Loading...
Header Logo
Keywords
Last Name

Shannon Lynn Macauley-Rambach, Ph.D.

TitleAssistant Professor
InstitutionWake Forest School of Medicine
DepartmentInternal Medicine - Gerontology
Address
vCardDownload vCard

    Collapse Biography 
    Collapse education and training
    Middlebury CollegeB.A.1999Biology & Psychology
    Washington UniversityPh.D.2009Neuroscience
    Washington UniversityFellowship2015Neurology
    Washington UniversityFellowship2011Internal Medicine

    Collapse Overview 
    Collapse overview
    Shannon L. Macauley, PhD is an Assistant Professor of Internal Medicine in the Section on Gerontology and Geriatric Medicine at Wake Forest University School of Medicine. She is also a member of the Sticht Center on Aging and Alzheimer’s Prevention and the Center for Diabetes, Obesity, and Metabolism. The focus of her research is to understand diseases of the central nervous system (CNS) and how alterations in metabolism, vascular function, and sleep impact healthy brain function. Ultimately, the goal is to leverage these findings as therapeutic targets for treating CNS diseases, including Alzheimer’s disease and lysosomal storage diseases (LSDs). Her work focuses on two main areas: 1) metabolic dysfunction in Alzheimer’s disease (AD) and 2) treatment strategies for neurodegenerative disorders, including AD and LSDs. To study AD, her laboratory uses rodent models, non-human primates, and human data to understand how metabolic or vascular perturbations affect the progression of Alzheimer’s-related pathology. For rodent studies, the laboratory uses a variety of in vivo techniques, including glucose clamps, in vivo microdialysis, in vivo biosensors, EEG/EMG recordings, and small animal neuroimaging to study the acute effects of metabolic challenges on cerebral metabolism, neuronal activity, Aß/tau dynamics, and sleep. For chronic studies, the laboratory uses rodent models and non-human primates to investigate how Alzheimer’s disease risk factors, like metabolic dysfunction or sleep disruptions, impact Aß/tau pathology, learning and memory, cerebral metabolism, and brain network connectivity.

    Previous work from the laboratory demonstrates that hyperglycemia, or elevations in blood glucose levels, are sufficient to increase neuronal activity and extracellular Aß levels in the hippocampus through the inhibition of inward rectifying, ATP-sensitive potassium (KATP) channels. This work was expanded from rodent models to a non-human primate model of naturally occurring type-2-diabetes to confirm that changes in blood glucose levels correlate with alterations plasma lactate, CSF Aß40, and CSF Aß42. This work illustrates a feed forward mechanism by which metabolic activity could drive neuronal activity to affect Alzheimer’s disease related pathology. Moreover, in humans, we found that acute disruption of slow wave activity in sleep correlated with increased CSF Aß40, suggesting this process is due to changes in neuronal activity. Therefore, current R01-funded work investigates the relationship between cerebral metabolism, neuronal activity, and sleep in AD. Moreover, the laboratory is exploring whether targeting metabolic changes due to disrupted sleep, Aß, or tau aggregation is sufficient to rescue sleep architecture and reduce Alzheimer’s related pathology.

    Shannon L. Macauley, PhD is an Assistant Professor of Internal Medicine in the Section on Gerontology and Geriatric Medicine at Wake Forest University School of Medicine. She is also a member of the Sticht Center on Aging and Alzheimer’s Prevention and the Center for Diabetes, Obesity, and Metabolism. The main focus of Dr. Macauley’s work is to understand diseases of the central nervous system (CNS) and how secondary mechanisms, such altered CNS metabolism, impact neuronal health and function. Her work is focused in two main areas: 1) the interplay between Alzheimer’s disease (AD) and type-2-diabetes (T2D) and 2) the understanding and treatment of lysosomal storage diseases (LSDs). As it relates to the relationship between AD and T2D, the Macauley lab uses mouse models to understand how metabolic perturbations, either systemically or within the brain, affect the progression of AD-related pathology, such as the production, clearance, and aggregation of amyloid-beta (Aß) or tau. She uses a variety of methods, including glucose clamps, in vivo microdialysis, and neuroimaging techniques to study the acute effects of metabolic challenges on Aß dynamics within the brain’s interstitial fluid (ISF) as well as chronic studies to investigate what metabolic factors impact the progression of AD-related pathology and functional deficits. Ultimately, the goal is to leverage these findings as therapeutic targets for treating neurodegenerative disorders.


