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NIH grant 1R01CA315100-01: Mapping and Manipulating Cancer-Associated Neuronal Networks
Institute: {'code': 'CA', 'abbreviation': 'NCI', 'name': 'National Cancer Institute', 'admin_org_id': '12500008', 'admin_funding_url': ''}. PI: Stephen Nicholas Housley. Award: $523554.
Start: 2026-08-06T00:00:00.
From growth, homeostasis, and regeneration, the nervous system is responsible for orchestrating and maintaining complex biologic processes in health and disease. It is therefore no surprise that the nervous system is emerging as a critical regulator of cancer. Recent data demonstrates that brain cancers establish bidirectional communication with their neuronal counterparts, creating cancer-neuronal circuits that promote tumor growth, invasion, and therapeutic resistance. These data highlight an underappreciated aspect of cancer biology and emphasize that cancer-neuron interactions are pivotal. Yet, whether peripheral cancer cells possess the ability to similarly interact with their local and systemic neural networks and the consequences of such potential interactions remains understudied. This is especially true for ovarian cancer (OC), which despite knowledge that the ovary is richly innervated and many of its core functions depend on innervation, little is known about potential OC-neuronal circuits, the molecular mechanisms governing these interactions, and therapeutic implications. The goal of this proposal is to fill this gap by developing foundational knowledge of OC neurobiology.
The central hypothesis of this proposal is that OC integrates into neuronal circuitry, remodels neuronal populations and exploits bidirectional interactions for its gain. This proposal will map ovarian-cancer neural circuits, define the consequences of cancer-neuron coupling, and test the potential for neuro-therapeutic interventions to serve as a new modality for OC. This proposal fuses classic and systems neuroscience approaches to explore ovarian-cancer neural interactions from a holistic perspective. Aim 1 will deliver the first multi-synaptic study of peripheral tumor innervation including spinal, supraspinal, and brain-wide connectivity patterns. By studying circuitry between control and cancer we will generate integrated cancer connectomes that will provide the foundations for developing new conceptual frameworks to understand information processing of cancer. Aim 2 will then use a four-pronged experimental approach to define the bidirectional molecular effects of OC-neuron coupling across. Aim 3 will test whether disrupting cancer-neuron interactions alters OC progression and response to therapy. Overall, these studies will provide foundational knowledge about changes to neuronal circuits induced by cancer and detail the cell-type specific effects of interaction with cancer. Functionally, these studies may open new avenues for OC therapy by credentialing the nervous system as a new modality. These innovative studies focus on a new discipline, incorporate new experimental approaches, and leverage new model systems which collectively represent new conceptual and technical research directions for the lab. Animal use is confined to studies for which no human substitute exists including the structural and functional neural circuit mapping of Aim 1, and the therapy-response studies of Aim 3 where computational models and in vitro methodologies do not capture the complex multisystem physiology of cancer-neuronal interactions.document fetched 2026-08-15 06:35