Dr. Kirill Martemyanov is Professor and Chair of the Department of Physiology & Biophysics at the University of Miami Miller School of Medicine. His laboratory dissects GPCR signaling logic in the nervous system with a particular emphasis on how “non-canonical” GPCR-like receptors control cAMP homeostasis, neuronal excitability, and synaptic plasticity across circuits relevant to affect, motivation, reward, and stress adaptation. In a series of mechanistic studies, his group established the orphan receptor GPR158 as a stress-inducible, glucocorticoid-responsive molecular switch in medial prefrontal cortex (mPFC) that tracks and drives vulnerability versus resilience to stress-induced depressive-like states: chronic stress elevates GPR158 in PFC, GPR158 gain-of-function in PFC is sufficient to induce depressive-like behaviors, and GPR158 loss produces a strong antidepressant-like, stress-resilient phenotype.

Mechanistically, his work links this behavioral control to cortical synaptic strengthening pathways—including AMPA receptor–dependent synaptic adaptations, elevated mPFC cAMP/PKA signaling, and downstream effects consistent with restoring synaptic efficacy and neurotrophic support (e.g., BDNF-linked biology).

More recently, Martemyanov’s group helped “deorphanize” GPR158 by identifying it as a metabotropic glycine receptor (mGlyR): glycine (and the related modulator taurine) directly bind an extracellular Cache domain on GPR158 and modulate signaling through the receptor’s associated RGS7/Gβ5 complex, producing measurable effects on cAMP and neuronal excitability without engaging classical GPCR G-protein activation or β-arrestin recruitment in standard assays.