Vanderbilt Institute of Chemical Biology

 

 

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VICB 2018-2019 Seminar Schedule

 

 

Fall 2018
Seminar Schedule


John Burke

University of Victoria

 

"Structural basis of phosphoinositide and Rab GTPase signaling and their roles in human disease"

 

Wednesday, August 29, 2018

12:15 P.M. — 1:15 P.M.

1220 MRB III

 

Key Lecture Points:

· My research focuses on the molecular basis for how phosphoinositides and Rab GTPases cooperate in signalling and membrane trafficking, and how dysregulation in these pathways mediate human disease.

· I will discuss our work on how phosphoinositide kinases can be mutated in human disease, and how they can be hijacked by viral pathogens to mediate viral infection.
· I will also discuss our work examining how phosphoinositides participate in the activation of Rab GTPases through the activation of Rab-GEF enzymes.

Mark Denison

VAnderbilt University medical center

 

"Encouraging Infidelity: Antiviral Strategies for MERS and Emerging Coronaviruses"

 

Wednesday, September 5, 2018

12:15 P.M. — 1:15 P.M.

1220 MRB III

 

Key Lecture Points:

· Coronaviruses are a family of RNA viruses that have shown remarkable capacity for trans-species movement and emergence, with human potential pandemic pathogens SARS-CoV and currently active MERS-CoV

· Coronaviruses may regulate their replication fidelity (mutations, recombination, resistance) by the functions of the RNA-dependent RNA polymerase and an unprecedented RNA dependent RNA proofreading exonuclease (ExoN

· We have identified nucleoside analog inhibitors that are effective against MERS, SARS and other CoVs even in the setting of ExoN
· The seminar will discuss the activity, mechanisms, resistance and impact on virus fitness of these nucleoside analog inhibitors

Donna Huryn

University of pittsburgh

 

"Discovery, Optimization and Characterization of Allosteric Inhibitors of the AAA ATPase p97"

 

Wednesday, September 19, 2018

12:15 P.M. — 1:15 P.M.

ROOM CHANGE: 898J PRB

 

Key Lecture Points:

· The AAA ATPase p97 is a master regulator of protein homeostasis, but exactly how it works is still being studied.
· Small molecules that modulate p97 have the potential to treat diseases such as cancer and neurodegeneration.
· We have developed novel, allosteric inhibitors ofp97 with the potential to be starting points fordrug discovery and to be useful tools tounderstand p97 biology.

 

Derek Wilson

York University

 

"Targeting Conformational Disorder: Accelerated Drug Development in Cancer and Neurodegenerative Disease"

 

Wednesday, September 26, 2018

12:15 P.M. — 1:15 P.M.

1220 MRB III

 

Key Lecture Points:

· We develop and apply rapid (millisecond) H/D exchange to explore the molecular origins of neurodegenerative disease and cancer
- We have defined new molecular processes associated with protein misfolding in Alzheimer's, catalysis in antibiotic resistance and target engagement in mAb protein therapeutics
- We translate our fundamental discoveries and novel methods to 'real world' drug development through collaboration with industrial partners in vaccine development, anti-amyloid drug development and cancer

 

Manfred Lindau

cornell

 

"The Membrane Fusion Nanomachine"

 

Wednesday, October 3, 2018

12:15 P.M. — 1:15 P.M.

1220 MRB III

 

Key Lecture Points:

· We investigate the molecular mechanism of membrane fusion and transmitter release with specific focus on the steps leading to fusion pore formation.
· We developed a time superresolution technique that beats the time resolution limit of photon statistics and frame duration and identified a rapid change in SNARE complex conformation specifically associated with fusion events.
· Using molecular dynamics simulation we determined a fusion pore structure that has properties that are fully consistent with experimental data. This fusion pore structure reveals a proteo-lipidic fusion pore

 

Scott Sheehan

eli lilly

 

"Perspectives on Technology Integrated Medicinal Chemistry"

 

Wednesday, October 10, 2018

12:15 P.M. — 1:15 P.M.

