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Speakers
	Dr. Erin Calipari Vanderbilt University Dr. Calipari received her PhD in Neuroscience in 2013 in the laboratory of Dr. Sara Jones at Wake Forest University School of Medicine where she studied how self-administered drugs altered dopaminergic function to drive addictive behaviors. She then went on to complete her postdoctoral training with Dr. Eric Nestler at Icahn School of Medicine at Mount Sinai, where she used circuit probing techniques to understand the temporally specific neural signals that underlie motivation and reward learning. She is currently an Assistant Professor at Vanderbilt University in the Department of Pharmacology. Her independent work seeks to characterize and modulate the precise circuits in the brain that underlie both adaptive and maladaptive processes in reward, motivation, and associative learning.
	Dr. Tim Harris Johns Hopkins University Timothy Harris is a research professor in the Department of Biomedical Engineering. He leads the Applied Physics and Instrumentation Group at the HHMI Janelia Research Campus, and is the originator of the project that produced the Neuropixels Si probe for extracellular recording in animals, mostly mice, and rats. He shares his time between Janelia and Johns Hopkins and is working on projects to enable recording 10-20,000 neurons in rodents and 30-50,000 neurons in non-human primates, as well as stimulate with high resolution. He received a BS in ����vlog�ٷ���� at California Polytechnical State University, San Luis Obispo, and a PhD in Analytical ����vlog�ٷ���� at Purdue University.
	Dr. Elizabeth Hillman Columbia University Elizabeth Hillman is professor of biomedical engineering and radiology at Columbia University and a member of the Mortimer B. Zuckerman Mind Brain Behavior Institute and Kavli Institute for Brain Science at Columbia. Hillman received her undergraduate degree in physics and Ph.D. in medical physics and bioengineering at University College London and completed post-doctoral training at Massachusetts General Hospital/Harvard Medical School. In 2006, Hillman moved to Columbia University, founding the Laboratory for Functional Optical Imaging. Hillman’s research program focuses on the development and application of optical imaging and microscopy technologies to capture functional dynamics in the living brain. Most recently, she developed swept confocally aligned planar excitation (SCAPE) microscopy, a technique capable of very high speed volumetric imaging of neural activity in behaving organisms such as adult and larval Drosophila, zebrafish, C. elegans and the rodent brain. Hillman’s research program also includes exploring the interrelation between neural activity and blood flow in the brain, as the basis for signals detected by functional magnetic resonance imaging (fMRI). Hillman is a fellow of the Optical Society of America (OSA), the society of photo-optical instrumentation (SPIE) and the American Institute for Medical and Biological Engineering (AIMBE). She has received the OSA Adolf Lomb Medal for contributions to optics, as well as early career awards from the Wallace Coulter Foundation, National Science Foundation and Human Frontier Science Program.
	Dr. Baljit Khakh University of California, Los Angeles Baljit Khakh completed his Ph.D. at the University of Cambridge in the laboratory of Patrick PA Humphrey. He completed postdoctoral fellowships in the laboratory of Graeme Henderson at the University of Bristol, and then in the laboratory of Henry A. Lester and Norman Davidson at California Institute of Technology. In 2001, Khakh became Group Leader at the MRC Laboratory of Molecular Biology in Cambridge, and in 2006 he moved to the University of California, Los Angeles where he is Professor of Physiology and Neurobiology. Khakh’s work has been recognized, including with the NIH Director's Pioneer Award, the Paul G. Allen Distinguished Investigator Award, and the Outstanding Investigator Award (R35) from NINDS.

