Veena Padmanaban, M.S., Ph.D.
Johns Hopkins University School of Medicine
Biography:
Veena Padmanaban, Ph.D. is a cancer biologist whose research explores how the nervous system shapes breast cancer progression and metastasis. She completed her Ph.D. at the Johns Hopkins School of Medicine, where she discovered that E-cadherin — a molecule traditionally viewed as a tumor suppressor — paradoxically promotes metastasis across multiple breast cancer models (Nature, 2019). As a postdoctoral fellow at The Rockefeller University in Dr. Sohail Tavazoie's laboratory, she led pioneering work demonstrating that sensory nerves actively drive breast cancer metastasis by releasing a neuropeptide that activates a pro-metastatic signaling pathway in cancer cells (Nature, 2024). This work further identified aprepitant — an FDA-approved anti-nausea agent already used in oncology — as an inhibitor of this nerve–cancer axis that significantly reduces tumor growth and metastasis in preclinical models. Dr. Padmanaban has recently launched her independent laboratory at the Johns Hopkins School of Medicine, where her group investigates how cancer cells co-opt and reprogram the peripheral nervous system across multiple stages of metastatic progression, with the goal of defining and therapeutically targeting neural dependencies in cancer. Her work has been recognized with numerous honors, including the Blavatnik Regional Award for Young Scientists, the Breakout Prize for Junior Investigators, the ASCB Merton Bernfield Award, and a Hope Funds for Cancer Research Fellowship.
Abstract:
Tumor innervation is associated with poor outcomes across multiple cancers, suggesting that the nervous system may play an active role in disease progression. We find that highly metastatic breast tumors acquire substantially greater sensory innervation than less-metastatic counterparts and that these sensory nerves are required for efficient tumor growth and metastasis. Mechanistically, breast cancer cells activate nearby sensory neurons, triggering release of the neuropeptide substance P, which initiates a signaling cascade that promotes tumor invasion, metastatic dissemination, and disease progression. Importantly, pharmacologic inhibition of this pathway using aprepitant, an FDA-approved substance P receptor antagonist, suppresses tumor growth and metastasis across multiple breast cancer models. Extending these studies beyond the primary tumor, we find that sensory innervation plays a strikingly different role at distant metastatic sites. Whereas sensory nerves promote progression at the primary tumor, sensory innervation within the metastatic microenvironment suppresses metastatic colonization through immune-dependent mechanisms, identifying local neural–immune interactions as a previously unrecognized barrier to metastatic progression. Notably, innervation at metastatic sites is dynamically regulated, suggesting that the neural landscape of metastatic niches changes over the course of disease. Together, these findings reveal that peripheral sensory nerves exert distinct, context-dependent effects on cancer progression and establish neural signaling as a dynamic regulator of metastatic fate. More broadly, they suggest that targeting neural signaling pathways may provide a clinically tractable strategy to prevent metastatic progression and relapse.
Veena Padmanaban, Ph.D. is a cancer biologist whose research explores how the nervous system shapes breast cancer progression and metastasis. She completed her Ph.D. at the Johns Hopkins School of Medicine, where she discovered that E-cadherin — a molecule traditionally viewed as a tumor suppressor — paradoxically promotes metastasis across multiple breast cancer models (Nature, 2019). As a postdoctoral fellow at The Rockefeller University in Dr. Sohail Tavazoie's laboratory, she led pioneering work demonstrating that sensory nerves actively drive breast cancer metastasis by releasing a neuropeptide that activates a pro-metastatic signaling pathway in cancer cells (Nature, 2024). This work further identified aprepitant — an FDA-approved anti-nausea agent already used in oncology — as an inhibitor of this nerve–cancer axis that significantly reduces tumor growth and metastasis in preclinical models. Dr. Padmanaban has recently launched her independent laboratory at the Johns Hopkins School of Medicine, where her group investigates how cancer cells co-opt and reprogram the peripheral nervous system across multiple stages of metastatic progression, with the goal of defining and therapeutically targeting neural dependencies in cancer. Her work has been recognized with numerous honors, including the Blavatnik Regional Award for Young Scientists, the Breakout Prize for Junior Investigators, the ASCB Merton Bernfield Award, and a Hope Funds for Cancer Research Fellowship.
Abstract:
Tumor innervation is associated with poor outcomes across multiple cancers, suggesting that the nervous system may play an active role in disease progression. We find that highly metastatic breast tumors acquire substantially greater sensory innervation than less-metastatic counterparts and that these sensory nerves are required for efficient tumor growth and metastasis. Mechanistically, breast cancer cells activate nearby sensory neurons, triggering release of the neuropeptide substance P, which initiates a signaling cascade that promotes tumor invasion, metastatic dissemination, and disease progression. Importantly, pharmacologic inhibition of this pathway using aprepitant, an FDA-approved substance P receptor antagonist, suppresses tumor growth and metastasis across multiple breast cancer models. Extending these studies beyond the primary tumor, we find that sensory innervation plays a strikingly different role at distant metastatic sites. Whereas sensory nerves promote progression at the primary tumor, sensory innervation within the metastatic microenvironment suppresses metastatic colonization through immune-dependent mechanisms, identifying local neural–immune interactions as a previously unrecognized barrier to metastatic progression. Notably, innervation at metastatic sites is dynamically regulated, suggesting that the neural landscape of metastatic niches changes over the course of disease. Together, these findings reveal that peripheral sensory nerves exert distinct, context-dependent effects on cancer progression and establish neural signaling as a dynamic regulator of metastatic fate. More broadly, they suggest that targeting neural signaling pathways may provide a clinically tractable strategy to prevent metastatic progression and relapse.
