Grace E. Stutzmann, PhD

RESEARCH | Publications | Service/Teaching

Neuroscience Discipline

Center for Neurodegenerative Disease and Therapeutics

My research interests focus on studying the early neuronal pathology that develops in Alzheimer's disease (AD), long before the deposition of plaques and tangles, and cognitive decline. To accomplish this, I use transgenic mice engineered to express human gene mutations that cause the inheritable form of AD, as well as human neurons derived from AD patients. With these tools, I can examine within individual neurons and entire networks how AD mutations impair neuronal functioning and synaptic plasticity across various stages of the disease process, with the goal of finding ways to block or reverse these impairments. By the time memory loss occurs in humans, the damage to the brain is often too extensive to reverse. My previous studies show that specific calcium-mediated signaling pathways are highly dysregulated in AD, and over time, facilitate the formation of amyloid plaques and tangles, interfere with neuronal signaling processes that support learning and memory, and eventually kill the cell. We are pursuing novel therapeutic strategies designed to prevent these early pathogenic processes, preserve synapses, and prevent memory impairment. This approach targets mechanisms upstream of amyloid and tau pathology. To achieve these goals, I use innovative techniques to study real-time activity in living neurons from rodents and humans, such as in vitro electrophysiology combined with 2-photon and CCD imaging of calcium signals within cellular compartments. In addition, extracellular recording techniques, immunohistochemistry, molecular biology and behavioral approaches are also incorporated. With my collaborators, we are also formulating and testing novel target compounds that impede the progression of AD pathology at its earlier stages. By combining the study of basic disease mechanisms in mice and human cells in parallel with drug discovery and therapeutic applications, we hope to develop effective options to prevent AD.

Education

Washington and Lee University
BS Biology/Psychology Cum laude
Omicron Delta Kappa (National Leadership Honor Society)

Stony Brook University
MA BioPsychology (Advisor: Dr. Rex Wang, PhD)

New York University
PhD Center for Neural Science (Advisor: Dr. Joseph LeDoux, PhD, Henry and Lucy Moses Professor of Science)

Training

Post Doctoral Research Fellow (Mentor: Dr. George Aghajanian)
Yale University School of Medicine
Departments of Psychiatry and Pharmacology

Post Doctoral Research Fellow (Mentors: Dr. Frank LaFerla, Chancellor's Professor and Dean; Dr. Ian Parker, FRS, AAAS Fellow) University of California, Irvine
Department of Neurobiology and Behavior

Current Appointment

Associate Professor, Neuroscience, Department of Foundational Sciences & Humanities
Director, Center for Neurodegenerative Disease and Therapeutics
The Chicago Medical School
Rosalind Franklin University of Medicine and Science
Founder and CSO, NeuroLucent, Inc.

Affiliations/Memberships

RFUMS:
Center for Stem Cell and Regenerative Medicine
TBI-PTSD Working Group
Women in Medicine and Science - RFUMS Executive Council

Association of Anatomy, Cell Biology and Neurobiology Chairpersons
SmartHealth Biotech Accelerator, North Chicago, IL

Honors, Awards, and Lectureships

2003 Al Nichols Young Investigator Award, UC Irvine Institute for Brain Aging and Dementia Fund for Advanced
Research in Priority Areas: Calcium Signaling Workshop Fellowship Award (Chile)
2004 Full Scholarship Award, Optical Microscopy in the Biological Sciences Course (UT San Antonio)
Dorothy Dillon Eweson Lecturer on the Advances in Aging Research, American Foundation of Aging Research (AFAR)
2006 AFAR-NYAS-GE Healthcare NeuroImaging Prize for Junior Investigators
2007 AFAR Travel Award, Biomarkers in Alzheimer's Disease (New York, NY)
2008 Board of Trustees Award, RFUMS
2009 Outstanding Contributor Award/The Alzheimer's Research Forum
Best Biological Paper/Microscopy Society of America Award "Seeing the Brain in Action: How Multiphoton Imaging has Advanced our Understanding of Neuronal Function" (2008) Microsc. Microanal. 14, 482-491.
2011, 2012, 2018 Dorothy Dillon Eweson Lecturer on the Advances in Aging Research (AFAR)
2018 “Researchers to Know: Advancing Medicine” IL Science and Technology Coalition
2020 Morris L. Parker Award for Research, RFUMS

