Research
Our lab studies the molecular mechanisms underlying prostate and bladder cancer initiation, progression, and therapeutic resistance, with the goal of uncovering actionable vulnerabilities and translating those findings into more effective treatments. The primary areas of research in our lab are listed below.
Genetic and Epigenetic Mechanisms in Prostate Cancer
First, we are studying the intersection of hormone receptor signaling and radiation resistance in prostate cancer. Altered signaling through the androgen receptor (AR) is known to drive prostate cancer by mediating the actions of testosterone and related androgens. Altered signaling through the AR creates conditions within tumors that promote resistance to hormone therapy and radiation. We are investigating the biology of nuclear hormone receptors in endocrine-driven cancers, with a specific focus on genetic and epigenetic modulating factors that are ‘hijacked’ by tumors to promote hormone therapy and radiation resistance. The actionable goal of this work is to develop more tailored combination therapies to more effectively cure high risk prostate cancer and minimize unnecessary toxicity.
Cell Lineage Plasticity in Urogenital Cancers
In addition, we are characterizing the evolutionary process that underlies the emergence of lethal variants of bladder and prostate cancer, including small-cell and neuroendocrine tumors. We are studying the heterogeneity that develops within the in-situ ecosystem of cancers using genetically engineered orthotopic mammalian model systems that replicate the anatomic, genetic, immune, and metabolic microenvironment of human cancers. By understanding the critical factors in these microenvironments which are required for lethal clones to emerge, thrive, and evade cancer treatments, we enable the design of targeted therapies that are more effective than those currently in use in the clinical setting.
Emerging Radiation Technologies
Furthermore, we explore the cellular and sub-cellular effects of new and emerging radiotherapy delivery technologies, including targeted stereotactic ablative radiation, particle therapy (e.g., proton, neutron, radiopharmaceuticals), and dose rate modulation (e.g., FLASH) in tumors and adjacent normal tissues. These technologies have potential to overcome resistance, reduce side effects, and maximize the therapeutic index of established therapies used in patients today.
Optimizing the Therapeutic Approach
Moreover, we are using spatially resolved molecular dissection and artificial intelligence tools to better integrate our laboratory’s findings with clinical data, including digital histopathology, medical imaging, and treatment records, with the goal of accelerating the transfer of knowledge from our laboratory bench to the patient’s bedside.
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