• Biobehavioral Imaging &

    Molecular Neuropsychopharmacology

    Laboratory

    at the National Institute on Drug Abuse

    Intramural Research Program

  • Who we are

    We are a group of scientists working to better understand the brain's involvement in normal and maladaptive behavior by developing and implementing innovative neurotheranostic technologies and by testing unconventional biomedical hypotheses

    I was born in a small coastal town in Greece. My family moved to Queens, NY when I was 3 years old and then back to Greece when I was 10. After high-school I moved back to NY for undergraduate studies at Stony Brook University (SBU) where I studied Economics and Mathematics. A summer research fellowship in my junior year exposed me to behavioral pharmacology and molecular imaging research and this experience led me to pursue a PhD in Integrative Neuroscience at SBU. My doctoral research was carried out at Brookhaven National Laboratory in Dr. Nora Volkow's Laboratory of Neuroimaging. After this, I moved to the Icahn School of Medicine at Mount Sinai where I spent 5 years in Dr. Yasmin Hurd's Molecular Neuropsychopharmacology laboratory. During this time I also co-founded Metis Laboratories. I moved to Baltimore in the summer of 2015 to establish the BIMN lab at the NIDA IRP where I am currently a Tenure-track Investigator with an adjunct Assistant Professor appointment in the Psychiatry Department at the Johns Hopkins School of Medicine.

    Juan L. Gomez, Ph.D. - IRTA Postdoctoral Fellow

    "I'm just sayin"

    A statement about my-[science]-self: I have a curiosity driven by the need to explore; doing my best to improve upon methods and techniques to devise a better way to catch that roadrunner.

     

    Thoughts on experience: High School - An introduction to the lab, samples, and 96-wells. As a junior, I volunteered my school breaks and weekends to assist a biology graduate collecting and analyzing water/soil samples from rivers in Arizona. I was one of the few high school students among undergraduates to present our findings at the annual Arizona State University poster day. I was hooked. Undergraduate (B.S.) - An undergrad is only an undergrad by name in the lab of Cheryl Conrad at Arizona State University (ASU) where I received a degree in Psychology. These early experiences sharpened my lab work ethic and expectations as a future academic. Graduate (Ph.D.) - Good work with those that work good with you. Mentored by Victoria Luine, we worked with Michael Lewis and others at Hunter College of CUNY (HC) on my dissertation. Collaborations were an integral part of my graduate career, and almost every lab at HC contributed to my development as a scientist, for which I am grateful. Postdoc #1 – Envy has no place in productive endeavors. At my first postdoc in the Behavioral Neuroscience department at Oregon Health & Science University (OHSU), I was exposed to a new level of research and opportunities. Working with Andrey Ryabinin I learned the value of independent research and perseverance during difficult times. Postdoc #2 - Further research is needed… I joined the BIMN lab in 2015. Thus far, the radioactive signal may show me the way.

    Jordi Bonaventura, Ph.D. - IRTA Postdoctoral Fellow

    "Really?"

    I was born and raised in the midwest of Catalonia. I moved to Barcelona to earn degrees in Chemistry (2004) and Biochemistry (2006), both from the University of Barcelona. I stayed at the University of Barcelona to join the Molecular Neurobiology lab in the Department of Biochemistry and Molecular Biology for my doctoral research. Under the mentorship of Drs. Vicent Casadó and Carme Lluís I studied the role of GPCR multi-receptor complexes in the pharmacology of neuromodulators, focusing on dopamine, adenosine and cannabinoid receptors. In 2013, I moved to Baltimore to join NIDA as a postdoc in Dr. Sergi Ferré's lab where I shifted focus to psychostimulants and their underlying mechanisms. In 2016, I joined the BIMN lab where I undertake a wide spectrum of neuroscientific approaches to interrogate and identify mechanisms and novel targets for substance abuse disorder (SUD) and other neuropsychiatric diseases. But more importantly, I cook, eat, drink, run and hike across the country.

