PIPages
Labs

Mary Kay Lobo

University of Maryland, Baltimore, MD·Neuroscience

Drugs such as fentanyl and cocaine reshape the brain circuits that assign value to rewards, and those changes outlast the drug itself. Research in this lab asks which specific brain cell types change, which genes and cellular processes inside them are altered, and how those changes drive behavior.

Fields

Neuroscience

Pharmacology

Genetics

Topics

opioid use disorder

fentanyl

cocaine

Grants
3 known grants, through Aug 2027

What they work on

  1. Map cellular, synaptic plasticity and molecular changes in defined cell subtypes of the medial prefrontal cortex and nucleus accumbens in mice exposed to fentanyl during the equivalent of human gestation, from weaning through adolescence.
  2. Test whether manipulating the molecular changes identified in specific prefrontal and accumbens cell subtypes causes the sex-specific anxiety-like behavior in males and reduced motivation in females after perinatal fentanyl exposure.
  3. Build CRISPR epigenome editing tools, including light-activated optogenetic versions, that turn fentanyl-regulated genes up or down selectively in D1 or D2 dopamine receptor medium spiny neurons, validating them first in Neuro2a cells and then in mouse brain.
  4. Use validated epigenome editing tools to alter hub genes, highly connected genes that control gene networks, and test by RNA sequencing of each neuron subtype whether their co-expression networks shift during fentanyl abstinence.
  5. Disrupt hub genes with light-controlled CRISPR tools at discrete time points of stress susceptibility, opioid intake and relapse, to test when these genes matter for behavior.
  6. Determine how excitatory inputs to the nucleus accumbens regulate mitochondrial dynamics in medium spiny neuron subtypes and influence cocaine seeking, using chemogenetics and intravenous cocaine self-administration.
  7. Test how mitochondrial fission in D1 medium spiny neurons, driven by the protein Drp1, affects the ventral pallidum and ventral tegmental area, measuring drug seeking, dopamine dynamics and molecular adaptations.
  8. Profile mitochondrial molecules, mito-omics and their transcription factor regulators across reward circuit neuron subtypes after cocaine self-administration, and use CRISPR epigenome tools to test which transcription factors control them.

More about the research

Two circuits recur across the projects: the nucleus accumbens, a hub for motivation, and its connected regions, including the medial prefrontal cortex, which supports decision-making and emotion. The projects also build tools for switching individual genes on or off in one cell type at a time.

Why it matters

Opioid and stimulant use disorders carry heavy health and economic costs, and synthetic opioid overdoses have risen steeply. Pinpointing the neuron subtypes, genes and mitochondrial processes disrupted by fentanyl and cocaine could reveal targets for treating addiction and relapse. Work on prenatal fentanyl exposure addresses a growing population of children at risk for lasting behavioral problems. The cell-type-specific epigenome editing tools developed here can be applied in other brain regions and other areas of neuroscience.

Known grants

From NIH and NSF research grants. Labs often have other funding we can't see.

Epigenome Editing in Opioid Action

NIH · Sep 2020 – Aug 2027

Lasting Neurological Effects of Perinatal Opioids

NIH · Sep 2022 – Jul 2027

Cocaine-induced mitochondrial mechanisms and molecular mediators in reward circuitry

NIH · Sep 2014 – Jun 2027

Closest labs

Heath Schmidt

University of Pennsylvania, PA·Neuroscience

Define how amylin receptors on specific cell types, dopamine and GABA neurons of the ventral tegmental area and D1- or D2-receptor medium spiny neurons of the nucleus accumbens, control oxycodone self-administration and relapse-like seeking, using viral gene delivery in transgenic rats.

Eric J. Nestler

Icahn School of Medicine at Mount Sinai, NY·Neuroscience

Identify stable "chromatin scars" left in the mouse nucleus accumbens by early life stress, using unbiased proteomic and next-generation sequencing screens in specific neuron types and keeping only marks also found in postmortem accumbens from depressed humans.

Giuseppe Giannotti

Washington State University, WA·Neuroscience·Early-career

Track the real-time activity of PVT neurons tagged with TRAP during spontaneous versus naloxone-precipitated withdrawal, using in vivo calcium imaging while rodents respond to heroin-linked cues.

The school

University of Maryland, Baltimore: 23 labs on PI Pages, $1.5B a year on research, 79 research doctorates a year.

More about University of Maryland, Baltimore

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