    Collapse Research 
    Collapse research activities and funding
    F31NS056718     (MACAULEY-RAMBACH, SHANNON L)May 1, 2007 - Dec 31, 2009
    NIH
    Cellular Pathology of Batten Disease
    Role: Principal Investigator

         (MACAULEY-RAMBACH, SHANNON)Jan 1, 2010 - Sep 15, 2011
    Batten Disease Support & Research Association Research Award
    Activated astrocytes as therapeutic targets in INCL
    Role: Principal Investigator

    F32NS080320     (MACAULEY-RAMBACH, SHANNON L)Apr 1, 2013 - Jun 30, 2015
    NIH
    Effects of Altered Glucose Utilization on AB Levels and Functional Connectivity
    Role: Principal Investigator

         (MACAULEY-RAMBACH, SHANNON L)Apr 1, 2015 - Mar 30, 2016
    DONOR'S CURE - NEW VISION AWARD
    Targeting the link between Alzheimer’s disease and diabetes with KATP channel modulators
    Role: Principal Investigator

    K01AG050719     (MACAULEY-RAMBACH, SHANNON L)Apr 1, 2016 - Sep 1, 2017
    NIH
    Effects of Hyperglycemia on Neuronal Activity, Cerebral Metabolism, and Amyloid-beta Levels
    Role: Principal Investigator

         (MACAULEY-RAMBACH, SHANNON & BAUER, ADAM)Apr 1, 2016 - Mar 30, 2018
    McDonnell Center for Systems Neuroscience
    Mapping glucose utilization in a mouse model of beta amyloidosis
    Role: Co-Principal Investigator

    R01AG061805     (Deep, Gagan / Molina, Anthony)Sep 30, 2018 - Apr 30, 2023
    NIH/NIA
    Exosome mediated alterations in cellular metabolism in the pathogenesis and progression of Alzheimer's disease
    Role: Co-Investigator

    R01AG065839     (Solingapuram Sai, Kiran)Sep 1, 2019 - Aug 31, 2024
    NIH/NIA
    Evaluating microtubule binding as a potential imaging biomarker for Alzheimer’s disease
    Role: Co-Investigator

    R01AG068330     (MACAULEY-RAMBACH, SHANNON L)Aug 1, 2020 - Apr 30, 2025
    NIH
    The metabolic interplay of sleep and Alzheimer's disease
    Role: Principal Investigator

    A20201775S     (Macauley-Rambach, Shannon L)Sep 1, 2020 - Jul 31, 2023
    BrightFocus Foundation
    KATP channel inhibition as a modifier of tau pathology in Alzheimer’s disease
    Role: Principle Investigator

