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Positions

New! Postdoctoral Position to Study the Role of Chemokine Receptors and Other GPCRs in Chronic Lymphocytic Leukemia

A postdoctoral position is available to study the role of G protein-coupled receptors (GPCRs), including chemokine receptors in the survival of chronic lymphocytic leukemia (CLL) cells.   Experimental approaches will include cellular and molecular biology to determine the effects of receptor activation and blockade on cell viability and an analysis of the underlying signaling pathways. Additionally, the role that cells from the microenvironment play in this process will be investigated.  The research will conducted in collaboration with Dr. Tracy Handel and Dr. Paul Insel (Skaggs School of Pharmacy and Pharmaceutical Sciences and Department of Pharmacology). A PhD in molecular/cell/cancer biology or related area is desired. Send CV and names/email of 3 referees to thandel@ucsd.edu.

Relevant Publications:

O'Hayre M, Niederst M., Fecteau J.F., Nguyen V.M., Kipps T.J., Messmer D., Newton A.C., Handel T.M. (2012) Mechanisms and Consequences of the Loss of PHLPP1 Phosphatase in Chronic Lymphocytic Leukemia (CLL). Leukemia. 26:1689-92. http://www.ncbi.nlm.nih.gov/pubmed/22237780

Fecteau J.F., Bharati I.S., O'hayre M, Handel T.M., Kipps T.J., Messmer D. (2011) Sorafenib-induced apoptosis of chronic lymphocytic leukemia cells is associated with downregulation of RAF and Mcl-1. Mol Med. 18:19-28 http://www.ncbi.nlm.nih.gov/pubmed/21979753

D. Messmer, J.F. Fecteau, M. O’Hayre, I,S. Bharati, T.M. Handel, and T.J. Kipps (2010) Chronic Lymphocytic Leukemia Cells Receive Raf-dependent Survival Signals In Response To CXCL12 That Are Sensitive To Inhibition By Sorafenib. Blood 17:882-9. http://www.ncbi.nlm.nih.gov/pubmed/21079155

M. O'Hayre, C.L. Salanga, T.J. Kipps, D. Messmer, P.C. Dorrestein, T.M. Handel (2010) Elucidating the CXCL12/CXCR4 Signaling Network in Chronic Lymphocytic Leukemia through Phosphoproteomic Analysis. PLoS One. 5:e11716. PMCID: PMC2908618 http://www.ncbi.nlm.nih.gov/pubmed/20661426

 

Postdoctoral Position to Study Chemokine Interactions with Glycosaminoglycans

Postdoctoral Positions involving structural and cell biology are available immediately in the laboratory of Professor Tracy Handel in SPPPS and the Dept of Pharmacology at UCSD. Our research is focused on the structure and function of chemokines and chemokine receptors. These proteins control the migration of cells during development, immune surveillance, and inflammation and are involved in numerous diseases including inflammatory diseases, atherosclerosis, cancer, and HIV. In addition to transmembrane receptors, chemokines have essential interactions with glycosaminoglycans (GAGs) which are structurally diverse linear carbohydrate polymers. These interactions control the localization and transport of chemokines as well as signaling, and are critical to their function. Available postdoctoral positions involve biophysical and structural investigations of chemokine:GAG complexes by (i) characterization of high affinity GAGs for specific chemokines to understand specificity, (ii) NMR and/or crystallography to obtain high resolution information, (iii) small angle X-ray scattering to determine oligomerization states and conformational changes. (iv) In addition, functional investigations of chemokine:GAG interactions will be used to probe structures involved in the discrete sequential steps of cell migration: transcytosis and cell surface presentation on GAGs, leukocyte arrest and transmigration. This work will be done in close collaboration with researchers at the Integrated Resource for Glycotechnology at the  Complex Carbohydrate Research Center at the University of Georgia:  http://glycotech.ccrc.uga.edu/.  The ideal candidate will have strong skills in molecular biology, protein expression, biochemistry and biophysics/structural biology. Experience in Cell biology and/or knowledge of NMR or crystallography are a plus. The candidate should be highly motivated, work well as a team, have excellent communication skills, and a strong publication record. Interested individuals should send a CV, a 1-2 page description of research experience, and contact information (email) for three referees to: thandel@ucsd.edu. Please write "Postdoctoral Application in Chemokine:GAG Structural Biology" in the subject header.

Relevant Publications:
T.M. Handel, Z. Johnson, M. Mack, R. Cirillo, V. Muzio, M. Teixiera, M. Déruaz, F. Borlat, T.N.C. Wells, and A.E.I. Proudfoot (2008) An Engineered Monomer of CCL2 has Anti-inflammatory Properties Emphasizing the Importance of Oligomerization for Chemokine Activity In Vivo. J Leukocyte Biology. 84(4):1101-8.

E.K. Lau, A. Kungl, C. Paavola, Z. Johnson, F. Borlat, A.E.I. Proudfoot, T.M. Handel. (2004) Identification of the Glycosaminoglycan Binding Site of the CC Chemokine, MCP-1; Implications for Structure and Function In Vivo. J Biol Chem 279:22294-305.

A.E.I. Proudfoot, T.M. Handel, Z. Johnson, E.K. Lau, P. Liwang, I. Clark-Lewis, F. Borlat, T.N.C. Wells and M. Kosco-Vilbois. (2003) Glycosaminoglycan Binding and Oligomerization are Essential for the In Vivo Activity of Certain Chemokines. PNAS 100:1885-1890.

 

Postdoctoral Position in Membrane Protein Structural Biology

Postdoctoral Positions in structural biology are available immediately in the laboratory of Tracy Handel in SPPPS and the Dept of Pharmacology at UCSD. These positions will be funded by the NIH Protein Structure Initiative (PSI:Biology) : http://www.nigms.nih.gov/Initiatives/PSI/.  The goal of our work is to determine the structures of chemokine receptors in complex with small molecules inhibitors and their natural protein ligands via X-ray crystallography. These receptors are 7 transmembrane G Protein-Coupled Receptors (GPCRs), and  are involved in an extraordinary number of diseases including HIV, inflammatory diseases, atherosclerosis and cancer.  Our team works in close collaboration with the laboratory of Ray Stevens who heads the Center for Membrane Protein Structure Determination GPCR Network at the Scripps Research Institute (http://gpcr.scripps.edu/). In addition to structure determination, we seek to understand the conformational changes associated with receptor activation by EPR in collaboration with Wayne Hubbell at UCLA, and by radiolytic footprinting with Mark Chance at Case Western Reserve.   Finally, we correlate structure with function using mutagenesis, cellular assays of receptor signaling, Bioluminescence Resonance Energy Transfer and other cell-based assays. Thus the ideal candidate will have strong skills in molecular biology, protein expression, biochemistry and biophysics/structural biology. Cell biology skills, knowledge of protein expression in insect and/or mammalian cells and knowledge of crystallography are a plus. The candidate should be highly motivated, work well as a team, have excellent communication skills, and a strong publication record. Interested individuals should send a CV, a 1-2 page description of their research experience, and contact information (email) for three references to: thandel@ucsd.edu. Please write "Structural Biology Postdoctoral Application" in the subject header.

Relevant Publication:
B. Wu, E.Y.T. Chien, C.D. Mol, G. Fenalti, W. Liu, V. Katritch, R. Abagyan, A. Brooun, P. Wells, F. C.  Bi, D.J. Hamel, P. Kuhn, T.M. Handel, V. Cherezov, R.C. Stevens (2010) Structures of the CXCR4 chemokine receptor in complex with small molecule and cyclic peptide antagonists. Science 330:1066-1071.