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Holly C. Hunsberger, PhD

Assistant Professor

Dr. Hunsberger received her undergraduate degree in Chemistry from West Virginia University. She then went on to pursue her PhD under the mentorship of Dr. Miranda Reed at West Virginia University. There she studied glutamate’s role in Alzheimer’s disease (AD) using novel microelectrode array technology. After receiving her PhD in Behavioral Neuroscience, she moved to New York City for her postdoctoral position under the mentorship of Dr. Christine Denny at Columbia University. There her work focused on how the metabolome differs between age-related cognitive decline and AD and how anxiety impacts AD progression. During that time, she also became interested in sex differences throughout aging and AD.

Lab Members

Hiring a Postdoctoral Scientist Fall 2022!

Kameron Kaplan, Graduate Student 
kameron.kaplan@my.rfums.org




Lainey Toennies, Laboratory Technician
lainey.toennies@rosalindfranklin.edu

 

 

 

RESEARCH

My current research interests focus on dissecting the effects of anxiety and anatomical sex on the neural circuits that are altered in aging and Alzheimer’s disease. In 2019, I was awarded a K99/R00 (K99AG059953) entitled, “The sex-specific impact of anxiety on Alzheimer’s disease progression,” from the National Institute of Aging (NIA). I aim to understand why females are more susceptible to AD and to create personalized therapeutics for males and females. I am working to bridge the gap between mouse and human studies of AD by partnering with clinical researchers to ask novel questions using big datasets.

Understanding Alzheimer’s Disease and Neuropsychiatric Syndromes

Alzheimer’s disease (AD), a progressive and debilitating neurodegenerative disorder, stands alone as one of the ten leading causes of death in the United States that cannot be prevented, slowed, or cured. Interestingly, psychiatric disturbances, such as depression and anxiety are observed in 90% of AD patients and these symptoms usually manifest long before AD onset. Although much of the field has focused on the link between depression and AD, recent clinical evidence supports that anxiety can predict the progression to AD above and beyond depression, brain atrophy, and cognitive impairment. Studying the relationship between anxiety and AD should thus provide crucial insights into the mechanisms underlying cognitive decline at a vital therapeutic time window. Additionally, anxiety and depression affect women more often than men and although two-thirds of AD patients are female, a majority of literature probing the etiology of the disease has been male-focused. In fact, the first documented AD patient was a woman, Auguste Deter. How exactly sex and anxiety impact AD progression remains unclear. To answer these questions, I use transgenic AD mice, behavior testing, whole brain imaging, optogenetics, and Ca2+ imaging.

Novel Transgenic Mice

The ArcCreERT2 mice are used to permanently tag activated neurons after an experience (Denny et al., 2014; Root et al., 2014). To achieve both temporal control and flexibility in transgene expression, a CreERT2 system was placed under the control of the Arc gene promoter. in vitro studies have established a requirement for Arc in long-term memory of hippocampus-dependent tasks. This line is unique in that, unlike previous semi-permanent tools, it allows for the permanent tagging of previously active neural ensembles. The ArcCreERT2 mice are bred to an enhanced yellow fluorescent protein (EYFP) line, allowing for indelible EYFP labeling of Arc+ cells after administration of 4-hydroxytamoxifen (4-OHT). Therefore, cells that express Arc+ after an experience will be tagged in green, thus allowing for a comparison between cells that are activated during one experience with those that are activated during a second experience. By crossing the ArcCreERT2 x EYFP mice with the APP/PS1 AD line, we can measure changes in neural circuitry between males and females, across ages, and throughout AD progression.

Current and Future Projects

  1. Examining how altered neuronal memory networks mediate cognitive decline and anxiety in male and female AD mice.
  2. Using human datasets to determine whether anxiety is a neuropsychiatric biomarker of dementia transition.
  3. Examining stressful and enriching prior life experiences and their impact on cognitive reserve across the lifespan in aging and AD mice.
  4. Using combinatorial anxiolytic compounds to treat AD (in collaboration with Dr. Christine Denny).
  5. Discovering the mechanisms underlying disrupted circadian patterns and sundowning behavior in AD mice (in collaboration with Dr. Christine Denny & Dr. Ryan Logan).

PATENTS & INVENTIONS

Compositions and methods for the treatment of Alzheimer’s disease and other neurodegenerative diseases
Patent Application No. 63/236,418
Filed: August 24, 2021

CURRENT RESEARCH SUPPORT

04/01/19-02/28/25
1K99AG059953-01A1 (PI: Hunsberger) 
NIA
K99/R00 NIH Pathway to Independence Award 
The sex specific impact of anxiety on Alzheimer's disease progression

09/01/20-03/01/22
R24AG061421 (PI: Hunsberger) 
NIA
Pilot Award
Using cognitive training to enhance cognitive reserve in aging mice

PAST RESEARCH SUPPORT

09/01/19-08/31/21
R21AG064774-01 (PI: Denny) 
NIA
Identification and manipulation of the neural ensembles mediating sundowning in an Alzheimer’s disease mouse model 
Role: Postdoctoral Researcher

11/01/16-10/31/18
2T32MH015174-40 
Translational Neuroscience Training Grant (PI: Hen)
NIMH
Role: Post-doctoral fellow
The primary goal of this proposal is to train postdoctoral fellows for careers as independent researchers at the interface between neuroscience and psychiatry as well as neurology.

