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Current Research and Scholarly InterestsWe study cancer biology, intestinal stem cells (ISC), and angiogenesis. We use primary organoid cultures of diverse tissues and tumor biopsies for immunotherapy modeling, oncogene functional screening and stem cell biology. Angiogenesis projects include blood-brain barrier regulation, stroke therapeutics and anti-angiogenic cancer therapy. ISC projects apply organoid culture and ko mice to injury-inducible vs homeostatic stem cells and symmetric division mechanisms.

Christin S Kuo

Assistant Professor of Pediatrics (Pulmonary Medicine)

BioDr. Kuo is a physician-scientist with expertise in single-cell genomics and pulmonary medicine. She has made pioneering contributions to pulmonary neuroendocrine cell (PNEC) biology by developing innovative strategies that established the first comprehensive framework for understanding the molecular and cellular diversity of normal PNECs and their roles in health and disease. Her discoveries have laid the foundation for this emerging field and her contributions are recognized internationally.

PNECs are exceedingly rare lung epithelial cells with specialized airway sensory, secretory, and stem cell functions. These neurosensory cells are thought to monitor airway oxygen, chemicals, mechanical deformation, infection, and injury, and serve as sentinels that signal this sensory information locally in the lung, to the brain through synapses with pulmonary sensory neurons and potentially globally throughout the body via secretion of myriad local signals and hormones. PNECs are also known to play critical roles in the control of breathing, cough, and respiratory physiology. Among their diverse physiologic functions, their response to injury has been most intensively studied in murine models and they are a cell of origin for high grade lung neuroendocrine tumors.

Dr. Kuo performed the first comprehensive anatomical mapping and lineage tracing studies of PNECs in mice which generated a foundational understanding of PNEC development (Kuo and Krasnow, Cell 2015). She also led single cell transcriptomic profiling studies that revealed a surprising diversity in PNEC sensors and signals (Kuo et al, eLife 2022). PNECs express over 25 different sensory receptor genes ("sensors") and over 40 different neuropeptide and peptide hormone genes ("signals"). Her scRNA-seq analysis of PNECs revealed a remarkable number and diversity of PNEC neuropeptide signals and their predicted cellular targets both within the lung and to innervating sensory neurons (Kuo et al., 2022, eLife).

In contrast to the advanced understanding of PNEC development, stem cell, and signaling function in mouse, little is known about human PNECs. To compare the findings of PNEC development, diversity, and function in mouse models to human diseases, her lab recently established a platform to systematically construct a human PNEC atlas. This foundational work created a molecular and anatomic framework for the entire human pulmonary neuroendocrine system and the diseases that are predicted to originate from distinct PNECs. Her lab has recently used this new PNEC atlas combined with single cell transcriptomic approaches to identify the molecular diversity of anatomically and functionally distinct human PNECs.

Dr. Kuo's studies with human models extends her lab’s current research aims to define the diverse neuroendocrine sensory and signaling interactions and the molecules that mediate them to their roles in lung cancer, neuroendocrine proliferative disorders such as diffuse idiopathic neuroendocrine cell hyperplasia (DIPNECH), neuroendocrine cell hyperplasia of infancy (NEHI) and major inflammatory and obstructive pulmonary diseases. Dr. Kuo’s lab engages a network of collaborators to develop and implement clinical protocols and strategically apply cutting-edge technologies to studying minor, but physiologically diverse airway sentinels.

Please visit the research website for additional information and current research areas (https://kuo.stanford.edu).