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The SPENCER LAb

University of Minnesota

Department of Pharmacology


WE ARE HIRING!

A post-doctoral position is available to lead the investigation of the role of dopamine transmission in regulating the neurobiological adaptations associated with drug relapse. The successful candidate should have a PhD in the biological sciences field, a record of scientific publication, and excellent communication skills. Please email Dr. Spencer at spencers@umn.edu if interested.

 
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about us

Our research program is aimed at identifying the neural mechanisms that underlie the development of drug addiction and relapse. Broadly, we are interested in studying the trajectory of neuroplasticity, neurochemistry, and behavior associated with addiction as a relapsing-remitting brain disorder. These interests extend to the comorbidities between drug addiction and other debilitating psychiatric diseases.

We are housed in the Department of Pharmacology within the Medical school at the University of Minnesota. Prospective graduate students can find information about applying to the program here. 

 

 

Location

 
 Our laboratory is physically located in the McGuire Translational Research Facility in Biomedical Discovery District on the University of Minnesota Twin-Cities Campus. We are part of the Medical Discovery Team on Addiction (MDTA), a multi-departmental initiative aimed at advancing research leading to innovative treatments for addiction.

Our laboratory is physically located in the McGuire Translational Research Facility in Biomedical Discovery District on the University of Minnesota Twin-Cities Campus. We are part of the Medical Discovery Team on Addiction (MDTA), a multi-departmental initiative aimed at advancing research leading to innovative treatments for addiction.

 
 
 
 
 
 
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Research

 

Overview

Addiction is characterized as a chronic neurodegenerative disease because a defining feature of the illness is a persistent vulnerability to relapse. The brain is designed to associate salient stimuli of positive or negative valence with the cues that predict these events in order to facilitate adaptive learning. In the addicted brain, it has been proposed that these normal learning systems are misappropriated resulting in the disease state. Chronic drug use results in a variety of maladaptive neuroadaptations that set the stage for drug relapse even after protracted abstinence periods. It is our hope that a better understanding of the trajectory of the neuroplasticity, physiology, neurochemistry, and behavior over the course of the development of relapsing-remitting addiction will aid in the rational design of new, more effective treatments for drug addiction.

Drug and other behavioral addictions share many common features and are often thought of as disease variants derived from a single common pathology. Indeed, over the past 50 years several unified theories of addiction have been posited with each adding to our understanding of the addiction process. Importantly, however, there is an appreciable divergence between different classes of abused drugs in terms of the psychological, neurobiological, and behavioral effects. For example, there are opposite synaptic and structural plasticity changes in the nucleus accumbens following withdrawal from psychostimulants versus opiates with the former producing potentiation and the latter resulting in synaptic depression. We feel that it is important to extend our addiction models to the study of these different classes of abused drugs beyond the prototypical stimulant cocaine as well as investigate relevant poly-drug use to gain a better understanding of the similarities and differences. In this way we may come closer to characterizing a convergent set of biological endophenotypes that exemplify addiction.

As a postdoctoral fellow, Dr. Spencer worked to develop innovative animal models to study neuroplasticity and behavior across various stages of addiction and relapse. We know that for cocaine both intrinsic excitability and excitatory synaptic strength is dynamically regulated in nucleus accumbens medium spiny neurons by chronic treatment, withdrawal, and re-exposure.  Surprisingly, earlier research has largely failed to consider the impact of voluntary resumption of drug intake during relapse on plasticity, which our model allows us to do. It remains to be seen what impact repeated drug relapse events might have on circuit function or long-term treatment outcomes.

In the Spencer lab we have a broad interest in studying mechanisms related to the development of addiction as well as relapse in the late stages of the disease. We also want to better understand risk factors and psychiatric comorbidities associated with drug addiction. We are currently pursuing studies in two general broad project areas (outlined below). New graduate students and postdocs candidates with interests in these areas should contact Dr. Spencer. 


