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 making nanoparticles using green sources (ex. lemongrass, eucalyptus, honey from the SU Beekeeper’s Club). The nanoparticles are characterized using including light scattering and electron microscopy. We are measuring singlet oxygen, a reactive species, generated from nanoparticles, and determining ways to either inhibit or harness these species for useful applications. Singlet oxygen is being used to cross-link proteins using a laser and potentially create artificial tissue on a microscope slide. The anti-cancer properties, anti-proliferative effects and immunomodulatory effects of various nanoparticles are being tested on cell lines. Finally, these nanoparticles are being used to determine the best candidate for deactivating dyes commonly used as food coloring.
We are also looking at the interaction of quadruplex DNA sequences associated with neurodegenerative disorders (ALS, Fragile X) with neurotransmitter molecules like dopamine, melatonin and serotonin. DNA binding experiments are being carried out using fluorescence spectroscopy, surface-enhanced Raman scattering (SERS) and computational methods.
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.
My research is primarily focused on the synthetic modification of small bioactive natural products to enhance their medicinal properties. Students in my lab gain exposure to a wide range of Organic Chemistry techniques and biological assays, which include chromatography, spectroscopy, antioxidant evaluation, DNA cleavage ability and inhibition of a protein that is the target of many anticancer drugs. I currently have several active research projects, two of which are highlighted below.
The combretastatins are phenolic compounds that have been isolated from plant sources, and are known to be potent inhibitors of the polymerization of tubulin, an important protein in cell division. They also exhibit strong antioxidant activities. We are interested in developing new sulfur containing derivatives of the combretastatins for evaluation of their antioxidant abilities, as well as their potential as tubulin polymerization inhibitors.
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, and other related compounds, and evaluate their potential as anticancer agents. This work is done in collaboration with faculty at Susquehanna University and other institutions.
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).
Lou Ann Tom
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 lab is focused on the synthesis and characterization of conjugated organic dye molecules. These dyes find use in various electronic and biological applications. By focusing on the synthesis of modular intermediates, we can rapidly make a variety of final targets and tailor dye functionality to these diverse purposes.
A major focus of our work is in developing dyes as photosensitizers for solar cells that are more cost efficient than currently available silicon-based solar panels. These dyes must be solution processable, absorb light in the visible spectrum, and possess anchoring functional groups that can bind the organic dye to an inorganic semiconductor. Conveniently, by using symmetric electron donating building blocks, we can easily synthesize structures with multiple carboxylic acid anchors that allow for stable devices and fine tuning of oxidation potentials and optical bands gaps.
Additionally, because of the modular structure of conjugated dyes, we can install a variety of electron accepting functional groups in conjugation with the electron donor in an A-D-A structure (A = acceptor, D = Donor) to create novel emissive materials. Using a rapid synthetic approach, we can investigate the optical properties of a series of analogous dyes in a short amount of time.
We use common characterization techniques such as NMR and IR spectroscopy to confirm the structure of targets. Our group also uses UV-vis spectroscopy, fluorescence spectroscopy, and cyclic voltammetry to evaluate the feasibility of a dye’s application in solar cells or as emissive materials.