A5056866538- Redox biology and oxidative stress
- Enzyme Structure and Function
- Experimental Learning in Engineering
- Problem and Project Based Learning
- Autoimmune and Inflammatory Disorders Research
- Engineering Education and Curriculum Development
- Nitrogen and Sulfur Effects on Brassica
- Melanoma and MAPK Pathways
- Phytase and its Applications
- Protein Structure and Dynamics
- Carbohydrate Chemistry and Synthesis
- Nitric Oxide and Endothelin Effects
- Complement system in diseases
- Cytokine Signaling Pathways and Interactions
- Cell death mechanisms and regulation
- Engineering Education and Pedagogy
- Biochemical and Molecular Research
- Chemical Synthesis and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Protein Kinase Regulation and GTPase Signaling
- Antibiotic Resistance in Bacteria
- Cancer, Hypoxia, and Metabolism
- Mechatronics Education and Applications
- Plant nutrient uptake and metabolism
- Galaxies: Formation, Evolution, Phenomena
Monash University
2012-2023
Australian Regenerative Medicine Institute
2022-2023
Minnesota State University, Mankato
2018-2020
Minneapolis Institute of Arts
2020
McMaster University
2020
Itasca Community College
2020
Michigan Technological University
2020
York College of Pennsylvania
2020
ARC Centre of Excellence in Advanced Molecular Imaging
2019
Front Range Engineering (United States)
2018
We have identified a class of molecules, known as 2-aminothiazoles (2-ATs), frequent-hitting fragments in biophysical binding assays. This was exemplified by 4-phenylthiazol-2-amine being hit 14/14 screens against diverse range protein targets, suggesting that this scaffold is poor starting point for fragment-based drug discovery. prompted us to analyze the context an academic fragment library used discovery (FBDD) and two larger compound libraries high-throughput screening (HTS). analysis...
Purple acid phosphatases belong to the family of binuclear metallohydrolases and are involved in a multitude biological functions, ranging from bacterial killing bone metabolism animals phosphate uptake plants. Due its role resorption purple phosphatase has evolved into promising target for development anti-osteoporotic chemotherapeutics. The design specific potent inhibitors this enzyme is aided by detailed knowledge reaction mechanism. However, despite considerable effort last 10 years...
The protein SPSB2 mediates proteosomal degradation of inducible nitric oxide synthase (iNOS). Inhibitors SPSB2-iNOS interaction may prolong the lifetime iNOS and thereby enhance killing persistent pathogens. We have designed a cyclic peptide, Ac-c[CVDINNNC]-NH2, containing key sequence motif mediating interaction, which binds to binding site on with Kd 4.4 nM, as shown by SPR, [(1)H,(15)N]-HSQC, (19)F NMR. An in vitro assay macrophage cell lysates showed complete inhibition interactions...
The zymogen protease plasminogen and its active form plasmin perform key roles in blood clot dissolution, tissue remodeling, cell migration, bacterial pathogenesis. Dysregulation of the plasminogen/plasmin system results life-threatening hemorrhagic disorders or thrombotic vascular occlusion. Accordingly, inhibitors this are clinically important. Currently, tranexamic acid (TXA), a molecule that prevents activation through blocking recruitment to target substrates, is most widely used...
SPRY domain‐containing SOCS box protein 2 (SPSB2) regulates inducible nitric oxide synthase ( iNOS ) by targeting it for proteasomal degradation. Inhibiting this interaction prolongs the intracellular lifetime of , leading in turn to enhanced killing infectious pathogens such as bacteria and parasites. SPSB2 recognizes a linear motif (DINNN) disordered N‐terminus ligands that target DINNN binding site on are potentially novel anti‐infective agents. We have explored 19 F NMR means probing...
SOCS5 can negatively regulate both JAK/STAT and EGF-receptor pathways has therefore been implicated in regulating the immune response tumorigenesis. Understanding molecular basis for activity may reveal novel ways to target key components of these signaling pathways. The N-terminal region coordinates critical protein interactions involved inhibition signaling, a conserved within N-terminus mediates direct binding JAK kinase domain. Here we have characterized solution conformation this...
