CIBA/YCC Travel Award
Amanda L Patrick
Next-generation spacecraft propellant performance and the ultimate fate of their exhuast plumes: Insights from mass spectrometry and collision-induced dissociation
In recent years, ionic liquid-based spacecraft propellants have gained a reputation as the next generation of propellants and intense research and development have gone into making this a reality. Ionic liquid systems are especially attractive targets for this application because (1) they have a low vapor pressure--making them inherently space compatible and much cheaper, easier, and safer to work with during loading and other ground activities--and (2) they are widely tunable--potentially leading to the development of a single propellant capable of operating in different types of thrusters. The two types of thrusters most commonly considered as complementary are high thrust chemical thrusters (for which hydrazine and its derivatives are the current norm) and electrospray thrusters (for which ionic liquids are already the prime candidate). Electrospray thrusters are based on the same technology and fundamental principles as analytical electrospray. When electropsray thrusters accelerate charged particles in space, a minute amount of thrust is imparted on the spacecraft in the opposite direction. Thus, electrospray thrusters allow for precision control and station-keeping. Ideally, a single ionic liquid would be able to serve as a propellant for either thruster system, depending on mission needs.While much research and development has gone into these technologies, our contribution has been in the area of evaluating the clustering and dissociation of candidate ionic liquids (with a focus on protic ionic liquid behavior due to their attractiveness as components of monopropellant chemical systems).
A second part of our work on this topic focuses on the fate of ionic liquid clusters and cations after they have been electrosprayed into the vacuum. Whereas chemical thrusters combust the fuel into small gases (e.g., carbon dioxide, water) prior to ejection into space, electrospray thrusters eject ionic liquids into space as bare ions or clusters. Given the low vapor pressure of ionic liquids clusters within a plume condensing back out on a surface is one worry and the general persistence of large organic molecules in space is another point of concern. Thus, we are investigating the breakdown pathways of ionic liquid cations in vacuum. Currently, our studies are focusing on collisional activation, but future work will also investigate the effects of photon and electron bombardment.
Michael Thomas Zumstein
Hydrolysis by extracellular enzymes and its importance for the biodegradation of polyesters in the environment
The accumulation of plastics in natural systems has become a major concern. A promising strategy to address this problem is to replace conventional, non-degradable plastics with biodegradable alternatives, particularly in single-use applications for which recycling is challenging. These applications include the use of plastics in agricultural mulch films. This contribution focusses on the biodegradation of poly(butylene adipate-co-terephthalate) (PBAT), a polyester that is marketed as a biodegradable material for mulch films. In a first set of experiments, we used stable-isotope labeling to demonstrate the biodegradation of all monomeric building blocks of PBAT in an agricultural soil. As expected, the biodegradation rate of PBAT was slower than the biodegradation rates of the free monomers. This finding demonstrated that the hydrolysis of PBAT by extracellular microbial enzymes was the rate-limiting step during its biodegradation in soil. In a second set of experiments, we therefore systematically assessed polymer- and enzyme-specific factors that control the rate of enzymatic PBAT hydrolysis. We found that both the chemical composition of PBAT as well as the accessibility of the enzyme’s active site govern this process. Furthermore, enzymatic hydrolysis was modulated by temperature – by virtue of its effects on polyester chain flexibility. Additionally, we found that when PBAT is not UV-stabilized, sunlight induces crosslinking of PBAT chains, reducing the rate of their enzymatic hydrolysis. Besides providing mechanistic insights into the biodegradation of specific polymers, this contribution will highlight the potential of novel analytical approaches to study both the enzymatic hydrolysis of polyesters as well as the biodegradation of polymers in complex environments.
High aspect ratio nanomaterials enable biomolecule delivery and transgene expression or silencing in mature plants
Genetic engineering of plants is at the core of sustainability efforts, natural product synthesis, and agricultural crop engineering. The plant cell wall is often a barrier that limits the ease and throughput with which exogenous biomolecules can be delivered to plants. Current delivery techniques suffer from host range limitations, low transformation efficiencies, toxicity, and unavoidable DNA integration into the host genome. Here, we demonstrate efficient diffusion-based biomolecule delivery into several species of mature plants with a suite of pristine and chemically-functionalized high aspect ratio nanomaterials. Efficient DNA delivery and strong transient protein expression is accomplished in mature Eruca sativa (arugula-dicot) and Triticum aestivum (wheat-monocot) leaves (Figure 1) and protoplasts. We also demonstrate a second nanoparticle-based strategy in which small interfering RNA (siRNA) is delivered to mature Nicotiana benthamiana leaves, to effectively silence a gene with 95% efficiency, and sustainable with repeated infiltrations of nanoparticle-grafted siRNA. Lastly, we demonstrate successful delivery of a CRISPR plasmid for transient Cas9 expression in Nicotiana benthamiana. Our work provides a promising tool for species-independent, targeted, and passive delivery of genetic material, without transgene integration, into plant cells for rapid and parallelizable testing of plant genotype-phenotype relationships.