SCIENTIFIC MEMBERSHIPS

  1. Travel Award Member, American College of Neuropsychopharmacology (ACNP)
  2. Member, Society for Neuroscience (SfN)
  3. Member, International Behavioral Neuroscience Society (IBNS)
  4. New Investigator Awardee, American Society of Clinical Psychopharmacology (ASCP)
  5. Member, Society of Biological Psychiatry (SOBP)
  6. New Investigator Award, ISTARRT Neuropsychiatric Syndromes PIA
  7. Member, ISTARRT Sex and Gender Differences PIA
  8. Past member, Columbia University Postdoctoral Society (Vice President, 2017)

HONORS & AWARDS

2021

  • Winter Conference on Brain Research (WCBR) Travel Award, Snowmass, CO
  • American College of Neuropsychopharmacology (ACNP) Travel Award, Puerto Rico
  • Neuropsychiatric Syndromes PIA: New Investigator Award, Alzheimer’s Association
  • Alzheimer’s Association International Conference (AAIC), Travel Award, Denver, CO.

2020

  • American Society of Clinical Psychopharmacology New Investigator Award Program, Miami Beach, FL
  • Society of Biological Psychology (SOBP) Travel Award, San Diego, CA
  • Plexon Postdoctoral Travel Award, IBNS, Glasgow, Scotland, UK
  • Butler-Williams Scholar (NIA)

2019

  • K99AG05995 “The sex-specific impact of anxiety on Alzheimer’s disease progression”
  • Trainee Professional Development Award, SfN, Chicago, IL
  • Leadership Development Program, SfN
  • NIA Research for Collaborative Center Network Workshop Travel Award, Los Angeles, CA
  • Reserve and Resilience research definitions Workshop Travel Award, Bethesda, MD

2018

  • Postdoctoral Research Symposium First Place Presenter, Columbia University
  • BrightFocus Foundation Travel Award (International Learning & Memory Conference), Huntington Beach, CA

2017

  • Children’s Hospital of Philadelphia Translational Neuroscience Workshop Award Recipient
  • ADDF Young Investigator Scholarship (Jersey City Conference)

2016

  • ADDF Young Investigator Scholarship (Miami Conference)
  • Eberly College of Arts and Sciences Travel Award, West Virginia University
  • Academic Affairs Travel Award, West Virginia University
  • Doctoral Student Travel Program, West Virginia University

2015

  • ADDF Young Investigator Scholarship (San Diego Conference)
  • STEM Mountains of Excellence Scholarship, West Virginia University
  • Behavioral and Biomedical Training Scholarship, West Virginia University
  • Academic Affairs Funding, West Virginia University
  • Eberly College of Arts and Sciences Dissertation Award, West Virginia University

2014

  • Behavioral and Biomedical Training Scholarship, West Virginia University
  • ADDF Young Investigator Scholarship (Jersey City Conference)

2013

  • Department of Psychology Student Research Fund, West Virginia University
  • Eberly College of Arts and Sciences Travel Award, West Virginia University
  • Academic Affairs Travel Award, West Virginia University

