Frigo Laboratory
Daniel E. Frigo
Principal Investigator
Cancer Systems Imaging
Associate Professor
Areas of Research
- Prostate Cancer
- Molecular Biology
- Genomics
- Drug Development
- Cancer Metabolism
The Frigo Laboratory aims to identify and therapeutically target novel signaling pathways in prostate cancer. The lab is currently focused on understanding how various signaling pathways — such as those regulated by the androgen receptor, CAMKK2, AMPK, mTOR and MYC — drive the progression of prostate cancer. The long-term goal of this work is to exploit these newly uncovered pathways for therapeutic purposes. Interestingly, many of these signaling pathways converge at various metabolic nodes. The end result is a shift in oncogenic metabolism that allows the cancer cells to utilize a diverse array of nutrients to the benefit of the cancer cell.
Goals of the Frigo Lab
- Identify the signaling pathways that promote prostate cancer progression
- Delineate the regulation and role of diverse signaling networks in cancer metabolism
- Leverage novel imaging techniques to study subcellular signaling events and cancer metabolism
- Develop new therapeutic approaches for the treatment of advanced prostate cancer
Steroid hormones are chemicals that are made in one part of our body and can travel great distances to signal specific events in other parts of our body. At the molecular level, steroid hormones communicate by binding to and activating a class of proteins known as nuclear receptors. These hormone-bound receptors can then turn on or off various cellular signaling pathways that collectively control different biological responses. For example, androgens, such as testosterone, are male sex steroid hormones that are produced mainly in the testes and can circulate through our bloodstream to various targets like the prostate where the hormone promotes the normal development of this organ by binding to and activating androgen receptors (ARs). Importantly, while androgens are required for males to develop normally, abnormal androgen signaling can promote prostate cancer.
Despite the known importance of androgens in prostate cancer, it is still unclear which of the hundreds to thousands of androgen-regulated signaling pathways are responsible for causing the progression of the disease. Moreover, it is now clear that there are new prostate cancer subtypes emerging as the result of next-generation AR-targeting drugs. These new cancer subtypes are androgen-indifferent and likely driven by unique mechanisms that need to be defined. To address this knowledge gap, my laboratory takes a multidisciplinary approach that encompasses fields spanning from genomics to pharmacology to biochemistry to molecular and cellular biology, testing in preclinical animal models of prostate cancer, as well as the development of new clinical trials. This approach facilitates the identification of those pathways that are actually driving the stages of the disease for which patients have limited treatment options. Most recently, we have been heavily focused on understanding how these pathways alter cellular metabolism to promote disease progression. Now, we are also positioned to then rapidly test whether these newly identified metabolic pathways represent realistic therapeutic targets and hence, set the foundation for developing mechanistically innovative drugs.