2022 Naff Symposium Committee

- Chair

Speakers
	Dr. Erin Calipari Vanderbilt University Dr. Calipari received her PhD in Neuroscience in 2013 in the laboratory of Dr. Sara Jones at Wake Forest University School of Medicine where she studied how self-administered drugs altered dopaminergic function to drive addictive behaviors. She then went on to complete her postdoctoral training with Dr. Eric Nestler at Icahn School of Medicine at Mount Sinai, where she used circuit probing techniques to understand the temporally specific neural signals that underlie motivation and reward learning. She is currently an Assistant Professor at Vanderbilt University in the Department of Pharmacology. Her independent work seeks to characterize and modulate the precise circuits in the brain that underlie both adaptive and maladaptive processes in reward, motivation, and associative learning.
	Dr. Tim Harris Johns Hopkins University Timothy Harris is a research professor in the Department of Biomedical Engineering. He leads the Applied Physics and Instrumentation Group at the HHMI Janelia Research Campus, and is the originator of the project that produced the Neuropixels Si probe for extracellular recording in animals, mostly mice, and rats. He shares his time between Janelia and Johns Hopkins and is working on projects to enable recording 10-20,000 neurons in rodents and 30-50,000 neurons in non-human primates, as well as stimulate with high resolution. He received a BS in ����vlog�ٷ���� at California Polytechnical State University, San Luis Obispo, and a PhD in Analytical ����vlog�ٷ���� at Purdue University.
	Dr. Elizabeth Hillman Columbia University Elizabeth Hillman is professor of biomedical engineering and radiology at Columbia University and a member of the Mortimer B. Zuckerman Mind Brain Behavior Institute and Kavli Institute for Brain Science at Columbia. Hillman received her undergraduate degree in physics and Ph.D. in medical physics and bioengineering at University College London and completed post-doctoral training at Massachusetts General Hospital/Harvard Medical School. In 2006, Hillman moved to Columbia University, founding the Laboratory for Functional Optical Imaging. Hillman’s research program focuses on the development and application of optical imaging and microscopy technologies to capture functional dynamics in the living brain. Most recently, she developed swept confocally aligned planar excitation (SCAPE) microscopy, a technique capable of very high speed volumetric imaging of neural activity in behaving organisms such as adult and larval Drosophila, zebrafish, C. elegans and the rodent brain. Hillman’s research program also includes exploring the interrelation between neural activity and blood flow in the brain, as the basis for signals detected by functional magnetic resonance imaging (fMRI). Hillman is a fellow of the Optical Society of America (OSA), the society of photo-optical instrumentation (SPIE) and the American Institute for Medical and Biological Engineering (AIMBE). She has received the OSA Adolf Lomb Medal for contributions to optics, as well as early career awards from the Wallace Coulter Foundation, National Science Foundation and Human Frontier Science Program.
	Dr. Baljit Khakh University of California, Los Angeles Baljit Khakh completed his Ph.D. at the University of Cambridge in the laboratory of Patrick PA Humphrey. He completed postdoctoral fellowships in the laboratory of Graeme Henderson at the University of Bristol, and then in the laboratory of Henry A. Lester and Norman Davidson at California Institute of Technology. In 2001, Khakh became Group Leader at the MRC Laboratory of Molecular Biology in Cambridge, and in 2006 he moved to the University of California, Los Angeles where he is Professor of Physiology and Neurobiology. Khakh’s work has been recognized, including with the NIH Director's Pioneer Award, the Paul G. Allen Distinguished Investigator Award, and the Outstanding Investigator Award (R35) from NINDS.

2022 Naff Symposium Committee

- Chair

The Department of ����vlog�ٷ���� Graduate Student Association (GSA) would like to invite you to a tailgating event on Saturday, November 20 from 10:00am-11:30am on the Tobacco Research, Lawn 1. This event is co-hosted by the Sri Lankan Student Association. A grill and some non-alcoholic beverages will be available. If you choose to bring your own alcohol, you must remain in compliance with .

The Tobacco Research, Lawn 1 is located on the corner of University Drive and Cooper Drive, directly adjacent to the Kentucky Tobacco Research and Development Center. You may view it on the campus map

We hope to see you there this Saturday!

Department of ����vlog�ٷ���� Graduate Student Association

The Department of ����vlog�ٷ���� Graduate Student Association (GSA) would like to invite you to a tailgating event on Saturday, November 20 from 10:00am-11:30am on the Tobacco Research, Lawn 1. This event is co-hosted by the Sri Lankan Student Association. A grill and some non-alcoholic beverages will be available. If you choose to bring your own alcohol, you must remain in compliance with .

