Postdoctoral Positions
Richard Klemke, Ph.D.
9500 Gilman Dr.
BSB1033
La Jolla, CA 92093
PHONE NUMBER:_858-822-5610
EMAIL: rklemke@ucsd.edu or kkazules@ucsd.edu
UCSD and the La Jolla scientific community provides an outstanding intellectual environment and
an excellent place to work and live.
San Diego Chamber of Commerce
Life in San Diego
Please send curriculum vitae, contact information and a brief statement of research and career goals to Richard Klemke, Ph.D. (rklemke@ucsd.edu). Salary and benefits commensurate with experience.
Postdoctoral Researcher Opportunities
1. Signaling mechanisms of cell migration and cancer metastasis
Description: Effective September 1, 2009 through January 1, 2010. Postdoctoral positions are available to study the signaling mechanisms that mediate cell migration and cancer cell metastasis. Postdoctoral fellows will study how cell surface receptors interpret extracellular cues and integrate these signals into intracellular signaling modules and scaffolds that regulate the migration machinery of the cell. Mechanistic studies will determine how G protein-coupled, tyrosine kinase, and adhesion receptors transmit signals that control the actin-myosin cytoskeleton to mediate cell movement, and determine how motile cells strategically position these signaling modules in the cell body and pseudopodium to target unique effector proteins. Researchers will utilize state-of-the-art molecular biology, biochemistry, proteomic, and fluorescence protein technologies as well as confocal and two-photon microscopy. The candidate will obtain an in depth knowledge of contemporary mechanisms of signal transduction and propagation as it relates to cell movement in healthy and diseased cells. The candidate will also work closely with clinicians at the Moores Cancer Center to obtain knowledge about deregulation of cell migration as it relates to clinical and animal models of cancer progression. The candidate must be experienced in molecular biology and cell culture and be familiar with protein biochemistry. Experience with confocal microscopy would be highly beneficial.
2. Investigating novel phosphoproteins and signaling networks that control cell migration.
Description: Effective September 1, 2009 through January 1, 2010.. Postdoctoral positions are available to investigate novel phosphoproteins and signaling networks that control cell migration. We have used large-scale proteomic, phosphoproteomic, and bioinformatics methodologies to identify novel proteins and map signaling networks that control cell polarization, migration, and cancer cell metastasis. PNAS 104:8328. 2007Several important new cytoskeletal-associated kinases, novel phosphorylation sites, and key signaling proteins have been identified and are now ready for physiological testing using siRNA knockdown technology, cell-based assays of cell migration, molecular biology, and confocal microscopy. The researcher will perform structure-function studies to determine how these new proteins couple to the migration machinery of the cell and determine whether they are deregulated in motility related diseases such as cancer metastasis. The candidate must be experienced in molecular biology and cell culture and be familiar with protein biochemistry. Experience with confocal microscopy would be highly beneficial.
3. Protein discovery and identification of phosphoprotein networks involved in cell migration and cancer metastasis.
Description: Effective September 1, 2009 through January 1, 2010.. Postdoctoral fellows will use proteomic, phosphoproteomic, and bioinformatics methodologies to identify novel phosphoprotein signatures and map global signaling networks that control cell polarization, migration, and cancer cell metastasis.[ PNAS 104:8328. 2007. ][Molecular & Cellular Proteomics 7:145-162, 2008]
[J. Proteome Res., 5 (4), 907 -915, 2006.] The candidate will use state-of-the-art large-scale mass spectrometry (LC-MS/MS, LTQ-ETD, Orbitrap, etc) combined with computational and biostatistical methods to predict and integrate protein interactions into functional networks that control cell migration. These researchers will also integrate their systems biology knowledge with others in the group functionally studying novel phosphoproteins and kinases to identify key proteins and signaling pathways involved in cell migration and cancer progression. Experience with mass spectrometry and computational programs used in protein identification and functional annotation are required.
4. In vivo mechanisms of cell migration, invasion, and vascular penetration.
Description: Effective September 1, 2009 through January 1, 2010.. Postdoctoral fellows will utilize high resolution intravital confocal and two-photon microscopy to visualize how human cancer cells invade tissues and gain access to vascular system in optically transparent transgenic zebrafish. [PNAS 104:17406. 2007] [Oncogene 27, 4509–4520. 2008.] We have discovered that the release of VEGF by tumor cells induces unique vascular holes in the endothelium of remodeling vessels. These openings most likely result from disruption of cell-cell junctions induced by VEGF receptor activation leading to down regulation of VE-cadherin. Most importantly, we discovered that the vascular opens serve as portholes which are utilized by highly metastatic cells to gain access to the blood system. Indeed, genetic manipulation combined with intravital real-time imaging has revealed that highly metastatic cells form unique invadapodia structures that penetrate deep into vessel openings allowing the cell to invade through the vessel wall. Researchers will investigate how known metastatic genes like RhoC and TWIST mediate cell invasion of complex tissues and work cooperatively with angiogenic agents that modulate the VEGF-Src-VE-cadherin signaling pathway to cause vascular disruption and cell metastasis. Using pharmacological agents, siRNA knockdown, and transgenic approaches that perturb this signaling axis, the researcher will gain an understanding of how developing tumors remodel the vasculature as well as the different invasive strategies utilized by metastatic cells to penetrate the vessel wall. The candidate will also learn computational 3-D rendering methods and gain an understanding of high resolution, whole animal imaging using contemporary confocal and two-photon microscopy. Experience in cell culture, light and flourescence microscopy, whole animal biology, cancer biology and angiogenesie, computational biology, and biostatistics is desirable.
5. Investigating the role of cytoskeletal signals that mediate neurite formation and axon and dendrite specification.
Description: Effective September 1, 2009 through January 1, 2010.. Postdoctoral projects are available to study the molecular signaling mechanisms that regulate neurite formation and growth cone guidance. Unique neurite purification methods combined with large-scale protein identification technology utilized in our laboratory has uncovered important new proteins and phosphoprotein signals that control neurite growth, retraction and guidance ( PNAS 105:1931. 2008). These novel proteins are now ready for physiological testing using siRNA knockdown technology, cell-based assays of neurite formation, molecular biology, and confocal microscopy. The candidate must be experienced in molecular biology and cell culture and be familiar with protein biochemistry. Experience with confocal microscopy and time-lapse imaging would be highly beneficial.
6. Other projects in the general areas of cell and cancer biology may be developed upon discussion with the research supervisor regarding the student's training goals.
Salary and benefits commensurate with experience. Please send curriculum vitae and a brief statement of research and career goals to rklemke@ucsd.edu.