Mechanisms of Somatosensory Development & Disease

A major determining factor in both healthy and pathological skin is the interaction between skin-innervating sensory afferent neurons, epithelial cells, and sensory receptors for touch and pain. The plasticity of these afferent neurons and the signaling of skin cells following irritation and nerve damage from injury or disease are important in recovering and maintaining healthy skin. When this signaling goes wrong, normally healthy responses become disruptive, chronic conditions. The SENse Lab has studied numerous somatosensory diseases, such as atopic dermatitis, xeroderma (dry skin), and psoriasis, and how worsening disease states progress physiologically at the site of disruption – the skin. 

The top-most layer of the skin, the epidermis, is predominantly populated by keratinocytes, or the primary epithelial cells of the skin. Previously, the SENse Lab identified a key signaling molecule released by keratinocytes that activates both primary afferent neurons and immune cells to promote inflammatory responses in the skin and airways. These keratinocyte-neuron interactions are thought to drive atopic dermatitis and atopic march, a phenomenon where patients with atopic dermatitis go on to develop asthma and allergic rhinitis.
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In the vein of sensory cell and neuronal interactions, the SENse Lab is currently studying the sensory mechanoreceptor cell that mediates light touch, the Merkel cell, and their attendant somatosensory afferent neurons. This unit, the Merkel cell-neurite complex, is unique to vertebrates and provides us with touch information on pressure, position, and features, such as shapes and edges. This project studies the dynamics of Merkel cell-neurite complex remodeling using in vivo time-lapse imaging to study how neurons and Merkel cells change their patterning during skin homeostasis.

Animated 3-D imaging of Merkel cells and attendant sensory afferent neurons.

Figure adapted from Hill RZ, Bautista DM. 2020. Trends in Neuroscience. doi: 10.1016/j.tins.2020.03.004.

Beyond just understanding the molecular players in sensory transduction, the lab is also interested in exploring how genetics and early environmental experiences shape the circuitry underlying sensory processing, such as tactile sensory seeking and avoidance behaviors and perceptual thresholds, and how such circuitry may differ in pathological conditions.

However, even healthy organisms can have altered perception of environmental stimuli through psychedelics.

Psychedelics have a long history of being used for their ability to change perception, but much remains to be discovered regarding the cellular and molecular mechanisms by which these changes in sensory processing occur. The SENse Lab is interested in understanding how psychedelics affect somatosensory transduction and dissecting the peripheral and central nervous system (PNS and CNS, respectively) mechanisms underlying these changes. Insights gained from this research could potentially yield novel treatment strategies for people dealing with sensory processing disorders, such as tactile hypersensitivity.

​Another sensory processing disorder the SENse Lab is interested in is peripheral neuropathy. Peripheral neuropathy is the damage or dysfunction of the peripheral nerves, which can result in numbness, sharp pain, tingling or burning sensations, muscle weakness, and allodynia, where typically gentle, non-nociceptive touch is perceived as painful. Chemotherapy induced peripheral neuropathy (CIPN) is a debilitating condition that occurs in 40-80% of cancer patients undergoing chemotherapy treatment. CIPN susceptibility varies among the population and it is unclear what genes or genetic networks determine the risk of CIPN and how these dysregulated networks give rise to the range of sensory symptoms. Our lab is currently identifying the biological factors that predispose individuals to CIPN and drive CIPN pathogenesis.

Time-lapse of neurite regrowth.

In healthy and disease states such as CIPN, there is typically a period of increased plasticity and growth of neurons following nerve damage. A Southeast Asian subspecies of mouse (Mus musculus castaneus) has previously been reported to regrow CNS axons after injury more effectively than other mice. Based on the natural variation in axon regeneration between the M. m. castaneous and the more commonly used M. m. musculus, the lab is using a novel screening method to identify the natural genetic variants underlying this regenerative phenotype to parse the biology of axon damage response and regeneration.