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Molecular and cellular neuroendocrinology – Tibor Harkany group

We carry out frontier and multidisciplinary research, primarily focusing on the topics of 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 and Molecular identity of sensory and hypothalamic neurons.

illustration adult mouse brain

Research news

Our research

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.
Illustration of Harkany laboratory research focus
Harkany Laboratory research focus. Photo: Tibor Harkany

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.

Publications

All publications from group members

  • Article: NATURE. 2024;628(8009):826-834
    Benevento M; Alpar A; Gundacker A; Afjehi L; Balueva K; Hevesi Z; Hanics J; Rehman S; Pollak DD; Lubec G; Wulff P; Prevot V; Horvath TL; Harkany T
  • Article: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2024;121(16):e2309211121
    Szodorai E; Hevesi Z; Wagner L; Hoekfelt TGM; Harkany T; Schnell R
  • Article: MOLECULAR PSYCHIATRY. 2024;29(4):859-873
    Zambon A; Rico LC; Herman M; Gundacker A; Telalovic A; Hartenberger L-M; Kuehn R; Romanov RA; Hussaini SA; Harkany T; Pollak DD
  • Article: NATURE COMMUNICATIONS. 2024;15(1):2762
    Hevesi Z; Bakker J; Tretiakov EO; Adori C; Raabgrund A; Barde SS; Caramia M; Krausgruber T; Ladstaetter S; Bock C; Hoekfelt T; Harkany T
  • Editorial comment: SCIENCE. 2023;382(6672):764-765
    Romanov RA; Harkany T
  • Editorial comment: ACTA PHYSIOLOGICA. 2023;239(2):e14033
    Harkany T; Hokfelt T
  • Review: JOURNAL OF NEUROENDOCRINOLOGY. 2023;35(9):e13320
    Cinquina V; Keimpema E; Pollak DD; Harkany T
  • Article: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2023;120(31):e2222095120
    Caramia M; Romanov RA; Syderomenos S; Hevesi Z; Zhao M; Krasniakova M; Xu Z-QD; Harkany T; Hokfelt TGM
  • Article: ACTA PHYSIOLOGICA. 2023;238(3):e13973
    Zupancic M; Tretiakov E; Mate Z; Erdelyi F; Szabo G; Clotman F; Hokfelt T; Harkany T; Keimpema E
  • Corrigendum: NATURE COMMUNICATIONS. 2023;14(1):3565
    Petersen J; Englmaier L; Artemov AV; Poverennaya I; Mahmoud R; Bouderlique T; Tesarova M; Deviatiiarov R; Szilvasy-Szabo A; Akkuratov EE; Reguera DP; Zeberg H; Kaucka M; Kastriti ME; Krivanek J; Radaszkiewicz T; Gomoryova K; Knauth S; Potesil D; Zdrahal Z; Ganji RS; Grabowski A; Buhl ME; Zikmund T; Kavkova M; Axelson H; Lindgren D; Kramann R; Kuppe C; Erdelyi F; Mate Z; Szabo G; Koehne T; Harkany T; Fried K; Kaiser J; Boor P; Fekete C; Rozman J; Kasparek P; Prochazka J; Sedlacek R; Bryja V; Gusev O; Adameyko I
  • Article: NATURE COMMUNICATIONS. 2023;14(1):3092
    Petersen J; Englmaier L; Artemov AV; Poverennaya I; Mahmoud R; Bouderlique T; Tesarova M; Deviatiiarov R; Szilvasy-Szabo A; Akkuratov EE; Pajuelo Reguera D; Zeberg H; Kaucka M; Kastriti ME; Krivanek J; Radaszkiewicz T; Goemoeryova K; Knauth S; Potesil D; Zdrahal Z; Ganji RS; Grabowski A; Buhl ME; Zikmund T; Kavkova M; Axelson H; Lindgren D; Kramann R; Kuppe C; Erdelyi F; Mate Z; Szabo G; Koehne T; Harkany T; Fried K; Kaiser J; Boor P; Fekete C; Rozman J; Kasparek P; Prochazka J; Sedlacek R; Bryja V; Gusev O; Adameyko I
  • Preprint: BIORXIV. 2023;BIORXIV
    Cronin SJF; Yu W; Hale A; Licht-Mayer S; Crabtree MJ; Korecka JA; Tretiakov EO; Sealey-Cardona M; Somlyay M; Onji M; An M; Fox JD; Turnes BL; Gomez-Diaz C; da Luz Scheffer D; Cikes D; Nagy V; Weidinger A; Wolf A; Reither H; Chabloz A; Kavirayani A; Rao S; Andrews N; Latremoliere A; Costigan M; Douglas G; Freitas FC; Pifl C; Walz R; Konrat R; Mahad DJ; Koslov AV; Latini A; Isacson O; Harkany T; Hallett PJ; Bagby S; Woolf CJ; Channon KM; Je HS; Penninger JM
  • Article: ACS CHEMICAL BIOLOGY. 2023;18(4):794-802
    Artukka E; Schnell R; Palmu K; Rosenqvist P; Szodorai E; Niemi J; Virta P; Schneider G; Metsa-Ketela M
  • Article: NEUROCHEMICAL RESEARCH. 2023;48(4):1242-1253
    Krassnitzer M; Boisvert B; Beiersdorf J; Harkany T; Keimpema E
  • Article: NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY. 2023;49(1):e12887
    Patthy A; Hanics J; Zachar G; Kovacs GG; Harkany T; Alpar A
  • Article: EMBO JOURNAL. 2022;41(24):e111648
    Glat M; Gundacker A; Rico LC; Czuczu B; Ben-Simon Y; Harkany T; Pollak DD
  • Article: NATURE COMMUNICATIONS. 2022;13(1):5944
    Korchynska S; Rebernik P; Pende M; Boi L; Alpar A; Tasan R; Becker K; Balueva K; Saghafi S; Wulff P; Horvath TL; Fisone G; Dodt H-U; Hokfelt T; Harkany T; Romanov RA
  • Review: NATURE REVIEWS NEUROSCIENCE. 2022;23(10):611-627
    Benevento M; Hoekfelt T; Harkany T
  • Article: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2022;119(16):e2200476119
    Ahmed M; Kaur N; Cheng Q; Shanabrough M; Tretiakov EO; Harkany T; Horvath TL; Schlessinger J
  • Article: VACCINES. 2022;10(4):516
    Hevesi Z; Gerges DA; Kapps S; Freire R; Schmidt S; Pollak DD; Schmetterer K; Frey T; Lang R; Winnicki W; Schmidt A; Harkany T; Wagner L
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