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Ovarian Cancer is the deadliest cancer among all of the gynecological malignancies, largely due to chemoresistance. Carboplatin is a widely accepted Platinum-based chemotherapy agent used for Ovarian cancer treatment. Carboplatin can work by inducing Ferroptosis, a novel type of cell death that differs from apoptosis. Ferroptosis involves the rapid accumulation of lipid peroxides (ROS’s) resulting in cell death. There are mechanisms in place to protect cells from Ferroptosis. One mechanism is through the gene-GPX4, which catalyzes the reduction of lipid peroxides. Chemoresistance in Ovarian Cancer may be related to their reliance on GPX4. Carboplatin has a cytotoxic profile when administered conventionally. Mesenchymal Stem cells have an innate homing ability to tumors. The cells can uptake and release chemotherapy in a time-dependent manner, without compromising their own cell integrity, making them ideal for safer targeted delivery. Using the CRISPR Cas9 Genetic-Engineering system, the gene GPX4 was deleted from OVCAR-3 Human Ovarian Cancer Cells that are resistant to Carboplatin. Antibiotic selection was used to kill off any Non-CRISPR transfected cells. Human Adipose-Derived Mesenchymal Stem cells were then primed with Carboplatin, and co-cultured with the CRISPR Ferroptosis susceptible OVCAR-3 cells. A group of Primed Stem cells were cultured independently, to verify cell integrity with exposure to Carboplatin. An MTT-Assay was used to determine cell proliferation (768 trials). The CoCulture group had a statistically significant lower proliferation rate compared with the “OVCAR-3 only” control (p &lt; .05). Thus, there could be potential in using Carboplatin loaded Human Mesenchymal Stem cells to target chemoresistant Ovarian Cancer.

Customized cancer cell weapons: Using CRISPR Cas9 genetic engineering and human adipose-derived mesenchymal stem cells to overcome platinum-based chemotherapy resistance in OVCAR-3 human ovarian cancer cells

Analysis of the rotational fine structure of the fundamental infrared band of HCl is a standard experiment in the physical chemistry laboratory curriculum. Although the absorption band was observed by Ångstrom and Palmer as early as 1893, the first spectrum showing sufficient resolution to distinguish not only the P and R branches but also the rotational fine structure was acquired in 1919 by Elmer S. Imes, the second African American to obtain a Ph.D. in physics. This spectrum, together with those obtained by Imes for HF and HBr, was of fundamental importance in demonstrating the need for a correct quantum theory of molecules. In celebration of the recent centenary of this spectrum, a number of extensions of the spectroscopy of the hydrogen halides beyond the standard curriculum are described here, including use of the research tool PGOPHER to facilitate data analysis, use of high-resolution linelist data from the HITRAN database to investigate overtones and hot bands, estimation of the bond dissociation energy from HITRAN data using Birge-Sponer extrapolation, and simulation of rovibrational bands based on high-level calculations of the ground state potential energy curve.

Using PGOPHER and HITRAN to extend spectroscopic analysis of hydrogen halides in the undergraduate laboratory

The mutarotation kinetics and equilibrium of glucose in aqueous solution are perturbed by the presence of metal cations, with Ca2+ showing one of the strongest effects, significantly shifting the equilibrium to favor the α-anomer. In this work we quantify this effect using a combination of polarimetry and 1H NMR. In the NMR measurements we use DOSY filtering to suppress the interfering HDO peak which originates in the rapidly-exchanging glucose hydroxyl protons. NMR and polarimetry give closely comparable results on anomeric abundance, although in agreement with literature studies on the unperturbed mutarotation equilibrium in aqueous glucose solutions we find that KNMR is consistently slightly smaller than Kpol. Polarimetric measurements confirm that the effect is largely cationic in character. and show that a catalytic effect of the cation on the mutarotation rate is diminished by increased solution viscosity at higher concentrations. Computational results on the glucose-Ca2+ system indicate that the dominant ion-molecule structures in solution are relatively undistorted ones with anomeric couplings 3JHCCH that are not strongly perturbed from their values for aqueous glucose solutions.

Effect of metal cations on glucose mutarotation: Complementary studies using polarimetry and DOSY-filtered NMR

Learning from biological systems such as Silicateins and their molecular mechanisms have paved the way for controlled synthesis of inorganic materials with advanced properties and high performances. In the case of zinc oxide (ZnO), conventional production methods are environmentally damaging and wasteful with the use of toxic and/or flammable solvents and precursors, extreme alkaline conditions requiring extra processing steps to neutralize, and lack satisfactory control of desired crystal habits for high value applications. Inspired by ZnO-binding peptides, we demonstrate a bioinspired synthesis and aspect ratio control of ZnO hexagonal prisms directly at 65°C using histidine in HMTA-zinc nitrate reaction system, with no seeding or substrate, yet well-defined morphology and conversion up to 40%. Histidine interferes with zinc ions, thereby stabilizing the system, affecting the conversion and particle morphology. We are now testing the performance of histidine in other ZnO synthesis systems to enable scalability of the bioinspired route.

