Lab of Metabolic Psychiatry
The goal of our research is to better understand the effects of chronic metabolic diseases, such as diabetes, on brain function. Given the high utilization of energy by the brain, we aim to explore the implications of altered metabolism at the behavioral, circuit, cellular and molecular levels. Currently, we use animal models of diabetes to identify the ways in which long-term exposure to hyperglycemia can lead to increased susceptibility to stress and to addiction- or depression- or anxiety-like syndromes. A major focus of our work is on hyperglycemia-induced changes in gene expression and chromatin structure within the brain’s reward and aversion circuitry, and the mechanisms by which those lasting adaptations alter neuronal and circuit function to produce behavioral abnormalities. Our goal is to eventually translate these findings to human patients.
Funding and Awards
Jessica Ables is awarded a NARSAD Young Investigator Grant. (October 2019)
Jessica Ables is elected to the Alpha Omega Alpha Honor Society. (June 2019)
Jessica Ables wins Best Poster, 2nd Place, Friedman Brain Institute Neuroscience Retreat. (May 2019)
Jessica Ables is elected to the Career Development Institute for Psychiatry Class of 2019. (January 2019)
Jessica Ables is named Laughlin Fellow, American College of Psychiatrists. (January 2019)
Jessica Ables presents Poster at Society for Biological Psychiatry: “Exploring the role of the Habenula-IPN in Affective States in Diabetes”. (May 2019)
Jessica Ables presents poster at ACNP: “Exploring the role of the Habenula-IPN in Affective States in Diabetes”. (December 2018)
Jessica Ables is named a Leon Levy Fellow in Neuroscience. (April 2018)
Jessica Ables is named Psychiatry Chief Resident for Research. (2018)
Jessica Ables receives the NIMH Outstanding Resident Award. (July 2017)
Jessica Ables is named as a Junior Mentor for the Icahn School of Medicine MSTP. (2017)
1. Nitric oxide in development of tolerance
The interpeduncular nucleus (IPN) is a GABAergic nucleus that is characterized by high expression of neuronal nitric oxide synthase (Nos1) as well as striking vascularity. We have recently found that Nos1 is increased in IPN after chronic exposure to nicotine. We hypothesize that this increase in Nos1 mediates the development of tolerance to the aversive effects of nicotine, as we found that eliminating Nos1 in the IPN reduces preference for a rewarding dose of nicotine (Ables et al. PNAS 2017). Our goal is to determine if this increase in Nos1 in the IPN generalizes to other drugs of abuse or to stress and might represent a target for treatment of addiction. Future studies will focus on visualizing nitric oxide release from the IPN and the effects of nitric oxide on the epigenome, transcriptome and function of neurons in the reward circuitry.
2. Cholinergic vulnerability to hyperglycemia
Animal models of diabetes indicate that cholinergic neurons are particularly vulnerable to persistent hyperglycemia and resulting oxidative and nitrosative stress, and we hypothesize that this vulnerability may contribute to the neurocognitive and affective impairments observed in diabetic patients. The medial habenula (MHb) is a highly conserved cholinergic nucleus in the epithalamus that projects to the IPN to regulate levels of serotonin, dopamine and epinephrine and, as a result, mood. The MHb is susceptible to degeneration after repeated administration of drugs of abuse, however, to date no one has examined the effect of persistent hyperglycemia on the functional or structural plasticity of the MHb. Our goal is to understand the molecular, cellular and functional consequences of persistent hyperglycemia on cholinergic neurons in the reward circuitry using cell-type specific epigenomic and transcriptional profiling in combination with viral-mediated gene transfer.
3. Axonal transcriptome
Recent research has revealed that neuronal axons have specialized mechanisms to regulate delivery and utilization of mRNAs independently of the neuronal cell body, where the nucleus resides. This is not surprising given that in many cases (e.g. motor neurons in the limbs), the axons are far removed from the cell body and require the ability to respond to stimuli on timescales that would prohibit gene expression from the nucleus and subsequent delivery to the distal axon. Projection neurons in the brain provide a unique opportunity to profile the transcripts that are utilized in discrete compartments of the cell, as the axons are physically separate from the cell body. Our lab is currently profiling axonal transcriptomes in specific cell populations in the normal mouse brain. Our goal is to determine how translation is locally regulated in response to various stimuli, including stress and metabolic derangements
Potential Postdocs and Graduate Students
Icahn School of Medicine at Mount Sinai is seeking enthusiastic, detail-oriented applicants. The School is one of the nation’s leading medical schools, ranked in the top 20 schools for NIH funding. The Psychiatry Department is ranked 4th among Psychiatry Departments in the nation for NIH funding and The Nash Family Department of Neuroscience at the Icahn School of Medicine is ranked number 1 in NIH funding and is undergoing rapid expansion. Both the Psychiatry and Neuroscience Departments offer an outstanding intellectual and multidisciplinary research environment with a commitment to translational research.
Postdoctoral candidates should have a Ph.D. and/or M.D and a strong basic science background in molecular/cellular neuroscience and be willing to commit to 4 years in the lab. Graduate students should have been accepted to the Biomedical or Neuroscience Graduate Program at Mount Sinai. Those with experience in animal behavioral testing and/or in vivo imaging are particularly encouraged to apply.
Interested candidates should submit their Curriculum Vitae and contact information for at least three professional references to Jessica.email@example.com.
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Icahn School of Medicine at Mount Sinai
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