Project 1: Examination of dopamine and glutamate interactions during cue-induced cocaine seeking and taking

Cue-induced transient synaptic plasticity (t-SP) at glutamatergic synapses on nucleus accumbens core medium spiny neurons occurs within 15 minutes and disappears within 2 hours. We have shown that cocaine taking after initiating cue-induced reinstatement rapidly reverses cue-induced transient synaptic plasticity in the accumbens, and demonstrates just how dynamic these neuroadaptations are within a modified 2-hour reinstatement session. Our results support a correlation between t-SP and motivated lever pressing and raises the possibility that cocaine-induced increases in extracellular dopamine may suppress t-SP.


Project 2: Understanding distinct and overlapping neural circuits encoding the rewarding versus the aversive properties of cannabinoids.

Tetrahydrocannabinol (THC) is the most widely used illicit drug worldwide, but enduring consequences of its use, especially in terms of neurobiology, are largely unknown. The drug displays a narrow dose reward window, but produces enduring neuroadaptations following chronic self-administration that resemble other drugs of abuse. Understanding how both reward and aversion are encoded with use of this drug will help guide development of therapeutics for treating cannabis use disorder as well as designing non-addictive cannabinergic therapies for disorders like chronic pain.


 

There is no scientific study more vital to man than the study of his own brain. Our entire view of the universe depends on it.
— Francis Crick
 
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People

 
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SadE SpenceR - assistant professor

Hometown: Grand Prairie, TX

Education: I received my undergraduate degree in Biology at the University of Alabama in Tuscaloosa (Roll Tide!) graduating Summa Cum Laude. My thesis research in the lab of Dr. Colleen McClung at the University of Texas Southwestern Medical Center in Dallas focused on circadian rhythms and affective disorders with a focus on understanding how the transcription factor CLOCK was involved in the regulation of dopamine transmission. During my postdoc in the lab of Dr. Peter Kalivas at the Medical University of South Carolina I worked to develop innovative animal models to study neuroplasticity and behavior across various stages of addiction and relapse.

Hobbies: When I'm not running a lab, I enjoy running and cooking.

 
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lexi willard - Technician

Hometown: Green Bay, WI

Education: I received my Bachelor's Degree in Neuroscience and Biomedical Science with a minor in Psychology from the University of Wisconsin, River Falls.

Research Interests: I have a wide variety of research interests within the realm of neuroscience ranging from neurodegenerative diseases, neuropsychpharmacology, and social neuroscience. In neuropsychpharmacology, I am most interested in better understanding relapse occurrences and relapse alleviation through pharmacological modulation. I’m also interested in how the use of multiple drugs concurrently affects neural transmission, neurochemistry, and behavior.

Career goals: Ideally, I would like to obtain a PhD in Neuroscience and study Creutzfeldt-Jakob’s Disease with an emphasis on possible pharmacological prion aggregation intervention.

Hobbies: Outside of lab I like to attend and watch various sporting events, horseback riding, skiing, traveling, fishing, and hiking.

 
 
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Amy chan

- technician

Hometown: Flint, MI

Education: I received my undergraduate degree in Biology with an emphasis in Neurobiology and minor in Chemistry, graduating Cum Laude from Macalester College in St. Paul, Minnesota.

Research Interests: I completed a senior honors thesis with Dr. Lucy Vulchanova in the department of neuroscience at the University of Minnesota, studying neuroimmune mechanisms of chronic pain after spinal cord injury. Pain, neuroimmunology, addiction, and neuropharmacology are my primary research interests and I ultimately plan on attending a graduate program in neuroscience to further explore these interests.

Hobbies: Outside of the lab, I enjoy spending time with my hedgehog, Belle, cooking, and traveling.

 
 
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Zia matti - Graduate student

Hometown: Various places within the US, but most recently North Carolina.

Education: I received a Bachelor's of Science in Biochemistry with a minor in Women's Studies from St. Cloud State University in St. Cloud, Minnesota. I am currently working on my Master's in Pharmacology here at the University of Minnesota.

Research Interests: I am interested in drug discovery and the mechanisms behind those drugs, specifically related to mental illness. As my past experience has dealt with the more chemical side of creating novel drugs, I am excited to learn about the biological and behavioral parts of the drug discovery process.

