My research projects involve the application of fundamental physical chemistry concepts and techniques in order to answer questions of biological and biophysical significance.
We are interested in developing biocompatible probes for the detection of small amounts of DNA sequences that are found at the ends of our chromosomes. These probes include metal complexes, nanoparticles, and novel water-soluble porphyrins that are being synthesized in Dr. Valentin's lab.
We are also making nanoparticles using green methods, with the goal of using these in toxicity studies. The nanoparticles are characterized using a variety of techniques including microscopy. DNA detection experiments are being carried out using fluorescence spectroscopy and surface-enhanced Raman scattering (SERS). Another important aspect of my research is instrument development and optimization.
We use a pulsed laser to generate singlet oxygen from xanthene dyes in order to cross-link proteins on a microscope stage. Cross-linked proteins can be used as prototypes for tissue engineering and drug delivery applications.
We are also interested in generating singlet oxygen from nanoparticles for the same purpose with the added goal of measuring the amount of singlet oxygen generated as a function of various parameters.
Students working in my lab gain hands-on experience in using laser techniques, nanomaterials synthesis and characterization, and a wide range of biophysical and biochemical applications.
Our lab broadly investigates the effect coordination environment has on the reduction and oxidation properties of transition metals. This research has applications in the field of organometallic chemistry for the rational design of transition-metal catalysts that perform desired electrochemical reactions.
We are currently focused on two different types of metal complexes; those bearing either redox non-innocent ligands (NILs) or Janus head ligands. NILs contribute their own electrochemical activity to transition-metal complexes and may interfere with the assignment of metal oxidation states. NILs can also act as electron reservoirs, temporarily storing electrons and preventing first-row transition metals from adopting unfavorable oxidation states.
Furthermore, single-electron transfer can produce ligand radicals which may aid in breaking and making bonds during catalytic cycles. Janus head ligands are a class of ligands that have two sets of donor atoms oriented in opposite directions. These ligands can be used to generate complexes containing multiple metal atoms and allow us to examine the redox properties of metals in close proximity to one another.
We use organic and inorganic synthetic techniques to make our molecules then investigate their structure and reactivity through NMR spectroscopy, X-ray diffraction, UV-visible spectroscopy and cyclic voltammetry. Please visit our group's research website for more information.
My research is primarily focused on the synthetic modification of small bioactive natural products to enhance their medicinal or insecticidal properties. The ultimate goal of my research projects is the discovery and development of new compounds with potential medicinal, cosmeceutical and insecticidal applications. I currently have three active projects centered around this theme, which are highlighted below.
Cannabichromene (CBC) is a cannabinoid that is present in Cannabis, and has demonstrated anticancer, antibacterial and antifungal activities. Although CBC is structurally similar to tetrahydrocannabinol (THC), it does not have the psychoactive effects associated with THC. Our goal is to develop a library of CBC derivatives for evaluation of the potential as anticancer and antibacterial agents.
Thujone, the major component of the essential oils of white cedar, is known for its anticancer and insecticidal properties. Our goal is to synthesize derivatives of thujone for evaluation of their insecticidal effects against spiders and fruit flies. Additionally, we are performing anticancer studies on human cervical and skin cancer cells.
Carvacrol and thymol are present in the essential oils of thyme and oregano, and have demonstrated numerous biological effects including anticancer, antimicrobial, antioxidant, insecticidal and tyrosinase inhibitory activities. As a result, they are common in cosmetic preparations and also used as preservative for food. We are focused on the synthesis of a number of compounds containing the carvacrol or thymol core. Compounds are evaluated for antioxidant, tyrosinase inhibitory, antibacterial and anticancer activities. Because of the potential for cosmeceutical applications, skin cancer cells and acne causing bacteria are primary targets.
Photosynthesis is a critical process that converts solar energy into chemical energy, thereby fueling the living world. In oxygenic photosynthesis, cyanobacteria and the chloroplasts sequester light to release oxygen from water and carbohydrates. Photosystem I (PSI) and photosystem II (PSII) utilize the energy for electron transfer from water to generate NADPH. PSI is a membrane bound protein with 96 cofactors. Phylloquinone plays is important as a participant in electron transfer process. The function of phylloquinone in PSI is not fully understood. We have incorporated foreign quinones into PSI and characterized the physiological and bioenergetic aspects using a blue-green algae, Synechocystis sp PCC 6803.
A series of PSI-substituted anthraquinone samples has been characterized by kinetic back reaction (P+700/FAFB-) by a homebuilt 820nm microsecond pump probe laser system. The experiment involves exciting the sample with a laser pulse that initiates the charge separation, P700. Since there is no electron acceptor past the 4Fe4S clusters, FA/B, the electron recombines with P700+. Wild type (phylloquinone) and menB (plastoquinone) show back reaction times of 100 ms and 3 ms, respectively. PSI containing highly reducing quinones should have lifetimes slower than PhQ (>100ms).