    Theresa Kopajtic, B.S. - Research Biologist

    I am a Marylander born and bred, where I attended Mercy High School and Towson University achieving a Bachelor of Science in Biology with a minor in Chemistry. During my storied tenure with the National Institute Against Drug Abuse, which spans nearly 28 years, I have had the privilege to work under the esteemed guidance of Dr. Michael Kuhar and Dr. Jonathan Katz. Since 1989 I have specialized in the field of pharmacology and drug development, specifically working with the dopamine transporter and the mu, kappa and delta opioid receptors. I live in a rural area of Maryland with my husband and two rambunctious black labs. I enjoy world travel, the culinary arts, gardening, and the ocean. My passions are my kids (adults now) and my grandson.

    Matthew Boehm, B.S. - Ph.D. Student (Brown University)

    I was born and raised in Minnesota, where the winters are cold and the people are nice. I attended college in St. Paul at the University of St. Thomas. I began taking biology courses in the hopes of pursuing a career as a pharmacist. However, as a curious sophomore I had a change of heart and began looking for research opportunities. I had a hard time choosing between my two main interests, ecology and mental health, so I ended up doing both. I studied methane emissions from shallow wetlands in the prairie pothole region under the mentorship of Leah Domine. I also examined the relationships between tobacco use, sleep and affective disorders under the guidance of J. Roxanne Prichard. After earning a Bacher of Science in Biology with minors in Chemistry and Psychology, I knew I wanted to pursue graduate research. I decided to make the brain my work and leave nature for play. I joined the Brown University-NIH Graduate Partnership Program in 2016 and am working towards a PhD in neuroscience. Besides striving to become a better scientist, I enjoy fishing, hiking and watching nature documentaries.

    Sherry Lam, B.S. - IRTA Postbaccalaureate Fellow

    I was born in Manhattan, New York. I graduated from Binghamton University with a Bachelor of Science in Integrative Neuroscience in 2017. As a sophomore, I was part of the Summer Research Immersion (SRI) program where I worked with Dr. Corinne Kiessling investigating how acetylcholine loss affects motor performance, treatment efficacy, and dyskinesia using a parkinsonian rat model. As a junior, I taught and guided students part of the Freshman Research Immersion (FRI) program throughout their research experiment. In summer 2016, I worked with Dr. Gabor Egervari in Dr. Yasmin Hurd’s Molecular Neuropsychopharmacology laboratory helping with a pilot study on how heroin-induced molecular disturbances on acetyl-H3 impacts cynomolgus monkey brain tissue using histone acetylation. I enjoy listening to music, knitting, and crocheting during my free time.

    Kelsey Wright - B.S. - IRTA Postbaccalaureate Fellow

    Rhode Island born and Rhode Island bred, I followed the greatest tradition of the smallest state by attending the University of Rhode Island where I received my Bachelor of Science in Cell & Molecular Biology. While attending the University of of Rhode Island, I took the motto “Think Big” to heart and worked in two laboratories as a part of three summer programs. As a part of Coastal Fellows, a URI-based research fellowship, I worked in Dr. Ying Zhang’s laboratory creating metabolic models of single cell organisms and learning applicable python programming. By my junior year I begun working in Dr. Nasser Zawia's laboratory as a part of the Rhode Island IDeA Network for Excellence in Biomedical Research (RI-INBRE) program, funded by the NIH. With Dr. Zawia's guidance I researched early life lead (Pb) exposure in tau-knockout mice and its relation to Alzheimer's disease. Outside of the lab I can be found building and crafting different projects.