Hobbies: When I am not in lab or studying for classes, I enjoy running, cuddling with my cat, zoning out to Netflix or Hulu, and traveling.

 

Rotating Graduate Students

 
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Sarah Mulloy - graduate Student

Hometown: Nashville, TN

Education: I graduated from Wake Forest University in 2018 with a Bachelor’s of Science in Biology and a Bachelor’s of Arts in Latin. I am currently a graduate student in the Graduate Program in Neuroscience (GPN) at the University of Minnesota.

Research Interests: My undergraduate research was in an invertebrate developmental neuroscience lab studying experience-based plasticity in the honey bee mushroom body brain regions. The experience I gained from this lab allowed me to discover my love for studying the neural circuitry and cellular mechanisms of behavior. My current research interests are very broad, but I aim to continue studying behavior both at the organismal and cellular level. Research in the Spencer Lab as a part of the Medical Discovery Team on Addiction appealed to me because models of addiction pose very interesting behavioral questions that can be analyzed with a wide variety of approaches.

Career goals: I hope to graduate from the GPN and continue a career in academic research, ultimately wanting to run my own lab one day!

Hobbies: When I am not studying or doing research, I spend my time painting and drawing, trying to keep my bonsai tree and fish Hades alive, and playing any type of board or video game.

 
 
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Ashley Anderson - graduate Student

Hometown: Cedar Rapids, IA

Education: I received my undergraduate degree in Neuroscience with a minor in Chemistry from Wartburg College in Waverly, IA. I am currently working on my Ph.D. in Pharmacology at the University of Minnesota.

Research Interests: My previous research experiences have included x-ray crystallography for antibiotic targets, how traumatic brain injury alters actin dynamics, and how novel protein interactions with postsynaptic density proteins change dendritic spine morphology. This broad range of experiences has made it difficult for me to narrow down my interests, but currently my research interests include the neuropharmacology of behavior, addiction, and toxicology, as well as the progression of neurodegeneration.

Hobbies: When I’m not in the lab or studying, I enjoy kickboxing, playing drumset, playing video games, and hanging out with my cat, Pixie.

 

Former Members

 
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Patrick Haley - Undergraduate Volunteer

Hometown: Fort Lauderdale, FL

Education: I am currently a senior at Macalester College studying Biology.

Research Interests: Previously I have worked in a clinical research facility that studied the efficacy of biologics in treating autoimmune disease. Pursuing my interests in immunology, I then worked in an Immunology lab at the University of Minnesota that aimed to identify specific markers of regulatory T cell progenitors, which are of potential interest in treating autoimmune disease. Recently, I have taken an interest in neuroscience and have begun work in the Spencer Lab to gain more experience via our research on addiction.

Hobbies: Other than studying and spending time in the lab, I enjoy playing football, working out, playing video games, and watching movies with my housemates.


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publications

Featured Publications:

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Relapse is a two-component process consisting of a highly motivated drug-seeking phase that, if successful, is followed by a drug-using phase resulting in temporary satiation. In rodents, cue-induce drug seeking requires transient synaptic potentiation (t-SP) of cortical glutamatergic synapses on nucleus accumbens core medium spiny neurons, but it is unknown how achieving drug use affects this plasticity. We modeled the two phases of relapse after extinction from cocaine self-administration to assess how cocaine use affects t-SP associated with cue-induced drug seeking.

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Photo credit: Rachel Poli. 

In our manuscript, we describe a model of intravenous delta9-tetrahydrocannabinol plus cannabidiol self-administration and reinstatement in the rat. We show that this self-administration is CB1 receptor dependent as it can be blocked by rimonabant. We report that cue-induced reinstatement is inhibited by administration of drugs that have been shown to reduce relapse to other drugs of abuse (n-acetylcysteine, nNOS inhibitor, and matrix metalloproteinase 9 inhibitor). Finally, we report that THC self-administration and extinction results in enduring changes in structural and functional plasticity in the nucleus accumbens.