    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    List All   |   Timeline
    1. Gibson EM, Bennett FC, Gillespie SM, Güler AD, Gutmann DH, Halpern CH, Kucenas SC, Kushida CA, Lemieux M, Liddelow S, Macauley SL, Li Q, Quinn MA, Roberts LW, Saligrama N, Taylor KR, Venkatesh HS, Yalçin B, Zuchero JB. How Support of Early Career Researchers Can Reset Science in the Post-COVID19 World. Cell. 2020 06 25; 181(7):1445-1449. PMID: 32533917.
      View in: PubMed
    2. Damuka N, Czoty PW, Davis AT, Nader MA, Nader SH, Craft S, Macauley SL, Galbo LK, Epperly PM, Whitlow CT, Davenport AT, Martin TJ, Daunais JB, Mintz A, Sai KKS. PET Imaging of [11C]MPC-6827, a Microtubule-Based Radiotracer in Non-Human Primate Brains. Molecules. 2020 May 13; 25(10). PMID: 32414052.
      View in: PubMed
    3. Carroll CM, Macauley SL. The Interaction Between Sleep and Metabolism in Alzheimer's Disease: Cause or Consequence of Disease? Front Aging Neurosci. 2019; 11:258. PMID: 31616284.
      View in: PubMed
    4. Kavanagh K, Day SM, Pait MC, Mortiz WR, Newgard CB, Ilkayeva O, Mcclain DA, Macauley SL. Type-2-Diabetes Alters CSF but Not Plasma Metabolomic and AD Risk Profiles in Vervet Monkeys. Front Neurosci. 2019; 13:843. PMID: 31555072.
      View in: PubMed
    5. Bashore AC, Liu M, Key CC, Boudyguina E, Wang X, Carroll CM, Sawyer JK, Mullick AE, Lee RG, Macauley SL, Parks JS. Targeted Deletion of Hepatocyte Abca1 Increases Plasma HDL (High-Density Lipoprotein) Reverse Cholesterol Transport via the LDL (Low-Density Lipoprotein) Receptor. Arterioscler Thromb Vasc Biol. 2019 09; 39(9):1747-1761. PMID: 31167565.
      View in: PubMed
    6. Day SM, Yang W, Wang X, Stern JE, Zhou X, Macauley SL, Ma T. Glucagon-Like Peptide-1 Cleavage Product Improves Cognitive Function in a Mouse Model of Down Syndrome. eNeuro. 2019 Mar/Apr; 6(2). PMID: 31040160.
      View in: PubMed
    7. Arnold SE, Arvanitakis Z, Macauley-Rambach SL, Koenig AM, Wang HY, Ahima RS, Craft S, Gandy S, Buettner C, Stoeckel LE, Holtzman DM, Nathan DM. Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums. Nat Rev Neurol. 2018 03; 14(3):168-181. PMID: 29377010.
      View in: PubMed
    8. Ju YS, Ooms SJ, Sutphen C, Macauley SL, Zangrilli MA, Jerome G, Fagan AM, Mignot E, Zempel JM, Claassen JAHR, Holtzman DM. Slow wave sleep disruption increases cerebrospinal fluid amyloid-ß levels. Brain. 2017 Aug 01; 140(8):2104-2111. PMID: 28899014.
      View in: PubMed
    9. Shyng C, Macauley SL, Dearborn JT, Sands MS. Widespread Expression of a Membrane-Tethered Version of the Soluble Lysosomal Enzyme Palmitoyl Protein Thioesterase-1. JIMD Rep. 2017; 36:85-92. PMID: 28213849.
      View in: PubMed
    10. Stanley M, Macauley SL, Caesar EE, Koscal LJ, Moritz W, Robinson GO, Roh J, Keyser J, Jiang H, Holtzman DM. The Effects of Peripheral and Central High Insulin on Brain Insulin Signaling and Amyloid-ß in Young and Old APP/PS1 Mice. J Neurosci. 2016 11 16; 36(46):11704-11715. PMID: 27852778.
      View in: PubMed
    11. Stanley M, Macauley SL, Holtzman DM. Changes in insulin and insulin signaling in Alzheimer's disease: cause or consequence? J Exp Med. 2016 07 25; 213(8):1375-85. PMID: 27432942.
      View in: PubMed
    12. Macauley SL. Combination Therapies for Lysosomal Storage Diseases: A Complex Answer to a Simple Problem. Pediatr Endocrinol Rev. 2016 Jun; 13 Suppl 1:639-48. PMID: 27491211.
      View in: PubMed
    13. Harris RA, Tindale L, Lone A, Singh O, Macauley SL, Stanley M, Holtzman DM, Bartha R, Cumming RC. Aerobic Glycolysis in the Frontal Cortex Correlates with Memory Performance in Wild-Type Mice But Not the APP/PS1 Mouse Model of Cerebral Amyloidosis. J Neurosci. 2016 Feb 10; 36(6):1871-8. PMID: 26865611.
      View in: PubMed
    14. Macauley SL, Stanley M, Caesar EE, Yamada SA, Raichle ME, Perez R, Mahan TE, Sutphen CL, Holtzman DM. Hyperglycemia modulates extracellular amyloid-ß concentrations and neuronal activity in vivo. J Clin Invest. 2015 Jun; 125(6):2463-7. PMID: 25938784.
      View in: PubMed
    15. Macauley SL, Holtzman DM. Recent Advances from the Bench Toward the Bedside in Alzheimer's Disease. EBioMedicine. 2015 Feb; 2(2):94-5. PMID: 26137544.
      View in: PubMed
    16. Macauley SL, Wong AM, Shyng C, Augner DP, Dearborn JT, Pearse Y, Roberts MS, Fowler SC, Cooper JD, Watterson DM, Sands MS. An anti-neuroinflammatory that targets dysregulated glia enhances the efficacy of CNS-directed gene therapy in murine infantile neuronal ceroid lipofuscinosis. J Neurosci. 2014 Sep 24; 34(39):13077-82. PMID: 25253854.
      View in: PubMed
