structure and function of chemokines/receptors......... with overall goal to contribute to drug...

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Chemokines/Receptors......... with Overall Goal to Contribute to Drug Development Multiple Sclerosis Rheumatoid Arthritis Neuroinflammati on Pain Transplant Rejection Asthma Allergy Atherosclerosis Cancer Metastasis Diabetes

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Page 1: Structure and Function of Chemokines/Receptors......... with Overall Goal to Contribute to Drug Development Multiple Sclerosis Rheumatoid Arthritis Neuroinflammation

Structure and Function of Chemokines/Receptors......... with Overall Goal to Contribute to Drug Development

Multiple Sclerosis

Rheumatoid Arthritis

Neuroinflammation

Pain

Transplant Rejection

Asthma

Allergy

Atherosclerosis

Cancer Metastasis

Diabetes

HIV

Page 2: Structure and Function of Chemokines/Receptors......... with Overall Goal to Contribute to Drug Development Multiple Sclerosis Rheumatoid Arthritis Neuroinflammation

Core Expertise: Biochemistry, Structural Biology, Cell Biology, Membrane Proteins

Qin et al, Accepted to Science. 2015

Example: CXCR4:vMIP-II

Page 3: Structure and Function of Chemokines/Receptors......... with Overall Goal to Contribute to Drug Development Multiple Sclerosis Rheumatoid Arthritis Neuroinflammation

Core Expertise: Biochemistry, Structural Biology, Biophysics, Cell Biology, Membrane Proteins

CCR2 with Small Molecule Cmpds Low off-rate and allosteric cmpds

decreasing off rate

+ allosteric cmpd

SPR for Interaction Affinities

Cell-Based Assays; e.g. Ligand inducedReceptor Internalization

Page 4: Structure and Function of Chemokines/Receptors......... with Overall Goal to Contribute to Drug Development Multiple Sclerosis Rheumatoid Arthritis Neuroinflammation

Proposed Collaborations with SSPPS Faculty

Ruben Abagyan: Docking and Structure analysis of chemokine receptors

Dio Siegel: Small molecule compounds for chemokine receptor structures

Bill Gewick: Natural products targeting chemokine receptors

Jim McKerrow and Larissa Podust: membrane protein targets in tropical diseases

Victor Nizet: Chemokines/receptors in microbial pathogenesis

Debbie Spector: Chemokine/receptors and CMV

Pieter Dorrestein: Chemokines/receptor in cell-cell communication by MS

Geoffrey Chang: Nanobodies/antibodies against chemokine receptors

Dong Wang: Stabilization of protein-protein complexes by disulfide locks for structure determination