The most common tumors seen in individuals with NF1 are peripheral nerve sheath tumors (cutaneous and plexiform neurofibromas). These tumors are typically slow growing, but can transform into malignant peripheral nerve sheath tumors (MPNSTs). MPNSTs are highly aggressive cancers, which frequently metastasize to other organs.

Research in the laboratories of Dr. Angela Hirbe and Dr. Corina Anastasaki are focused on generating new models of these tumors using a combination of genetically engineered mice and patient-derived cancers. Dr. Angela Hirbe and Dr. Aadel Chaudhuri are using advanced DNA detection methods to monitor cancer development and progression, whereas Dr. Corina Anastasaki is working to understand how nerves control neurofibroma growth.

Genetics of malignant peripheral nerve sheath tumors

In order to discover new therapeutic approaches for MPNSTs, Dr. Angela Hirbe and her colleagues are using advanced genetic and genomic methods to define the molecular changes responsible for MPNST development and metastasis.

Developing next-generation models of peripheral nerve sheath tumors

Using a combination of approaches, including mouse and human cellular engineering, Dr. Angela Hirbe and Dr. Corina Anastasaki are developing next-generation models of plexiform neurofibroma and malignant peripheral nerve sheath tumors.

Role of nerves in peripheral nerve sheath tumor development

Neurofibromas also form and grow in an environment rich in nerves. While not conventionally thought to control tumor development and progression, recent studies have revealed that nerve cells are important drivers of plexiform neurofibroma growth.

Dr. Gutmann, Dr. Anastasaki and colleagues are focused on defining the mechanisms by which nerves control neurofibroma growth, and identifying therapies that safely block neuron activity-driven tumor expansion. Dr. Yuan Pan is working with Dr. Angela Hirbe to determine how nerves and neuronal hyperactivity control MPNST growth.

Developing novel treatments for peripheral nerve sheath tumors

One of the areas of intense study in the laboratory of Dr. Angela Hirbe is the development and evaluation of promising drugs for the treatment of malignant peripheral nerve sheath tumors. In collaboration with Dr. Aadel Chaudhuri, Dr. Hirbe and her team are also investigating the use of circulating tumor DNA in the blood as an early marker of malignant transformation.