The Harkany group carries out frontier and multidisciplinary research, primarily focusing on the following topics:
- Endocannabinoid signaling in the developing nervous system,
- Molecular mechanisms of psychoactive drug action in the fetal brain,
- Calcium-binding protein functions in the nervous system, with particular emphasis on hypothalamic neuropeptide and hormone release,
- Molecular identity of sensory and hypothalamic neurons.
Endocannabinoid signaling during neuronal development
During the recent past, significant research activity was dedicated towards understanding the system-level, cellular and molecular organization of endocannabinoid signaling networks in the developing cerebral cortex. These studies identified endocannabinoids as axon guidance cues, and demonstrated that sub-cellular enzymatic arrangements for endocannabinoid metabolism are such that endocannabinoid signals focus in growth cones, allowing for an autocrine action for these bioactive lipids. Notably, these molecular studies also suggested that BRCA1 is a candidate ubiquitin ligase involved in determining the turnover of monoacylglycerol lipase, a rate-limiting enzyme of endocannabinoid degradation. In addition, a combination of unbiased proteomics, mouse genetics and molecular pharmacology studies demonstrated that THC from Cannabis spp. impairs synaptic organization of the cerebral cortex by modifying cytoskeletal instability. In particular, SCG10/brain-specific stathmin-2 was identified as a key molecular target downstream from CB1 cannabinoid receptors.
Calcium sensor proteins in the nervous system
Another line of research is aimed at identifying novel calcium-binding proteins (particularly sensors) in the central nervous system. A prime example is secretagogin, which is expressed during embryonic development, localizes to migrating neuronal contingents, which mature into specific and distinct subtypes of olfactory, amygdala, hippocampal and hypothalamic neurons. Recent data show that secretagogin's calcium-sensor function is required for the molecular control of CRH release in the hypothalamus upon acute stress. These studies, also combining single cell transcriptome analysis with unbiased proteomics, defined a hitherto unknown population of parvocellular neurons in the paraventricular nucleus of the hypothalamus controlling the induction of the HPA axis upon acute stress.
Tibor Harkany - Professor
Katarzyna Malenczyk - Associated
Roman Romanov - Postdoc