Daniel E. Frigo
Cancer Systems Imaging
Areas of Research
- Prostate Cancer Research
- Imaging Research
- Molecular Biology Research
- Genomics Research
- Drug Development Research
The mission of Frigo's lab is to identify and therapeutically target novel hormone-regulated signaling pathways in prostate cancer.
The goals of my lab are the following:
- Identify the pathways downstream of androgen receptor signaling 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 tumor 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. 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 and testing in preclinical animal models of prostate cancer. This approach facilitates the identification of those androgen-regulated 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.
The Frigo laboratory 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.
R01 CA184208 (Frigo) 1/27/15—12/31/19
Genetic & Metabolic Dissection of the CAMKKbeta Signaling Axis in Prostate Cancer
The goal of this project is to use a combination of in vitro and in vivo models to define the specific role(s) of AR-mediated CaMKKb signaling in prostate cancer and test whether it represents a viable drug target in preclinical animal models.
RSG-16-084-01 - TBE (Frigo) 7/1/16--6/30/20
American Cancer Society
Therapeutic Targeting of Autophagy in Prostate Cancer
The goal of this project is to define the specific role(s) of androgen receptor-mediated autophagy in prostate cancer and test whether is represents a viable drug target in preclinical animal models.
R21 CA191009 (Frigo) 2/1/15—1/31/17
Androgen Receptor- and Myc-Mediated Glutamine Metabolism in Prostate Cancer
The goal of this proposal is to use a combination of preclinical models to understand the relationship between AR signaling and glutamine metabolism to determine whether their intersection represents a viable therapeutic target.
U24DK100469 (Sreekumaran) 5/21/14--8/31/15
Metabolic Dissection of Aberrant Glutamine Metabolism in Prostate Cancer
The goal of this pilot grant sponsored through the Mayo Clinic Metabolomics Resource Core (MCMRC) Pilot and Feasibility Program is to leverage the existing strengths MCMRC to understand the relationship(s) between AR signaling and glutamine metabolism using stable isotope metabolic flux analyses.
Role: Subaward PI
W81XWH-12-1-0204 (Frigo) 6/1/12—5/31/15
The CaMKK beta-AMPK Signaling Axis as a Biomarker and Therapeutic Target for Advanced Prostate Cancer
The primary goal of this proposal is to use a combination of molecular biology and preclinical models to define the specific role(s) of the CaMKKb-AMPK signaling axis in prostate cancer.
R03 CA164908 (Frigo) 5/14/12--4/30/15
Modulation of Branched-Chain Fatty Acids for the Prevention of Prostate Cancer
The goal of this project is to understand how certain aspects of our Western diet and our endocrine system affect prostate cancer risk.
Golfers Against Cancer Award (Frigo) 2/24/14--2/23/15
Golfers Against Cancer
Validation of a Next-Generation Inhibitor of Autophagy for the Treatment of Aggressive Prostate Cancer
The goal of this proposal is to test the efficacy of a promising next-generation inhibitor of autophagy in a battery of preclinical models of prostate cancer and hence, determine whether this compound is ready for clinical trials.
Imaging Core Seed Grant (Frigo) 12/1/12--11/30/14
CPRIT (via UH Small Animal Imaging Core)
Development of Xenograft Mouse Models of Advanced Prostate Cancer
The goal of this proposal is to develop a combination of different xenograft in vivo models for the purpose of testing the specific roles of various androgen-mediated signaling pathways in prostate cancer.
Golfers Against Cancer Award (Frigo) 2/24/12--2/23/14
Golfers Against Cancer
Development of a CaMKKb-Selective Antagonist for the Treatment of Advanced Prostate Cancer
The goal of this project is to use a combination of synthetic chemistry, molecular biology and preclinical models to develop and evaluate analogs of the panCaMKK inhibitor STO-609 for use in the treatment of aggressive prostate cancer.
Imaging Core Seed Grant (Frigo) 3/1/14--11/30/14
CPRIT (via UH Small Animal Imaging Core)
Validation of Autophagy as a Therapeutic Target using In Vivo Imaging
The goal of this study is to define the role of autophagy in advanced prostate cancer and test whether it represents a viable drug target.
R03 DK092434 (Frigo) 7/1/11--6/30/13
Androgenic Regulation of Autophagy in the Prostate
The goal of this project is to use a combination of metabolomics and molecular and cellular biology to define the specific role(s) of androgen-mediated autophagy in prostate epithelial cells.
K01 DK084205 (Frigo) 7/1/09--6/30/13
Nonclassical Signaling of the Androgen Receptor Polyproline Domain
The major goal of this project is to determine the impact of a particular domain of the androgen receptor, and its interacting cofactors, on androgen-regulated signaling.