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VICB Weekly Seminar Schedule - Fall 2014

Paul Baker — AB SCIEX
Wednesday, September 3, 2014 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"New Strategies in Lipid Profiling: Resolving the Complexity of the Lipidome Using Differential Mobility Separation"  

Key Lecture Points:
·   Unambiguous lipid profiling is challenging due to extensive isobaric overlap of different lipid molecular species within the lipidome
·   Two general methods for lipid profiling by mass spectrometry are used: the ‘shotgun’ approach and the liquid chromatography approach—both have their benefits and limitations
·   A new technique to resolve lipid classes from a complex mixture, Differential Mobility Separation (DMS), has been developed that resolves issues related to isobaric interference
·   DMS can be used with LC or infusion techniques and cleanly resolves different lipid categories and classes; a novel approach to lipid profiling will be presented
·   The use of DMS has been extended to rapidly resolve eicosanoid enantiomers, triglyceride positional isomers and hexosyl ceramide isomers without the need for complex chromatography

Qi Zhang — UNC Chapel Hill
Wednesday, September 10, 2014 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"Chemical Tools to Monitor and Regulate Lipid Signaling Pathways"

Key Lecture Points:
·  The roles of phosphatidylinositides in development and diseases are not well understood
·  We have developed new chemical approaches to probe signaling pathways regulated by PIs
·  The application of these chemical tools to probe the role of PIs and ARF in the canonical Wnt/β
  catenin pathway will also be discussed

Matt Holden — Universit of Massachusetts, Amherst
Wednesday, September 17, 2014 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"Caught in the Act: Direct Measurement of Protein Translocation Across Membranes" 

Key Lecture Points:
·  Directed macromolecular transport across membranes key in 21st century medicine
·  We employ a model membrane to quantitate transport as a function of lipids and forces
·  Membrane asymmetry can be a driving force for carrier-mediated transport
·  We also measure protein transport through toxins
·  On route to mechanistic studies of proton-powered Brownian Ratchet
· Model membrane also used for screening ion channel/drug interactions
· Developed a teaching kit based on model membrane system

Dong Wang — UCSD, Skaggs School of Pharmacy & Pharmaceutical Sciences
Wednesday, September 24, 2014 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"Transcriptional Fidelity Control and Lesion Recognition" 

Key Lecture Points:
·   Structural basis of Pol II elongation complex
·  Three key checkingpoint steps for transcriptional fidelity
·  Structural features of nucleic acids recognized by Pol II
·  DNA modification recognition by Pol II
·  Lesion recognition by Pol II

David Rotella — Montclair State University
Wednesday, October 1, 2014 — 9:00 A.M. to 10:00 A.M. — 214 Light Hall
"1) A Natural Product Template for Medicinal Chemistry 2) Toward the Synthesis of Conformationally Restricted Diamine Scaffolds" 

Co-Sponsored by the Department of Pharmacology

Key Lecture Points:
·   Semi synthetic and synthetic analogs of the natural product (-)-epigallocatechin gallate were evaluated for activity as Hsp90 inhibitors, HCV entry inhibitors and for neuroprotective activity.
·  Structure activity trends were established for the first time for Hsp90 activity; HCV and neuroprotective structure activity studies are ongoing.
·  More "drug-like" analogs of epigallocatechin gallate were identified that are being used for discovery of second generation compounds.
·  Novel, conformationally restricted diamines were and are being synthesized as templates for structure-activity studies with selected GPCRs and enzyme.

Daniel Rabinovich — University of North Carolina, Charlotte
Wednesday, October 8, 2014 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"The World of X-Rays on Postage Stamps: From Radiology to Protein Crystallography" 

Key Lecture Points:
·  A philatelic tribute to the International Year of Crystallography (2014)
·  An overview of the key scientists involved in the discovery of X-rays and the development of X-ray crystallography
·  Postage stamps used to describe molecular structures and the impact of X-ray diffraction in chemistry, biochemistry, mineralogy, medicine, physics, and related fields 

Alexander Tropsha — University of North Carolina, Chapel Hill
Wednesday, October 15, 2014 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"Integration of Cheminformatics with Additional Data Streams Offers Improved Strategies for Identifying Novel Bioactive and Safe Compounds" 

Key Lecture Points:
This lecture will address...
·  Common challenges facing cheminformatics investigations including data quality (chemical and biological data curation), dataset “modelability," model acceptance criteria, statistical predictive power vs. transparency and interpretability of models.
·  Examples of application of QSAR models to virtual screening resulting in the discovery of novel experimentally confirmed hit compounds.
·   Novel integrative strategies for predicting in vivo effects of chemicals by concordant exploitation of both computed descriptors of chemical structures and additional data streams such as short term biological assay data or side effect profiles.
·   M odel interpretation and will end the talk by summarizing current and developing trends in the field of chemical data modeling.

George Wang — Georgia State University
Wednesday, November 12, 2014 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"Chemical Biology of Carbohydrates: Design a Synthetic Probe to Investigate a New Drug Mechanism, and Making Glycoconjugate Libraries"

Key Lecture Points:
·  Design, synthesize and biological investigation of the cellular target and mechanism of a antitumor drug for cancer stem cells
·  Chemo-enzymatic synthesis of several sugar libraries for biological evaluation

Robert Eoff — University of Arkansas
Wednesday, November 19, 2014 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"Translesion DNA Polymerase Kappa Activity is Regulated by the Aryl Hydrocarbon Receptor and Promotes Genomic Instability in Glioma Cells" 

Key Lecture Points:
· Translesion DNA synthesis is involved in the replication stress response
· Mis-regulation of translesion polymerases (pols), such as human pol kappa, occurs in many cancers
· The aryl hydrocarbon receptor stimulates pol kappa expression in glioma cells, which promotes genomic instability
· Indole-derived compounds can act as inhibitors of DNA synthesis
· Small-molecule inhibitors of translesion pols may sensitize tumor cells to genotoxic anti-cancer drugs


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