Kaie Hall
Program: Unspecified
Current advisor:
Undergraduate university: Howard University
Research summary
Torpor is a physiological state characterized by hypometabolism and hypothermia entered by a diverse range of mammalian species as a survival strategy to conserve energy during periods of environmental stress. Torpor, like hibernation, has been associated with a wide range of physiological effects, from tissue preservation and protection from muscle atrophy to age-related decline. Across hibernating species a profound reduction in circulating leukocytes during torpor has been consistently observed. It has recently been found that we can induce torpor using either chemogenetics or focused ultrasound targeted to the preoptic area of the brain. Using these technologies we can induce a synthetic torpor, recapitulating the hypometabolism and hypothermia observed in natural hibernators, raising the question of whether the associated leukopenia can also be synthetically induced.
Currently no published data exists characterizing the effect of synthetic torpor on the immune system. Before synthetic torpor can be safely and rationally translated into clinical medicine, a rigorous understanding of its immunological consequences is essential. Natural hibernation provides a compelling biological precedent — multiple studies in hibernating mammals including thirteen-lined ground squirrels, brown bears, monito del montes, among others demonstrated a profound leukocytopenia during torpor, thought to be driven in part by temperature-dependent alterations in sphingosine-1-phosphate mediated lymphocyte trafficking. If synthetic torpor recapitulates this immune phenotype in a controllable and reversible manner, it represents a fundamentally novel approach to immune modulation with broad therapeutic implications. Current immunosuppressive therapies, while effective, carry significant risks including opportunistic infection, malignancy, and end-organ toxicity resulting from their systemic and sustained mechanisms of action. A synthetic torpor based approach would offer immune modulation that is titratable, reversible upon cessation of the intervention, and mechanistically distinct from pharmacological immunosuppression. Establishing whether synthetic torpor produces leukocytopenia is therefore the critical first step toward determining whether this approach can be harnessed therapeutically in conditions characterized by pathological immune activation, including sepsis, autoimmune disease, and transplant rejection.
Graduate publications