Scientific Advisory/Consulting/Service Roles

Councilor, Chicago Chapter of the Society for Neuroscience (2009-2011)
Alzheimer’s Research Trust, Expert Referee Panel (Great Britain) (2009-present)
Alzheimer’s Research Forum (2009-present)
Alumni in Residence Program, Washington and Lee University (2009-present)
Key Opinion Leader, The Campaign to Prevent Alzheimer’s Disease 2020 [PAD2020] (2010-present)
Italian Scientific Research Council (2010-present)
Society for Neuroscience Program Committee (2014-2017)
AFAR National Scientific Advisory Council (2014-present)
NIH Startup Business Challenge; Team Advisor, Illinois Institute of Technology (2014-present)
Neuroscience Program Committee, DePaul University (2014-present)
Advisory Board Member ‘CNS: Research to Clinic’ (2014-present)
Alzheimer’s Drug Discovery Foundation Scientific Review Board (2015-present)
Medical and Scientific Advisory Board, Alzheimer’s Association, IL Chapter (2015-present)

Research | Publications | Service/Teaching

Research

2005-present Rosalind Franklin University of Medicine and Science/The Chicago Medical School (Neuroscience DISCIPLINE, Department of foundational Sciences & Humanities)

My lab utilizes electrophysiological, multi-photon imaging, and molecular approaches to examine early mechanisms of neurodegenerative processes, particularly in aging, Alzheimer's disease, and traumatic brain injury. We have identified several aberrant calcium channels and related signaling pathways that appear to be drivers of pathogenic cycles in Alzheimer's and other neurological disorders. In particular, the ryanodine receptor is strongly implicated, and we have begun novel drug development strategies targeting this calcium channel as a means to develop therapeutic approaches to preserve cognitive function in aged and diseased brains.

Current Funding

NIH/NIA RF1 AG047237 Stutzmann, co-PI 8/15/2016-3/30/2021 “Novel Drug Discovery for AD Targeting Ryanodine Calcium Channels”

NIH/NIA R56 AG055497 Stutzmann, PI 8/01/2018-7/30/2021 (NCE) NCE “Cellular and synaptic signaling mechanisms driving early AD pathology”

DoD AZ170142 Stutzmann, PI 7/01/2018-6/30/2021 “Identifying common mechanisms driving synaptic deficits between TBI and AD”

NIH/NIA 3R01NS100514-03S1 Stutzmann (co-I) 6/01/2019 –6/31/2021 NIH Supplement to “Reprogramming Cell Fate for Repair” (Daniel Peterson, PI).

NIH/NINDS 1R01NS114570 Stutzmann (co-I) 7/01/2020 –6/30/2025 “Calcium and the Pathophysiology of Neurodegenerative Disorders” (Andrew Marks, PI).

NIH/NIA 1RF1AG065628 Stutzmann (PI) 7/01/2020 –6/30/2025 “Intracellular Organelle Deficits Driving Alzheimer’s Disease”.

2001-2005 University of California, Irvine (Department of Neurobiology and Behavior - Ian Parker and Frank LaFerla, PI's)

In vitro whole-cell electrophysiological recording, multi-photon imaging and molecular/transgenic studies examining mechanisms of neuronal calcium signaling, and mutations related to Alzheimer's disease and neurodegenerative diseases.