Renee Bouley received her Bachelors in Science from Grand Valley State University in Michigan. From there she moved on to pursue her PhD at the University of Notre Dame in the laboratories of Shahriar Mobashery and Mayland Chang. Renee pursued the discovery of a novel class of antibiotics called the quinazolinones. Since graduating from Notre Dame she has begun a postdoctoral position at the University of Michigan in the laboratory of John Tesmer using structural biology to guide the design of selective inhibitors of G-protein coupled receptor kinases.
Discovery of new quinazolinone antibiotics for the treatment of methicillin-resistant Staphylococcus aureus
Methicillin-resistant Staphylococcus aureus (MRSA) displays broad resistance to the β-lactam class of antibiotics by expressing an additional penicillin-binding binding protein (PBP), called PBP2a, which displays low affinity to the β- lactams. The quinazolinones were discovered through in silico screening of a 1.2 million compound library against the PBP2a active site. The quinazolinones affect peptidoglycan synthesis through inhibition of PBP2a and PBP1 of S. aureus. Elucidation of the structure of PBP2a in complex with the lead quinazolinone showed binding to the allosteric site, which produced conformational changes at the active site. An initial lead quinazolinone was identified that demonstrated excellent solubility and good pharmacokinetics in mice. This compound was the result of over 60 structural variations of the initial hit compound, which allowed us to deduce a structure-activity relationship for the quinazolinones. Ten compounds were selected based on antibacterial activity to be tested for in vivo efficacy, pharmacokinetics, and in vitro cytotoxicity. Three compounds from this library, all containing carboxylic acid functionalities, demonstrated good in vivo efficacy as well as pharmacokinetics. From these variations a new lead compound was identified that shows a higher volume of distribution, more potent in vitro antibacterial activity, and efficacy in vivo.
Zachary Reinert is a postdoc at UC Irvine in the Jenn Prescher lab working on developing new bioluminescent tools for challenging imaging applications. He obtained his B.S. from UMBC and his PhD from the University of Pittsburgh under the guidance of Seth Horne.
Engineered Luciferases as Off-the-Shelf Reporters of Pathogenic Bacteria
Clostridium difficile (C. difficile) is a prolific pathogen that infects 500,000 Americans each year and causes severe gastrointestinal stress. C. difficile infection (CDI) often occurs when antibiotics disrupt protective gut microbes, enabling pathogen colonization. CDI is especially problematic in nursing homes where aged residents are frequently overprescribed broad- spectrum antibiotics that can perturb the microbiota. In addition, accurate diagnoses of CDI are challenging as they require outsourced clinical tests. The increased turnaround times for such assays often delay critical treatments and prolong patient suffering. To address these needs, we are developing point-of-care tests for CDI that are readily deployed in nursing homes. These assays comprise engineered, light-emitting enzymes (luciferases) as sensors for secreted proteases from C. difficile. In the absence of the pathogen, the luciferase remains trapped in an inactive conformation, resulting in minimal to no light emission. In the presence of the pathogen, though, the luciferase enzyme is liberated by a C. difficile specific protease and is able to produce photons. The emitted light can be detected by eye or standard cameras, enabling rapid readout of C. difficile presence.
Dr. Linh Pham joined Texas A&M University – Central Texas in 2015 as an Assistant Professor of Chemistry. Since 2007 Dr. Pham has conducted research in multidisciplinary fields, including: nano-material chemistry (quantum dots and quantum wells), magnetochemistry (single-molecule magnets and single-chain magnets) and biochemistry (HIV-1 proteases). Her teaching interests include, but are not limited to, biochemistry, analytical chemistry, inorganic chemistry and instrumental analysis. Dr. Pham is also the recipient of many awards and grants such as the University of Florida Best Teaching Award, American Chemical Society Travel Grant and Service-Learning Grant at Texas A&M University-Central Texas.
