Fellowships in Structure-Function Studies of Chemokines and Receptors;Identification of Novel Therapeutics

Tracy M. Handel

Fellowship Director
Tracy Handel, Ph. D.
Professor
UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences

Research Background:

Dr. Handel's research program is focused on structural and functional studies of chemokines and their receptors. These proteins control cell migration and activation in the context of development, routine immune surveillance and inflammation. However inappropriate regulation or utilization of chemokines/receptors is associated with many diseases including atherosclerosis, rheumatoid arthritis, multiple sclerosis, neuro-inflammatory diseases, and cancer metastasis. Certain chemokine receptors also function as the portals by which HIV and certain strains of malaria enter cells. Using structural (X-ray crystallography and NMR), biochemical, and cell biology approaches, the lab seeks to understand how these proteins function at the molecular level. Through such studies it has been possible to identify several novel strategies by which modified chemokine ligands function as receptor antagonists. With our SSPPS colleagues, we are also interested in identifying small molecule inhibitors from marine natural product sources. The laboratory also has a concerted effort to express and crystallize chemokine receptors for structural and other biophysical studies involving interaction with ligands, downstream signaling partners and activation mechanisms. These receptors are membrane proteins form the G Protein-Coupled Receptor Class. We are particularly interested in complexes with small molecule lead compounds to aid the drug discovery process. Finally, we are interested in the functional role of chemokines/receptors in cancer metastasis and growth. For more information, go to: Handel Lab.

Area of Fellowships:

Structure-Function Studies of Chemokines and Receptors; Identification of Novel Therapeutics

  1. Development of modified chemokines that function as receptor antagonists
  2. Discovery of novel antagonists from marine natural products (collaboration with William Gerwick, SIO/SSPPS)
  3. Novel approaches to expression of chemokine receptors for structural studies
  4. The role of chemokines/receptors in breast cancer metastasis and growth using in vivo studies, cell based assays and proteomics
  5. The mechanisms and synergy between chemokines in chronic lymphocytic leukemia (CLL) using cell based assays and phosphoproteomics.

Objectives of the Fellowship Program:

Possible Coursework/Training

  • Structural Biology and Biophysics
  • Biochemistry
  • Immunology
  • Cancer Biology
  • Therapeutic approaches
  • Oral and Written Skills

Unique skills fellows will acquire during the program:

Depending on project, there is potential to learn a diverse array of laboratory approaches including (i) structural and biophysical methods, (ii) protein biochemistry (molecular biology, protein expression and purification), (iii) cell biology involving binding and functional assays of chemokine-receptor activation, signal transduction, (iv) proteomics using mass spectrometry

Time allocation: Two years