1220 MRB III

 

Key Lecture Points:

· Lead Generation perspectives
· A fragment based approach to the discovery of
beta-secretase inhibitors
· The democratization of molecular design and the
evolving role of the medicinal chemist

 

Bart Decorte

Kodib

 

"Accessing Biologically Relevant Novel Chemical Space via the Architectural Transformation of Natural Products"

 

Wednesday, October 17, 2018

12:15 P.M. — 1:15 P.M.

1220 MRB III

 

Key Lecture Points

· Natural products and semisynthetic derivatives
continue to have a profound impact on human
health
· Synthetic efforts based on natural products
have primarily focused on improving their
drug-like features while targeting utility in the
same biological space
· A case study in which natural product building
blocks with known biological activity were
architecturally transformed to access
biologically relevant novel chemical space will
be presented

Phil Dawson

scripps research

 

"Making New Connections In Synthetic Protein Chemistry"

 

Wednesday, October 24, 2018

12:15 P.M. — 1:15 P.M.

1220 MRB III

 

Key Lecture Points

· Our focus is the development and utilization of methods to incorporate unnatural chemical groups into proteins
· We have developed a chemical approach for the production of the large polypeptide chains that comprise protein molecules, enabling us to change the structure of a protein in ways impossible by natural means
· Our goal is to introduce non-coded amino acids and other chemical groups into proteins to better understand the molecular basis of protein function

 

Jason Gestwicki

University of California-San Francisco

 

"Inhibitors of Protein-Protein Interactions in the Chaperone Networks to Treat Misfolding Diseases"

SEMINAR CANCELLED

Wednesday, November 7, 2018

12:15 P.M. — 1:15 P.M.

1220 MRB III

 

Key Lecture Points

· Chaperone networks regulate protein folding and homeostasis
· The protein-protein interactions between the chaperones are possible drug targets
· We have developed high-throughput screening methods to identify and optimize inhibitors of these PPIs

 

Kamil Godula

University of California-San Diego

 

"Chemical Tools for Engineering Glycan Interactions at the Cell-Matrix Interface"

 

Wednesday, November 14, 2018

12:15 P.M. — 1:15 P.M.

1220 MRB III

 

Key Lecture Points

· Synthetic glycoconjugate materials inconjunction with membrane engineering approachesenable precision tailoring of glycocalyxcomplexity with respect to the structure andorganization of glycan determinants
· Chemical glycoengineering allows forinvestigation the effects of glycan receptorpresentation at the glycocalyx interface inInfluenza A-host cell interactions.
· Glycocalyx engineering enables tuning of growthfactor activity at the surface of stem cells tomanipulate their differentiation

 

Ben Garcia

University of pennsylvania

 

"Quantitative Proteomics for Understanding Epigenetic Mechanisms in Cancer"

 

Wednesday, November 28, 2018

12:15 P.M. — 1:15 P.M.

1220 MRB III

 

Key Lecture Points

· Proteomics
· Histone modification
· Cancer epigenetics

 

The Garcia Lab utilizes high-resolution mass spectrometry to explore cellular signaling, epigenetic mechanisms and chromatin regulation.  We are especially interested in understanding how protein and nucleic acid modifications mediate their canonical functions and regulate nuclear processes.

 

Georgios Skiniotis

stanford

 

"CryoEM Insights Into GPCR acFvaFon and Signaling"

 

Wednesday, December 5, 2018

12:15 P.M. — 1:15 P.M.

1220 MRB III

 

Abstract:
Recent technological breakthroughs have enabled single-particle electron cryo-microscopy (cryoEM) to achieve close to atomic resolution structures of macromolecular complexes. The methodology is now displaying its hidden potential, and has already become a principal choice of method for characterizing the structure of relatively large macromolecular assemblies including membrane receptors. GPCRs and their complexes have been challenging targets for cryo-EM analysis, both because of their dynamic nature and also due to their relatively small size that can limit accurate alignment for 3D reconstructions. Nevertheless, near atomic resolution cryoEM maps of GPCRs are now within reach, opening up unprecedented opportunities to uncover molecular mechanisms and facilitate drug discovery.

 

Here, I will give an overview our more recent cryo-EM work to obtain the structures of several pharmacologically important GPCR complexes.

