Title: Post-doctoral fellow
Department: Medicine / Institute for Transformative Molecular Medicine
School: Medicine
Location: Wolstein Research Building, 4th floor, 2103 Cornell Road
Supervisor Name and Title: Jonathan Stamler, MD
Professor of Medicine; Director, Institute for Transformative Molecular Medicine
POSITION OBJECTIVE
The NIH-funded project examines protein-S-nitrosylation in regulating G protein-coupled receptor signaling pathways in the lung in health and in models of asthma. Desired expertise includes experience with in vivo physiology of mouse lung and mouse physiology assessments (ideally using flexiVent or other ventilator), GPCR signaling pathway analysis in vivo and in model cell systems, and biochemical / enzymology / proteomic methods. The Stamler lab is a dynamic environment engaged in a wide array of basic and translational studies seeking to understand protein S-nitrosylation as an enzymatically-regulated post-translational modification that alters protein functions broadly in physiology and in pathophysiology/disease, and to manipulate this for therapeutic benefit (see Molecular Cell 2022 82:3089-3102; Cell Reports 2022 41:111538; Cell 2019 176:1014-1025; Nature 2019 565:96-100; Mol Cell 2018 70:473-487; Mol Cell 2018 69:451-464).
Working under limited supervision, coordinate research work in biomedical environment to define the involvement of specific genes in allergic asthma. Utilize genetically-modified mice to induce allergic asthma, and quantify its effects on airway function in live mice. Mouse tissues will be harvested for biochemical assessments to support in vivo phenotypes. Data and materials will be shared with a multisite program project grant (PPG) group with the overall objective of understanding how protein S-nitrosylation contributes to and protects from asthma in mouse models, and comparing this to data from human-derived biopsy samples and human primary cells.
ESSENTIAL FUNCTIONS
- Coordinate laboratory research activities. Follow approved animal protocol and standard workflow to induce asthma-like state in mice. Perform mouse surgery to install ventilator system, and measure airway reaction to bronchoconstrictor and bronchorelaxant drugs to quantify lung dysfunction. Isolate bronchoalveolar lavage fluid for assessment of immune cell infiltration into lung. Isolate mouse tissues to perform histology staining for lung integrity and biochemical assays to measure protein levels (western blot) and S-nitroso-protein levels (SNO-RAC). Utilize samples from human primary airway epithelial and smooth muscle cells to validate findings in mice. Maintain ongoing records of work and analysis performed (lab notebook) and maintain archive of all data generated. (72%)
- Work closely with the principal investigator and with supervising investigator, keeping them informed of progress and difficulties. (5%)
- Evaluate adequacy of techniques; study and test new procedures and analyze data. Troubleshoot issues with techniques and analysis. Compare results across multiple experiments and distinct mouse models to assure consistency and understand differences. Devise and test new techniques and evaluate new target proteins identified in other aspects of the PPG. (10%)
- Supervise students and technicians, specifically training in techniques and overseeing their use. (5%)
- Organize overall research work and recent progress in summary presentations for oral/visual presentation to local research group at regular meetings and to the off-site members of the PPG in regular meetings. May co-author research projects, providing assistance in data analysis and interpretation, in detailed recordkeeping of procedures and results, and in written descriptions of methods and results in manuscripts. (5%)
NONESSENTIAL FUNCTIONS
Perform other duties as assigned. (3%)
CONTACTS
Department: Daily contact with PI and/or direct supervisor to discuss research and maintain workflow. Weekly research group lab meetings with other lab members.
University: Rare contact with other departments to share information.
External: Regular contact with other members of multisite PPG group to exchange information (regular biweekly meeting, annual PPG meeting), and with PPG core facilities as needed to share materials (typically human cells or cell lysates) and data.
Students: Contact with student employees to supervise and to exchange information, could vary from none to daily.
SUPERVISORY RESPONSIBILITY
May supervise students and technicians
QUALIFICATIONS
Experience: 3 to 5 years of related research experience required. Rodent handling experience for at least 1 year strongly recommended. Experience with rodent asthma models, mouse surgery, and flexiVent or similar ventilator system is a strong plus.
Education/Licensing: Ph.D. degree in a natural science-relevant field required.
REQUIRED SKILLS
- Has knowledge of commonly-used concepts, practices, and procedures in biochemistry (particularly western blotting), in animal handling, physiological assessment and surgery (flexi-Vent experience a plus), and in asthma models in mice.
- Ability to act independently on general instructions to perform the functions of the job. Ability to modify pre-established guidelines and procedures to optimize productivity and to overcome obstacles.
- Ability to operate laboratory equipment.
- Ability to meet consistent attendance.
- Ability to interact with colleagues, supervisors and customers face to face.
WORKING CONDITIONS
General laboratory environment. Will work extensively with laboratory mice. May have exposure to hazards, particularly including dust mite allergens used for allergic asthma modeling in mice.
APPLICANT INSTRUCTIONS
Interested candidates should send a cover/motivation letter and a CV with the names and
contact information of 2-3 references to Justin Donnelly (jcd109@case.edu)