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The Warfel lab studies the role of hypoxia (low oxygen) in driving therapeutic resistance and tumor metastasis. Hypoxia is arguably the most well established characteristic of solid tumors that has yet to be effectively targeted therapeutically, and it is a significant obstacle to the successful treatment of cancer.  Our goal is to expand our understanding of how hypoxia influences signaling networks to promote cell survival and migration, and translate these basic concepts to clinical applications that will directly impact patient care. 

Chemical works

Characterization of HIF-independent signaling mechanisms in hypoxia

The prevailing dogma is that hypoxic changes are conveyed by altering gene expression patterns via activation of  which for the hypoxia-inducible factor (HIF) transcription factors. As a result, the HIF-1 independent and post-translational mechanisms used by cancer cells to sense and respond to oxygen are not known.  This project will explore how acute and chronic hypoxia change the human kinome, which will provide new opportunities to therapeutically address hypoxia in cancer.

Determine microenvironmental factors that drive tumor evolution

Unlike most cancers, prostate cancers are not characterized by genetic drivers, so microenvironmental factors drive disease progression. In many cases, prostate cancer is slow growing and does not require treatment. However, due to a lack of accurate diagnostic tools, many patients undergo unnecessary surgery and/or are androgen deprivation therapy, which has negative consequences for the patient quality of life. This research will to identify biomarkers that can distinguish indolent from aggressive disease, a process that I believe is driven by hypoxia. The ability to identify organ confined tumors that are likely to metastasize, from those that will not, would reduce over-treatment and shift the paradigm for patients with early-stage disease.

Embryonic Stem Cells

Targeting tumor hypoxia

To complement our efforts to understand fundamental biological changes that occur in response to hypoxia, we have a growing drug discovery effort to selectively target hypoxic cancer cells. We have ongoing efforts to realize the potential of PIM as a cancer target. We developed the first PROTAC targeting PIM kinases. As an unbiased approach to find new molecules to kill hypoxic cancer cells, we have expanded into large-scale drug phenotypic drug screening to identify drugs that show synthetic lethality in hypoxia.

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