Job Description

Requisition Number 07046
Department Name: Immunology and Microbiology - CA
Position Type: Full Time
Position Title Postdoctoral Associate
Position Summary:

Hepatitis B virus (HBV) is a major worldwide threat with over 257 million people chronically infected, and with over 887,000 deaths per year. Chronic hepatitis B causes 40% of cases of hepatocellular carcinoma, which is the second leading cause of cancer-related mortality worldwide. The current vaccine has no beneficial effect on established chronic infection. Current therapeutic treatments suppress HBV replication, but are not curative, due to the persistence of the viral covalently closed circular DNA (cccDNA) transcriptional template in infected hepatocytes in addition to the failure of chronically infected patients to develop an immune response robust and sustained enough to totally clear the infection. Therefore, most of the patients cannot interrupt their drug treatments for their entire lives.

One strategy to cure HBV consists in the elimination of HBV by killing infected cells but keeping intact non-infected cells. We developed a new strategy to hijack the viral replication machinery to kill HBV-infected hepatocytes while preserving uninfected hepatocytes. This strategy consists in infecting HBV-infected hepatocytes with adeno-associated virus vectors encoding the reverse complement open reading frame of genes of interest that will only be recognized and reverse transcribed by the HBV polymerase/reverse transcriptase present in infected cells, triggering the protein expression of the genes of interest. We developed adeno-associated virus vectors, which deliver the reverse complement open reading frame of human caspase-9 - an initiator of the apoptosis caspase pathway - into infected livers that induces the killing of HBV-infected but not uninfected hepatocytes, leading to the elimination of HBV reservoirs without damaging liver functions.

We obtained solid in vitro data that demonstrates that our new approach, which consists of hijacking viral machinery strategy, kills HBV-infected cells while preserving uninfected cells. Our next step is to duplicate these attractive findings in vivo.

Position Description

A Postdoctoral position is immediately available to test our approach, in four distinct mouse models developed in our lab. Among them, we have i) an HBV transgenic mouse model; ii) an HBV humanized liver mouse model; iii) an adeno-associated vector-HBV transduction mouse model; and iv) a new in vivo imaging mouse model allowing in live detection of implanted bioluminescent human hepatocytes expressing HBV. The ultimate goal of these in vitro and in vivo studies is to demonstrate that this novel therapeutic strategy, which exploits the viral replication machinery to induce apoptosis and cell death, lead to the elimination of normally resilient HBV reservoirs, and eventually to a cure. These studies should also lead to numerous publications, national and international presentations, and new avenues of attractive research.

Our lab website provides additional information about the ongoing projects of our lab: http://www.scripps.edu/gallay.

Location: San Diego, California
Additional Information:
Physical Requirements:

This position works in a laboratory or vivarium environment. Further details of the physical requirements of established essential functions for this position will be addressed/discussed during the interview process.

Basic Qualifications:

Must possess a Ph.D. A pending doctoral degree may also be considered with approval of the Principal Investigator. Please send a curriculum vitae (CV) to Dr. Philippe Gallay at gallay@scripps.edu.

Lab website: http://www.scripps.edu/gallay

Preferred Qualifications:
Compensation: Salary is commensurate with experience.
Job Closing Date:
Open Until Filled Yes
Job Posting Category Postdoctoral
EEO Statement

The Scripps Research Institute is an Equal Opportunity Employer. All qualified applicants are encouraged to apply and will receive consideration for employment without regard to race, color, religion, sex, sexual orientation, gender identity, national origin, disability, protected veteran status, or any other legally protected characteristic or status.

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