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This is a comprehensive review of the role that glutamate signal transduction in the nucleus accembens plays in addiction-related behaviors. As a major input structure of the basal ganglia, the nucleus accumbens integrates information from cortical and limbic structures to mediate goal-directed behaviors. Chronic exposure to drugs of abuse disrupts plasticity in this region producing adaptations that serve as the molecular basis for relapse vulnerability, allowing drug-associated cues to engender a pathologic motivation for drug seeking. 


Recent Peer-Reviewed Publications

 1.     Spencer S*, Neuhofer D*, Chioma V, Garcia-Keller C, Schwartz D, Allen N, Scofield M, Ortiz T, Kalivas PW. (2018) A model of Δ9‐tetrahydrocannabinol (THC) self-administration and reinstatement that produces heroin-like synaptic plasticity in nucleus accumbens. (In press)

 

2.     Spencer S and Kalivas PW. (2017) Glutamate transport: a new bench to bedside mechanism for treating substance abuse. International Journal of Neuropsychopharmacology20(10):797-812. PMID: 28605494. PMCID: 5632313.

 

3.     Melis M, Frau R, Kalivas PW, Spencer S, Chioma V, Zamberletti E, Rubino T, Parolaro D. (2017) New vistas on cannabis use disorder. Neuropharmacology124:62-72. PMID: 28373077. PMCID: 5865400.

 

4.     Smith AW, Scofield MD, Heinsbroek JA, Gipson CD, Neuhofer D, Roberts-Wolfe D, Spencer S,Stankeviciute N, Smith RJ, Allen A, Lorang M, Griffin III W, Boger HA, Kalivas PW. (2017) Accumbens nNOS interneurons regulate cocaine relapse.  Journal of Neuroscience37(4):742-756. PMID: 28123012. PMCID: 5296777.

 

5.     Spencer S, Garcia-Keller C, Roberts-Wolfe D, Heinsbroek JA, Mulvaney M, Sorrel A, Kalivas PW. (2017) Cocaine use reverses striatal plasticity produced during cocaine seeking. Biological Psychiatry81(7):616-624.  PMID: 27837917. PMCID: 5346331.

>Featuredin“Early Career Investigator Commentary”article: Ferguson, D. (2017) Cocaine mediates the Cellular Mechanisms of Satiation.Biological Psychiatry81(7):e47-e48.

 

6.    Brown RM, Kupchik YM, Spencer S, Garcia-Keller C, Spanswick DC, Lawrence AJ, Simonds SE, Schwartz DJ, Jordan KA, Jhou TC, Kalivas PW. (2017) Addiction-like synaptic impairments in diet-induced obesity. Biological Psychiatry81(9):797-806. PMID: 26826876. PMCID: 4889544.

 

7.     Scofield MD, Heinsbroek JA, Gipson CD, Kupchik YM,Spencer S, Smith AW, Roberts-Wolfe D, Kalivas PW. (2016) The nucleus accumbens: mechanisms of addiction across drug classes reflect the importance of glutamate homeostasis. Pharmacological Reviews68(3):816-71. PMID: 27363411. PMCID: 4931870. 

 

8.    Garcia-Keller C, Kupchik Y, Gipson C, Brown RM, Spencer S, Bollati F, Roberts-Wolfe D, Heinsbroek J, Cancela LM, Kalivas PW. (2015) Glutamatergic mechanisms of comorbidity between acute stress and cocaine self-administration. Molecular Psychiatry21(8):1063-9. PMID: 26821978. PMCID: 4823171. 

 

9.    Sidor MM, Spencer SM, Dzirasa K, Parekh PK, Tye KM, Warden MR, Arey RN, Enwright JF III, Jacobsen JPR, Kumar S, Remillard EM, Caron MG, Deisseroth K, McClung CA. (2015) Daytime spikes in dopaminergic activity drive rapid mood-cycling in mice. Molecular Psychiatry20(11):1406-19.PMID: 25560763. PMCID: 44929295. 

 

10.  Ozburn AR, Falcon E, Twaddle A, Nugent A, Gillman A, Spencer SM, Arey RN, Mukherjee S, Lyons-Weiler JF, Self DW, McClung CA. (2015) Direct regulation of diurnal Drd3 expression and cocaine reward by NPAS2. Biological Psychiatry77(5):425-433. PMID: 25444159. PMCID: 4315729.