    Dondre Marable B.S. - IRTA Postbaccalaureate Fellow

    I was born in Virginia and attended America’s second oldest college, The College of William & Mary, where I received a Bachelor of Science in Neuroscience. I have bounced around many research areas trying to find my passion. As a freshman, I participated in the HHMI’s SEA-PHAGES program where I was able to isolate and sequence a Mycobacterium Smegmatis bacteriophage from local soil samples in hopes of identifying a novel phage. The following year, I worked in a cognition lab studying implicit bias against same sex couples and analyzing how children process smoking and drinking stimuli depending on their parents consumption behaviors. In the summer after my junior year, I was supported by the Amgen Foundation to conduct a summer research project at Stanford University. I worked in a neurosurgery lab run by Dr. Theo Palmer, under the mentorship of Dr. Brooke Babineau. Here, I studied the effects of maternal immune activation via LPS and Poly(I:C) on the developing murine brain and its links to autistic phenotypes using various behavioral paradigms. Besides learning about the brain, I enjoy working out, cooking, and relaxing with friends.

    Weilin Chan - Research Volunteer

    I'm a premed undergraduate student at Johns Hopkins University majoring in Behavioral Biology. I'm originally from Ardsley, New York and went to high school at Phillips Exeter Academy in New Hampshire. In the summer after my freshman year of college, I worked with Dr. Michaelides in Dr. Yasmin Hurd's Molecular Neurospychopharmacology laboratory at the Icahn School of Medicine at Mount Sinai helping with a study on exposure of adolescent rats to tetrahydrocannabinol and their subsequent heroin self administration analyzed using magnetic resonance spectroscopy (MRS). In the summer of 2016, I was a summer intern at NIDA working in the BIMN lab. That summer I continued working on the MRS study and helped conduct several behavioral experiments. During the school year, I come to the lab regularly to help conduct experiments and continue learning about the research conducted here. In February of 2017, I studied ethnic minority cultures and local medicine practices in Kunming, China. After graduating, I hope to attend medical school, and am considering specializing in neurology, pediatrics, and emergency medicine. In my free time, enjoy playing volleyball, camping, trying new food, and listening to NPR podcasts.

  • What we think we do

    Chemogenetics-based neurotheranostics for precision medicine applications

    Precision medicine offers significant advantages over conventional medical treatment. Within precision medicine, theranostics comprises a strategy that combines THERApeutic and diagNOSTIC strategies to provide a personalized treatment approach encompassing disease diagnosis, drug delivery, and disease/therapy monitoring using a single agent. Theranostic strategies confer improvement in treatment efficacy compared to conventional medicine and specifically afford significant promise for precision psychiatry, neurology and other areas. Such neurotheranostic interventions are particularly timely considering the recent development of breakthrough translational neuromodulatory technologies. One such technology, called chemogenetics, offers the unprecedented ability to control neuronal activity in a cell type-specific manner in the freely-moving subject, without the need for chronically-implantable devices. Furthermore, chemogenetics offers another advantage for clinical applications, which is that it can be combined with clinical molecular imaging diagnostic methods such as positron emission tomography (PET) and magnetic resonance imaging (MRI). This combination extends the therapeutic component of chemogenetics to encompass its use in precision medicine-based neurotheranostics.

     

    We are currently developing and characterizing novel, selective, and potent neurotheranostic ligands for chemogenetic technologies and combining their use with translational molecular imaging using PET and MRI.

    Development of high-sensitivity, noninvasive, translational molecular imaging PET probes

    We are developing novel imaging applications for various biologically-relevant targets.

     

    Right: Noninvasive imaging of elemental trace zinc throughout the body of a mouse. High levels of zinc are observed in the brain, spine, nasal area, joints, and liver.

     

    Non-invasive, quantitative, and longitudinal cell type- specific biobehavioral molecular imaging

    a) PET image coregistered to MRI showing non-invasive assessment of dopamine D2/D3 receptors using [11C]raclopride in mouse striatum.