    17. Macauley SL, Roberts MS, Wong AM, McSloy F, Reddy AS, Cooper JD, Sands MS. Synergistic effects of central nervous system-directed gene therapy and bone marrow transplantation in the murine model of infantile neuronal ceroid lipofuscinosis. Ann Neurol. 2012 Jun; 71(6):797-804. PMID: 22368049.
      View in: PubMed
    18. Roberts MS, Macauley SL, Wong AM, Yilmas D, Hohm S, Cooper JD, Sands MS. Combination small molecule PPT1 mimetic and CNS-directed gene therapy as a treatment for infantile neuronal ceroid lipofuscinosis. J Inherit Metab Dis. 2012 Sep; 35(5):847-57. PMID: 22310926.
      View in: PubMed
    19. Macauley SL, Pekny M, Sands MS. The role of attenuated astrocyte activation in infantile neuronal ceroid lipofuscinosis. J Neurosci. 2011 Oct 26; 31(43):15575-85. PMID: 22031903.
      View in: PubMed
    20. Reddy AS, Kim JH, Hawkins-Salsbury JA, Macauley SL, Tracy ET, Vogler CA, Han X, Song SK, Wozniak DF, Fowler SC, Klein RS, Sands MS. Bone marrow transplantation augments the effect of brain- and spinal cord-directed adeno-associated virus 2/5 gene therapy by altering inflammation in the murine model of globoid-cell leukodystrophy. J Neurosci. 2011 Jul 06; 31(27):9945-57. PMID: 21734286.
      View in: PubMed
    21. Kielar C, Wishart TM, Palmer A, Dihanich S, Wong AM, Macauley SL, Chan CH, Sands MS, Pearce DA, Cooper JD, Gillingwater TH. Molecular correlates of axonal and synaptic pathology in mouse models of Batten disease. Hum Mol Genet. 2009 Nov 01; 18(21):4066-80. PMID: 19640925.
      View in: PubMed
    22. Macauley SL, Sands MS. Promising CNS-directed enzyme replacement therapy for lysosomal storage diseases. Exp Neurol. 2009 Jul; 218(1):5-8. PMID: 19361502.
      View in: PubMed
    23. Macauley SL, Wozniak DF, Kielar C, Tan Y, Cooper JD, Sands MS. Cerebellar pathology and motor deficits in the palmitoyl protein thioesterase 1-deficient mouse. Exp Neurol. 2009 May; 217(1):124-35. PMID: 19416667.
      View in: PubMed
    24. Macauley SL, Sidman RL, Schuchman EH, Taksir T, Stewart GR. Neuropathology of the acid sphingomyelinase knockout mouse model of Niemann-Pick A disease including structure-function studies associated with cerebellar Purkinje cell degeneration. Exp Neurol. 2008 Dec; 214(2):181-92. PMID: 18778708.
      View in: PubMed
    25. Lin D, Donsante A, Macauley S, Levy B, Vogler C, Sands MS. Central nervous system-directed AAV2/5-mediated gene therapy synergizes with bone marrow transplantation in the murine model of globoid-cell leukodystrophy. Mol Ther. 2007 Jan; 15(1):44-52. PMID: 17164774.
      View in: PubMed
    26. Kielar C, Maddox L, Bible E, Pontikis CC, Macauley SL, Griffey MA, Wong M, Sands MS, Cooper JD. Successive neuron loss in the thalamus and cortex in a mouse model of infantile neuronal ceroid lipofuscinosis. Neurobiol Dis. 2007 Jan; 25(1):150-62. PMID: 17046272.
      View in: PubMed
    27. Griffey M, Macauley SL, Ogilvie JM, Sands MS. AAV2-mediated ocular gene therapy for infantile neuronal ceroid lipofuscinosis. Mol Ther. 2005 Sep; 12(3):413-21. PMID: 15979943.
      View in: PubMed
    28. Passini MA, Macauley SL, Huff MR, Taksir TV, Bu J, Wu IH, Piepenhagen PA, Dodge JC, Shihabuddin LS, O'Riordan CR, Schuchman EH, Stewart GR. AAV vector-mediated correction of brain pathology in a mouse model of Niemann-Pick A disease. Mol Ther. 2005 May; 11(5):754-62. PMID: 15851014.
      View in: PubMed
    29. Shihabuddin LS, Numan S, Huff MR, Dodge JC, Clarke J, Macauley SL, Yang W, Taksir TV, Parsons G, Passini MA, Gage FH, Stewart GR. Intracerebral transplantation of adult mouse neural progenitor cells into the Niemann-Pick-A mouse leads to a marked decrease in lysosomal storage pathology. J Neurosci. 2004 Nov 24; 24(47):10642-51. PMID: 15564580.
      View in: PubMed
    30. Sleat DE, Wiseman JA, El-Banna M, Kim KH, Mao Q, Price S, Macauley SL, Sidman RL, Shen MM, Zhao Q, Passini MA, Davidson BL, Stewart GR, Lobel P. A mouse model of classical late-infantile neuronal ceroid lipofuscinosis based on targeted disruption of the CLN2 gene results in a loss of tripeptidyl-peptidase I activity and progressive neurodegeneration. J Neurosci. 2004 Oct 13; 24(41):9117-26. PMID: 15483130.
      View in: PubMed
    31. Macauley SL, Horsch AD, Oterdoom M, Zheng MH, Stewart GR. The effects of transforming growth factor-beta2 on dopaminergic graft survival. Cell Transplant. 2004; 13(3):245-52. PMID: 15191162.
      View in: PubMed
    Macauley-Rambach's Networks
    Click the "See All" links for more information and interactive visualizations!
    Concepts Expand Description
    _
    Co-Authors Expand Description
    _
    Similar People Expand Description
    _
    Same Department Expand Description
    Physical Neighbors Expand Description
    _