Assay Development for Early Target Biology Co-Op (Oncology Discovery): Jan 2020-June 2020

  • Opportunity Profile:
    • Assay Development for Early Target Biology, Co-Op: January 2020 to June 2020
      At Bristol-Myers Squibb, we are a team dedicated to discovering, developing and delivering innovative medicines that help patients prevail over serious diseases. Our commitment is to foster a globally diverse and inclusive workforce with a high-performing culture that is agile, entrepreneurial and accountable.  This enables our business strategy while encouraging excellence, growth, achievement, innovation and a balance between our personal and professional lives. 
      By combining the reach and resources of a global pharmaceutical company with the can-do spirit and agility of a biotechnology company, we are becoming a leader for the future – a next-generation BioPharma leader. 
      For more on BMS Cambridge please watch our video “Cambridge: A Culture of Collaboration” on Youtube
      Current Six-Month Co-op Opportunity
      Oncology Discovery (CAM)
      Goal: Establish Patient-derived models of acquired resistance to immunotherapies in order to identify effective drug combinations for cancer
      Immunotherapy has revolutionized the landscape of cancer treatment. The use of antibodies against immune checkpoints, such as CTLA-4 and PD-1/PD-L1, has shown clear clinical benefit in a subset of patients with advanced cancers. However, despite these initial encouraging results, a significant fraction of patients either fail to respond or will develop resistance after initial response. Treatment failure may be explained via several mechanisms including pathway alterations within tumor or immune cells, the presence of a low number of immunogenic antigens, defective antigen presentation, and/or the expression of alternative immune checkpoint molecules.
       Given the complexity by which cancers can evade the immune system, it is presently challenging to predict whether an individual patient will respond to immunotherapy as well as the causal mechanism behind this. Understanding this will ultimately guide treatment decisions that could be used to overcome resistance and increase rates of response. Platforms that allow for unbiased and systematic analysis of resistance mechanisms on a patient-by-patient basis would greatly contribute to our understanding of factors that determine a successful anti-tumor immune response.
      A successful co-op will participate in establishing 2D and 3D cell culture models from patient biopsy samples, consisting of different cancer types, whose disease has progressed while on immunotherapy. This platform will then be used to identify drug combinations that halt the growth of resistant tumor cells by leveraging both pharmacological and genetic screening approaches (including CRISPR-Cas9 technology).
      To achieve the above goal, this project will involve the following assignments:
      1. Work/plan with manager to identify relevant patient samples for development (10%)
      2. Complete requisite safety trainings for working in laboratory
      3. Meet and interact with team members to understand scope and remit of site’s and group’s focus and priorities
      4. Familiarize self with target biology and on-going research
      5. Work with manager to plan out strategies to 1) enhance our understanding of patient resistance mechanisms-of-action, 2) develop patient derived cell lines, 3) explore methods to characterize patient samples, and 4) use of forward genetic screens for target identification and validation studies
      6. Development, optimization and execution of protocols to derive and characterize cell lines from patient samples (80%)
      7. Learn and master basic laboratory skills
      8. Handling and harvesting fresh/frozen human tumor tissues and needle biopsies
      9. Design different 2D and 3D culture conditions to enhance success rates for cell line development
      10. Establish methods to isolate, immortalize, and culture stromal cells from tumor samples
      11. Genomic and transcriptomic profiling of cell lines by next-generation sequencing
      12. Expand and grow relevant patient derived tumor cell lines and optimize methods and conditions for forward genetic screening
      1. Education and Training: 10%
      2. Attend lab meetings, group meetings and site wide invited speaker seminars
      3. Present project progress at lab/group meetings as appropriate
      Enrolled in Bachelor’s or Master’s degree program in the Sciences. Desired backgrounds/degrees include:
      • Environmental Science, Environmental Studies
      • Natural Sciences (Chemistry orBiology)
      Key Learnings:
      • Knowledge of model development and characterization of cell lines to study drug resistance to IO therapy
      • Basics of forward genetic screens, including CRISPR screening, to identify new targets
      • Basics of cancer target validation process, including how drug targets are selected and validated
      • Basics of translational medicine and resistance mechanisms to IO
      • Essential laboratory skills including design and optimization of assays for drug screening
      • Problem solving skills
      • Skills required to work in a team-environment with all members focused on a common goal
        Key Deliverables at Project Completion:
      • At end of the co-op assignment, the student will be required to create a presentation reflecting their learnings and recommendations.