Biography
Dr. Tunc-Ozcan received a B.A. degree in Psychology (2004) and an M.A. degree in Developmental Psychology (2006) from Bogazici University in Turkey. She earned her Ph.D. (2017) from Northwestern University, Interdepartmental Neuroscience Program (NUIN). Following her Ph.D., she worked as a postdoctoral fellow at the Northwestern University Neurology Department until she was appointed as an Assistant Professor at the University of New Mexico, Department of Neurosciences.
Personal Statement
My research focuses on understanding how neural circuits and gene networks react to stressful experiences that produce lasting changes in the brain, how such changes can predict adaptive and maladaptive behaviors, and thereafter modulate these changes to prevent and reverse neuropsychiatric disease-like states. In my graduate work, I focused on quantitative genetic methods, epigenetic regulation, imprinted genes, neuroendocrinology, and animal behavior tests. I discovered an epigenetic mechanism for the transgenerational effects of fetal alcohol exposure and developed an ex vivo model with potential therapeutic targets. During my postdoc, I explored molecular techniques to manipulate signaling pathways at the cellular level and created tools to modulate cell-type-specific activity. Using targeted mutant mice, I identified a common signaling pathway for antidepressant action. By using excitatory and inhibitory DREADDs in a cell-type specific manner, I showed that activating immature hippocampal neurons, even without an increase in their number, exerted a rapid antidepressant effect and reversed the effects of unpredictable chronic mild stress. Because the neuronal activity is determined by its presynaptic inputs, I identified the first-order presynaptic partners of mature and immature dentate gyrus using monosynaptic retrograde rabies virus tracing. My next goal is to manipulate the activity of dentate gyrus neuronal circuits by combining rabies tracing with DREADDs, specifically targeting mature and immature neurons separately in a projection-specific manner. Getting inputs from the same region does not mean the same message is delivered to each input recipient; therefore, a detailed input map of the dentate gyrus with various behavioral and molecular phenotypes will help to identify subtle differences and lead to the discovery of critical neuronal circuits. It also will produce the building blocks for my future studies, where I aim to reconstruct cellular networks, classify neurons more precisely, and elucidate their circuit-level functions by employing cell-type-specific tracing of input and output (cTRIO) and integrating single-cell RNA sequencing. Ultimately, this comprehensive approach will contribute to understanding how specific genes, cell types, and neuronal circuits influence disease predisposition and progression, sex differences, and novel therapeutic developments.
Areas of Specialty
Behavioral neuroscience
Animal models of anxiety and depression
Neural circuits
Hippocampus
Epigenetics
Achievements & Awards
2022 - Dr. Samuel M. Nabrit Conference Early Career Scholars Travel Award, Brown University
2021 - NIH K99/R00 Pathway to Independence Award (National Institute of Mental Health)
2017-2019 NIH T32 (AG020506) Training Grant
2016 - Graduate School Travel Award, Northwestern University
2015 - Genes, Brain & Behavior Meeting Travel Award
2014 - Interdepartmental Neuroscience Program Research Award, Northwestern University
2013 - Research Society on Alcoholism/FASDSG Conference Travel Award
2012 - Graduate Student Chapter Travel Award, Society for Neuroscience (SfN)
2007 - UNICEF fellowship for the adaptation of the Big Brothers-Big Sisters program to Turkey
2006 - MA awarded with High Honors, Bogazici University
2004 - Cambridge Trust Scholarship for graduate school
2004 - BA awarded with Honors, Bogazici University
2001-2004 - Turkish Government bachelor’s degree scholarship
1999-2004 - Bogazici University full college scholarship
Key Publications
Journal Article
Tunc-Ozcan, Elif, Peng, C, Y Zhu, Y, Dunlop, S, R Contractor, A, Kessler, J, A 2019 Activating newborn neurons suppresses depression and anxiety-like behaviors. Nature communications, vol. 10, Issue 1, 3768
Journal Article
Tunc-Ozcan, Elif, Brooker, S, M Bonds, J, A Tsai, Y, H Rawat, R, McGuire, T, L Peng, C, Y Kessler, J, A 2021 Hippocampal BMP signaling as a common pathway for antidepressant action. Cellular and molecular life sciences : CMLS, vol. 79, Issue 1, 31
Journal Article
