Rath Lab – University of Copenhagen

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Department of Neuroscience > Research Groups > Rath Lab

Rath Lab


Lab leader: Martin Fredensborg Rath, MSc, PhD, Associate professor.

Circadian rhythms are endogenous rhythms with a 24-hour period that enable living organisms to synchronize biological functions to the ambient light regime. In the mammalian brain circadian rhythms are regulated by the photoneuroendocrine system consisting of the suprachiasmatic nucleus of hypothalamus, the pineal gland and the retina. In a combined effort involving neuroanatomical and molecular biological techniques, we are studying development and function of the circadian system of the mammalian brain.

Homeobox genes in development and adult function of the mammalian circadian neuroendocrine system. We have shown that homeobox gene-encoded transcription factors in are essential in both development and mature function of the circadian neuroendocrine system with focus on the pinealocyte, the principal melatonin-producing cell-type of the pineal gland.

The circadian system of the mammalian brain: circadian function and hormonal regulation of local peripheral clocks in the neocortex and cerebellum.  We have shown that the circadian system extends from the hypothalamus into other parts of the brain, including the cerebral cortex and the cerebellum, both of which receive a circadian input from the hypothalamus. In the cerebral cortex, the circadian clock is located in neurons, as evidenced by our finding of rhythmic expression of clock genes in these cells. Our most recently published results on a novel conditional knockout mouse show that disruption of the cortical circadian clock affects monoamine signaling and induces symptoms of depression; thus, we have used a basic scientific approach to shed light on the etiology of a major psychiatric disorder.


CV

Academic degrees
2005: MSc in Human Biology, Faculty of Health Sciences, UCPH
2009: PhD in Medical Sciences, Faculty of Health Sciences, UCP

Academic positions (selected)
2004-2007: Visiting research associate, Section on Neuroendocrinology (PI: Dr. David C. Klein), National Institutes of Health (NIH), Bethesda, MD, USA
2009-2013: Postdoc, Department of Neuroscience and Pharmacology (DNP), UCPH
2013-2014: Assistant professor (tenure-track), DNP, UCPH
2014-2017: Associate professor of Structural Neurobiology , DNP, UCPH
2017-: Associate professor of Structural Neurobiology , Department of Neuroscience, UCPH

Bibliometric data
Peer-reviewed journal articles: 34
First authorships: 10
Senior authorships: 7
Corresponding authorships: 15
H-index: 16

Grants (selected)
2009: The Danish Council for Independent Research (3,200,000 DKK)
2010: The Lundbeck Foundation (1,300,000 DKK).
2013: The Lundbeck Foundation (1,500,000 DKK).
2015: The Novo Nordisk Foundation (1,500,000 DKK).
A total of 8,500,000 DKK.

Academic assessments
2011, 2013, 2014: Associate professor qualified (UCPH)
2016: Full professor qualified (Aarhus University)

Invited talks (selected)
2007: Workshop on the Biology of Pax4, National Institutes of Health, Bethesda, MD, USA
2008: Gordon Research Conference on Pineal Cell Biology, Lucca, Italy
2010: Gordon Research Conference on Pineal Cell Biology, Galveston, TX, USA
2013: XII Latin-American Symposium of Chronobiology, Mendoza, Argentina
2016: Annual meeting of Society for Biological Rhythms, Columbia University, NYC, USA
2018: Society for Research on Biological Rhythms Meeting, Amelia Island, FL, USA (scheduled)

Teaching (selected)
2009.: Teaching and examination in neuroanatomy, gross anatomy, histology and embryology for medical students
2010-2015: Director and organizer of PhD-course in Molecular Methods in Neuroanatomy,
2012-: Organizer of pregraduate course in Neuroanatomy for medical students
2013-: Supervision of bachlelor, master’s and PhD-students
2017-: Director and organizer of PhD-course in Anatomy of the Central Nervous System

Peer-reviewed publications

34) Bering T, Carstensen MB and Rath MF (2017) Deleting the Arntl clock gene in the granular layer of the mouse cerebellum: impact on the molecular circadian clockwork. J Neurochem doi:10.1111/jnc.14128.

33) Rohde K, Bering T, Furukawa T and Rath MF (2017) A modulatory role of the Rax homeobox gene in mature pineal gland function: Investigating the photoneuroendocrine circadian system of a Rax conditional knockout mouse. J Neurochem doi:10.1111/jnc.14120.

