Department of Materials Science and Engineering
New medical diagnostic technology is needed for physicians to make accurate and timely decisions regarding treatment of patients for infectious diseases. For example, patients with acute respiratory symptoms indicating a potentially systemic infection require immediate treatment, yet clinicians lack a reliable method to quickly diagnose the patient’s condition. State of the art equipment requires a high level of expertise and expense; in addition these methods have low throughput. As a PhD student in Material Science and Engineering, the goal of my research is to create a low-cost and high-performing device for measuring bacterial fermentation products for use as specific indicators of infection or biofilm formation on the time of a few hours or less. Identification of microbes associated with infections allows for targeted antibiotic treatment. In addition, such a device could also monitor surfaces for biofilm formation that will help mitigate the prevalence of hospital acquired infections.
Materials Science and Engineering
Scarcity and access to geological deposits of platinum limit its availability for widespread applications. Single atom catalysts (SACs) simultaneously offer the potential for high catalytic activity and the most efficient use of material. Yet it has proven challenging to identify supports enabling high catalytic activity while at the same time inhibiting aggregation of metal adatoms. Graphene is modified via defects and dopants – specifically, single vacancy and pyridinic N-doping in order to affect interactions between substrate and metal adatoms. Density functional theory (DFT) calculations will be employed to identify how the local molecular environment on graphene can be used to stabilize clusters of 1-3 atoms of different earth abundant metals (including Fe, Mo, V, and Ta in addition to Pt). We compare the performance of earth abundant transition metal atoms with platinum in order to find alternatives to this precious metal.
Odor, toxicity, and reactivity have not been comprehensively examined at Orange County Landfills. Gases emitted from these sites affect over 3 million people that call Orange County “their home.” Over the past year, I have been collecting whole air samples in stainless steel canisters. I am trying to track changes in harmful gas emissions at the landfills. Using a highly sensitive method called gas chromatography, I can determine concentrations for over 100 gases emitted at the landfills. The results have been rather shocking. Air near the landfills is 1 million times smellier than it should be–this directly affects disadvantaged communities living nearby. The landfill air also contains toxic gases like the carcinogen, benzene–these can cause cancer for landfill operators. Lastly, the landfill air contains compounds that damage our environment–gases that can lead to smog and hot summers. In this presentation, I will discuss the importance of studying landfills, my sampling method, and my results so far.
Molecular Biology & Biochemistry
Each year more than 100,000 people in the US are diagnosed with B-cell malignancies. Since these malignancies rely heavily on cap-dependent (eIF4F) protein translation for production of critical pro-survival proteins that support their survival and proliferation, we aim to target this ‚ÄúAchilles Heel‚Äù process using small molecule inhibitors. I aim to sensitize non-Hodgkin‚Äôs lymphoma (NHL) cells to killing by targeted therapy, venetoclax, a small molecule inhibitor of BCL-2 (pro-survival protein) that has demonstrated impressive responses and received FDA approval in chronic lymphocytic leukemia (CLL) and others. We hypothesize that NHL cell survival depends on BCL-2 and other pro-survival proteins, facilitated by eukaryotic translation initiation factor 4E (eIF4E)-eIF4G1 interaction and is promoted by mTOR signaling pathway. We sensitize NHL cells to venetoclax treatment by combinational therapy with ‚ÄúSBI-0640756‚Äù (SBI-756) – a novel inhibitor targeting the scaffolding protein eIF4G1 that is critical for eIF4F complex formation. We discovered profound synergy between SBI-756 and venetoclax in vitro and in vivo, which leads to cancer cell death by apoptosis. Also, we showed that SBI-756 prevents cap-dependent translation, even among cells that were genetically edited to lack upstream regulators or developed resistance mechanisms. SBI-756 treatment reduced Mcl-1, Bcl-xL, and survivin pro-survival proteins in NHL cells. Hence, this project highlights a novel combination for treatment of aggressive lymphomas, and establishes its efficacy using preclinical models.
Bioluminescence imaging with luciferase-luciferin pairs is routinely used to monitor cellular interactions in real time and in vivo. While powerful, this technology has rarely been applied to multicomponent imaging due to a lack of distinguishable probes. To address this limitation, we are expanding the bioluminescence toolkit by engineering mutant luciferases that are resolved by substrate preference (i.e., ‚Äúorthogonal pairs‚Äù). Our strategy relies on chemically modified luciferins that are selectively processed by mutant luciferases. In this work, we developed a new class of hybrid luciferins containing disubstituted cores. These scaffolds comprise two steric appendages, and were designed to be occluded from the luciferase active site. Surprisingly, the disubstituted luciferins were found to be robust bioluminescent emitters. The unique patterns of light output provided clues into key enzyme-substrate interactions necessary for orthogonality. Further screening provided a collection of mutant luciferases that were selective for the hybrid analogs. These probes were also shown to be compatible with existing bioluminescent tools, suggesting that they will be useful for visualizing multicellular diseases such as cancer metastasis.