SPRY domain-containing suppressor of cytokine signaling box protein (SPSB) 2-deficient macrophages have been found to exhibit prolonged expression inducible nitric oxide synthase (iNOS) and enhanced killing persistent pathogens, suggesting that inhibitors the SPSB2-iNOS interaction potential as novel anti-infectives. In this study, we describe design, synthesis, characterization cyclic peptidomimetic constrained by organic linkers improve stability druggability. SPR, ITC, (19)F NMR analyses...
Abstract The Membrane Attack Complex (MAC) is responsible for forming large β-barrel channels in the membranes of pathogens, such as gram-negative bacteria. Off-target MAC assembly on endogenous tissue associated with inflammatory diseases and cancer. Accordingly, a human C5b-9 specific antibody, aE11, has been developed that detects neoepitope exposed C9 when it incorporated into complex, but not present plasma native C9. For nearly four decades aE11 routinely used to study complement,...
Following its secretion from cytotoxic lymphocytes into the immune synapse, perforin binds to target cell membranes through Ca(2+)-dependent C2 domain. Membrane-bound then forms pores that allow passage of pro-apoptopic granzymes cell. In present study, structural and biochemical studies reveal Ca(2+) binding triggers a conformational change in domain permits four key hydrophobic residues interact with plasma membrane. However, contrast previous suggestions, these movements membrane do not...
SPSB2 mediates the proteasomal degradation of iNOS. Inhibitors SPSB2-iNOS interaction are expected to prolong iNOS lifetime and thereby enhance killing persistent pathogens. Here, we describe synthesis characterization two redox-stable cyclized peptides containing DINNN motif required for binding. Both analogues bind with low nanomolar affinity binding site on SPSB, as determined by SPR (19)F NMR, efficiently displace full-length from in macrophage cell lysates. These provide a foundation...
Abstract The purpose of this research is to analyze the effectiveness, and student's self-reported engagement with gamification tools on a learning technical concepts when used in project-based (PBL) engineering classroom environment. Gamification, as defined study, use game-based elements such online audience response systems automated feedback non-game situations. By adding classroom, we hope further build active collaborative environment that our PBL program already provides. Five...
SPRY domain- and SOCS box-containing proteins SPSB1, SPSB2, SPSB4 interact with inducible nitric oxide synthase (iNOS), causing the iNOS to be polyubiquitinated targeted for degradation. Inhibition of this interaction increases levels, consequently cellular (NO) concentrations, has been proposed as a potential strategy killing intracellular pathogens. We previously described two DINNN-containing cyclic peptides (CP1 CP2) potent inhibitors murine SPSB–iNOS interaction. In study, we report...
Abstract Engineering education models have recently embraced the entrepreneurial mindset as a desired outcome of undergraduate engineering education. Interdisciplinary active learning strategies been suggested an effective pedagogy for engaging student engineers in Recent research suggests that active, social context can lead to improvements learner innovation, problem-solving, curiosity, retention and accessibility knowledge, value-creation, other outcomes. Much recent adoption...
SPRY domain-containing SOCS box proteins SPSB1, 2, and 4 mediate the proteasomal degradation of inducible nitric oxide synthase (iNOS) thereby modulate amount NO available for combating infectious organisms. A highly conserved Asp-Ile-Asn-Asn-Asn (DINNN) motif found at N-terminus iNOS binds to SPSB2 with nanomolar affinity. The design specific potent inhibitors iNOS–SPSB interactions will be aided by a better understanding this DINNN sequence SPSB2. Although crystal structures SPSB complexes...
Perforin is a pore-forming protein whose normal function enables cytotoxic T and natural killer (NK) cells to kill virus-infected transformed cells. Conversely, unwanted perforin activity can also result in auto-immune attack, graft rejection aberrant responses pathogens. critical for the of granule exocytosis cell death pathway therefore target drug development. In this study, by screening fragment library using NMR surface plasmon resonance, we identified 4,4-diaminodiphenyl sulfone...