Conformational Sampling and Non-Dimer Aggregates of HIV-1 Protease Containing Darunavir Promoted Mutations
Darunavir (DRV) is a highly potent human immunodeficiency virus protease inhibitor (HIV-1 PR) that is oftentimes effective when drug resistance has emerged against first generation inhibitors. Characterization of conformational sampling, dimeric structure and stability of six HIV-1PR constructs containing DRV selected mutations were investigated. Stability of the dimeric form of HIV-1 PR is impacted by accumulations of non-active site DRV drug pressure selected mutations that generate higher-order aggregates as interrogated by dynamic light scattering (DLS), differential scanning calorimetry (DSC), spin-labeling electron paramagnetic resonance spectroscopy (EPR), circular dichroism (CD) and differential scanning fluorescence (DSF) studies. The higher-order aggregate is soluble in water and undergoes a reversible transformation to the dimeric state that is either induced by a drop in solution pH or addition of DRV or substrate analog.
Merlis P. Álvarez-Berrios
Dr. Merlis Alvarez-Berrios received a B.S. degree in chemical engineering from the University of the Atlantic in 2008 and her Ph.D. in chemical engineering from the University of Puerto Rico at Mayaguez in 2014. After completing her graduate studies, she became a postdoctoral research associate at the University of North Carolina, at Charlotte. Currently, she is an assistant professor at the Inter American University of Puerto Rico, Ponce Campus. Her research interests include target-specific drug delivery systems and the application of nanoparticles in the petroleum field.
In vitro evaluation of folic acid-conjugated redox-responsive mesoporous silica nanoparticles for the delivery of cisplatin
The use of cisplatin(IV) prodrugs for the delivery of cisplatin have gained significant attention, because of their low toxicity and reactivity. Recent studies have shown that targeted cisplatin(IV)-prodrug nanoparticle-based delivery systems can improve the internalization of the cisplatin(IV) prodrug. We hypothesized that folic acid-conjugated mesoporous silica nanoparticles (MSNs) containing cisplatin(IV) prodrug could target cancer cells that over- express the folate receptor and deliver the active cisplatin drug upon intracellular reduction. To prove this hypothesis, internalization and localization studies in HeLa cancer cells were performed using flow cytometry and confocal microscopy. The ability of MSNs to escape from the endolysosomal compartments, the formation of DNA adducts, and the cytotoxic effects of the MSNs were also evaluated. Our results confirmed that this MSN-based delivery platform was capable of delivering cisplatin into the cytosol of HeLa cells, inducing DNA adducts and subsequent cell death.
Benjamin Smith received a B.A. in chemistry from Lawrence University in 2007 and a Ph.D. from Penn State University in 2013. At Penn State, Ben completed his dissertation, "The Self-and Directed Assembly of Nanowires" under the direction of Dr. Christine Keating. After graduation, he spent one year teaching at Juniata College and is currently assistant professor of chemistry at Saint Francis University. His research interests include nanoparticles and green chemistry.
Assembling and Aligning Multicomponent Nanowires with van der Waals Forces
Self-assembly methods create ordered particle arrays by balancing van der Waals, electrostatics, and other forces naturally found within particle systems. While self-assembly is often spontaneous, scalable, and works under ambient conditions, predicting and/or controlling how particles self-assemble requires a strong understanding of particle interactions. Naturally, complex particles (particles with both shape and material anisotropy) have complex particle-particle and particle-substrate interactions. To better understand the assembly behavior of asymmetric particles and to create novel self-assembly methods, we explored the self-assembly behavior of multicomponent nanowires. We examined silica-coated, multi-cored, metallic nanowires (about 4 µm long and 300 nm in diameter). Aqueous solutions of these particles quickly sedimented to the substrate forming particle-dense arrays, which were observed through optical microscopy. To examine small changes in interparticle forces within these systems, we varied both (1) particle segment materials and lengths and (2) the surface materials and patterns. We found that differences in van der Waals interactions (even very small differences) influenced assembly greatly, specifically how particles aligned within their assembled structures. Experimental results were compared to results from Monte Carlo simulations.
Stafford W. Sheehan
Stafford Sheehan is founder and CEO of Catalytic Innovations, a start-up company commercializing molecular electrocatalyst and renewable fuel technology. Under Staff's leadership, Catalytic Innovations has developed processes ranging from the reduction of carbon dioxide to ethanol, to electrocatalytic processing of waste water for purification and reuse. He acts as the chief scientist for engineering firm Waste Hub, which is leading the plant-level engineering and commercialization for many similar technologies. He received his undergraduate degree from Boston College, and completed his PhD at Yale University specializing in physical chemistry.
