PostDoc Fellow - Understanding mechanisms of innate and acquired resistance to BH3 mimetics and optimization of their therapeutic use in cancer

  • Company: MedImmune
  • Location: Waltham, Massachusetts
  • Posted: February 21, 2017
  • Reference ID: R-003867
At AstraZeneca, we believe in the potential of people who share our passion for science. By thinking boldly and working collaboratively to pursue discoveries beyond imagination, you'll develop further and faster than you thought possible. We'll complement your drive and determination to meet unmet patient needs around the world with the inspiration and opportunities to enhance your niche expertise and build your skills. So if you're curious about what science can do, come and make a difference.
Cancer is one of the greatest challenges facing medical science today. In our Oncology Team, you'll push the boundaries of science every day to overcome that challenge. We've been at the centre of some of the biggest breakthroughs in oncology. In lung cancer, for example, we've brought together complementary expertise to aid discovery and accelerate development in new medicines through a variety of partnerships and initiatives. We're also early adopters of new technologies to support innovation, including gene editing, genome editing techniques and a next-generation sequencing platform for companion diagnostics in oncology. But we're not stopping there. With a world-class pipeline and some of the best experts in the industry, we're in a great position to develop even more innovative therapeutic approaches.
Main duties and responsibilities
BH3 mimetics, such as the recently approved Bcl2-selective inhibitor ventoclax, are promising anti-cancer agents that are showing encouraging clinical activity. Part of a multidisciplinary Oncology drug discovery team focused on bringing new medicines to cancer patients, you'll help develop a better understanding of why some cancers are sensitive to BH3 mimetics while others are not, and applying that understanding to optimise the therapeutic benefit of this promising new class of anti-cancer agents.
Your objectives will be to develop a molecular understanding of why BH3 mimetics induce apoptosis in some tumor cells but not in others, and identify clinically-actionable biomarkers that accurately predict sensitivity to BH3 mimetics. This will involve identifying a panel of cell lines across haematological and solid cancer types, with a range of sensitivities to individual BH3 mimetics, and evaluating the Bcl2 family member status across the cell panel. Your role will also entail pharmacologically and genetically manipulating the cell lines to identify molecular dependencies, as well as identifying targeted therapies that when combined with individual BH3 mimetics reverse innate resistance to BH3 mimetics.
Opportunities and training will be provided to develop both in vitro and in vivo models of resistance to selective BH3 mimetics. Access to state-of-the art genetic, molecular and proteomic platforms for characterisation and genetic and chemical tools to validate mechanisms and identify approaches to overcome resistance will also be available.
Essential requirements
  • PhD and/or MD in relevant area of biology
  • Strong desire to learn and perform cancer research in an industry setting
  • Strong scientific background in cell biology, preferably cancer
  • Experience with design and execution of in vitro and/or in vivo experiments to determine the effects of therapeutics on biological systems
  • Experience with a variety of laboratory techniques including cell culture, compound handling, western blotting, RTPCR and proliferation/viability assays
  • Highly motivated, innovative and reliable with the ability to effectively problem solve
  • Flexible, collaborative and team-oriented mindset
  • Strong publication track record
  • Effective communication and presentation skills.
Desirable requirements
  • Strong scientific background in Bcl2 family biology and familiarity with the mechanism of action of BH3 mimetics
  • Prior experience in understanding resistance mechanisms to oncology drugs
  • Additional technical skills including apoptotis assays, flow cytometry, siRNA-based gene silencing, gene editing based gene deletion, NGS sequencing, and proteomic profiling.
To apply for this position, please click the apply link below
AstraZeneca is an equal opportunity employer. AstraZeneca will consider all qualified applicants for employment without discrimination on grounds of disability, sex or sexual orientation, pregnancy or maternity leave status, race or national or ethnic origin, age, religion or belief, gender identity or re-assignment, marital or civil partnership status, protected veteran status (if applicable) or any other characteristic protected by law. AstraZeneca only employs individuals with the right to work in the country/ies where the role is advertised.
This is a 2-year, fixed-term contract opportunity,  plus 1 year which will be merit based.  The role will be based in Waltham, MA, USA, with a competitive salary on offer.
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