    A large portion of our research program relies on the use of advanced quantitative molecular imaging via positron emission tomography (PET). We perform PET studies using our dedicated scanners by employing a variety of radioligands depending on experimental need. These can be procured commercially or custom made to perform non-invasive and longitudinal assessments of brain metabolic activity, neuroinflammation, neurotransmitter displacement, and receptor occupancy/target engagement of candidate compounds or other processes.

     

    b) DREADD-assisted metabolic mapping (DREAMM) showing metabolic activation of a network comprising cingulate gyrus (CG), olfactory tubercle (OT) and extended amygdala (ExA) in response to DREADD-mediated inhibition of prodynorphin-expressing neurons in a region of the amygdala, the periamygdaloid cortex.

    We implement DREAMM either in an exploratory fashion, to determine whole-brain functional networks recruited during behaviorally-relevant contexts in freely-moving conditions, or to corroborate in vivo functional connectivity of a defined cell-type or projection. To date, DREAMM has been used to examine functional anatomy related to a variety of cell-types/projections in distinct brain regions in both mice and rats.

     

    c) Biobehavioral molecular imaging in a freely-moving rat using RatCAP tomography.

    We utilize the revolutionary RatCAP (Rat Conscious Animal PET) for dynamic, non-invasive whole-brain molecular imaging assessments during simultaneous behavioral experimentation in freely-moving rats including DREAMM and receptor occupancy assessment without anesthesia.

    Synchrotron X-Ray Fluorescence Microscopy of Zn (red) , Fe (green) and Cu (blue) in the rodent striatum

    Trace metals and neurobiology

    Metals such as Fe, Zn and Cu are essential for normal neurobiological functioning and many disease states are characterized by metal imbalances. However, the precise involvement of such metals in general neurobiology, and in disease states like addiction and substance abuse are not well understood. Since these metals are found in trace amounts within the brain, obtaining accurate measures of their content in such tissue requires advanced physical approaches such as X-ray fluorescence spectroscopy and imaging. We utilize techniques such as total reflection X-ray fluorescence in our lab as well as synchrotron X-ray fluorescence studies at national synchrotrons.

     

    Right: Synchrotron X-Ray Fluorescence Microscopy of Zn (red) , Fe (green) and Cu (blue) in the mouse striatum showing discrete localization of each trace metal to distinct regional compartments.

    Neuroscience & Artificial Intelligence

    We are exploring the interface of neuroscience and AI by leveraging the Brain Observatory dataset from the Allen Institute to examine the performance of novel machine and deep learning neural network architectures at decoding visual stimuli from calcium data derived from the parcellated visual cortex of the mouse. This approach is also yielding interesting novel facets of the biological properties of visual stimulus encoding by discrete cell types of the visual cortex. Our recent preprint describing the use of deep learning for visual decoding can be found here.

     

    Left: Example GCaMP6f trace data alongside a representative machine learning architecture we are implementing for visual stimulus decoding using neuronal calcium data derived from discrete cell-types.

    Discovery of novel neurobiological mechanisms involved in substance abuse

    Example workflow approach used for identifying candidate "Superconnector" genes derived from experiments examining effects of cocaine exposure on regional brain transcriptional expression.

    We develop bioinformatic workflows using public data and resources which identify candidate genes and predict their involvement in cocaine abuse. We then confirm mechanistic involvement of discrete candidates in cocaine abuse liability using a variety of molecular, biochemical, transgenic, imaging and behavioral approaches.

  • What we really do

    Motivational Valence is Determined by Striatal Melanocortin 4 Receptors​

    Chemogenetics Revealed: DREADD Occupancy and Activation via Converted Clozapine

    Dopamine D2 Receptor Signaling in the Nucleus Accumbens Comprises a Metabolic-Cognitive Brain Interface Regulating Metabolic Components of Glucose Reinforcement​

    Acute engagement of Gq-mediated signaling in the bed nucleus of the stria terminalis induces anxiety-like behavior

    Elucidation of The Behavioral Program and Neuronal Network Encoded by Dorsal Raphe Serotonergic Neurons