Generation of Renewable Fuel using Catalytic Wastewater Electrolysis
Organic-containing waste water from manufacturing in the pharmaceutical, cosmetic, dairy, dye, adhesive, pesticide, and other industries are extremely high volume, hazardous to the environment, and energy-intensive to remediate. In many cases, they possess low pH which further complicates their treatment. Current state-of-the-art technologies to treat organic waste water use multi-step treatment which includes bio-digestion stages, which are unstable, energy-intensive, and costly. Here, we show an alternative method for organic waste water treatment using selective catalytic electrolysis. Using recently discovered surface-bound molecular electrocatalysts, which possess the stability of heterogeneous oxides and the selectivity of homogeneous molecular complexes, we are able to selectively oxidize harmful organic compounds down to ppm concentrations in aqueous environments.
Caroline R Szczepanski
Utilizing Heterogeneous Network Formation to Tune Surface Roughness: A Method to Control Coating Wettability
Caroline Szczepanski received a BS in Chemical Engineering from Lafayette College in May 2009 and a PhD in Chemical & Biological Engineering from the University of Colorado – Boulder in December 2014. During her graduate studies, she researched the design of heterogeneous polymer networks utilizing polymerization induced phase separation. Since graduating, she has taken a postdoctoral research position at the Université de Nice in Nice, France to study the development of polymer coatings and surfaces with unique surface morphologies to control wettability.
Jessica Lee Klockow
Development of a Multimodal Smart Probe for Imaging Enzyme Activity in Brain Gliomas
Dr. Jessica Klockow received her PhD in Chemistry from the University of Missouri and synthesized fluorescent molecular sensors and logic gates for the direct detection of neurotransmitters in live cells. She is currently a postdoctoral scholar in the Molecular Imaging Program at Stanford (MIPS) and is developing activatable multimodal imaging tools for brain gliomas. Her research interests involve chemical synthesis, fluorescent probes, neuroscience, and in-vivo molecular imaging techniques.
Division of Organic Chemistry
Sébastien Laulhé grew up in Venezuela, Mexico, and France. After obtaining his Master’s Degree in chemical engineering from the National Engineering Graduate School of Chemistry (ENSCM) in Montpellier, he started a Ph.D. program at the University of Louisville with Michael H. Nantz. Together, they developed new oximation reagents for quantitative high throughput GC-MS analysis of biological samples. After graduating in 2013, Dr. Laulhé became a postdoctoral associate at Duke University working with Jennifer L. Roizen. Dr. Laulhé currently develops catalysts and cross-coupling strategies.
Division of Inorganic Chemistry
Shaoguang Zhang obtained his BEn at Beijing Institute of Technology in 2008. He obtained PhD in Chemistry (Advisor: Prof. Zhenfeng Xi and Prof. Wen-Xiong Zhang) in Peking University in 2013. He started as a postdoctoral researcher (Advisor: Dr. Morris Bullock) at PNNL. His research focuses on the utilization and generation of renewable energy, especially on heterolytic cleavage of hydrogen by Mo-based complexes and electrocatalytic oxidation of alcohol by metal complexes with pendant base as functional proton relay.
Huan Liang obtained his BSc at Tianjin University in 2003, followed by PhD in Chemistry (Advisor: Professor Marco Ciufolini) in the University of British Columbia in 2010. Then he started as an NSERC fellow (Advisor: Professor E.J. Corey) at Harvard University. In 2012, he accepted an Instructor position (Mentor: Dr. Neil Vasdev) in the Division of Nuclear Medicine and Molecular Imaging, Harvard Medical School and Massachusetts General Hospital. In 2013, Dr. Liang was promoted to Assistant Professor. His research focuses on the discovery of new chemical methods, new ligands and the understanding of function of biological targets and subsequently transition new biomarkers into disease models.
Michelle L. Personick
Michelle Personick is a postdoctoral researcher working with Professor Cynthia Friend at Harvard University on the design of mesoscale gold alloy catalysts for energy-efficient chemical transformations. She received her Ph.D. from Northwestern University in 2013 under the guidance of Professor Chad Mirkin, where her research focused on controlling the shape and crystallinity of gold and silver nanoparticles. In the summer of 2015, she will be joining the chemistry department at Wesleyan University as an assistant professor.
