Cancer Metabolism Research
Developing Novel Metabolically-Targeted Chemotherapeutics
Our goal is to identify, characterize and optimize novel metabolically-targeted chemotherapeutics.
The aberrant metabolism of cancer cells remains a promising but elusive therapeutic target. While normal cells demonstrate a balance between growth and energy production, cancer cells focus on synthesizing new biomass rather than efficient energy (ATP) generation. The Annes lab utilizes novel screening platforms to discover drugs that specifically target the deranged metabolic program of neoplastic (tumor) cells.
A Tumor Syndrome Caused by Mitochondrial Gene Mutation
Paragangliomas (PGLs) and Pheocromocytomas (Pheos) are tumors of neuroendocrine cells (right, sympathetic neuroendocrine cells shown in gray). These tumors occur as part of an inherited syndrome (hPPGL Syndrome) in >40% of afffected patients.
Suprisingly, the hPPGL Syndrome is most frequently caused by mutation of a mitochondrial enzyme complex: Succinate Dehydrogenase (SDH). The discovery that the components of a mitochondrial enzyme act as a classic tumor suppressor gene raises important questions:
(1) How does altered mitochondrial metabolism initiate cellular transformation?
(2) What are the therapeutic suceptabilities associated with altered mitochondrial metabolism?
Answering these questions is a major focus of our research effort.
Tumors of the adrenal medulla are called pheochomocytomas. These tumors can secrete high levels of adrenaline-like sustances that cause severe blood pressure lability.
A Genetic Mitochondrial Tumor Model
We use genetically modified mice, cells and tumor samples to leverage the biology of a rare hereditary cancer syndrome and establish novel chemical screening platforms. Our strategies are aimed at overcoming current impediments to developing metabolically-targeted chemotherapeutics.