1999-2000 Yale University School of Medicine (Departments of Psychiatry and Pharmacology - George Aghajanian, PI)

In vitro sharp and whole cell electrophysiological recordings in cortical and hippocampal slices examining effects of serotonin and adenosine on neuronal activity in relation to psychosis and drugs of abuse.

1995-1999 New York University (W.M. Keck Foundation Laboratory of Neurobiology, Center for Neural Science - Joseph E. LeDoux, Henry and Lucy Moses, PI)

Intracellular and extracellular in vivo and in vitro electrophysiology, iontophoresis, and immunohistochemistry studies examining effects of serotonin and stress hormones on amygdala neurons.

1992-1994 SUNY at Stony Brook (Department of Psychiatry - Rex Wang, PI)

Electrophysiology, in vivo single unit recording, iontophoresis and behavior studies examining serotonergic and dopaminergic involvement in psychosis and drugs of abuse.

Lab Members

	Rosalind Helfrich rosalind.helfrich@rosalindfranklin.edu Research Assistant (847) 578-3000 x3378
	Sarah Mustaly, PhD sarah.mustaly@my.rfums.org Graduate Student (847) 578-3000 x3378
	Sean Schrank, PhD Graduate Student
	Nikki Barrington, PhD Graduate Student
	Daniel Steinbrenner, PhD Senior Research Associate

Research | Publications | Service/Teaching

Recent Publications

Peer-Reviewed Publications

Padovan-Neto FE, Jurkowski L, Murray C, Stutzmann GE, Kwan M, Ghavami A, Beaumont V, Park LC, West AR. (2018) Age- and sex-related changes in cortical and striatal nitric oxide synthase in the Q175 mouse model of Huntington’s disease. Nitric Oxide, 83:40-50. PMID:30528913

Chakroborty S, Hill E. Christian DT, Helfrich R, Riley S, Kapecki N, Mustaly S, Seiler FA, Schneider C, Peterson DA, West AR, Vertel BM, Frost WN, Stutzmann GE. (2019) Reduced presynaptic vesicle stores mediate cellular and network plasticity defects in an early-stage mouse model of Alzheimer’s disease. Molecular Neurodegeneration, 22;14(1):7. PMID: 30670054

Schrank S, McDaid J, Briggs CA, Mustaly-Kalimi S, Brinks D, Houcek A, Singer O, Bottero V, Marr RA, Stutzmann GE. (2020) Human induced neurons from PS1 mutant patients model early aspects of Alzheimer’s disease pathology. International Journal of Molecular Sciences. 21(3). PMID: 32033164

Lacampagne A, Liu X, Reiken S, Bussiere R, Meli AC, Lauritzen I, Teich AF, Zalk R, Saint N, Arancio O, Bauer C, Duprat F, Briggs CA, Chakroborty S, Stutzmann GE, Shelanski ML, Checler F, Chami M, Marks AR (2017) Post-translational remodeling of ryanodine receptor induces calcium leak leading to Alzheimer’s disease-like pathologies and cognitive deficits. Acta Neuropathol, 134(5):749-767.  doi: 10.1007/s00401-017-1733-7  PMID: 28631094

Jamnia N, Urban JH, Stutzmann GE, Chiren S, Reisenbigler E, Marr R, Peterson DA, Kozlowski DA (2016) A clinically relevant closed-head model of single and repeat concussive injury in the adult rat using a controlled cortical impact device. J Neurotrauma, 34(7):1351-1363.  doi: 10.1089/neu.2016.4517  PMID: 27762651

Christian DT, Wang X, Chen EL, Sehgal LK, Ghassemlou MN, Miao JJ, Estepanian D, Araghi CH, Stutzmann GE, Wolf ME (2016) Dynamic Alterations of Rat Nucleus Accumbens Dendritic Spines over two Months of Abstinence from Extended-Access Cocaine Self-Administration. Neuropsychopharmacology, 42(3):748-756.  doi: 10.1038/npp.2016.168  PMID: 27555380