Danielle A. Guarracino, PhD
Assistant Professor – The College of New Jersey
From 2010 to the present, Dr. Guarracino has been a tenure-track Assistant Professor at The College of New Jersey, where she has taught undergraduate classes in General Chemistry, Organic Chemistry, Biochemistry, and upper-level Chemical Biology. Her research focuses on using macrocyclic peptides as first generation therapeutics to probe protein-protein interactions, as well as artificial peptide helical structures.
Meng (Chloe) Rowland, PhD
Postdoctoral Associate – Johns Hopkins University
Meng (Chloe) Rowland is a postdoctoral fellow in the laboratory of Dr. James Stivers at Johns Hopkins University School of Medicine, working to unravel the mystery of DNA repair enzyme’s genome search mechanism. She received her Ph.D. in organic chemistry with Dr. Michael Best at University of Tennessee, Knoxville, where her research focused on developing chemical tools to characterize membrane-protein binding interactions.
Yijun Huang is a postdoctoral fellow working with Professor John D Lambris at University of Pennsylvania on the development of new generations of complement inhibitor compstatin. He obtained his PhD degree in Pharmaceutical Sciences with Professor Alexander Doemling at University of Pittsburgh (2011), where his research focused on discovery of small molecule inhibitors of p53-Mdm2 interaction. He obtained his MS degree in Chemistry from Texas Christian University (2008) under the guidance of Professor David E Minter. He also holds BS degree in Chemistry and MS degree in Organic Chemistry from Nanjing University (Nanjing, China).
Wen Zhang joined NJIT’s Newark College of Engineering in the Department of Civil and Environmental Engineering as assistant professor in 2012. Wen received his B.S from Tsinghua University in 2004, M.S. from Tongji University in 2007, and Ph.D. from Georgia Institute of Technology in 2011. His research interests are developing innovative solutions for addressing water-energy nexus challenges with state-of-art nanotechnology and environmental biotechnology.
Leslie Aldrich is a postdoctoral fellow working with Stuart Schreiber at Harvard University and the Broad Institute on the development of small-molecule autophagy modulators as tools to study the underlying biology of Crohn’s disease. She obtained her Ph.D. in synthetic organic chemistry with Craig Lindsley at Vanderbilt University, where her research focused on the total synthesis of alkaloid natural products and the synthesis and optimization of natural product analogs with anticancer activity. She began her career in organic synthesis and chemical biology with Kevin Bucholtz at Mercer University, where she synthesized potential ligands for the PPAR δ nuclear receptor.
Joseph Baker earned his B.S. in Physics in 2003 from the University of Nevada, Las Vegas. He then studied at the University of Arizona, receiving his Ph.D. in Physics in 2011. While at the University of Arizona, Dr. Baker studied computational biochemistry in the research group of Dr. Florence Tama. In Dr. Tama’s group, his interests included the dynamics of multidrug transporters and bacterial type IV pili. Dr. Baker joined the Voth group in January 2012 as a postdoctoral scholar, where he studies large protein complexes and engages in public outreach activities with the Center for Multiscale Theory and Simulation.
Benjamin J. Stokes received his B.Sc. degree from the University of Wisconsin-Madison in 2004 and completed his Ph.D. studies under the supervision of Tom G. Driver at the University of Illinois at Chicago in 2010. He began postdoctoral research with Matthew S. Sigman at the University of Utah in 2011. He is sponsored by an NIH Ruth L. Kirschstein postdoctoral fellowship.
Benjamin Yancey received a B.S. in 2007, an M.S. in 2009, and completed his Ph.D. in chemistry in August of 2011 at the University of Mississippi. His undergraduate and graduate research was focused on polymer electrolytes and their properties under Prof. Jason Ritchie. His last year of graduate studies, he worked as a research associate at the University of Alabama at Birmingham where he worked on hybrid materials applying for a patent in June 2011 under Prof. Eugenia Kharlampieva. Since September 2011 he has been a Postdoctoral Fellow at UAB under Prof. Sergey Vyazovkin.
Kristin J. Labby
Kristin Jansen Labby is currently a postdoctoral fellow in the lab of Sylvie Garneau-Tsodikova at the University of Michigan studying aminoglycoside resistance enzymes in tuberculosis. She completed her PhD in the fall of 2012 under the supervision of Richard B Silverman at Northwestern University. Her thesis work concerned mechanistic studies of nitric oxide synthase, an enzyme implicated in several disease states including neurodegeneration. During the 2011-2012 academic year, Kristin participated in Reach for the Stars, Northwestern University’s NSF GK-12 program. Kristin hopes to continue outreach opportunities throughout her independent research career.