The Tobacco Research, Lawn 1 is located on the corner of University Drive and Cooper Drive, directly adjacent to the Kentucky Tobacco Research and Development Center. You may view it on the campus map

We hope to see you there this Saturday!

Department of ����vlog�ٷ���� Graduate Student Association

Title: Probing the Assembly, Functional Relevance, and Dynamics of AcrA in Multi Drug Efflux in Escherichia coli

Abstract: Efflux pumps and low permeability of the outer membrane of gram-negative bacteria are major culprits in drug resistance. The most studied of these multidrug efflux pumps is the AcrAB-TolC, a complex of three proteins, the inner membrane transporter AcrB, the periplasmic adaptor AcrA and outer membrane factor TolC. This pump exports a wide range of molecules such as dyes, detergents, and antibiotics out of the bacteria system into the external environment. AcrB and TolC exist as obligate trimers, but the structure of AcrA during the assembly process is not well defined. My research aims to explore the functional and structural dynamics of the AcrAB-TolC pump to target the efflux pumps for effective antibiotic development. To achieve this, it is important to understand its structure, behavior, and function within the cell. The dominant negative effect of inactive AcrA and AcrB mutants was investigated, and we proved that once formed, the complex remains bound and does not dissociate easily. We also speculated that the assembly of the AcrAB-TolC is a precisely controlled process involving delicate proof-reading mechanisms that prevent the formation of futile complex.

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Facutly Advisor: Dr. Yinan Wei

Title: Photocatalytic Applications of TIO2 For Catechol Degradation and α-FE2O3 for Carbon Dioxide Reduction

Abstract: Natural and anthropogenic processes are emitting organic and inorganic pollutants, such as phenolic compounds and carbon dioxide (CO₂), and polluting the atmosphere. In addition, to meet the energy demand of the world’s growing population, the use of nonrenewable fossil fuels is causing their depletion. Heterogenous semiconductor photocatalysis is a clean and low-cost methodology, which can simultaneously contribute to solve the above energy and environmental problems. In this work, photocatalytic degradation of catechol, an organic pollutant, is explored with Degussa P25 (mixed phase of titanium dioxide, TiO₂), and CO₂ reduction is accomplished with potassium doped iron oxide.

Degussa P25 is used to study the degradation of catechol at the air solid interface because of low cost, stability, and abundant sources of TiO₂. Catechol forms a chelate with TiO₂ and shows an absorption band in the visible range through ligand to metal charge transfer transition. The photocatalytic activity of catechol degradation on TiO₂ surface is reported at variable wavelength of irradiation. The generation and quantification of reactive oxygen species and redox pairs has been studied with scavengers. Finally, the apparent quantum efficiency (AQE) for catechol loss and CO₂ and carbon monoxide (CO) growths are determined.

Potassium doped iron oxides of varying composition (100 Fe:x K, 0 £ x £ 5) are synthesized using an incipient wetness impregnation method. The structure, composition, and properties of the catalysts are investigated by diffraction methods, thermal analysis, and multiple spectroscopies. UV-visible light excites the catalysts in the presence of pure CO₂ or air under a saturated water vapor atmosphere. The AQE for the CO(g) production shows maximum for 100 Fe:1 K catalyst.

The study creates a path for the application of semiconductor photocatalysis in air purification, water splitting, and fuel production.

Faculty Advisor: Dr. Marcelo Guzman

Title: Succinylated polyethyleneimine gene delivery agents for enhanced transfection efficacy