Anthony J. Hinrich, Francine M. Jodelka, Jennifer L. Chang, Daniella Brutman, Angela Bruno, Clark A. Briggs, Bryan D. James, Grace E. Stutzmann, et al. (2016) Therapeutic Correction of ApoER2 Splicing in Alzheimer’s Disease Mice Using Antisense Oligonucleotides. EMBO Molecular Medicine, 8(4):328-45.  doi: 10.15252/emmm.201505846  PMID: 26902204

Chakroborty S, Kim J, Schneider C, West A, Stutzmann GE (2015) Nitric oxide signaling is recruited as a compensatory mechanism for sustaining synaptic plasticity in Alzheimer’s disease mice. Journal of Neuroscience, 35(17), 6893-902.  doi:  10.1523/JNEUROSCI.4002-14.2015  PMID: 25926464

Briggs CA, Schneider C, Richardson JC, Stutzmann GE (2013) Beta amyloid peptide plaques fail to alter evoked neuronal calcium signals in APP/PS1 Alzheimer's disease mice. Neurobiology of Aging, 34(6):1632-43.  doi: 10.1016/j.neurobiolaging.2012.12.013  PMID: 23337342

Chakroborty S, Briggs C, Miller MB, Goussakov I, Schneider C, Kim J, Wicks J, Richardson J, Conklin V, Cameransi B, Stutzmann GE (2012b) Stabilizing ER calcium channel function as an early prevention strategy for Alzheimer’s disease. PLoS One, 7(12): e52056.10.1371/journal.pone.0052056  PMID: 23284867

Ferrario CR, Goussakov I, Stutzmann GE, Wolf ME. (2012) Withdrawal from cocaine self-administration alters NMDA receptor-mediated Ca²⁺ entry in nucleus accumbens dendritic spines. PLOS One, 7(8): e40898.  doi: 10.1371/journal.pone.0040898  PMID: 22870207

Chakroborty S, Kim J, Schneider C, Jacobson C, Molgó J, Stutzmann GE. (2012a) Early pre- and postsynaptic calcium signaling abnormalities mask underlying synaptic depression in presymptomatic Alzheimer's disease mice Journal of Neuroscience, 32(24):8341-53.  doi: 10.1523/JNEUROSCI.0936-12.2012  PMID: 22699914

Stutzmann GE (2011) Altered ryanodine receptor expression in mild cognitive impairment and Alzheimer’s Disease. Neurobiology of Aging 33(5):1001.e1-6.  doi: 10.1016/j.neurobiolaging.2011.03.011  PMID: 21531043

Goussakov I, Chakroborty S, Stutzmann GE (2011) Generation of dendritic Ca2+ oscillations as a consequence of altered ryanodine receptor function in AD neurons. Channels, 5(1):9-13.  doi: 10.1523/JNEUROSCI.2474-10.2010  PMID: 20826675

Perez MF, Ford K, Goussakov I, Stutzmann GE, Hu XT (2011) Repeated Cocaine Exposure Decreases Dopamine D2-Like Receptor Modulation of Ca2+ Homeostasis in Rat Nucleus Accumbens Neurons. Synapse, 65(2):168-180.  doi: 10.1002/syn.20831  PMID: 20665696

Goussakov I, Miller M, Stutzmann GE (2010) NMDA-mediated Ca2+ influx drives ryanodine receptor activation in dendrites of young Alzheimer's disease mice. Journal of Neuroscience, 30(36):12128-37.  doi: 10.1523/JNEUROSCI.2474-10.2010  PMID: 20826675

Chakroborty S, Goussakov I, Miller MB, Stutzmann GE (2009) Deviant ryanodine receptor-mediated calcium release resets synaptic homeostasis in presymptomatic 3xTg-AD mice. Journal of Neuroscience, 29: 9458-9470.  doi: 10.1523/JNEUROSCI.2047-09.2009  PMID: 19641109  *Faculty of 1000 Recommended Reading Award