Introducing medicinal chemistry research to middle school students: a multi-faceted approach from a GK-12 experience
The NSF GK-12 program Reach for the Stars at Northwestern University presents graduate students with the unique opportunity to serve as “scientist in residence” at a local K-12 school. This presentation details the partnership between graduate fellow Kristin Labby and Pamela Sims, a science teacher at Nettelhorst Middle School in Chicago. The GK-12 experience typically includes regular classroom visits and the design and execution of non-traditional lessons with ties to the graduate fellow’s research. Kristin and her teacher partner went beyond the classroom and culminated the academic year with a student field trip to the Northwestern campus. During their visit, students rotated through five stations, hosted by a diverse group of scientists, with hands-on activities specially designed to include aspects of Kristin’s medicinal chemistry research. This presentation will include specific examples of activities as well as general considerations for adapting such an event to other institutions.
Dustin W. Janes is a Postdoctoral Researcher with Christopher J. Ellison at the McKetta Department of Chemical Engineering at the University of Texas at Austin. Applying photochemistry in new, unexpected ways is a major theme of all of his current projects. His main focus is on creating methods to replicate block copolymer thin film patterns continuously and over large areas to enable high-throughput nanopatterning technologies. Prior to this, he earned his B.S. from Tulane University and his Ph. D. from Columbia University with Christopher J. Durning, both in Chemical Engineering. His dissertation concentrated on understanding how sorption and diffusion of small molecules in a polymer was affected by the addition of nanoparticles.
Replicating Thin Film Block Copolymer Patterns With Light Activated Chemistries
To help enable high-throughput nanopatterning technologies, a strategy to replicate nanopatterns formed by the self-assembly of lamellae-forming block copolymer (BCP) was investigated. To accomplish this, liquid compositions (i.e. conformal layers) are placed between the surfaces of the “master” poly(styrene-block-methyl methacrylate) film and transparent “replica” substrate that solidify and covalently bind to the BCP upon exposure to light. The conformal materials able to replicate the BCP pattern were comprised of a multifunctional acrylic monomer, a benzophenone compound, and a visible wavelength photoinitiator. The replication is light activated, scalable to large areas, occurs below the glass transition of the BCP, and takes less than 1 h. Scanning electron micrographs of the replica samples show that specific patterns can be copied. Control experiments conducted with alternative liquid compositions indicate that interfacial photosensitization of the BCP by excited benzophenone is the primary mechanism by which pattern replication takes place.
Max Majireck is currently a Postdoctoral Fellow at Harvard University and the Broad Institute of MIT & Harvard working with Stuart Schreiber on the development of small molecule probes for various cancer targets. Prior to this, he earned a Ph. D. in synthetic organic chemistry at Pennsylvania State University under Steven M. Weinreb working on the total synthesis of complex natural products and the discovery of new methodologies for organic synthesis. As an undergraduate student, he gained 3 years of experience in inorganic synthesis with Prof. Charles E. Kriley (Grove City College) and Ian P. Rothwell (Purdue University). In addition, he had a valuable summer research experience in chemical engineering at CONSOL Energy Research and Development investigating new technology for the reduction of mercury emissions from coal-fired power plants.
Small Molecule Inhibitors of EZH2
EZH2 is a histone methyltransferase and catalytic subunit of the Polycomb Repressor Complex-2 (PRC2) that selectively methylates histone H3 lysine 27 (H3K27), a pivotal chromatin mark that plays a key role in defining cell states and is misregulated in many human cancers. One of the primary mechanisms of oncogenesis in these cancers is thought to be caused by an overabundance of the repressive mark H3K27me3 (trimethylated H3K27) and the resultant silencing of crucial tumor suppressor genes. Very recently, non-Hodgkin lymphomas were identified containing heterozygous mutations of EZH2 at tyrosine 641 (Y641) in the catalytic domain. In these cancers, a critical wild-type/mutant EZH2 partnership is likely the key mechanism for driving H3K27 trimethylation. To test this hypothesis, we are developing the first wild-type selective EZH2 inhibitor to 1) perturb the function of wild-type EZH2 in lymphomas harboring heterozygous Y641 EZH2 mutations and 2) In collaboration with the National Cancer Institute's Cancer Target Discovery and Development (CTD2) Network project at the Broad Institute, we will evaluate this compound in 949 extensively characterized and genetically defined cancer cell lines in order to identify genetic signatures that predict sensitivity to EZH2 inhibition.
