Deborah E. Cabin, PhD

Professor, Emeritus

Education 

Johns Hopkins University, BA, Biology, 1978

Johns Hopkins University School of Medicine, PhD, Physiology, 1996

Postdoctoral Fellow, Dr. Roger H. Reeves, Dept. of Physiology, Johns Hopkins School of Medicine, Baltimore, MD, 1996-1998

Postdoctoral Fellow, Dr. Robert L. Nussbaum, Genetic Disease Research Branch, National Human Genome Research Institute, Bethesda, MD, 1998-2006

  • 2006-2019 | Assistant Professor. McLaughlin Research Institute, Great Falls, MT

    2019 - 2021 | Associate Professor. McLaughlin Research Institute, Great Falls, MT

    2021-Present | Professor, Vice President. McLaughlin Research Institute, Great Falls, MT

    2006-2016 | Adjunct Faculty. Center for Structural and Functional Neuroscience, University of Montana, Missoula, MT

    2008-Present | Affiliate Faculty, Dept. of Cell Biology and Neuroscience, Montana State University, Bozeman MT

  • Research in my lab has focused for many years on the protein alpha-synuclein and its role in Parkinson's disease. Mutations in alpha-synuclein cause a rare familial form of Parkinson's disease, but the protein is also implicated in the more common sporadic Parkinson's. We are interested in 1) the mechanism by which alpha-synuclein causes disease more, 2) alpha-synuclein's normal functions in neurons more, and 3) using human alpha-synuclein to develop a progressive mouse model of Parkinson's disease. more.

    A more recent interest is prion disease.  Prion disease is caused by misfolded prion protein.  We do not yet understand how misfolded prion protein causes disease, but we know the misfolding propagates through the brain, as a misfolded molecule acts as a template to cause another molecule to unfold.  In a collaboration with Eric Minikel and Socia Vallabh at the Broad Institute and with Ionis Pharmaceuticals, we have shown that lowering prion protein levels in mice using oligonucleotides directed at the prion protein messenger RNA can prolong lifespan significantly.  We are continuing this work using humanized mouse models.  more.

    Prion diseases are rare in humans, but mechanistically there are similarities with more common neurodegenerative diseases like Parkinson’s, Alzheimer’s, and Huntington’s.  These are all protein misfolding disorders, with different proteins affected in each case.  In Parkinson's disease, alpha-synuclein is the misfolded protein.  We predict that lowering the levels of the specific proteins involved in each of these diseases should be a useful therapeutic that will slow or stop disease progression.

  • PrP concentration in the central nervous system: regional variability, genotypic effects, and pharmacodynamic impact.

    Mortberg MA, Zhao HT, Reidenbach AG, Gentile JE, Kuhn E, O'Moore J, Dooley PM, Connors TR, Mazur C, Allen SW, Trombetta BA, McManus AJ, Moore MR, Liu J, Cabin DE, Kordasiewicz HB, Mathews J, Arnold SE, Vallabh SM, Minikel EV. JCI Insight. 2022 Feb 8:e156532. doi: 10.1172/jci.insight.156532. Online ahead of print. PMID: 35133987

    Prion protein lowering is a disease-modifying therapy across prion disease stages, strains and endpoints.

    Minikel EV, Zhao HT, Le J, O'Moore J, Pitstick R, Graffam S, Carlson GA, Kavanaugh MP, Kriz J, Kim JB, Ma J, Wille H, Aiken J, McKenzie D, Doh-Ura K, Beck M, O'Keefe R, Stathopoulos J, Caron T, Schreiber SL, Carroll JB, Kordasiewicz HB, Cabin DE, Vallabh SM. Nucleic Acids Res. 2020 Nov 4;48(19):10615-10631. doi: 10.1093/nar/gkaa616. PMID: 32776089

    Antisense oligonucleotides extend survival of prion-infected mice.

    Raymond GJ, Zhao HT, Race B, Raymond LD, Williams K, Swayze EE, Graffam S, Le J, Caron T, Stathopoulos J, O'Keefe R, Lubke LL, Reidenbach AG, Kraus A, Schreiber SL, Mazur C, Cabin DE, Carroll JB, Minikel EV, Kordasiewicz H, Caughey B, Vallabh SM. JCI Insight. 2019 Jul 30;5(16):e131175. doi: 10.1172/jci.insight.131175. PMID: 31361599

    Cabin, D.E. and G. Carlson, 2008. Gene Mapping to Gene Targeting: Application of Mouse Genetics to Human Disease, in The Molecular and Genetic Basis of Neurological and Psychiatric Disease, ed. R.N. Rosenburg et al., Lippincott, Williams, & Wilkins, Philadelphia, PA.

