Who we are
We are a group of scientists working to better understand the brain's involvement in normal and maladaptive behavior by developing innovative technologies and testing unconventional hypotheses
I was born in Kavala, a small coastal town in Greece. My family moved to Queens, NY when I was 3 years old and then back to Kavala 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. - Research Fellow
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.
Oscar Solís, Ph.D. - IRTA Postdoctoral Fellow
I was born and raised in the tropical state of Guerrero in Mexico. After high school, I moved to Puebla, where I obtained a BSc in Biochemistry and a MSc degree in Physiology at the Autonomous University of Puebla. During my undergraduate studies, with Dr. Gonzalo Flores at the Physiology Institute, I worked on the alterations of cortical and striatal neurons in a rodent model of Parkinson disease. Then, after being accepted into the Ph.D. program in Neuroscience in Madrid, Spain, I joined the Neurobiology of Basal Ganglia Lab at Cajal Institute. Under the guidance of Prof. Rosario Moratalla, I studied the behavioral and molecular/structural/functional traits relevant to L-DOPA-induced dyskinesia and drug addiction. In my free time, I enjoy playing football, running, traveling and spending time with my family and friends.
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. - Research Technician
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.
Meghan Carlton, B.S. - IRTA Postbaccalaureate Fellow
I grew up in Hopewell, New Jersey. Very early in my academic career I realized that I loved all of my science coursework and as high school progressed, I became primarily interested in studying the brain. I attended the University of Pittsburgh focused on studying neuroscience and I completed my bachelor’s degree in 2019. As a sophomore, I joined Dr. Alberto Vazquez’s lab where I worked for 2.5 years with a mouse model of Alzheimer’s disease. My undergraduate thesis was focused on optogenetic cortical stimulation and changes in plaque deposition. In my free time I enjoy making art, doing triathlons and eating large quantities of humanely sourced, organic, non-GMO vegan foods washed down with a glass of Chianti.
Emilya Ventriglia B.S., M.S. - IRTA Postbaccalaureate Fellow
In a Steinbeckian gesture, I moved from my hometown of Oklahoma City, OK to southern California in the pursuit of great opportunity. My passion for neuroscience was fully realized during my studies at the University of California, San Diego. In 2019 I graduated with a B.S. in Physiology & Neuroscience with a minor in music, continued by a M.Sc. in Biology in 2020. Beginning the Spring of my senior year, I began full-time research in the Banghart Lab at UCSD as a continuous BS/MS student, cutting my teeth on behavioral pharmacology and activity-dependent neuroplasticity. I worked primarily with mouse-models for persistent inflammatory pain and opioid-induced hyperalgesia in the vlPAG, the latter being the subject of my thesis. Beyond the bench I enjoy being outdoors, listening to music, and dabbling in different arts.
What we think we do
We are developing and characterizing novel, selective, and potent neurotheranostic ligands for chemogenetic technologies and combining their use with translational molecular imaging.
Figure: 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 afford significant promise for precision psychiatry and neurology. Such neurotheranostic interventions are particularly timely given recent developments in 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. A key feature of chemogenetic technologies is that they can be combined with clinical molecular imaging diagnostic methods such as positron emission tomography (PET). This particular combination extends the therapeutic component of chemogenetics to encompass its use in precision medicine-based neurotheranostics.
Optogenetics is a revolutionary technology that consists of unique ion channels expressed in neural tissue which upon light stimulation can either activate or inhibit neurons with exquisite temporal precision. Optogenetics has had a tremendous impact on basic neuroscience research. However, its impact in translational brain applications has been limited. One reason for this, is that to date, opsins have not been able to be visualized noninvasively in intact subjects. As such we are working on a noninvasive reporter detection system for optogenetics. This scalable system consists of chimeric opsins tagged with a small protein epitope and a clinically-used PET radioligand and permits noninvasive, quantitative, and longitudinal detection of opsins in the brain in translational and potentially, also in clinical applications.
Figure: A novel reporter opsin called ChRERa elicits light-driven neuronal activation and can be visualized noninvasively in cells bodies and at their terminal projections sites using PET.