Kathleen Garber is a postdoctoral researcher with Erin Carlson at Indiana University. Her research is in the field of proteomics, where she is working on the development of chemical methods for the detection of phosphorylated proteins. She obtained her Ph.D. in chemistry with Laura Kiessling at the University of Wisconsin—Madison as an NSF Graduate Fellow. She worked on the development of a glycomimetic scaffold for targeting carbohydrate binding proteins, which she applied to DC-SIGN, a receptor involved in HIV infection. She began her career in bioorganic chemistry synthesizing fluorescent chemosensors with Scott Van Arman at Franklin & Marshall College.
Chemical tools for the selective detection of phosphorylated proteins
Protein phosphorylation is a ubiquitous posttranslational modification that regulates cell signaling in both prokaryotes and eukaryotes. The dysregulation of kinases and phosphatases has been linked to many disease processes in humans, including cancer. Accordingly, protein kinases are important drug targets in the pharmaceutical industry. Kinases have recently been identified as potential drug targets in the search for antibacterial agents. Although the study of phosphorylated proteins has made great progress in the last decade, global phosphoproteomics studies are still challenges for several reasons, including the instability of the phospho-amino acid bonds and the low abundance of phosphoproteins. These issues are particularly exacerbated when examining phosphorylation at sites other than Ser, Thr and Tyr. To address these challenges, we are pursuing the development of a chemical method capable of specifically targeting phosphorylated amino acids in order to identify phosphoproteins from complex biological samples.
Ashley Galant obtained a B.S. in Biochemistry from Denison University in Granville, OH, and her PhD in Plant Biology from Washington University in St. Louis, MO. Her graduate research focused on the characterization of the soybean thiol-redox proteome, including the crystal structure of the enzyme homoglutathione synthetase. Currently, she is a postdoctoral Research Chemist with the USDA-ARS, Citrus and Subtropical Products Unit. There, she is investigating the nanostructure and stability of the hydrocolloid pectin as a component of beverage clouds, and laying the groundwork for development of an industry-applicable rapid detection assay for monitoring product quality.
Characterization of pectin from Citrus sinensis (sweet orange) juice.
In plants, pectin is one of a group of long-chain polysaccharides that are synthesized for the purposes of maintaining cellular structural integrity. While its core element is a backbone of α-( 1,4)-galacturonic acid residues, its chemical composition can be quite variable, encompassing arabinan- and galactan- based decorations, methyl and acetyl esterification, etc. Due to its relative abundance and utility as a thickening agent, pectin is incorporated into a wide variety of food products. As in plants, the presence of different modifications can alter pectin’s rheological properties, making pectin from some sources better suited to particular applications. Globally, the majority of pectin is extracted from oranges, and while the yield and composition of pectin from orange peels have been relatively well characterized, comparatively less is known about the pectin found in processed orange juice. Here we report new insights on the chemical composition of pectin from frozen concentrated orange juice.
Professor Mindy Levine received her PhD from Columbia University, where she worked with Ronald Breslow studying the origin of homochirality. She then spent two years at MIT doing an NIH-funded post-doctoral fellowship with Professor Timothy Swager. Dr. Levine started her independent career at the University of Rhode Island in 2010, studying supramolecular organic chemistry. She currently supervises a research group of 3 graduate students and 4 undergraduate students. She has obtained numerous internal grants and travel awards to support her research group.
Synthesis of fluorescent macrocycles and polymers by click chemistry
Reported herein is the synthesis of a variety of fluorescent macrocycles and polymers via the Huisgen 1,3-dipolar cycloaddition reaction of azides and alkynes. The macrocycles are synthesized in one step from bis-alkynyl anthracenes and biphenyl bis azides; the conjugated polymers are synthesized from the same anthracene moieties and phenyl bis-azides. The resulting fluorescent molecules can be used for a variety of applications, including the fluorescent sensing of toxic polycyclic aromatic hydrocarbons and nitroaromatic explosives. Both of these sensing applications are discussed herein.
State University of New York, College at Geneseo
Simultaneous Measurement of Chargeand Fluorescence from Single CdSe Quantum Dots.
Jeffrey Peterson is currently an assistant professor of chemistry at SUNY Geneseo. He earned his PhD in chemistry from the University of Rochester working with Todd Krauss, and was a National Research Council postdoctoral fellow at JILA-NIST with David Nesbitt. His current research interests include novel multiparameter approaches to investigate single molecule phenomena, with an emphasis on nanomaterial photophysics.