    Cabin, D.E., S. Gispert-Sanchez, D. Murphy, G. Auburger, R.R. Myers, R.L. Nussbaum, 2005. Exacerbated synucleinopathy in mice expressing A53T SNCA on a Snca null background.  Neurobiol. of Aging 26(1):25-35.

    Cabin D.E.*, Shimazu K.*, Murphy D., Cole N.B., Gottschalk W., McIlwain K.L,. Orrison B., Chen A., Ellis C.E., Paylor R., Lu B. Nussbaum R.L., 2002.  Synaptic vesicle depletion correlates with attenuated synaptic responses to prolonged repetitive stimulation in mice lacking alpha-synuclein. J Neurosci. 22(20):8797-807. *These authors contributed equally.

    Pletcher, M., T. Wiltshire, D.E. Cabin, M. Villanueva, and R.H. Reeves.  2001. Use of Comparative Physical and Sequence Mapping to Annotate Mouse Chromosome 16 and Human Chromosome 21.  Genomics 74: 45-54.

    Touchman, J.W., A. Dehejia, O. Chiba-Falek, D.E. Cabin, B.M. Orrison, M.H. Polymeropolous, and R.L. Nussbaum.  2001. Human and Mouse Alpha-Synuclein Genes:  Comparative Genomic Sequence Analysis and Identification of a Novel Gene Regulatory Element. Genome Research 11: 78-86.

    Cabin, D.E., J. W. McKee-Johnson, L. Matesic, T. Wiltshire, E. Rue, A.E. Mjaatvedt, Y.K. Huo, J.R. Korenberg, and R.H. Reeves. 1998. Physical and comparative mapping of distal mouse chromosome 16. Genome Research 8: 940-950.

    Murakami, Y., T. Nobukuni, K. Tamura, T. Maruyama, T. Sekiya, Y. Arai, H. Gomyou, M. Ohki, D. Cabin, P. Frischmeyer, P. Hunt, and R.H. Reeves.1998. Localization of Tumor Suppressor Activity Important in Non-Small Cell Lung Carcinoma on Chromosome 11q. Proc. Natl. Acad. Sci. 95: 8153-8158.

    Reeves, R.H., E. Rue, M.P. Citron, and D.E. Cabin. 1997. High Resolution Recombinational Map of Mouse Chromosome 16. Genomics 43: 202-208.

    Cabin, D.E., K. Gardiner, and R.H. Reeves. 1996. Molecular Genetic Characterization and Comparative Mapping of the Human PCP4 Gene. Somatic Cell and Molecular Genetics 22: 167-175.

    Mjaatvedt, A.E.*, D.E. Cabin*, S.E. Cole, L.J. Long, G. Breitwieser and R.H. Reeves. 1995. Assessment of a mutation in the H5 domain of Girk2 as a candidate for the weaver mutation. Genome Research 5: 453-463. *These authors contributed equally

What is Parkinson’s Disease?

Parkinson's disease (PD) is a chronic and progressive movement disorder, meaning that symptoms continue and worsen over time. Nearly one million people in the US are living with Parkinson's disease. The cause is unknown, and although there is presently no cure, there are treatment options such as medication and surgery to manage its symptoms.Parkinson’s involves the malfunction and death of vital nerve cells in the brain, called neurons. Parkinson's primarily affects neurons in the an area of the brain called the substantia nigra. Some of these dying neurons produce dopamine, a chemical that sends messages to the part of the brain that controls movement and coordination. As PD progresses, the amount of dopamine produced in the brain decreases, leaving a person unable to control movement normally.The specific group of symptoms that an individual experiences varies from person to person. Primary motor signs of Parkinson’s disease include the following.

  • tremor of the hands, arms, legs, jaw and face

  • bradykinesia or slowness of movement

  • rigidity or stiffness of the limbs and trunk

  • postural instability or impaired balance and coordination

Scientists are also exploring the idea that loss of cells in other areas of the brain and body contribute to Parkinson’s. For example, researchers have discovered that the hallmark sign of Parkinson’s disease — clumps of a protein alpha-synuclein, which are also called Lewy Bodies — are found not only in the mid-brain but also in the brain stem and the olfactory bulb.These areas of the brain correlate to nonmotor functions such as sense of smell and sleep regulation. The presence of Lewy bodies in these areas could explain the nonmotor symptoms experienced by some people with PD before any motor sign of the disease appears. The intestines also have dopamine cells that degenerate in Parkinson’s, and this may be important in the gastrointestinal symptoms that are part of the disease.

Source: https://www.parkinson.org/about-us