Mentors

Ingo Mellinghoff, M.D.
Thomas Graeber, Ph.D.

Research Interests:

Metabolic phenotyping of PTEN-deficient tumors for PET-tracer development.

My project proposes a new methodology of PET-tracer development, based on genome wide transcriptional profiling and interrogation of the transcriptome through GSEA, a new analytical technique that focuses on functionally related gene sets, as opposed to individual genes. It aims to discover a PET-tracer specifically for PTEN deficient cells, but the approach could potentially be extended to other cell transforming lesions ( HER2/neu, oncogenic EGFR alleles). It involves 3 steps:

1. To identify metabolic programs that are enriched in PTEN deficient cells. Gene expression profiling will be performed on PTEN-isogenic cell lines, selected glioblastoma patients with defined PTEN status, and murine prostate cancer from prostate-specific conditional PTEN knockout mice. A large compendium of metabolic pathways will be tested for enrichment.
2. Confirmation of pathway activation through immunoblotting of representative pathway members.
3. Screening for suitable radiolabeled metabolites. Uptake of radiolabeled metabolic substrates of the enriched pathway will be examined in PTEN-deficient cells. Any candidate tracers identified will then be tested in animal models and ultimately in the clinic.

The current focus on PTEN is based on a) access to PTEN-cancer models and datasets within the UCLA Pharmacology Department, b) therapeutic implications, as PTEN status impacts the response of tumors to EGFR and mTOR kinase inhibitors, c) lack of tracer for diseases such as prostate cancer and glioblastoma, in which loss of PTEN occurs at a high frequency.

Resident in Medicine
Caritas St. Elizabeth’s Medical Center
Boston, Massachusetts