 

11.  Spencer S, Brown RM, Quintero GC, Kupchik YM, Thomas C, Reissner KJ, Kalivas PW. (2014) Alpha2delta-1 signaling in nucleus accumbens is necessary for cocaine-induced relapse. Journal of Neuroscience34(25):8605-8611. PMID: 24948814. PMCID: 4061396.

>Featuredin“Research Highlights”article: Bucci M. (2014) Your channels on Drugs. Nature Chemical Biology10(8):607.

 

12.  Reissner KJ, Thomas CA, Brown RM, Spencer S, Tran PK,Kalivas PW. (2014) Chronic administration of the glial modulator propentofylline impairs cue-primed reinstatement to cocaine. Neuropsychopharmacology39(2):499-406. PMID: 23985782. PMCID: 3870775.

 
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News and Notes from Around the Lab


2018

  • December 9-13, 2018 - Dr. Spencer travels to Hollywood, Florida for the American College of Neuropsychopharmacology (ACNP) Annual Meeting

  • December 3, 2018 - First five rat pups born in the Spencer Lab!

  • November 5, 2018 - January 18, 2019 - Ashley Anderson joins the lab as a rotating graduate student in the department of pharmacology

  • November 2-7, 2018 - Dr. Spencer and Lexi travel to San Diego for the annual Society for Neuroscience (SfN) conference

  • September 25, 2018 - Zia Matti joins the lab as a masters graduate student in the department of pharmacology

  • September 21, 2018 - Dr. Sade Spencer gives a new faculty lecture at the 2018 department of pharmacology annual retreat

  • September 20-December 11 2018 - Patrick Haley joins the lab as an undergraduate volunteer

  • September 4 - October 26, 2018 - Sarah Mulloy joins the lab as a rotating graduate student in the department of neuroscience

  • August 15, 2018 - First 8 rats arrive in the lab!

  • July 9, 2018- Amy Chan joins the lab as a technician

  • June 4, 2018- Alexis Willard joins the lab as a technician

  • April 2018- New article " A Model of Δ9-Tetrahydrocannabinol Self-administration and Reinstatement That Alters Synaptic Plasticity in Nucleus Accumbens" accepted in Biological Psychiatry.

  • March 31, 2018 - The Spencer Lab officially opens


 
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CONTACT US

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Postdoctoral Fellows

We are now accepting applications for Postdoctoral Fellows with a starting time frame in the Fall 2018 or early 2019. 

       Current graduate students with planned defense dates in 2018 and early 2019 are encouraged to apply or contact us directly to discuss postdoctoral opportunities (please use the contact form at the bottom of the page or email spencers@umn.edu). Interested candidates please email a cover letter that briefly details career goals and prior research experience, along with your CV, and the names and emails of three references. 

The Spencer Lab at the University of Minnesota will provide a dynamic research environment with exceptional resources for training in neuroscience behavioral pharmacology. Together, we will design studies that allow you to incorporate your research expertise, and to acquire the tangible and intangible skills necessary for your desired career path.  

 

Graduate Students

There will be many opportunities for lab rotations and exciting dissertation projects! We are currently part of the Pharmacology graduate program, but will affiliate with Neuroscience graduate program in the near future.

 

Undergraduates

Highly motivated undergraduate students from University of Minnesota or surrounding institutions that are interested in gaining lab experience and assisting with cutting-edge neuroscience projects can contact us using the form below. We will ask that you send your CV, a brief statement detailing prior research experience, your scientific or medical interests, and your weekly availability during the semester and/or summer sessions. 

 

meet ups!

If you would like to meet with Dr. Spencer in person, she will be attending the following conferences/meetings this year:

·       Nov. 3-7 2018: Society for Neuroscience Meeting (SfN), San Diego, CA

·       Dec. 9-13, 2018: American College of Neuropsychopharmacology (ACNP) Annual Meeting, Hollywood, FL