Abstract: Gene therapy aims to treat patients by altering or controlling gene expression. Today, most current clinical approaches are viral-based due to their inherent gene delivery activity. However, there is still a significant interest in nonviral alternatives for gene delivery, particularly synthetic lipids and polymers, that do not suffer the immunogenicity, high cost, or mutagenesis concerns of viral vectors. Polymeric vectors are of particular interest due to the ability to further tune the polymer properties through the incorporation of additional functional units such as targeting ligands or shielding domains. Polyethylenimine (PEI), a highly cationic polymer, is often considered a benchmark for polymer-based gene delivery and thus serves as an excellent model for investigating gene delivery mechanisms. One reason PEI, especially branched PEI, is thought to outperform many other cationic polymers is due to the presence of secondary and tertiary amines. These amines are thought to help facilitate escape from endocytic vesicles via a 'proton-sponge' mechanism. Despite its successful use for gene delivery, PEI was initially developed for use in common processes such as water purification. As such, the properties of PEI should not be expected to be optimal for gene delivery. In this dissertation, our research efforts focused on the incorporation of negatively charged succinate groups to the PEI backbone to create succinylated zwitterion-like PEI (zPEIs). Specifically, we focused on the synthesis and characterization of zPEIs as well as the impact of zPEI on DNA condensation and gene expression.

This dissertation will discuss the results of three projects. In project (1), we studied the suitability of minimally modified zPEIs for gene expression. In this work, we reveal that modification of PEI amines as low as 2% was sufficient to provide significant improvements in gene delivery particularly in the presence of serum proteins. In project (2), we investigate the self-assembly of DNA induced by modified and unmodified branched PEIs using small-angle X-ray scattering (SAXS). Modified PEIs included both succinylated zPEI and acetylated PEIs (acPEI) both modified from 0-40%. We demonstrate that changing the degree of modification significantly alters the packing density of the resulting polyplexes. While acPEI shows a continuous decrease in DNA packaging efficiency with increasing degree of modification, zPEI shows a crossover behavior where DNA-DNA interhelical spacings increase at low succinylation but decrease at higher degrees of succinylation. Studies on the pH dependence on the inter-DNA spacing also shows that lowering the pH leads to tighter DNA packaging for all PEIs studied. In project (3), we studied the efficacy of zPEI polyplexes at varying protein concentrations ranging from 0-10 mg/mL of bovine serum albumin (BSA). These high protein concentrations are comparable to in vivo protein concentrations. We show that while PEI/DNA transgene expression decreases with higher protein concentrations, the zPEI studied stayed approximately constant over the protein range studied. To test if these conditions may lead to the formation of a protein corona on the nanoparticles, which was recently shown to enhance serum-free transfection in unmodified bPEI/DNA, we also measured the transgene expression of polyplexes pre-treated to form a protein corona to uncoated polyplexes.

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Faculty Advisor: Dr. Jason DeRouchey

Abstract:

Electron bifurcation is considered as a third fundamental mode of energy conservation mechanism, in which endergonic and exergonic redox reactions are coupled. The newly discovered flavin based electron bifurcation in Electron transfer flavoproteins (ETFs) helps to reduce low potential ferredoxin, which provides electrons to drive biologically demanding reactions such as atmospheric dinitrogen fixation in diazotroph and methane production in methanogens. Current research demonstrates the capacity for electron bifurcation in the Rhodopseudomonas palustris ETF (RpalETF) system. RpalETF contains two chemically identical but functionally different FADs: ET-FAD is bound in highly mobile domain II, which sits in a stable base created by domains I and III. Bf-FAD is buried in between domain I and III. The two flavins execute contrasting, complementary electron transfer reactions. Whereas one mediates single electron transfer (ET-FAD), the other accepts electrons pairwise (Bf-FAD), yet both flavins’ sites include a conserved Arg sidechain. R273 favors the ASQ of ET-FAD, whereas R165 near the Bf-FAD appears not to, possibly due to neutralization of its positive charge by nearby C174. R273 forms a pi- pi stacking interaction with ET-FAD whereas R165 appears to form hydrogen bond interactions with Bf-FAD. To learn whether the active site arginine residues each have different effects on their respective neighboring flavins, we replaced each of the Args in turn with chemically conservative, and divergent substitutions. Our data shows, R273 plays a vital role in BfETF by stabilizing the ASQ of the ET-FAD, whereas R165 favors binding of the Bf-FAD that is essential for electron bifurcation in RpalETF. Along with the electron bifurcation studies, we report an irreversible, pH dependent, site selective, enzyme mediated, anaerobic chemical modification of ET-FAD to a pink amino FAD, which opens a new perspective with which to understand the 726 nm band formed in bifurcating ETF.

