Postdoctoral Fellow - kinases, oncogenes, drug discovery
kinases, oncogenes, drug discovery, cell signaling
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.
These projects will afford the postdoctoral fellow a unique opportunity to develop high-throughput screen, 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.
The Center for Cancer Research (CCR) is working to solve the most pressing problems in the field through basic, translational and clinical cancer research to create the cancer medicines of tomorrow and is dedicated to preparing the next generation of cancer researchers. Read more about CCR, the benefits of working at CCR and hear from our staff on their CCR experiences.
The NCI CCR is dedicated to preparing the next generation of cancer researchers and offers a training environment that is second-to-none in quality of science and mentoring by outstanding principal investigators, including nine members of the National Academy of Science and eight members of the National Academy of Medicine. CCR offers fellows access to cutting-edge technologies and cores, a highly collaborative environment, awards and research forums to recognize outstanding post docs, continuous scientific symposia and lectures featuring leading researchers, a strong commitment to translational research, and a vibrant clinical research program housed in the world’s largest dedicated research hospital, the NIH Clinical Center.
Interested candidates must have a Ph.D. and/or an M.D. Candidates should have experience in cell biology, molecular biology, cell signaling, biochemistry, and it is plus if candidates have experience in bioinformatics.
Copy number alterations are frequently observed in HNSCC and LSCC. The most common is distal amplification of chromosome 3 (3q26-3q29, the 3q amplicon), which includes two protein kinases the lab is intensely investigating. We have discovered that catalytic inhibition of these kinases is insufficient to suppress all their pro-oncogenic activities, therefore, there is a strong rationale to develop PROTACs, 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:
- Define kinase-dependent and -independent mechanisms of tumorigenesis using PROTACs.
- Development of high-throughput screening methods to identify lead PROTAC compounds.
- Evaluate optimized PROTACs in animal models of HNSCC and LSCC.
- Gain experience in development of PROTACs and useing medicinal chemistry to solve problems in membrane permeability, PK, and metabolism
This position is located at CCR’s campus in Frederick, Maryland. Frederick is the second largest city in Maryland but retains a “small town” feel, surrounded by mountain views, wineries, orchards, and a vibrant Main Street community. It is less than an hour’s drive from the NIH main campus as well as the Appalachian Trail, Washington, D.C., Baltimore, and Gettysburg. The city offers many outstanding schools, a balanced and thriving economy, and a highly educated workforce.
Send a cover letter, CV including bibliography, and contact information for three references to Dr. John Brognard at the following email address: firstname.lastname@example.org.
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