Recently my research group has been monitoring changes during P+700/FAFB- recombination by lowering the temperature (298K - 77K). There are two branches that the electron can travel from P700 to FA/FB, the A-Branch and B-Branch. One branch is favored and results in faster electron recombination kinetics. By inserting significantly more reducing anthraquinones, we can observe the electron transfer distribution between branches. Lowering the temperature has shown that the faster branch is retarded forcing the slow branch to take the primary load. By adjusting the reduction potential in the A1 site, we can determine if the differences occur at the A1 containing anthraquinone site or at other points in the electron transfer chain.
Research in the my lab is focused on understanding the role that histones and histone variants play in epigenetic regulation of DNA-templated processes such as transcription, DNA-damage response and repair, and DNA replication. Specifically, we are interested in the histone H2A variant H2A.Z. H2A.Z is placed in distinct regions of chromatin. H2A.Z has a variety of important functions including: regulating the expression of genes, preventing the ectopic spread of heterochromatin from telomeres into the chromosome, and regulating the separation of chromosomes during cell division. Indeed, misplacement of H2A.Z leads to a number of cellular defects. There are three main areas of study in my lab: 1) understanding how the cell distinguishes between the canonical histones and histone variants; 2) understanding the mechanism(s) whereby H2A.Z is deposited onto chromatin; and 3) understanding the biological function(s) of H2A.Z phosphorylation and SUMOYlation (two novel posttranslational modifications recently found to decorate H2A.Z). To carry out this research, the we use the model organism Saccharomyces cerevisiae (baker's yeast).
Studies in my lab utilize a variety of biochemical and genetic techniques. These techniques include: manipulation of DNA to systematically introduce mutations on histones and other chromatin-related genes, genetic manipulation of yeast, isolation and purification of biomolecules, isolation of chromatinzed proteins, quantitative Western and Far Western blot analysis, affinity immunoprecipitation, reverse transcriptase polymerase chain reaction, Chromatin Immunoprecipitation, and high throughput phenotypic analysis (spotting assay).
My research is in developing molecularly imprinted polymers designed to detect low levels of specific analytes, such as pharmaceuticals and pesticides from matrices such as water, and the potential for removal of sulfur-containing compounds from diesel fuel for pollution concerns. My research has expanded to include investigation into the potential for photocatalytic degradation of common pharmaceuticals for disposal. There is potential for misuse and improper disposal of drugs left unused by patients, and therefore environmental contamination. Photodegradation of drugs by UV radiation is being studied as a convenient method to reduce the cost of disposal and the risk of improper disposal.
Two additional research projects involve analyses using spiders. The elucidation of sex pheromones in spiders is being investigated using SPME followed by GC/MS could potentially lead to the development of novel and natural pesticides against crop pests. The accumulation of heavy metals in spiders collected from brownfield sites is also being studied to determine if levels of heavy metals can provide information on the potential transfer of metals in the food chain.
Another research project is the analysis of Susquehanna River water and sediment for metals using atomic absorption spectroscopy and potentially x-ray fluorescence.
A final research project involves the development of molecularly imprinted polymers (MIPs) to detect low levels of variety of compounds including insecticides, pain killers, antibiotics, and other pharmaceuticals that are used commonly and have the potential to end up in the environment and in river water.
My research is focused on how to use interesting methodologies in organic synthesis to make new products, and how these methodologies can be used as a teaching tool for students while applying principles of Green Chemistry. One example is applying the use of microwave irradiation to enhance reactions of Frustrated Lewis Pairs, a sterically hindered combination of Lewis acid and base that are capable of breaking the bond of molecular hydrogen and serve as main-group reducing agents. These reactions, although useful, require strict environmental conditions that are not readily accessible in undergraduate settings. Applying microwave irradiation makes these reactions easier to handle, allowing more flexible reaction conditions. It also makes these reactions safer, generates less waste, and allows us to monitor reactions in real time, fulfilling several green chemistry principles.
Another aspect of my research is to develop a synthetic strategy for the total synthesis of natural products with potential biological implications. We are studying a general synthetic route for the total synthesis of lobophorol A, a recently isolated marine compound with antibiotic activity. This route will allow us to prepare similar synthetic derivatives to study their biological activities, and to evaluate structure-activity relationships of the different functional groups involved in this interesting marine compound. Several of the synthetic methods used for these syntheses include environmentally-friendly versions of known organic reactions.