Lab Interests

schematicThe figure to the right shows a cartoon diagram of the generic cytokine signal transduction pathway that occurs for a number of alpha-helical cytokines.   In this system, cellular communication is initiated by cytokine induced receptor oligomerization.  These oligomerization events activate intra-cellular JAK kinases which subsequently phosphorylate the intracellular domains of the receptors.  These phosphorylated sites recruit STAT (Signal Transducers Activators of Transcription) molecules to the receptor complex.  The STATs dimerize upon JAK kinase phosphorylation and  translocate to the nucleus where they enhance gene transcription events and ultimately cellular function.

The main objective of the lab is to define the structural and energetic basis for the specific recognition of cytokines by their receptors using x-ray crystallography and other biophysical methods including surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). These studies provide basic knowledge on protein:protein interactions that are essential to the proper regulatory control of cellular functions.  The molecules chosen for study are the alpha helical cytokines interferon gamma (IFN-g), interleukin 10 (IL-10), IFN-alpha and their receptors.  The presence or absence of IFN-g and IL-10 have been  implicated in numerous chronic inflammatory diseases including inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis.  The biological activities of IL-10 have also been linked to several B-cell malignancies.  IFN-alpha is currently an important clinical drug  in hairy cell leukemia and hepatitis C therapies.

The structural and energetic data obtained from these studies is clearly relevant for developing novel proteins and small molecules (agonists and antagonists) that can modulate the biological responses mediated by the receptor-ligand complexes.  Our data is also being used for studies on protein folding and design.

Lab Resources

The lab is well equipped for protein expression (E. coli, Sf9, Drosophila, and Mammalian cell culture), protein purification (Pharmacia AKta and Perseptive Biocad systems), protein interaction analysis (Biacore 2000 surface plasmon resonance machine) and protein crystallization.  In addition to our own computing network of clustered SGI workstations, the lab has full access to all equipment available in the Center for Biophysical Sciences and Engineering that is shared among six research groups.  Equipment available includes, 2 RAXIS IV's, 1 RAXIS II X-ray systems which are each equipped with liquid nitrogen cooling systems.  The lab also has dedicated access to the SERCAT synchrotron beamline located at the Advanced Photon Source (APS) in Chicago.  My lab has appropriate computational resources for graphics and modeling studies.  We also have access to the UABGRID of supercomputers, which allows us to perform computationally intensive molecular dynamics and docking studies.  Biophysical analysis equipment include Mass Spectrometers, a Pharmacia Biacore 2000, and serveral  micro calorimeters.  Several additional campus centers are well equipment for ultracentrifugation, Mass Spec (MALDI-TOF, Electro Spray), DNA sequencing and Flow Cytometry.

Graduate Education

UAB offers a large number of opportunities for graduate education.  Please visit the Graduate Biomedical Sciences website and specifically look at the Immunology, Microbiology, and Structural Biology Themes for more information.

Post-Doctoral / Staff Positions

No positions are currently available.