PUBLICATIONS

  1. Hunsberger HC, Sharay SE, Rudy CC, Weitzner DS, Pfitzer JC, McDonald KL, Hong H, Bhattacharya S, Suppiramaniam V, Reed MN. (2021) Differential effects of human P301L tau expression in young versus aged mice. Int J Mol Sci. 22(21). PMID: 34769068.
  2. Chen BK, Luna VM, Shannon ME, Hunsberger HC, Mastrodonato A, Stackmann M, McGowan JC, Rubinstenn G, Denny CA. (2021) Fluroethylnormemantine, a novel NMDA receptor antagonist, for the prevention and treatment of stress-induced maladaptive behavior. Biological Psychiatry. Epub ahead of print.
  3. Anacker C, Syndor E, Chen BK, LaGamma CT, McGowan JC, Mastrodonato A, Hunsberger HC, Shores R, Dixon R, McEwen B, Byne W, Meyer-Bahlburg HFL, Bockting W, Ehrhardt AA, and Denny CA. (2020) Behavioral and neurobiological effects of GnRH agonist treatment in mice - potential implications for puberty suppression in transgender individuals. Neuropsychopharmacology. 46(5). PMID: 32919399.
  4. Hunsberger HC, Greenwood BP, Tolstikov V, Narain NR, Kiebish MA, and Denny CA. (2020) Divergence in the metabolome between natural aging and Alzheimer’s disease. Sci Reports 10:12171. PMID: 32699218.
  5. Mastrodonato A, Cohensedgh O, LaGamma CT, McGowan JC, Hunsberger HC, and Denny CA. (2019) Prophylactic (R,S)-ketamine selectively protects against inflammatory stressors. Behav Brain Res. 378:112238. PMID: 31563463.
  6. Hunsberger HC, Pinky P, Smith W, Suppiramaniam V, Reed MN (2019). The role of APOE4 in Alzheimer’s disease: strategies for future therapeutic interventions. Neuronal Signal. 3(2): PMID: 32269835.
  7. Setti S, Hunsberger HC, Reed MN (2017). Alterations in hippocampal activity and Alzheimer’s disease. Transl Issues in Pscyhol Sci. 3(4): 348-356. PMID: 29862310.
  8. Hunsberger HC, Konat GW, Reed MN (2017). Peripheral viral challenge elevates extracellular glutamate in the hippocampus leading to seizure hypersusceptibility. J Neurochem. 141(3): 341-346. PMID: 28244106.
  9. Hunsberger HC, Setti SE, Heslin RT, Quintero JE, Gerhardt GA, Reed MN (2017). Using enzyme-based biosensors to measure tonic and phasic glutamate in Alzheimer’s mouse models. J Vis Exp. 123: 55418. PMID: 28518111. (https://www.jove.com/video/55418/using-enzyme-based-biosensors-to-measure-tonic-phasic-glutamate5).
  10. Hunsberger HC, Wang D, Petrisko TJ, Alhowail A, Setti SE, Suppiramaniam V, Konat GW, Reed MN (2016). Peripherally restricted viral challenge elevates extracellular glutamate and enhances synaptic transmission in the hippocampus. J Neurochem. 138(2): 307-316. PMID: 27168075.
  11. Hunsberger HC, Hickman JE, Reed MN (2016). Riluzole rescues alterations in rapid glutamate transients in the hippocampus of rTg4510 mice. Metab Brain Dis. 31(3): 711-715. PMID: 26744018.
  12. Hunsberger HC, Weitzner DS, Rudy CC, Hickman JE, Libell EM, Speer RR, Gerhardt GA, Reed MN (2015). Riluzole rescues glutamate alterations, cognitive deficits, and tau pathology associated with P301L tau expression. J Neurochem. 135(2): 381-389. PMID: 26146790.
    1. Editorial Highlight: Whitcomb DJ & Molnar E (2015). Is riluzole a new drug for Alzheimer’s disease? J Neurochem. 135: 207-209. PMID: 26451974.
  13. Hunsberger HC, Rudy CC, Batten SR, Gerhardt GA, Reed MN (2015). P301L tau expression affects glutamate release and clearance in the hippocampal trisynaptic pathway. J Neurochem. 132(2): 169-182. PMID: 25319522.
  14. Hunsberger HC, Rudy CC, Weitzner DW, Zhang C, Tosto DE, Xu Y, Reed MN (2014). Effect size of memory deficits in mice with adult-onset P301L tau expression. Behav Brain Res. 272: 181-195. PMID: 25004446.
  15. Rudy CC, Hunsberger HC, Weitzner DS, Reed MN (2014). The role of the tripartite glutamatergic synapse in the pathophysiology of Alzheimer’s disease. Aging Dis. 6(2): 131-148. PMID: 25821641.
  16. Povroznik JM, Rudy CC, Hunsberger HC, Tosto DE, Reed MN (2014). Effects of an alpha-5GABAA inverse agonist on MK-801-induced learning deficits in an incremental repeated acquisition task. Behav Pharmacol. 25(4): 331-335. PMID: 25006978.

MEDIA

2021

2020

2017

2015

SERVICE

2021

  • IBNS Peer Mentor Program
  • Project Encephalon Brain Awareness Week: Lecture on Learning and Memory

2018

  • Biobus Mentor, Variety Boys and Girls Club of Queens, NY
  • Columbia Neuroscience Outreach: High School Lab visit and Lecture

2017-2018

  • Columbia Postdoctoral Poster Session Judge, Columbia University

2016-2017

  • “Scientista” Symposium Poster Judge, Microsoft Technology Center, NY
  • “This is Research” Symposium Poster Judge, Auburn University

2012-2014

  • Psychology 101 Undergraduate Capstone Poster Session Judge, West Virginia University
  • Student Ambassador for Visiting Professors, West Virginia University
  • Behavioral Neuroscience Training Committee, West Virginia University Student Representative
  • Graduate Interview Weekend Coordinator, West Virginia University