposing Accelerates Drug nections between research- Promises for Medicine and Energy” Discovery for Neglected Tropical Diseases” ers at all levels. Following Professor Stephen Craig, Duke University, Professor Jeremy Rawson, University of are 2013–2014 speakers. “Mechanochemical Remodeling: From New Windsor, “Sulfur-Nitrogen Heterocycles: Reactions to Adaptive Materials” From Radicals to Magnetism, Coordination Mitchum E. Warren Jr. Lecture Chemistry and Catalysis” Professor Daniel Nocera Dr. Bryan Dickinson, Faculty Candidate, Harvard University, “The Artificial Leaf: “Molecular Imaging and Evolution Dr. Sarah Slavoff, Faculty Candidate, Personalized Energy for 1 (× 6 Billion)” Approaches to Probing the Chemistry of “Discovery and Functional Characterization of Living Systems” Peptides Translated from Human Short Open Reading Frames” Dr. Joe Fox, University of Delaware, “Trans- cycloalkenes: Tools for Synthesis, Biology, and Dr. Steven Townsend, Faculty Candidate, Materials Science” “Target-Oriented Total Synthesis: From Small Molecules to Biologics” Professor G.B. Hammond, University of Louisville, “Does Pixie Dust Exist? Professor Rajesh Viswanathan, Case Western Rethinking the Role of Counterions in Ionic Reserve University, “Harnessing Genomes and Chemical Reactions” Building Molecules to Investigate Biosynthetic Mechanisms” Dr. Ken Hsu, Faculty Candidate, “Lipid

The Warren Lecture Committee 2014, L to R: Metabolism in the Mammalian Immune Dr. Martin Von Bergen, Helmholtz Centre Anna Bitting, Kelly Gilmore, Michael Turo, Response” for Environmental Research, “Signaling in Dr. Daniel Nocera, Noah Orfield, Dan Sprague Proteomics and the Neglected Majority” Professor Ivaylo Ivanov, Georgia Tech Bircher Lecture University, “Structurally Distinct Complexes Professor David Walba, University of Dr. John Rogers of Ubiquitin and Sumo-Modified PCNA Colorado at Boulder, “Supramolecular University of Illinois at Urbana-Champaign, Lead to Distinct DNA Damage Response Stereochemistry in Liquid Crystals: From Pico “Materials for Electronics That Can Dissolve Pathways” Projectors to the First Fluid Conglomerate to in Your Body” Organic Nanoparticles for Photovoltaics” Professor Motomu Kanai, The University Sigma-Aldrich Lecture of Tokyo, “Merging Organic Synthesis and Dr. A. Joshua Wand, University of Professor Daniel Romo Life Science with Catalysis: from Asymmetric Pennsylvania, “Recent Advances in NMR Texas A&M University, “Natural Products Catalysis to Amyloid Oxidation” Spectroscopy of Encapsulated Proteins Fueling Both Scaleable and Microscale & Nucleic Acids Dissolved in Low Synthetic Methodology to Impact Biology” Dr. Laszlo Kurti, University of Texas Viscosity Fluids” Professor Franklin Davis Southwestern, “Exploiting the Extraordinarily Temple University, “Asymmetric Syn- Versatile N-O Bond: Rapid Synthesis of Professor Donald Watson, University of thesis of Homotropinones, Tropinones, Tropanes and Cocaine Derivatives using Biaryls, Carbazoles, Aziridines and Primary Delaware, “Transition Metal-Catalyzed Sulfinimines (N-Sulfinyl Imines)” Aromatic Amines” Methods for Introducing Heteroatoms into Hydrocarbon Frameworks” Professor Andrew Link, Vanderbilt University, “Systems Analysis of Protein Professor Gavin Williams, North Complexes and Proteomes to Identify Carolina State University, “Synthetic COLLOQUIA SPEAKERS 2013-2014 Regulatory Modules in the Biological Biology Approach to Reprogramming the Dr. Erik Alexanian, University of North Networks” Biosynthesis of Natural Products” Carolina at Chapel Hill, “New Strategies for Professor Taifo Mahmud, Oregon State Dr. Willy Wriggers, D. E. Shaw & Co., “From Hydrocarbon Functionalization” University, “Mechanistic Understanding and Atoms to Living Organisms: Emergent Professor Craig Aspinwall, The University Rational Engineering of Natural Products Complexity of Multiscale Computational of Arizona, “Stabilized Lipid Membranes: Biosynthetic Pathways” Modeling” The Future of Biomimetic Sensors and Dr. Yang Zhang, University of Michigan, Separations?” “Genome-Wide Protein Structure Prediction and Structure-Based Function Annotation” 1. Liquid Helium Fill/Vent Port

2. Liquid Nitrogen Fill/ Vent Port

3. Bore Tubes of Magnet

4. Sample

5. Superconducting Magnet

6. Outer Steel Shell

7. Vacuum Space/Radiation Shields

8. Liquid Nitrogen Reservoir (75l, 14 days)

9. Liquid Helium Reservoir (78l, 23 days)

10. Cryoshims and Associated Electronics

Magnet Data: 300MHz Oxford Built 1999 Running until 2013 7.05 T, 300MHz, 39.77A

Department of Chemistry VU Station B, Box 351822 • Nashville, TN 37235-1822

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GIVING TO VANDERBILT CHEMISTRY DESIGN AND PHOTOGRAPHY VANDERBILT UNIVERSITY CREATIVE SERVICES College of Arts and Science EDITOR Office of Development and Alumni Relations SANDRA E. FORD (615) 343-3118 vanderbilt.edu/cas/giving

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