32) Bering T, Carstensen MB, Wörtwein G, Weikop P and Rath MF (2017) The circadian oscillator of the cerebral cortex: Molecular, biochemical and behavioral effects of deleting the Arntl clock gene in cortical neurons. Cereb Cortex doi:10.1093/cercor/bhw406.

31) Møller M, Rath MF, Ludvigsen M, Honoré B and Vorum H (2017) Diurnal expression of proteins in the retina of the blind cone-rod homeobox (Crx-/-) mouse and the 129/Sv mouse: a proteomic study. Acta Ophthalmol doi:10.1111/aos.13429.

30) Rath MF, Coon SL, Amaral FG, Weller JL, Møller M and Klein DC (2016) Melatonin synthesis: Acetylserotonin O-methyltransferase (ASMT) is strongly expressed in a subpopulation of pinealocytes in the male rat pineal gland. Endocrinology 157:2028-2040.

29) Yamazaki F, Møller M, Fu C, Clokie SJ, Zykovich A, Coon SL, Klein DC and Rath MF (2015) The Lhx9 homeobox gene controls pineal gland development and prevents postnatal hydrocephalus. Brain Struct Funct 220:1497-1509.

28) Rohde K, Rovsing L, Ho AK, Møller M and Rath MF (2014) Circadian dynamics of the cone-rod homeobox (CRX) transcription factor in the rat pineal gland and its role in regulation of arylalkylamine N- acetyltransferase (AANAT). Endocrinology 155:2966-2975.

27) Rath MF, Gothilf Y, Guido M and Munoz E (2014) Circadian system development and plasticity. Biomed Res Int 2014:436760.

26) Rath MF, Rovsing L and Møller M (2014) Circadian oscillators in the mouse brain: molecular clock components in the neocortex and cerebellar cortex. Cell Tissue Res 357:743-755.

25) Rohde K, Møller M and Rath MF (2014) Homeobox genes and melatonin synthesis: regulatory roles of the cone-rod homeobox (CRX) transcription factor in the rodent pineal gland. Biomed Res Int 2014:946075.

24) Rath MF, Rohde K, Klein DC and Møller M (2013) Homeobox genes in the rodent pineal gland: roles in development and phenotype maintenance. Neurochem Res 38:1100-1112.

23) Rovsing L, Rath MF and Møller M (2013) Hypothalamic neurosecretory and circadian vasopressinergic neuronal systems in the blind cone-rod homeobox knock out mouse (Crx-/-) and the 129sv wild type mouse. J Comp Neurol 521:4061-4074.

22) Karlsen AS, Rath MF, Rohde K, Toft T and Møller M (2013) Developmental and diurnal expression of the synaptosomal-associated protein (Snap25) in the rat pineal gland. Neurochem Res 38:1219-1228.

21) Rath MF, Rohde K, Fahrenkrug J and Møller M (2013) Circadian clock components in the rat neocortex: daily dynamics, localization and regulation. Brain Struct Funct 218:551-562.

20) Rath MF, Rohde K and Møller M (2012) Circadian oscillations of molecular clock components in the cerebellar cortex of the rat. Chronobiol Int 29:1289-1299.

19) Coon SL, Munson PJ, Cheruki PF, Sugden D, Rath MF, Møller M, Clokie S, Fu C, Olanich ME, Rangel Z, Werner T, NISC Comparative Sequencing Program , Mullikin JC and Klein DC (2012) Circadian changes in long noncoding RNAs in the pineal gland. Proc Natl Acad Sci U S A 109:13319-13324.

18) Rovsing L, Clokie S, Bustos DM, Rohde K, Coon SL, Litman T, Rath MF, Møller M and Klein DC (2011) Crx broadly modulates the pineal transcriptome. J Neurochem 119:262-274.

17) Rohde K, Klein DC, Møller M and Rath MF (2011) Rax: developmental and daily expression patterns in the rat pineal gland and retina. J Neurochem 118:999-1007.

16) Bustos DM, Bailey MJ, Sugden D, Carter DA, Rath MF, Møller M, Coon SL, Weller JL and Klein DC (2011) Global daily dynamics of the pineal transcriptome. Cell Tissue Res 344:1-11.

15) Savastano LE, Castro AE, Fitt MR, Rath MF, Romeo HE and Muñoz EM  (2010) A standardized surgical technique for rat superior cervical ganglionectomy. J Neurosci Methods 192:22-33.