Noninvasive, quantitative, and longitudinal cell type-specific mapping of brain activity
We implement chemogenetics, optogenetics, pharmacological, magnetic, or electrical stimulation with PET imaging in awake, freely-moving animals either in an exploratory fashion, to determine whole-brain functional networks recruited during behaviorally-relevant contexts, or to corroborate functional connectivity of a defined neuron-type, region, pathway or peripheral tissue/organ. We use such approaches to map functional anatomy related to a variety of cell-types/projections in distinct brain regions in basic and translational research.
Figure: DREADD-assisted metabolic mapping (DREAMM) showing metabolic activation of a brain network comprising cingulate gyrus (CG), olfactory tubercle (OT) and extended amygdala (ExA) in response to DREADD-mediated inhibition of prodynorphin-expressing neurons in a discrete subregion of the amygdala, the periamygdaloid cortex.
Biobehavioral molecular imaging
A considerable portion of our research program relies on the use of advanced quantitative molecular imaging via positron emission tomography (PET). We perform PET studies by employing a variety of radioligands depending on experimental need. These can be procured commercially or are custom made to perform noninvasive and longitudinal assessments of brain metabolic activity, neuroinflammation, neurotransmitter displacement, and receptor occupancy/target engagement of candidate compounds or other processes.
Figure: PET image coregistered to MRI showing non-invasive assessment of dopamine D2/D3 receptors using [11C]raclopride in mouse striatum.
Development of molecular imaging PET probes
We are developing novel imaging agents & applications for endogenous targets including non-invasive visualization of mu opioid receptors and elemental Zn2+
Figure: Noninvasive imaging of elemental trace zinc uptake throughout the body of a mouse. High levels of zinc are observed in the brain, spine, nasal area, joints, and liver.
Trace metals and addiction - Zinc potentiates dopamine neurotransmission and cocaine seeking
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 normal neurobiology, and in disease states like addiction are not well understood. Zn specifically is transported into synaptic vesicles via its ZnT3 transporter and is co-released from presynaptic terminals along with glutamate but its function is not well understood. We are currently exploring a role for Zn and ZnT3-positive neurons and circuits on in vivo dopamine neurotransmission, cocaine abuse vulnerability, and motivated behaviors.
Figure: At physiological concentrations, Zn increases the affinity of cocaine at its main endogenous target, the dopamine transporter. Cocaine also decreases synaptic Zn2+ levels in the brain.
Characterization of drugs of abuse - focus on ketamine enantiomers & metabolites
Ketamine is a controlled substance, has abuse potential, and can induce undesirable side effects. Nevertheless, it is considered to be generally safe and is a widely-used dissociative anesthetic and rapid-acting pain medication. The recent discovery that a single subanesthetic dose of ketamine (a racemic mixture in equal proportion of S-ketamine and R-ketamine enantiomers) produces rapid and long-lasting antidepressant effects in individuals with major depressive disorder (MDD), bipolar depression, and treatment-resistant depression (TRD) has been hailed as a key psychiatric breakthrough. Ketamine is generally regarded as a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist but also shows considerable affinity for other receptors. Though preclinical studies have investigated ketamine pharmacology and abuse liability, no study to date has characterized the precise in vitro and in vivo pharmacological properties and the abuse liability of its enantiomers. S-ketamine (esketamine, SpravatoTM) was recently approved by the FDA as an intranasal formulation for TRD and human trials assessing efficacy of R-ketamine in depression are currently underway. As depression shares strong comorbidity with substance use disorders, we are working to better understand the abuse liability of each enantiomer.
A ketamine metabolite, (2R,6R)-hydroxynorketamine (HNK), has been recently implicated in underlying ketamine's efficacy in preclinical models of depression. We are also working on the pharmacological characterization of HNK, for which clinical trials are also underway.
Figure: Structures of racemic ketamine, its enantiomers, and its (2R, 6R)-HNK metabolite
SARS-CoV-2 and COVID-19
Our labs specializes in discovery and characterization of drug-receptor and protein-receptor interactions. As such we are using our capabilities to identify novel receptors for the SARS-CoV-2 Spike protein.
