Research in the Nicewicz Group focuses on developing new catalysts and methods for organic synthesis. In particular, our group seeks to harness the power of photoinduced electron transfer processes to drive the development of new asymmetric bond forming reactions. Additionally, we seek to apply these new reactions to the synthesis of biologically-active, complex natural products.
Applying lithographic fabrication techniques from the computer industry, the DeSimone Group focuses on creating nanoscale particles using the PRINT©, Particle Replication in Non-wetting Templates, technology. Developed in DeSimone's lab, PRINT© enables precise control over particle features such as size, shape, chemical composition, deformability, and surface functionality. Multidisciplinary in nature, the DeSimone Group's research shows significant promise for novel applications in both life and materials science, ranging from improved vaccines to new medicines and targeted drug delivery approaches, to particulate surfactants and colloids for emerging technologies in robotics and displays.
Assistant Professor Brian Hogan has been honored for his recent graduation from the Carolina Center for Public Service's Thorp Faculty Engaged Scholars program. Brian was one of nine members of the Thorp Faculty Engaged Scholars, FES, Class IV who worked over the past two years to strengthen partnerships between the University of North Carolina at Chapel Hill and the surrounding community.
The program, an initiative of the Carolina Center for Public Service, brings together selected faculty from across campus to engage in a two-year experiential, competency-based curriculum designed to advance their scholarship. Scholars participate in sessions in community settings to learn from Carolina faculty and their community partners and build relationships through work such as training teachers to integrate experiential learning into their classrooms. Brian is the academic director for the Scholars' Latino Initiative, a program dedicated to increasing college access for Latino high school students. He helped build "SLIence," a collaboration between McDougle Middle School and the Scholars’ Latino Initiative.
Wnt/β-catenin signaling is of significant interest due to the roles it plays in regulating development, tissue regeneration and disease. Transcriptional reporters have been widely employed to study Wnt/β-catenin signal transduction in live cells and whole organisms and have been applied to understanding embryonic development, exploring oncogenesis and developing therapeutics. Polyclonal heterogeneity in reporter cell lines has historically been seen as a challenge to be overcome in the development of novel cell lines and reporter-based assays, and monoclonal reporter cell lines are commonly employed to reduce this variability.
Published in Integrative Biology, researchers in the Allbritton Group describe how A375 cell lines infected with a reporter for Wnt/β-catenin signaling were screened over short (<6) and long (>25) generational timescales. To characterize phenotypic divergence over these time-scales, a microfabricated cell array-based screen was developed enabling characterization of 1119 clonal colonies in parallel. This screen revealed phenotypic divergence after <6 generations at a similar scale to that observed in monoclonal cell lines cultured for >25 generations. Not only were reporter dynamics observed to diverge widely, but monoclonal cell lines were observed with seemingly opposite signaling phenotypes. Additionally, these observations revealed a generational-dependent trend in Wnt signaling in A375 cells that provides insight into the pathway's mechanisms of positive feedback and self-inhibition.
Typically, diesel fuel is made from crude oil, but scientists can make high-grade diesel from coal, natural gas, plants or even agricultural waste, using a process called Fischer-Tropsch, or FT. Just about any carbon source is an option. FT Diesel is the ideal liquid transportation fuel for automobiles, trucks and jets. It's much cleaner burning than conventional diesel, and much more energy efficient than gasoline. But, FT Diesel is expensive to make and generates lots of waste.
With support from the National Science Foundation, NSF, and its Center for Enabling New Technologies Through Catalysis, CENTC, chemists from around the United States, including professor Maurice Brookhart from Carolina, are working together to improve the cost and energy efficiency of alternative fuels. CENTC scientists have invented and patented, and are bringing toward commercialization, catalysts that will convert light hydrocarbons into FT Diesel, improving the process, whether it's diesel made from traditional sources, such as oil, or alternative sources, such as biomass.
NSF: Miles O'Brien, Science Nation Correspondent; Ann Kellan, Science Nation Producer
Caitlin McMahon, a third year graduate student in the Alexanian Group, has been selected by the ACS Division of Organic Chemistry to receive a 2014-2015 Graduate Fellowship. Awardees for this highly competitive award are selected by an independent committee, and evidence of research accomplishments is an important factor in the selection process. Caitlin will travel to the 2015 National Organic Symposium to present a poster of her research.
Caitlin's research focuses on the development of metal-catalyzed organic reactions, with the goal of discovering new ways to form carbon-carbon bonds and expanding the methodology available to synthesize organic building blocks. More specifically, she has developed a palladium-catalyzed, intermolecular Heck-type reaction using alkyl electrophiles - significantly expanding the scope of the widely-utilized Heck reaction. She is currently studying carbonylative metal-catalyzed reactions, building functionalized organic molecules by forming two carbon-carbon bonds in one step under mild conditions.
The synthesis of prodrugs is a common approach to overcome drug delivery issues, including poor aqueous solubility or permeability, and to provide site-specific release. Nanotechnology can be a powerful tool to improve drug delivery, but does so by altering the biodistribution of the encapsulated small molecule. In a report published in NanoLetters, researchers in the DeSimone Group, in collaboration with a number of Centers, Institutes, and Departments here at UNC, combined the merits of both approaches to improve the pharmacokinetics and toxicity of the chemotherapeutic docetaxel by passively targeting an encapsulated docetaxel prodrug to solid tumors, where it could selectively release and convert to active docetaxel.
The Group used PRINT technology, Particle Replication in Nonwetting Templates, to prepare nanoparticles to passively target solid tumors in an A549 subcutaneous xenograft model. An acid labile prodrug was delivered to minimize systemic free docetaxel concentrations and improve tolerability without compromising efficacy.
Many central biological processes are mediated by complex RNA structures, but the higher-order interactions for most RNAs are unknown, which makes it difficult to understand how RNA structure governs function. As published in Nature Methods, a team of students in the Weeks lab have invented a new approach -- selective 2'-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP) -- that makes possible de novo and large-scale identification of RNA functional motifs.
SHAPE-MaP melds chemistry invented in the Weeks lab with readout by massively parallel sequencing to make it possible to detect structure-selective chemical reactions in RNA on genome-wide scales. SHAPE-MaP represents a "no compromises" approach for interrogating the structure of RNA, enables analysis of low-abundance RNAs, and is ultimately poised to democratize RNA-structure analysis.
At the Department of Chemistry, we feel strongly that diversity is crucial to our pursuit of academic excellence, and we are deeply committed to creating a diverse and inclusive community. We support UNC's policy, which states that "the University of North Carolina at Chapel Hill is committed to equality of opportunity and pledges that it will not practice or permit discrimination in employment on the basis of race, color, gender, national origin, age, religion, creed, disability, veteran's status, sexual orientation, gender identity or gender expression."