Stutzmann GE, Smith I, Caccamo A, Oddo S, Parker I, LaFerla F (2007) Enhanced ryanodine-mediated calcium release in mutant PS1-expressing Alzheimer mouse models. Annals of the New York Academy of Science, 1097: 265-277.  doi: 10.1196/annals.1379.025  PMID: 17413028

Stutzmann GE, Smith I, Caccamo A, Oddo S, LaFerla FM, Parker I (2006) Enhanced ryanodine receptor recruitment contributes to Ca2+ disruptions in young, adult and aged Alzheimer’s disease mice. Journal of Neuroscience, 26(20) 5180-5189.  doi: 10.1523/JNEUROSCI.0739-06.2006  PMID: 16687509

Stutzmann GE, Caccamo A, LaFerla FM, Parker I (2004) Dysregulated IP3 signaling in cortical neurons of knock-in mice expressing an Alzheimer's-linked mutation in presenilin1 results in exaggerated Ca2+ signals and altered membrane excitability. Journal of Neuroscience, 24(2) 508-513.  doi: 10.1523/JNEUROSCI.4386-03.2004  PMID: 14724250

Stutzmann GE, LaFerla FM, Parker I (2003) Ca2+ signaling in mouse cortical neurons studied by two-photon imaging and photoreleased inositol triphosphate. Journal of Neuroscience, 23(3):758-65.  doi: 10.1523/JNEUROSCI.23-03-00758.2003  PMID: 12574404

Marchant J, Stutzmann GE, Leissring M, LaFerla F, Parker I (2001) Multiphoton-evoked color change of DsRed as an optical highlighter for cellular and subcellular labeling. Nature Biotechnology, 19:645-649.  doi: 10.1038/90249  PMID: 11433276

Stutzmann GE, Marek GJ, Aghajanian GK (2001) Adenosine preferentially suppresses serotonin2A-receptor enhanced EPSC’s in layer V neurons of the medial prefrontal cortex. Neuroscience, 105:55-69.  doi: 10.1016/S0306-4522(01)00170-1  PMID: 11483300

Stutzmann GE, LeDoux JE (1999) GABAergic antagonists block the inhibitory effects of serotonin in the lateral amygdala: a mechanism for modulation of sensory inputs related to fear conditioning. Journal of Neuroscience, 19(11):1-4.  doi: 10.1523/JNEUROSCI.19-11-j0005.1999  PMID: 10341269

Stutzmann GE, McEwen BS, LeDoux JE (1998) Serotonin modulation of sensory inputs to the lateral amygdala: dependency on corticosterone. Journal of Neuroscience, 18(22):9529-38.  doi: 10.1523/JNEUROSCI.18-22-09529.1998  PMID: 9801389

Li XF, Stutzmann GE, LeDoux JE (1996) Convergent but temporally separated inputs to lateral amygdala neurons from the auditory thalamus and auditory cortex use different postsynaptic receptors: in vivo intracellular and extracellular recordings in fear conditioning pathways. Learning and Memory, 3(2-3):229-42.  doi: n/a  PMID: 10456093

Minabe Y, Emori K, Toor A, Stutzmann GE, Ashby CR (1996) The effect of the acute and chronic administration of CP 96,345, a selective neurokinin1 receptor antagonist, on midbrain dopamine neurons in the rat: a single unit, extracellular recording study. Synapse, 22(1):35-45.  doi: 10.1002/(SICI)  PMID: 8822476

Invited Reviews

McDaid J, Mustaly-Kalimi S, Stutzmann GE (2020) Ca²⁺ Dyshomeostasis Disrupts Neuronal and Synaptic Function in Alzheimer's Disease. Cells. 10;9(12):2655.

Stutzmann GE (2021) RyR2 calcium channels in the spotlight-I'm ready for my close up, Dr. Alzheimer! Cell Calcium. 94:102342. Epub ahead of print. PMID: 33444912.

