Fulcrum Therapeutics is pioneering small molecule therapeutic approaches to gene regulation in genetically defined diseases. The current opening is for a Scientist or Senior Scientist within the fast-paced, innovative, in vivo pharmacology team.
Essential Areas of Responsibility:
The successful candidate will independently design, execute and interpret mechanistic in-vivo pharmacology research projects in the areas of genetically defined central nervous system (CNS) and musculoskeletal disorders. The candidate will participate as part of a multi-disciplinary team to conduct experiments aimed at building relationships between pharmacokinetic and pharmacodynamic effects of potential drug candidates in support of non-clinical drug discovery. In addition to their lab-based responsibilities, the candidate will be responsible for: 1) maintaining a working knowledge of current experimental techniques and literature in their scientific specialty; 2) designing innovative research studies to support discovery of development candidates and generation of intellectual property; 3) contributing to and leading discovery project team activities; 4) presenting scientific data internally and at scientific conferences; 5) authoring study reports, regulatory documents and scientific manuscripts; and 6) managing external research collaborations and engagement with scientific advisors and consultants. The person in this position will be expected to work collaboratively with others across multiple disciplines.
- Design, execution and analysis of in-vivo and ex-vivo pharmacology studies using innovative rodent models of CNS and musculoskeletal disorders. Responsibilities include rodent handling, drug delivery via multiple routes of administration (IV, SC, ICV, PO), necropsy, sample collection, behavioral analyses, statistical analysis, etc.
- Execution of studies aimed at building pharmacologic relationships between drug exposure, target engagement, pharmacodynamic biomarkers and disease protein gene expression in rodents.
- Develop robust assay methods to quantify disease target gene expression modulation, and chromatin or histone modification in normal or diseased tissue, blood and/or CSF. Studies involve engraftment of novel human neural precursor cells into the CNS to build relevant disease models.
- Develop robust assay methods to measure pharmacodynamic protein endpoints in normal or diseased tissue, blood and/or CSF.
- Perform mechanistic pharmacology studies using genetic techniques including CRISPR, RNAi/shRNA, ASO, etc.
- Collaborate effectively with colleagues from in vitro biology, in vivo biology and translational medicine teams to execute responsibilities.
- Coordinate with CROs to design, execute and analyze the data from the aforementioned in vivo experiments.
- Ph.D (with 3+ years of post-doctoral or industry experience), MS (with 5+ years of equivalent experience) or BS/BA (with 8+ years of equivalent experience).
- Extensive experience with rodent handling, drug administration and expertise with ex-vivo techniques (such as RT-PCR, ELISA, protein analysis via western blot, WES, and/or MSD) allowing for mechanistic interrogation of models of CNS and musculoskeletal disorders is necessary.
- Hands-on experience performing small animal surgeries (including catheterization, osmotic pump implantation and intra-cranial device implantation).
- Demonstrated ability to thrive in team environment.
- Strong experimental background and ability to bring a rigorous, analytical approach to problem solving.
- Excellent presentation and oral/written communication skills applied to technical study reports, notebook organization, manuscript preparation and statistical applications. Maintenance of laboratory notebooks in compliance with Fulcrum Therapeutics policies.
- Experience working on cross-functional drug discovery project teams is preferred.
- Preference will be given to candidates with experience performing small animal surgeries and a background in CNS related rare diseases and/or muscle cell biology.
- The successful candidate will have outstanding initiative, be highly motivated to drive our science forward, learn new techniques and procedures, and be able to effectively conceive and execute complex mechanistic studies in diverse diseases.