Research

We explore biology, genetics and therapy (including immunotherapy) in the pediatric neural cancers ependymoma, medulloblastoma, and neuroblastoma; and in adult glioblastoma. The lab has a long history of generating autochthonous germline transgenic mouse models and non-germline models, driving initiating genes in either murine or human cells, to generate in vivo models that accurately reflect human disease

 

We are studying how kinases signal to Myc in some of these tumors. With respect to kinase biology, we are

  1. Testing novel and emerging drugs that target kinases, focused on EGFR and downstream pathways including MAP kinase, PI3K, Akt, and mTOR.
  2. Understanding how EGFR and the glioblastoma-variant EGFRvIII contribute to tumor intrinsic signaling, and to the tumor microenvironment in glioblastoma.
  3. Evaluating how mutations in neurofibromatosis I (NF1) drive therapy resistance.
  4. Evaluating mechanistic rationales for combining targeted agents.

 

With respect to Myc, we are

  1. Studying cancer stem and progenitor cells to model Myc-driven tumors in appropriate cellular contexts in vivo.
  2. Characterizing the tumor microenvironment to understand how Myc contributes to an immune desert that drives resistance to immunotherapy.
  3. Employing mass spectrometry to identify interacting proteins that represent novel targets in Myc driven cancers.
  4. Exploring condensate biology, to understand the importance of liquid -liquid phase separation to transformation by Myc proteins.
  5. Studying translation control to identify translational targets downstream of Myc, that may be missed in conventional RNA sequencing.

 

With respect to models, we are

  1. Identifying transcription factors expressed in candidate cells of origin for specific cancers and introducing relevant transcription factors into human stem cells to derive representative cells of origin.
  2. Introducing tumor initiating genes in representative cells of origin to generate more accurate models.
  3. Generating isogenic models representing distinct cell states.
  4. Developing in vivo systems to study metastases.
  5. Identifying and testing epigenetic vulnerabilities.