Date Posted: Jan 15, 2018
Application Deadline: Open Until Filled
A postdoctoral position for studying asymmetric cell division in oligodendrocyte progenitors and cancer stem cells is available in the Petritsch laboratory at University of California San Francisco, CA, USA.
The Petritsch lab has discovered that oligodendrocyte progenitor cell (OPC) undergo asymmetric cell division (ACD) to generate a balanced number of self-renewing and differentiating progeny (Sugiarto et al., Cancer Cell, 2011, 20, 328-40. PMCID: PMC3297490). With our collaborators, we found that OPC give rise to the frequently malignant brain tumors called gliomas in a genetically engineered mouse model (Persson et al., Cancer Cell, 2010, Cancer Cell 6, 669-82. PMCID: PMC3031116). More recently, we also discovered that ACD is tumor suppressive and regulated by cell polarity protein and membrane- and actin-associated scaffold Lethal giant larvae1 (Lgl1) through endocytosis (Daynac et al., Nat. Comm., in revision, 2018). These data raise several mechanistic questions that need to be addressed to fully understand homeostasis and regeneration in the brain and to find novel approaches to treat gliomas.
We are seeking a highly motivated postdoctoral candidate who is interested in closing the gap in our mechanistic understanding of asymmetric cell division and neoplastic transformation. Future projects are aimed to
1. Investigate the effects of lipid second messenger signaling in endocytosis disruption, asymmetric division of OPC and neoplastic transformation using molecular and biochemical and in vivo approaches in genetically engineered mouse models.
2. Using time-lapse imaging, single cell microfluidics and cell biologic analyses to distinguish between a transcriptional/epigenetic and post-transcriptional/protein sorting mechanism for ACD and cell fate decisions.
More recently, we uncovered that the deregulation of ACD in cancer stem cells provides a therapeutic opportunity to overcome therapy resistance in glioblastoma (Lerner et al, Cancer Research, 201675, 5355-66. PMCID: PMC4698003). Our recent studies raise the concern that small molecule inhibitor monotherapy targeting the MAPK pathway including BRAFV600E, may not effectively eliminate the cancer stem cells, which may explain therapy resistance and tumor recurrence in patients treated with BRAF inhibitor monotherapy. Our data provided rationale for testing pharmacologic inhibition of BRAFV600E inhibition and immunetherapy in preclinical mouse models.
Using our recently developed mouse model of BRAFV600E mutated malignant astrocytoma (Grossauer et al., Oncotarget, 2017, 7, 75839-75853), we aim to
1. Conduct preclinical studies to determine the effectiveness of combination therapies, including immune checkpoint blockades and small molecule inhibitors, as an effective strategy against BRAFV600E-mutant glioma and specifically cancer stem cells.
2. Analyze the changes in the cancer stem cell compartment in response to combination therapies using flow cytometry
3. Assess globally the effects of therapies on the tumor microenvironment including the immune compartment using immunofluorescence and CyTOF analyses.
The Petritsch laboratory is currently supported by NIH funding (two R01, one R21) and multiple private research awards. Qualified applicants will be encouraged to apply for a departmental T32 trainee award. Candidates should have a Ph.D., M.D. or M.D./Ph.D. and no more than two years of postdoctoral experience We are looking for an enthusiastic individual with a positive attitude towards challenging projects, and who seeks the opportunity to succeed in a productive environment by using excellent facilities. The applicants must have very strong publication records with first-author papers in high-impact journals and must be highly motivated with the drive to succeed. The applicants must be able to design and conduct experiments, prepare and present their researches at scientific conference; write and edit/revise research manuscripts and grant proposals, and proficient in English communications. Good written and oral presentation skills and a good command of the relevant literature in the field are therefore essential.
Experience in advanced molecular and cell biology techniques, or in vivo studies is a prerequisite. A strong background in one or more of the following areas is advantageous: models of progenitor or stem cell biology, immune system, brain tumor biology, signal transduction, genome editing.
Please submit a cover letter, your resume, reprints of relevant publications, and name and contact information of minimum of three references. An above NIH-standard salary for postdoctoral researchers ($48,216 for 0 yrs experience plus a stipend to accommodate high-living costs) with an excellent compensation and benefits package will be provided.
UCSF is an Equal Opportunity/Affirmative Action Educator and Employer and invites applications from all qualified individuals. Applications from women and minorities are especially sought.