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Grace E. Stutzmann, PhD

Associate Professor

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 that have been engineered to express the human gene mutations that cause the inheritable form of AD. With these mice, I can examine within individual neurons how the AD mutations impair neuronal functioning and synaptic transmission 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, may facilitate the formation of amyloid plaques and tangles, interfere with neuronal signaling processes that support learning and memory, and eventually kill the cell. To achieve these goals, I use innovative techniques to study real-time activity in living neurons, 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. I am also examining target compounds that can impede the progression of AD pathology. The strategy is to normalize aberrant signaling pathways that are present prior to the formation of late stage markers of the disease.

Education
Washington and Lee University
B.S. Biology/Psychology Cum laude 
Omicron Delta Kappa (National Leadership Honor Society)

Stony Brook University
M.A. 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
Department of Neuroscience
The Chicago Medical School
Rosalind Franklin University of Medicine and Science

RFUMS Affiliations/Memberships
Center for Stem Cell and Regenerative Medicine
Neurodegeneration and Repair Consortium
TBI-PTSD Working Group

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 Federal 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  Dorothy Dillon Eweson Lecturer on the Advances in Aging Research (AFAR)
2012  Dorothy Dillon Eweson Lecturer on the Advances in Aging Research (AFAR)

Lab Members

 Clark Briggs Clark Briggs, PhD
clark.briggs@rosalindfranklin.edu
Senior Research Associate
(847) 578-3000 x3529
 Shreaya Chakroborty Shreaya Chakroborty, PhD
shreaya.chakroborty@rosalindfranklin.edu
Postdoctoral Research Fellow
(847) 578-3000 x3529
  Rosalind Helfrich
rosalind.helfrich@rosalindfranklin.edu
Research Technician
(847) 578-3429x3540
  Nicolas Kapecki
nicolas.kapecki@rosalindfranklin.edu
Laboratory Technician
(847) 578-3429x3540

2009

 LabSHot-s Stutzmann Coven

2008

2008 Angela  and Shreaya 2008
2008 2008 2008

 Lab Misfit

Dear Santa,
Angela wants a cell culture system with an AD fibroblast line.  Shreaya wants an audio amplifier and an espresso machine.  Clark wants a computer.  Megan wants a vertical gel slab electrophoresis system and better antibodies. 

Publications

Peer Reviewed

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.

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.

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

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,1(19):1-4

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.

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.

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.

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

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

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.

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.*Faculty of 1000 Recommended Reading Award

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.

Perez MF, Ford K, Goussakov I, Stutzmann, GE, Hu XT (2011) Chronic exposure to cocaine disturbs dopamine D2 receptor modulation of Ca2+ homeostasis in rat nucleus accumbens neurons. Synapse65(2):168-80.

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.

Stutzmann GE (2011) Altered ryanodine receptor expression in mild cognitive impairment and Alzheimer’s Disease. Neurobiology of Aging 33(5):1001.e1-6

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

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.

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.

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.

Invited Reviews

Stutzmann GE, Parker I (2005) Dynamic multi-photon imaging: a live view from cells to systems.  Physiology, 20:15-21.

Stutzmann GE (2005) Calcium dysregulation, IP3, and Alzheimer’s disease. The Neuroscientist, 11(2):110-5.

Stutzmann GE (2007) The pathogenesis of Alzheimer disease: Is it a lifelong ‘calciumopathy’?  The Neuroscientist, 13(5):546-59

Stutzmann GE (2008) Seeing the brain in action: how multiphoton imaging has advanced our understanding of neuronal function.  Microscopy and Microanalysis, 14(6):482-91. *Best Biological Paper Award.

Demuro A, Parker I, Stutzmann GE (2010) Calcium signaling and amyloid toxicity in  Alzheimer's disease. Journal of Biological Chemistry, 285(17):12463-8.

Stutzmann GE, Mattson MP (2011) Endoplasmic reticulum Ca2+ handling in excitable cells in health and disease. Pharmacological Reviews, 63(3):700-27.

Chakroborty S, Stutzmann GE (2011) Early calcium dysregulation in Alzheimer's disease: setting the stage for synaptic dysfunction. Life Science, 54(8):752-762.

Chakroborty S, Stutzmann GE (2013) Calcium Channelopathies and Alzheimer’s Disease: Insight into Therapeutic Success and Failures.  European Journal of Pharmacology.

Research Areas

2005-present     Rosalind Franklin University of Medicine and Science/The Chicago Medical School (Department of Neuroscience)  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. 

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 Professor of Science, 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.