Rawat, R, Tunc-Ozcan, Elif, McGuire, T, L Peng, C, Y Kessler, J, A 2022 Ketamine activates adult-born immature granule neurons to rapidly alleviate depression-like behaviors in mice. Nature communications, vol. 13, Issue 1, 2650
Journal Article
Tunc-Ozcan, Elif, Wert, S, L Lim, P, H Ferreira, A, Redei, E, E 2018 Hippocampus-dependent memory and allele-specific gene expression in adult offspring of alcohol-consuming dams after neonatal treatment with thyroxin or metformin. Molecular psychiatry, vol. 23, Issue 7, 1643-1651
Gender
Female
Languages
- Turkish
- English
Research and Scholarship
1- My earliest work using animal models of fetal alcohol exposure (FAE) found that FAE causes disruptions of maternal-fetal thyroid homeostasis. I showed that supplementing ethanol-consuming dams with thyroid hormone (T4) alleviates cognitive function and gene expression changes in adult offspring. Additionally, I discovered that FAE-affected hippocampal phenotypes have matrilineal transmission to the next generation, which could be consistently reversed by T4 supplementation to the ethanol-consuming grandmothers. Moreover, these studies were the first to show altered glucose metabolism in in-utero alcohol-exposed pups and their offspring. This led me to study hippocampal insulin-pathway genes. I presented the involvement of insulin pathway-related events on the cognitive effects of FAE through long-lasting epigenetic changes via maternal transmission of allele-specific expression of imprinted genes. Overall, embryonic exposure to teratogens leads to developmental defects in subsequent generations through epigenetic modifications. My unique contribution to this field was that T4 treatment could stop the generational transmission of FAE effects and eliminate it as a risk factor to the naïve next generation.
2- Even though maternal T4 treatment could be an effective medication to interfere with the vicious cycle of intergenerational FAE effects, treatments for post-alcohol exposure are also needed, especially for the prevention of generational transmission after the damage has occurred. Thus, I developed and validated an ex vivo primary hippocampal culture system of FAE that is fast and cost-effective for post-alcohol exposure drug screening. The potential of this ex vivo model is demonstrated by the identification of two drugs, each of which reversed FAE-related hippocampal gene expression changes and memory deficits in the subsequent in vivo studies. I also showed that the mechanism by which these treatments are effective is via restoring the FAE-induced decrease in hippocampal DNA methytransferase 1 (Dnmt1) expression. The convergent, successful effect of neonatal T4 and metformin treatments on the expression of Dnmt1 in the adult FAE-exposed hippocampus provides a specific hope for the diagnosis and treatment of FASD.
3- As a postdoctoral fellow, I initiated a series of studies using a chemogenetic approach to target the hippocampal neural activity selectively. By using excitatory and inhibitory mutant G-protein coupled receptors (DREADDs) in a cell-type specific manner, I showed that the activity of immature dentate gyrus neurons is both necessary and sufficient for antidepressant action. Interestingly, activating immature neurons, even without an increase in their number, exerted a rapid antidepressant effect and reversed the effects of unpredictable chronic mild stress. This suggested a potential mechanism to explain the rapid antidepressant effects of Ketamine. Therefore, in a separate project, I mentored a graduate student to use the chemogenetic approach in combination with a transgenic mouse model and showed that activation of immature dentate gyrus neurons is necessary and sufficient for the rapid behavioral effects of Ketamine.
4- In another project, I identified hippocampal bone morphogenetic protein (BMP) signaling as a potential common pathway for antidepressant activity, where inactivation of this pathway is sufficient to induce a therapeutic effect. Specifically, the treatment of mice with six different classes of antidepressants, as well as electroconvulsive therapy, decreased BMP signaling in the dentate gyrus of the hippocampus. Prevention of this decrease blocks the effects of antidepressant treatment on molecular and behavioral phenotypes. Conversely, inhibition of BMP signaling in hippocampal neural progenitor cells, using targeted mutant mice and inhibitory DREADDs, is sufficient to produce an antidepressant effect. I also collaborate with other Kessler lab members in defining the relationship between hippocampal neurogenesis and aging-associated behavioral changes by using DREADDs and implementing different behavioral paradigms.