Nørremølle Group

Medical Genetics Program 

Main Research Areas

picture of mouseMolecular genetics of inherited, neurodegenerative disorders, especially Huntington disease. Investigations of genetic and cellular factors influencing the pathological mechanism and disease progression.

Practical Laboratory Experience

Basal DNA-techniques (PCR, DNA-sequencing, cloning etc.), basal RNA-techniques (p-PCR), protein analysis (western blotting), cell culture, in vitro expression (transfection, viral transduction), animal experiments.

Research profile and current research programme

In the Nørremølle research group our goal is to understand the pathogenic mechanisms causing the cellular damage in inherited neurodegenerative disorders, with specific focus on Huntington disease. In this disease, despite a well-characterized disease-causing mutation, neither the physiological functions nor the mechanisms behind the pathological changes are known. Right now we concentrate on investigating the metabolic changes observed in both neuronal and non-neuronal cell types in Huntington disease cell and animal models. We study mitochondrial function and oxidative stress in order to understand the importance of these processes in the disease, and aiming to characterize new targets for future treatment strategies.

In another line of research, we analyze the DNA sequence of the huntingtin gene region in Danish patients with Huntington disease, looking for DNA variants that modify the disease onset or progression. The rationale is that genes carrying these variants represent possible targets for treatment: modifying the modifiers.

In addition to our work in Huntington disease research we participate in collaborations investigating other inherited neurodegenerative disorders.

Teaching profile

Anne Nørremølle is course director of the course in Medical Genetics, offered to students of medicine as well as molecular biomedicine. This course runs twice a year with a total of 576 students per year. We aim to constantly develop the teaching methods and curriculum in order to optimize the student’s motivation and learning outcome. In addition, we offer a course in Gene Therapy for master level students of molecular biomedicine, biochemistry, biology and biotechnology. This course conveys up-to-date knowledge of a quickly developing field of research through original scientific papers and lectures from scientist in the field. Finally, the Nørremølle group has supervised numerous bachelor-, master- and Ph.D.-students, all of which have graduated with very good or excellent grades.

Selected publications

  • Nielsen SM, Vinther-Jensen T, Nielsen JE, Nørremølle A, Hasholt L, Hjermind LE, Josefsen K. Liver function in Huntington's disease assessed by blood biochemical analyses in a clinical setting. J Neurol Sci. 2016 Mar 15;362:326-32.

  • Vinther-Jensen T, Nielsen TT, Budtz-Jørgensen E, Larsen IU, Hansen MM, Hasholt L, Hjermind LE, Nielsen JE, Nørremølle A. Psychiatric and cognitive symptoms in Huntington's disease are modified by polymorphisms in catecholamine regulating enzyme genes. Clin Genet. 2015 Jun 17.

  • Nielsen SM, Hasholt L, Nørremølle A, Josefsen K. Progressive Impairment of Lactate-based Gluconeogenesis in the Huntington's Disease Mouse Model R6/2. PLoS Curr. 2015 Apr 20;7.

  • Bečanović K, Nørremølle A, Neal SJ, Kay C, Collins JA, Arenillas D, Lilja T, Gaudenzi G, Manoharan S, Doty CN, Beck J, Lahiri N, Portales-Casamar E, Warby SC, Connolly C, De Souza RA; REGISTRY Investigators of the European Huntington's Disease Network, Tabrizi SJ, Hermanson O, Langbehn DR, Hayden MR, Wasserman WW, Leavitt BR. A SNP in the HTT promoter alters NF-κB binding and is a bidirectional genetic modifier of Huntington disease. Nat Neurosci. 2015 May 4.

  • Vinther-Jensen T, Larsen IU, Hjermind LE, Budtz-Jørgensen E, Nielsen TT, Nørremølle A, Nielsen JE, Vogel A. A clinical classification acknowledging neuropsychiatric and cognitive impairment in Huntington's disease. Orphanet Journal of Rare Diseases 2014 Jul 17;9:114

  • Petersen MH, Budtz-Jørgensen E, Sørensen SA, Nielsen JE, Hjermind LE, Vinther-Jensen T, Borch Nielsen SM, Nørremølle A. Reduction in mitochondrial DNA copy number in peripheral leukocytes after onset of Huntington’s disease. Mitochondrion 2014 May 15;17C:14-21.

  • Aidt FH, Nielsen SM, Kanters J, Pesta D, Nielsen TT, Nørremølle A, Hasholt L, Christiansen M, Hagen CM. Dysfunctional mitochondrial respiration in the striatum of the Huntington's disease transgenic R6/2 mouse model. PLoS Curr. 2013 Apr 2;5.

  • Josefsen K, Nielsen SMB, Campos A, Seifert T, Hasholt L, Nielsen JE, Nørremølle A, Skotte NH, Secher NH, Quistorff B. Reduced gluconeogenesis and lactate clearance in Huntington's disease. Neurobiol Dis. 2010 Dec;40(3):656-62. Epub 2010 Aug 19.

  • Nørremølle A, Budtz-Jørgensen E, Fenger K, Nielsen JE, Sørensen SA, Hasholt L. 4p16.3 haplotype modifying age at onset of Huntington disease. Clinical Genetics 2009 Mar;75(3):244-50.

  • Nørremølle A, Hasholt L, Petersen CB, Eiberg H, Hasselbalch SG, Gideon P, Nielsen JE, Sørensen SA. Mosaicism of the CAG repeat sequence in the Huntington disease gene in a pair of monozygotic twins. Am J Med Genet A. 2004 Oct 1;130A(2):154-9.

  • Hasholt L, Abell K, Nørremølle A, Nellemann C, Fenger K, Sørensen SA. Antisense downregulation of mutant huntingtin in a cell model. J Gene Med. 2003 Jun;5(6):528-38.

  • Nørremølle A, Grunnet M, Hasholt L, Sørensen SA. Cells exposed to a huntingtin fragment containing an expanded polyglutamine tract show no sign of ion channel formation: results arguing against the ion channel hypothesis. J Neurosci Res. 2003 Jan 1;71(1):132-7.

  • Nellemann C, Abell K, Nørremølle A, Løkkegaard T, Naver B, Röpke C, Rygaard J, Sørensen SA, Hasholt L. Inhibition of Huntington synthesis by antisense oligodeoxynucleotides. Mol Cell Neurosci. 2000 Oct;16(4):313-23.

  • Makransky G, Bonde MT, Wulff JS, Wandall J, Hood M, Creed PA, Bache I, Silahtaroglu A, Nørremølle A. Simulation based virtual learning environment in medical genetics counseling: an example of bridging the gap between theory and practice in medical education. BMC Med Educ. 2016 Mar 25;16(1):98.