Bioinspired synthesis of nanomaterials: Case study of zinc oxide

Individuals with medical implants are often at risk of developing life-threatening thrombi on the surface of these devices. Fibrinogen (Fgn) facilitates platelet recruitment by laterally aggregating at its αC domains into interconnected fibers that provide structure for thrombi. Thus, one method of preventing thrombogenesis is by inhibiting this process. The calculated optimal adsorption cites of the in silico human Fgn NJm on a hydrophobic thermoplastic surface model were congruent with existing literature, suggesting that on a polystyrene (PS) surface, Fgn is positioned with its αC domain exposed. Allowing a molecule to bind to the exposed αC domain will prevent the Fgn proteins from laterally aggregating. This study generated an in vitro bovine model of fiber formation on a hydrophobic PS surface to investigate the proficiency of a hydrophilic 14-peptide sequence derived from the Aα635-648 region of fibronectin, P-12 (PSHISKYILRWRPK), in achieving that end. Various amounts of bovine Fgn and P-12 were plated on PS and submerged in phosphate-buffered saline at various intervals. 100 μg/mL of Fgn acted as the monolayer that would initiate fibrin cluster formation, an additional 4 mg/mL of Fgn that, uninterrupted, would aggregate to form fibers, and 10μM of P-12 were added to investigate its impact on Fgn polymerization. Large fibers were observed in the absence of P-12, supporting the previous reports that the αC domains of the monolayer were opened by the hydrophobic interaction. Significantly smaller fibers were present when the P-12 was added alongside the surface monolayer, suggesting P-12 displaced certain sections, while minimal fiber formation occurred when P-12 was added afterward, which suggests that P-12 binds with Fgn to prevent the formation of fibrin clusters. This experiment confirms that P-12 blocks the ability of Fgn to execute fiber formation and that P-12 can displace Fgn from surfaces. If medical implants are manufactured with hydrophobic surfaces, this study suggests the introduction of P-12 can be used to mitigate thrombosis.

Development of a short peptide to prevent non-thrombogenic clot formation on hydrophobic surfaces

Electrocatalytic synthesis of H2O2 via two-electron oxygen reduction reaction (2e- ORR) has attracted tremendous interest in diversified fields, including wafer cleaning, paper manufacturing, and public sanitation. However, developing inexpensive, highly active, and selective catalysts is still a challenge for the large-scale electroproduction of H2O2. Here, we report a fluorine and sulfur dual-doping strategy for metal-free nanofibers to achieve comparable performances to metal-based catalysts. The optimized F/S dual-doping catalysts can afford an onset potential of 0.814 V versus reversible hydrogen electrode (RHE) and highly enhanced H2O2 selectivity of nearly 100%, superior to most of the recently reported carbon-based and metal-based counterparts. Experimental and theoretical computation results demonstrate that the manipulated free energy profiles and reduced energy barrier originate from the synergistic effect of intermolecular charge transfer coupled with electron spin redistribution in the adjacent carbon active sites, owing to the fluorine and sulfur heteroatom doping, respectively. This work can open the door to the design and implementation of inexpensive, large-scale, and highly efficient catalysts for the electroproduction of H2O2, and enjoys versatility to be extended to other catalytic fields, such as CO2 reduction, water splitting, and ammonia production.

Highly active and selective metal-free nanofibers for H2O2 electroproduction via F/S dual-doping

Recent Research

Glass micropipettes were widely used as a tool to inject or aspirate materials from living cells. We have been working on the development of ion-selective micropipettes. Here we demonstrate the measurement of sodium and potassium ions at the same time with ion-selective double-barrel micropipettes

Simultaneous measurement of sodium and potassium ions with ion-selective double-barrel micropipette

T-cell receptor (TCR) is a protein complex on T cells' surface responsible for antigen recognition. The receptor allows antigens bound to the major histocompatibility complex (MHC) molecules expressed on antigen-presenting cells (APC) to be recognized. This specific recognition is vital in the cellular immune response. The complex is a membrane-anchored and disulfide-linked heterodimeric set of glycoproteins with about 95% consisting of an alpha-beta chain (TCRαβ) and 5% gamma-delta (TCRγδ) chains. The prevalent αβ chains consist of two extracellular domains, the variable (V) and constant (C) region, with the C region adjacent to the cell membrane, the transmembrane domain and a short cytoplasmic tail and the V region bonded to the MHC complex and a cysteine-containing sequence. TCRα is specifically of major interest in this study, as it contains sites with increased amino acid variability present in its V domain. These complementarity-determining regions (CDRs) determine specific antibody binding to the receptors and includes CDR1, CDR2, CDR3 and HV4 involved in pMHC (Peptide-bound MHC) recognition. Initiation of specific mutations in these domains ensures efficient protection against pathogens and the generation of an immune response. We will present our work on the expression and purification of TCRα and initial structural characterization using NMR. A study of the structure and dynamics of these transmembrane domains will give a better structural and functional understanding of the TCRα and TCR complex.

Recombinant Expression and Characterization of TCRa from the T-cell Receptor Complex

Paid Submissions

Fabrication of cationic cellulose nanocrystals-polymer conjugates as potential immunomodulators

Preparation of stable poly(vinyl alcohol) thin films from aqueous solution on silicon wafer

Electrocatalysis in differentiating DNA polymorphism

Role of roast on chemical characteristics of cold brew coffee

Towards understanding the thermal remediation of degraded archival reel-to-reel audio tapes

Chromatographic behavior of bivalent bispecific antibodies on hydrophobic interaction chromatography columns

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