Mustaly-Kalimi S, Littlefield AM, Stutzmann GE. (2018) Calcium Signaling Deficits in Glia and Autophagic Pathways Contributing to Neurodegenerative Disease. Antioxid Redox Signal.  [Epub ahead of print] doi: 10.1089/ars.2017.7266 PMID: 29634342

Alzheimer’s Association Calcium Hypothesis Workgroup (2017) Calcium Hypothesis of Alzheimer's disease and brain aging: A framework for integrating new evidence into a comprehensive theory of pathogenesis. Alzheimers Dement. 13(2):178-182.e17. doi: 10.1016/j.jalz.2016.12.006 PMID: 28061328

Briggs CA, Chakroborty S, Stutzmann GE (2017) Emerging pathways driving early synaptic pathology in Alzheimer’s disease. Biochem Biophys Res Commun. 483(4):988-997. doi: 10.1016/j.bbrc.2016.09.088 PMID: 27659710

Shim, SS, Stutzmann GE (2016) Inhibition of glycogen synthase kinase-3: an emerging target in the treatment of traumatic brain injury. Journal of Neurotrauma. 33(23):2065-2076. doi: 10.1089/neu.2015.4177 PMID: 26979735

Chakroborty S, Stutzmann GE (2014) Calcium channelopathies and Alzheimer's disease: insight into therapeutic success and failures. Eur J Pharmacol. 739:83-95. doi: 10.1016/j.ejphar.2013.11.012 PMID: 24316360

Chakroborty S, Stutzmann GE (2011) Early calcium dysregulation in Alzheimer's disease: setting the stage for synaptic dysfunction. Sci China Life Sci. 54(8):752-62. doi: 10.1007/s11427-011-4205-7 PMID: 21786198

Stutzmann GE, Mattson MP (2011) Endoplasmic reticulum Ca2+ handling in excitable cells in health and disease. Pharmacol Rev. 63(3):700-27. doi: 10.1124/pr.110.003814 PMID: 21737534

Demuro A, Parker I, Stutzmann GE (2010) Calcium signaling and amyloid toxicity in Alzheimer's disease. J Biol Chem. 285(17):12463-8. doi: 10.1074/jbc.R109.080895 PMID: 20212036

Stutzmann GE (2008) Seeing the brain in action: how multiphoton imaging has advanced our understanding of neuronal function. Microsc Microanal.  14(6):482-91. *Best Biological Paper Award. doi: 10.1017/S143192760808080X PMID: 18986602

Stutzmann GE (2007) The pathogenesis of Alzheimer disease: Is it a lifelong ‘calciumopathy’? Neuroscientist, 13(5):546-59. doi: 10.1177/1073858407299730 PMID: 17901262

Stutzmann GE (2005) Calcium dysregulation, IP3, and Alzheimer’s disease. Neuroscientist, 11(2):110-5. doi: 10.1177/1073858404270899 PMID: 15746379

Stutzmann GE, Parker I (2005) Dynamic multi-photon imaging: a live view from cells to systems. Physiology, 20:15-21. doi: 10.1152/physiol.00028.2004 PMID: 15653835

Research | Publications | Service/Teaching

Service/Teaching

Service

University Service – Leadership Roles (RFUMS)

University Service – Committee Membership (RFUMS)

Neuroscience Service

Teaching

RFUMS Chicago Medical School

Medical Neuroscience, Lecturer (2006-2018)
Essentials of Clinical Reasoning (2012-present)
Clinical Epidemiology (2013-present)
Clinical Genetics (2012-2014)
Introduction to Bioethics and Health Law (2012)

RFUMS IGPBS Graduate Program

Neurophysiology, Course Director (2008-present)
Molecular and Cell Biology II (2009-present)
Neuroscience Course (2010-present)
Systems (2014-present)
Brain Frontiers, Lecturer (2007)
Neuronal Signaling (2012)