Mary Kay Lobo

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

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.

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The school

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

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