 

 

Will Pomerantz

univerity of minnesota

 

"Inspiration from Fluorination: Chemical Biology Approaches To Probe Molecular Recognition Events in Transcription"

 

Key Lecture Points

Development of Protein-Based Fluorine NMR for:
1. Characterizing molecular mechanisms of protein-protein interactions
2. Fragment-based drug design
3. Epigenetic inhibitor development

 

Wednesday, December 12, 2018

12:15 P.M. — 1:15 P.M.

1220 MRB III

Winter/Spring 2019
Seminar Schedule

Eric Brown

McMaster univerity

 

"A Path of Ceased Resistance: Systems Approaches to Antibiotic Drug Discovery"

 

Wednesday, January 16, 2019

12:15 P.M. — 1:15 P.M.

1220 MRB III

 

Key Lecture Points
· Modern target-focused antibacterial drug discovery has failed to deliver new antibacterial drugs.
· The Brown lab is developing new technology to
chart genetic and chemical interactions on a
genome-scale
· These approaches are facilitating discovery
efforts targeting the cell surface and nutrient
stress in bacteria

 

Lara Mahal

New York univerity

 

"TBA"

 

Wednesday, January 23, 2019

12:15 P.M. — 1:15 P.M.

1220 MRB III

 

Traci Lyons

univerity of colorado - Denver

 

"TBA"

 

Wednesday, February 6, 2019

12:15 P.M. — 1:15 P.M.

1220 MRB III

 

Jing Yang

Bristol-myers squibb

 

"The Discovery of Orally Active Small Molecule PAR4 Antagonists"

 

Wednesday, February 13, 2019

12:15 P.M. — 1:15 P.M.

1220 MRB III

 

Key Lecture Points

The balance between antithrombotic efficacy and
bleeding with currently available antiplatelet
drugs is suboptimal and many patients remain at
high risk of future atherothrombotic events. Thus
there is a clear need for newer agents that can
provide equivalent or superior antithrombotic
efficacy with an lower bleeding profile. Our
research is focused on protease-activated
receptor 4 (PAR4), a low affinity thrombin
receptor, as a promising antiplatelet drug target
to provide a potentially safer treatment for
arterial thrombosis. Below is an outline of our
research:
· Discovery of first-in-class orally active,
potent and selective PAR4 antagonists including
BMS-986120
· Preclinical studies of PAR4 antagonist in
non-human primate thrombosis and hemostasis
models
· Antithrombotic effect of BMS-986120 in human ex
vivo thrombosis chamber study
· First-in-human tolerability, PKPD and gene
variant effects of BMS-986120

 

Pamela England

University of California-San Francisco

 

"TBA"

 

Wednesday, February 20, 2019

12:15 P.M. — 1:15 P.M.

1220 MRB III

 

Shannon Hughes

National cancer institute

 

"TBA"

 

Wednesday, February 27, 2019

12:15 P.M. — 1:15 P.M.

1220 MRB III

 

Albert Bowers

university of north carolina

 

"TBA"

 

Wednesday, March 6, 2019

12:15 P.M. — 1:15 P.M.

1220 MRB III

 

Robert Abramovitch

michigan state university

 

"TBA"

 

Wednesday, March 13, 2019

12:15 P.M. — 1:15 P.M.

1220 MRB III

 

Elizabeth Read

university of california-irvine

 

"TBA"

 

Wednesday, March 20, 2019

12:15 P.M. — 1:15 P.M.

1220 MRB III

 

Lynette Cegelski

stanford

 

"TBA"

 

Wednesday, March 27, 2019

12:15 P.M. — 1:15 P.M.

1220 MRB III

 

Alanna Schepartz

yale

 

"TBA"

 

Wednesday, April 3, 2019

12:15 P.M. — 1:15 P.M.

1220 MRB III

 

Dean R. Madden

dartmouth

 

"TBA"

 

Wednesday, April 10, 2019

12:15 P.M. — 1:15 P.M.

1220 MRB III

 

Ken Hsu

University of Virginia

 

"TBA"

 

Wednesday, April 17, 2019

12:15 P.M. — 1:15 P.M.

1220 MRB III

 

 

Jennifer Allen

amgen

 

"TBA"

 

Wednesday, April 24, 2019

12:15 P.M. — 1:15 P.M.

1220 MRB III

 

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