Project Grant R01DK143587

The National Institute of Diabetes and Digestive and Kidney Diseases awarded Icahn School of Medicine at Mount Sinai $814,028 on September 1, 2026, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) to investigate the cellular and molecular mechanisms mediating mechanosensitivity and interoceptive signaling in the mouse distal colon.

The funded research focuses on uncovering how the colon generates gut-derived interoceptive signals through the sensory nervous system. Mount Sinai's laboratories employ genetic tools enabling precise manipulation of molecularly distinct neuronal populations, including targeted cell ablation and optogenetic activation, to study the role of PIEZO2 channels as mechanoreceptors in colon-innervating spinal visceral afferents. Preliminary findings identify a neural circuit linking tachykinin receptor 3-positive neurons in the spinal dorsal horn (TACR3SDH neurons) to prodynorphin-expressing neurons in the parabrachial nucleus (PDYNPBN neurons) in processing visceral signals. The research will investigate whether TACR3SDH neurons form functional synaptic connections with colon-innervating spinal visceral afferents and project to PDYNPBN neurons, testing the central hypothesis that this distinct circuit mediates interoceptive signaling from the colon.

Performance occurs in New York, New York, with an ultimate completion date of May 30, 2030. The award is a Project Grant, an assistance type supporting extramural basic and clinical biomedical research improving understanding of disease mechanisms and leading to improved prevention, diagnosis, and treatment.