    DREAMM: A biobehavioral imaging methodology for dynamic in vivo whole-brain mapping of cell type-specific functional networks

    Whole-brain circuit dissection in free-moving animals reveals cell-specific mesocorticolimbic networks

    Impaired periamygdaloid-cortex prodynorphin is characteristic of opiate addiction and depression

    PET imaging predicts future body weight and cocaine preference​

    Dopamine D4 receptors modulate brain metabolic activity in the prefrontal cortex and cerebellum at rest and in response to methylphenidate​

    Limbic activation to novel versus familiar food cues predicts food preference and alcohol intake

    Dopamine-related frontostriatal abnormalities in obesity and binge-eating disorder: Emerging evidence for developmental psychopathology​

    Translational Neuroimaging in Drug Addiction and Obesity

  • News

    New paper published: Striatal MC4R as an interface for reward and aversion.

    Motivational valence is determined by striatal melanocortin 4 receptors

    https://www.jci.org/articles/view/97854

    New preprint on visual decoding of neuronal calcium using neural networks

    Mike's interview for the journal Science: Could deep brain stimulation help zap diabetes?

    Science

    http://www.sciencemag.org/news/2018/05/could-deep-brain-stimulation-help-zap-diabetes

    Mike's interview for the American Psychiatric Association (APA): DREADDs Could Guide More Targeted Treatments in Future

    Psychiatric News

    https://psychnews.psychiatryonline.org/doi/full/10.1176/appi.pn.2018.3b16

    Research highlight about your recent work on chemogenetics

    Our recent work highlighted in the journal Nature Methods

    September 29 2017

    Mike gives an invited talk at Janelia Reearch Campus HHMI 

    September 20 2017

    Research highlight about your recent work on chemogenetics

    Our recent work highlighted in the journal Nature Chemical Biology

    September 19 2017

    New paper published! Chemogenetics revealed...

    August 3rd 2017

    Chemogenetics revealed: DREADD occupancy and activation via converted clozapine

    New paper published! Brain dopamine and peripheral glucose...

    June 5th 2017

    Dopamine D2 Receptor Signaling in the Nucleus Accumbens Comprises a Metabolic-Cognitive Brain Interface Regulating Metabolic Components of Glucose Reinforcement​

    Welcome to the lab Sherry Lam, Kelsey Wright and Dondre Marable!!

    June 4th 2017

    Mike gives an invited talk at the BrainPET 2017 meeting in Berlin on DREAMM methodology

    April 5th 2017

    Spring 2017

    On to PhD!!! Congratulations to Randy and Lionel for being admitted to grad school!! Randy will attend the Biomedical Science PhD program at Icahn School of Medicine at Mount Sinai and Lionel will attend the Neuroscience PhD program at Johns Hopkins.

    November 2016 SfN Meeting in San Diego

    Lionel presenting his poster at SfN 2016. Think Zinc!!

    November 2016 SfN Meeting in San Diego

    Randy presenting his poster at SfN 2016.

  • Alumni

    Randall J. Ellis, B.S.

    IRTA Postbaccalaureate Fellow

    2015-2017

    Current - Ph.D. student

    Biophysics & Systems Pharmacology

    Icahn School of Medicine at Mount Sinai

    Lionel A. Rodriguez, B.S.

    IRTA Postbaccalaureate Fellow

    2015-2017

    Current - Ph.D. student,

    Neuroscience

    Johns Hopkins University

    Margaret Jokoh

    RTURP Research Fellow

    Summer 2016

    Current - Student, Loyola University

    Kat Daly, B.S.

    Lab rotation, NIH GPP program

    Spring 2016

    Current - Ph.D. student

    JHU/NIH GPP Program

  • Where to find us

    NIDA IRP

    Biomedical Research Center

    251 Bayview Blvd

    Baltimore MD 21224

    tel: 1-443-740-2894

    fax: 1-443-740-2122