The 2019 NARSAD Young Investigator grantees from the Brain and Behavior Research Foundation include six faculty members from the Icahn School of Medicine at Mount Sinai. Their research aims are listed below.

Jessica Ables, MD, PhD, seeks to determine the effect of increased blood sugar on vulnerability to stress, gene expression, structure and function of neurons in the striatum, habenula and midbrain in a mouse model of diabetes. These brain areas have been shown to be key in regulating mood and anxiety. Dr. Ables will look at specific cell types within each area, which is more informative than analyzing gene expression in the region as a whole, hoping that by sequencing and targeting specific cell types, it may be possible to identify a vulnerable population or specific pathway that may be targeted to develop new treatments for depression and anxiety.

Magdalena Janecka, PhD, is exploring the theory that risk for ASD is partly influenced by changes in DNA methylation, an epigenetic process in which molecules (methyl groups) bind to DNA, effectively switching particular genes on and off. This project seeks to discover and understand the functional significance of rare “epimutations” in ASD—changes in DNA methylation that have severe effects on genes that influence autism risk. After discovering epimutations, the team will explore whether they are linked to changes in the genetic code; and investigate the characteristics of the genes with the epimutations, which will highlight the impact they may have on a developing baby

Philipp Mews, PhD, is exploring the hypothesis that permanent changes in chromatin structure—the complex bundle in which our DNA is packaged in the cell—underlie the dysregulation of gene activation patterns characterizing drug addiction. There is currently no direct link between drug-induced alterations in chromatin and the aberrant gene regulation observed during relapse. Dr. Mews seeks to determine which neuronal subtypes are responsible within the nucleus accumbens, which is composed of two opposing types of medium spiny neurons, the D1 and D2 dopamine receptor-expressing subtypes. These exhibit dramatic differences in activity and effects on drug reward. This project aims to identify the precise epigenetic mechanisms that establish and preserve the molecular pathology in these distinct striatal subpopulations.

Laurel Morris, PhD, has developed an ultra-high field MRI procedure that provides much improved images of the ventral tegmental area (VTA), a brain area linked with the problem of motivation in depression. This project will consist of a randomized controlled trial to train individuals with major depressive disorder to modulate their own VTA activity during an ultra-high field MRI scanning session. Previous studies have shown that the activity of the VTA can be changed in healthy volunteers if they are trained to use certain thought patterns while watching their own VTA activity in real-time. The hope is that such biofeedback training is feasible in patients with major depressive disorder.

Agnes Norbury, PhD, wants to test new theories suggesting that people only use new information to update an older fear memory if they think that the same causes are responsible for events during Young Investigator Grant Program 2019 28 both the original fear memory and current learning episode. In other words, new learning that an object or situation is safe may fail to update an older memory of that object or situation being harmful if the individual reasons that the difference in context across these events means that is unlikely that they are the result of the same underlying factors. The team will test if this new theory can explain excessive avoidance behavior in individuals with an anxiety disorder or PTSD, using an online game to test how they learn about negative events.

Allison Waters, PhD, notes that advances in white matter imaging have provided maps of the brain whose great detail help explain the difficulty of precision-targeting a treatment like deep brain stimulation (DBS), a method that involves surgically implanting electrodes deep within specific brain areas such as a large and complex white matter fiber bundle called the anterior limb of the internal capsule (ALIC), a promising target for DBS to treat OCD. This project seeks to develop a patient-level, electrophysiological read-out of the cortical response to DBS at specific white matter targets within the ALIC. The probe is to be validated on the level of individuals, which could allow for individualized DBS “tuning.”

 

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