Join the seminar here: ; Password: 764392

Abstract: Cancer is a worldwide public health crisis that requires new and improved drugs to be developed to extend survival rates and improve the quality of life for the patient. Platinum-based drugs are used in approximately 50% of cancer treatment regimens. These drugs are highly effective in many kinds of cancer; however, cancers can develop platinum resistance and these drugs have troubling side effects that reduced their use and efficacy. To overcome these disadvantages, many other metals have been studied for their anticancer properties. Notably, the anticancer properties of ruthenium-based agents have drawn considerable attention with multiple ruthenium complexes entering clinical trials. Unlike platinum complexes, which are flat (square planar), ruthenium compounds can adapt a multitude of 3D structures, which leads to many possible mechanisms of actions.

One of the most promising applications of ruthenium(II) complexes is their ability to act as photodynamic therapy (PDT) and photoactivated chemotherapy (PACT) agents. Both of these methodologies use light to “turn on” a non-toxic light-sensitive drug to form highly cytotoxic species that can kill cancer cells. These methods are appealing as they present a way to control the cytotoxic species to spatially isolated regions of the body. This control can reduce damage to healthy cells and reduce harmful side effects. Ruthenium(II) polypyridyl complexes are especially well suited for these applications as they have highly tunable excited states that can be tuned with careful ligand modification and selection.

Ruthenium complexes have also shown great promise as non-light-activated anticancer drugs. The coordination of small pharmacologically active molecules to ruthenium(II) polypyridyl complex is one promising method to develop potential ruthenium-based drugs. This strategy aims to create drugs that are greater than the sum of their parts by achieving synergistic mechanisms of action not achievable with either component individually.

Here we report on the synthesis and anticancer properties of Ru(II) complexes designed for PDT, PACT, and light-independent anticancer mechanisms. Highly potent lead compounds are identified and explored for PDT and light-independent anticancer applications. These lead compounds incorporated organometallic ligands with ruthenium(II) polypyridyl scaffolds to modulate their excited-state properties to produce improved PDT agents. The integration of O,O-chelating ligands into various ruthenium(II) scaffolds produced a range of complexes suitable for PDT, PACT, and light-independent mechanisms. Notably, the majority of these complexes possessed low submicromolar potency and low in vivo toxicity. Our results presented here show multiple new strategies for making new ruthenium(II) anticancer agents. These new methods have promising implications for bioinorganic research because they further expand our understanding of how to use ruthenium(II) complexes for biological applications.

Abstract: Protein-protein interactions (PPIs) are vital to many biological processes, including gene expression, and immune reactions to pathogens. There are approximately 650,000 PPIs in humans with pertinent physiological functions. Aberrant expression of PPIs leads to improper function and contributes to a plethora of disease conditions including cancer. Thus, PPIs represent an enormous target space for drug discovery and chemical probes. Direct targeting of clinically relevant PPIs with small molecules remains an unmet medical need. The development of small-molecule inhibitors of PPIs is a challenging enterprise and, in most cases, considered undruggable due to large protein surfaces, lack of deep binding pockets, and enzymatic activities. Despite these limitations, significant progress has been made in the area of compound development that selectively targets oncogenic PPIs and those underlying inflammation. This talk will focus on the identification and rational design of small-molecule inhibitors of PPIs, as applied to distinct protein targets, including the proto-oncogene product c-MYC, which dimerizes with MAX; the immunotherapeutic target programmed death receptor (PD-1) and programmed death ligand-receptor (PD-L1), and the epigenetic target AT-rich interacting domain 4B (ARID4B). The fundamentals of the small-molecule drug discovery process will be covered. More so, the use of in silico methods and synthetic chemistry to discover gold-based small-molecule covalent inhibitors of the intrinsically disordered protein, MYC, as well as the first-in-class small molecule inhibitors of ARID4B will be presented. This talk will also shed light on the medicinal chemistry of the recently identified dual-action small molecule inhibitors that perturb both Poly(ADP-ribose) polymerase (PARP) and PD-1/PD-L1 pathways.

Attend the seminar .