14) Rovsing L, Rath MF, Lund-Andersen C, Klein DC and Møller M (2010) A neuroanatomical and physiological study of the non-image forming visual system of the cone-rod homeobox gene (Crx) knock out mouse. Brain Res 1343:54-65.

13) Klein DC, Bailey MJ, Carter DA, Kim JS, Shi Q, Ho AK, Chick CL, Gaildrat P, Morin F, Ganguly S, Rath MF, Møller M, Sugden D, Rangel ZG, Munson PJ, Weller JL and Coon SL (2010) Pineal function: impact of microarray analysis. Mol Cell Endocrinol 314:170-183.

12) Kim JS, Bailey MJ, Weller JL, Sugden D, Rath MF, Møller M and Klein DC (2010) Thyroid hormone and adrenergic signaling interact to control pineal expression of the dopamine receptor D4 gene (Drd4). Mol Cell Endocrinol 314:128-135.

11) Kim JS, Coon SL, Weller JL, Blackshaw S, Rath MF, Møller M and Klein DC (2009) Muscleblind-like 2: Circadian expression in the pineal gland is controlled by an adrenergic-cAMP mechanism. J Neurochem 110:756-64.

10) Larsen KB, Lutterodt M, Rath MF and Møller M (2009) Expression of the homeobox genes PAX6, OTX2, and OTX1 in the early human fetal retina. Int J Dev Neurosci 27:485-492.

9) Bailey MJ, Coon SL, Carter DA, Humphries A, Kim JS, Shi Q, Gaildrat P, Morin F, Ganguly S, Hogenesch JB, Weller JL, Rath MF, Møller M, Baler R, Sugden D, Rangel ZG, Munson PJ and Klein DC (2009) Night/day changes in pineal expression of >600 genes: central role of cAMP. J Biol Chem 284:7606-7622.

8) Rath MF, Bailey MJ, Kim JS, Coon SL, Klein DC and Møller M (2009) Developmental and daily expression of the Pax4 and Pax6 homeobox genes in the rat retina: localization of Pax4 in photoreceptor cells. J Neurochem 108:285-294.

7) Rath MF, Bailey MJ, Kim JS, Ho AK, Gaildrat P, Coon SL, Møller M and Klein DC (2009) Developmental and diurnal dynamics of Pax4 expression in the mammalian pineal gland: Nocturnal down-regulation is mediated by adrenergic-cyclic AMP signaling. Endocrinology 150:803-811.

6) Klitten LL, Rath MF, Coon SL, Kim JS, Klein DC and Møller M (2008) Localization and regulation of dopamine receptor D4 expression in the adult and developing rat retina. Exp Eye Res 87:471-477.

5) Bak M, Silahtaroglu A, Møller M, Christensen M, Rath MF, Skryabin B, Tommerup N and Kauppinen S (2008) MicroRNA expression in the adult mouse central nervous system. RNA 14:1-13.

4) Rath MF, Morin F, Shi Q, Klein DC and Møller M (2007) Ontogenetic expression of the Otx2 and Crx homeobox genes in the retina of the rat. Exp Eye Res 85:65-73.

3) Muñoz EM, Bailey MJ, Rath MF, Shi Q, Morin F, Coon SL, Møller M and Klein DC (2007) NeuroD1: developmental expression and regulated genes in the rodent pineal gland. J Neurochem 102:887-899.

2) Møller M, Rath MF and Klein DC (2006) The perivascular phagocyte of the mouse pineal gland: an antigen presenting cell. Chronobiol Int 23:393-401.

1) Rath MF, Muñoz E, Ganguly S, Morin F, Shi Q, Klein DC and Møller M (2006) Expression of the Otx2 homeobox gene in the developing mammalian brain: embryonic and adult expression in the pineal gland. J Neurochem 97:556-566.


Lab members:

Martin Fredensborg Rath, MSc, PhD, Associate professor.

 Kristian Rohde, MSc, PhD, Postdoc.

Tenna Bering, DVM, PhD-student:
http://cns.ku.dk/staff/?id=315510&vis=medarbejder

Rikke Lundorf, Laboratory technician:
http://cns.ku.dk/staff/?id=307493&vis=medarbejder

  

Morten Møller, MD, DrMedSci, Professor emeritus.