Center for Cancer Research
To improve the lives of cancer patients by solving important, challenging and neglected problems in cancer research and patient care.
Post-doctoral Fellow - kinases, oncogenes, drug discovery
Position is with:
The worldwide frequency of head and neck squamous cell carcinoma (HNSCC) is approximately 800,000 new cases per year, with 430,000 deaths annually, statistics which remain unchanged for several decades. Lung squamous cell carcinoma (LSCC) is the second most common form of lung cancer with approximately 530,000 cases and 450,000 deaths worldwide per year. Treatment options for HNSCC and LSCC patients are primarily limited to surgery, radiotherapy, and platinum-based chemotherapy, or combinations thereof. Therefore, there is an urgent need for new therapies in these two cancer subtypes.
Copy number alterations are frequently observed in HNSCC and LSCC. The most common is distal amplification of chromosome 3 (3q26-3q29, the 3q amplicon)3, which includes numerous protein kinases the lab is intensely investigating. We have discovered that catalytic inhibition of several of these kinases is insufficient to suppress all their pro-oncogenic activities, therefore, there is a strong rationale to develop PROTACs (degraders), which will target these kinases for degradation. PROTACs are molecules that have two parts: a ligand that binds to an E3 ubiquitin ligase and an inhibitor that binds the target kinase. Therefore, PROTACs will deliver our target kinases to the E3 ubiquitin ligase, targeting the kinases for proteasomal degradation.
The overall goals of the research projects are as follows:
1. Define kinase-dependent and -independent mechanisms of tumorigenesis using PROTACs.
2. Development of high-throughput screening methods to identify lead PROTAC compounds and novel small molecule kinase inhibitors.
3. Evaluate optimized PROTACs in animal models of HNSCC, LSCC, and other SCCs.
4. Gain experience in development of PROTACs and using medicinal chemistry to solve problems in membrane permeability, PK, and metabolism.
These projects will afford the postdoctoral fellow a unique opportunity to develop high-throughput screens, participate in drug discovery, elucidate novel mechanisms of tumorigenesis, and work on pre-clinical models of cancer. The overarching aim is to identify lead compounds that can ultimately be used to treat patients with LSCC and HNSCC. Please contact John Brognard directly with any questions.
Qualifications and Job Details:
- Degree Required:
- Ph.D. or equivalent
- M.D. or equivalent
- Location: Frederick, Maryland
- Appointment Type: Training Position
- Work Schedule: Full-time position
- Citizenship: US Citizenship not required - (ie, permanent resident, visa)
- Stipend: Commensurate with experience
REQUIRED SKILLS: Candidates should have experience in cell biology, molecular biology, cell signaling, biochemistry, and it is plus if candidates have experience in bioinformatics.
About the NCI Center for Cancer Research:
The Center for Cancer Research (CCR) is home to nearly 250 basic and clinical research groups located on two campuses just outside of Washington, D.C. CCR is part of the National Cancer Institute (NCI) and makes up the largest component of the research effort at the National Institutes of Health (NIH). Centrally supported by long-term funding and a culture of complete intellectual freedom, CCR scientists are able to pursue the most important and challenging problems in cancer research. We collaborate with academic and commercial partners and advocacy groups across the world in efforts to prevent, diagnose and treat cancer and HIV/AIDS. The CCR research portfolio covers the full spectrum of biological and biomedical research. Our work ranges from basic to translational and clinical, and our clinical trials are conducted in the NIH Clinical Center, the world’s largest hospital dedicated to clinical research that offers a robust infrastructure to support CCR’s patients on an estimated 250 open studies. The success of CCR is grounded in an exceptionally strong discovery research program that provides the foundation for the seamless translation of insights from bench to bedside. Read more about CCR, the benefits of working at CCR and hear from our staff on their CCR experiences.
Frederick is the second largest city in Maryland but retains a “small town” feel, surrounded by mountain views with a vibrant Main Street community. The city offers outstanding schools, a balanced and thriving economy and a highly educated workforce.
How to Apply:Submit:
- Three References
- Cover Letter
Contact Name: John Brognard
Contact Email: firstname.lastname@example.org
For questions contact: John Brognard, email@example.com
HHS, NIH, and NCI are Equal Opportunity Employers