Job Summary
Seeking bright and motivated postdoctoral fellow to work under Dr. Yael Mosse as part of a growing, multidisciplinary team that she oversees, focused on developing targeted and immune-therapies for childhood cancers. The postdoc will work as part of a highly collaborative team, both at Penn/CHOP and institutions across North America.
Our research is focused on neuroblastoma, a common and often devastating childhood cancer of the peripheral nervous system. This position has two central projects, both focused on therapeutic targeting of the dominant oncogenes driving the growth of neuroblastoma: MYCN and ALK.
- Amplification of the MYCN oncogene is present in over 40% of high-risk neuroblastomas, and many high-risk neuroblastomas without MYCN amplification show overexpressed MYC protein. Therapeutic targeting of MYC(N) proteins directly remains challenging. MYC family proteins are small basic helix-loop-helix transcription factors with an inherently unstructured N-terminus and no known binding pockets for small molecular interactions. That said, it is now clear that these proteins coordinate complex protein interactomes that likely vary by cellular, spatial and temporal contexts. Advances in structural biology and medicinal chemistry now allow an unprecedented opportunity to drug these previously undruggable oncoproteins. The objective of this multi-institution project is to develop drugs that will directly degrade and/or destabilize the MYCN oncoprotein in pediatric cancer models, and to provide preclinical proof-of-concept to bring these compounds to clinical trials.
- Our discovery of gain-of-function mutations in ALK as the genetic etiology of familial NB provided the impetus for this second project. Moreover, these same mutations are the most frequent somatic single nucleotide mutation in this disease and have been shown to act as oncogenic drivers by promoting ligand-independent ALK tyrosine kinase activity. This project is focused on the development of highly specific antibody-based approaches to target cell surface anaplastic lymphoma kinase oncogene (ALK) on neuroblastomas and other ALK-expressing pediatric cancers.
These are both high-impact projects and there is the possibility of taking on one of the two proposed projects:
This job is open to those seeking first or second post-docs., scientist or research associate positions. Preference also given to post-docs eligible for K99/R00 awards and those seeking future independent academic careers. PhD with a publication record strongly encouraged.
Background
Dr. Yael Mosse ‘s clinical and research specialty is neuroblastoma, a cancer that starts in the nerve tissues of infants and young children. The Children’s Hospital of Philadelphia has developed the nation’s foremost clinical and research team devoted to children with neuroblastoma, and offers the possibility of clinical trials that are not available elsewhere.
In Yael Mosse‘s lab, researchers have made great strides in the knowledge of the hereditary predisposition and progression of neuroblastoma. They discovered the gene mutations that are the primary cause of the inherited version of neuroblastoma and that also play a significant role in high-risk forms of the more common, non-inherited form of the disease. These findings are helping translate knowledge from the lab to new and — one day — curative ideas for patients. Along with the possibility of new therapeutics, physicians at CHOP can also offer noninvasive screening for patients with a history that suggests a genetic predisposition to developing neuroblastoma.
The focus of Dr. Mossé’s lab research involves the genetic mutations responsible for neuroblastoma. The team recently discovered that a region of chromosome 2 was associated with the disease, and identified mutations in the anaplastic lymphoma kinase (ALK) gene. ALK is an oncogene (cancer causing gene) whose mutations are both genetic and acquired. Many pharmaceutical companies already make drugs that turn off the ALK gene, so Dr. Mossé’s team is now working on translating its discovery to the therapeutic use of ALK inhibiting drugs.
Dr. Mossé’s lab currently has a multi-institutional trial open through the Children’s Oncology Group for all children with relapsed neuroblastoma with the goal of bringing this therapy up-front for the treatment of newly diagnosed patients with neuroblastoma.
When Dr. Mossé started as a fellow with John M. Maris, MD, who is the premier expert in neuroblastoma, she found it intriguing to learn there were families with a history of the cancer. She decided to investigate this, and what had started as a side project – with luck and perseverance – turned out to result in a major scientific discovery.
Every experiment Dr. Mossé and her team does in the lab is focused on thinking about individual patients and how to develop new therapies. With a lot of determination, they have been able to translate the studies into clinical trials and move from patient to lab – and back to patient. Dr. Mossé believes she works with a tremendous team. Together, they have created a model that is branching out from neuroblastoma to all childhood cancers.