Figure: Saturation binding assay assessing radiolabeled I125-Spike against recombinant human ACE2.
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.
Figure: 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.
What we really do
Tools & Resources
Radioligands & Imaging Agents
Our lab has pioneered the use of the agents below for non-invasive localization of chemogenetic and optogenetic switches in various species with the ultimate goal being human application.
[3H]ASEM - In vitro PSAM4-GlyR & PSAM4-5HT3 quantification
[18F]ASEM - Longitudinal In vivo PSAM4-GlyR & PSAM4-5HT3 quantification
[3H]Clozapine - In vitro hM3Dq/hM4Di quantification
[3H]Compound 13 (C13) - In vitro hM3Dq/hM4Di quantification
[18F]JHU37107 (J07) - Longitudinal In vivo hM3Dq/hM4Di quantification
Optogenetics (coming soon)
Our lab has developed the first DREADD agonists that exhibit high affinity, high in vivo potency, and high brain penetrance in several species, which favors clinical translation. These compounds require very low systemic doses (<0.1 mg/kg) to facilitate rapid and remote activation of chemogenetic switches in the brain.
Plasmids & Viral Vectors
For translational and clinical gene therapy applications, chemogenetic/optogenetic switches need to be optimized to drive efficient expression and trafficking to the cell membrane, where their respective actuators would achieve maximum efficacy. For this reason, our goal has been to optimize existing chemogenetic/optogenetic gene therapy constructs for optimal expression and targeting. One way of doing this is to strip bulky and potentially toxic fluorescent reporters, typically used in such designs, and which are not useful for translational and clinical applications. Our strategy is to leverage the use of our translational PET-based reporters for non-invasive and longitudinal quantification of chemogenetic/optogenetic switches along with small epitopes (e.g. HA-tag) whenever in vitro detection would be necessary.
Interview on CODA Biotherapeutics at STAT
February 5 2020
Presentation at the Brain Initiative's "Chemogenetic Innovations in the Manipulation & Monitoring of Labeled Neurons Workshop"
NIH Brain Initiative Workshop
December 10 2019
Presentation at the ACNP 2019 Annual Meeting describing our optogenetics molecular imaging technology
ACNP 2019 "Hot Topics"
December 10 2019
"Changing the Locks" article and interview for Chemistry World about our work and that of others on chemogenetics.
May 20 2019
Interview for Science magazine: Could deep brain stimulation help zap diabetes?
May 23 2018
Interview for the American Psychiatric Association (APA): DREADDs Could Guide More Targeted Treatments in Future
March 16 2018
Research highlight about our recent work on chemogenetics
Our recent work highlighted in the journal Nature Methods
September 29 2017
Research highlight about our recent work on chemogenetics
Our recent work highlighted in the journal Nature Chemical Biology
September 19 2017
Theresa Kopajtic, B.S.
Current - Retired
Kelsey Wright, B.S.
IRTA Postbaccalaureate Fellow
Current - Ph.D. Student
Dondre Marable, B.S.
IRTA Postbaccalaureate Fellow/Diversity Fellow
Current - Entrepreneur/Industry
Weilin Chan, B.S.
Special Volunteer/Summer Student
Current - M.D. Student
University of Buffalo
Randall J. Ellis, B.S.
IRTA Postbaccalaureate Fellow
Current - Ph.D. student
Biophysics & Systems Pharmacology
Icahn School of Medicine at Mount Sinai
Lionel A. Rodriguez, B.S.
IRTA Postbaccalaureate Fellow
Current - Ph.D. student,
Johns Hopkins University
RTURP Research Fellow
Current - Student, Loyola University
Kat Daly, B.S.
Lab rotation, NIH GPP program
Current - Ph.D. student
JHU/NIH GPP Program
Where to find us
NIDA Intramural Research Program
Biomedical Research Center
251 Bayview Blvd
Baltimore MD 21224