Capture-and-Release of Alkynyl Peptides
Katherine Windsor is an NIEHS postdoctoral fellow with Ned A. Porter at Vanderbilt University. Her research in the field of lipid oxidation chemistry focuses on the synthesis of alkynyl-derivatized peptides and small molecules and the development of a cobalt-based capture-and-release method for these alkynyl compounds. In 2010, Katherine completed her PhD in organic chemistry with Robert J. McMahon at the University of Wisconsin-Madison, where she studied the reactivity of carbon-rich, enediyne-containing compounds. She obtained her undergraduate degree in chemistry from the University of Notre Dame, where research with Xavier Creary initiated her interest in physical organic chemistry.
Queensborough Community College
Solution-Phase Synthesis of Mg Nanoparticles for Applications in Single-Walled Magnesium Nanocomposite Materials.
TirandaiHemraj-Benny is an Assistant Professor of Chemistry in the Chemistry Department at Queensborough Community College,CUNY. She joined the department in August 2008 after spending a year and half as an Adjunct Professor in the Chemistry and Physics Department at Old Westbury College, SUNY. Dr. Hemraj-Benny received her baccalaureate degree from York College and her doctoral degree from Stony Brook University, SUNY in 2006. Her research interest involves the purification and functionalization of Single-Walled Carbon Nanotubes (SWNTs). She is also interested in increasing the learning outcomes of non-science majors in studying chemistry.
Cellular Tomography of C. alibcans and E. coli Treated with Lethal and Sub-lethal Concentrations of LL-37.
Modi Wetzler graduated with a double major in Chemistry and English for the State University of New York, Buffalo, and then received his Ph.D. in Chemistry from the University of California at Berkeley in 2007. Dr. Wetzler then began a postdoctoral research appointment with Prof. Annelise Barron at Stanford University studying the microcidal mechanisms of antimicrobial peptides and peptoids; work which he continues today as a Research Assistant Professor at Clemson University.
Mechanistic insights into the rhodium-catalyzed activation of carboncarbon single bonds
Jeff Johnson began studying chemistry as an undergraduate at Gustavus Adolphus College. Following graduate studies at the University of Wisconsin-Madison under the supervision of Chuck Casey, Jeff headed west for an NIH postdoctoral fellowship with Tomislav Rovis at Colorado State University. These experiences covered a breadth of inorganic and organic chemistry, including mechanistic analysis, the development of organic methodology and natural product synthesis. Since 2007 Jeff has been an assistant professor of chemistry at Hope College in Holland, MI. His research focuses on the mechanistic elucidation of carbon-carbon bond activation reactions and the development of transition metal-catalyzed organic methodology.
University of Arizona
Optimizing Algae for Competitive Biofuel Production
Dr. John Kyndt is a biochemist who is currently working in the field of Algae for Enhanced Biofuel production. He obtained his PhD at the University of Ghent in Belgium and is currently a Research Assistant Professor at the University of Arizona (Tucson). He has ample publications and one patent in the area of photo-sensing and signaling in biological systems. As part of continuing education he recently received an Associate certificate in Entrepreneurship from the McGuire Entrepreneurship Center (Eller College of Management, University of Arizona).
University of Missouri, Columbia
Synthesis and reactivity of Group 11 amidinate complexes
Justin was born in Albany, NY but moved to Florida in high school. He obtained his BA Chemistry from New College of Florida and did most of his undergraduate research at Lawrence Livermore National Laboratory with Annie Kersting. In 2009 he obtained his PhD from the University of California, Irvine with William J. Evans and went to Los Alamos National Laboratory to work with Richard Martin learning density functional theory. His postdoctoral studies were conducted at Texas A&M University with Drs. John Fackler, Oleg Ozerov and Michael Hall. He is now an assistant professor at the University of Missouri, Columbia.
College of William and Mary
Identification of Organic Dyes and Pigments in Oil Paints using Surface-Enhanced Raman Microspectroscopy
Kristin L. Wustholz is an Assistant Professor of Chemistry at the College of William and Mary. She received her Ph.D. in 2007 from the University of Washington studying single-molecule fluorescence in dyed salt crystals in the laboratories of Bart Kahr and Philip J. Reid. Her postdoctoral research with Richard P. Van Duyne at Northwestern University focused on surface-enhanced Raman spectroscopy (SERS) and plasmonics of individual molecules and nanoparticles. At William and Mary, her research focuses on studying the optical properties of dyes in organic-based solar cells and historical artworks.ages, and other content