McLean Hospital 115 Mill Street Belmont, MA 02478
Elif Engin, PhD, grew up in Ankara, Turkey, and earned her undergraduate and master’s degrees at Middle East Technical University (METU) in Ankara. She completed her doctoral work in the laboratory of Dr. Dallas Treit in Edmonton, Alberta, and was awarded a PhD Thesis Award from the Canadian Psychological Association. Dr. Engin joined the Laboratory of Genetic Neuropharmacology at McLean Hospital as a post-doctoral fellow in 2009 and was promoted to instructor in 2012. Since 2018, she has been the director of the Stress Neurobiology Laboratory.
Dr. Engin is the recipient of several honors and fellowships, including the NARSAD Young Investigator Award, the Andrew P. Merrill Memorial Research Fellowship, Eleanor and Miles Shore Research Fellowship and the Alfred Pope Award for Young Investigators.
Dr. Engin and the members of the Stress Neurobiology Laboratory (SNL), which was established in 2018, seek to improve our understanding of the genetic, brain circuit-level, and behavioral disruptions observed in stress-related disorders—such as anxiety and mood disorders—with the ultimate goal of assisting in the identification of novel prevention and treatment strategies.
Anxiety and mood disorders are estimated to affect more than 40 percent of Americans at some point in their lives, and for many, throughout their lives. Current treatments are only partially effective in improving the symptoms and have multiple undesirable side effects. The efforts to develop new treatments based on the underlying genetics is fraught with the complexity of multiple risk genes interacting with each other and the environment. Thus, an understanding of how multiple factors may converge on similar disruptions in brain circuits to generate specific symptoms would open up avenues to intervene at the most meaningful level to reverse the disruptions. Dr. Engin and her lab are particularly interested in the role of disruptions in inhibitory neurotransmission in anxiety and mood disorders.
One example of Dr. Engin’s work at SNL involves gamma amino butyric acid (GABA), which is the main inhibitory neurotransmitter in the central nervous system. The actions of GABA on neurons are mediated by two classes of receptors: fast-acting GABAA receptors and the slower GABAB receptors. These receptors maintain the balance between excitation and inhibition in the brain. The precise activity of GABAA receptors regulates what is known as brain oscillations or brain rhythms, i.e., the coordinated activity of a large population of neurons that enables communication between different brain areas.
GABA is reduced and the expression of GABAA receptors is altered in several brain areas in patients with anxiety or mood disorders. GABAA receptors are a highly diverse family of receptors encoded by 19 different genes, with different anatomical and cellular expression and different pharmacological properties. Dr. Engin’s work examines which GABAA receptors regulate the activity of which brain circuits and in what manner in the healthy brain, as well as which of these processes are disrupted in mood and anxiety disorders.
To do this, Dr. Engin and the SNL use animal experimental systems, as well as a combination of molecular, pharmacological, electrophysiological, and behavioral techniques, to study the roles of specific GABAA receptor subtypes or other inhibitory molecules in shaping the activity of brain circuits relevant to mood and anxiety disorders. In one line of Dr. Engin’s research, genetic modifications are induced to alter the expression of specific GABAA receptor subtypes in specific cell populations or circuits to be able to delineate the effects of this on circuit activity and behavior. In another line of research, Dr. Engin and her team examine the effect of environmental factors, such as early life experiences, stress, or exposure to chemicals on the expression and function of GABAA receptors and other inhibitory molecules.
Over the long term, Dr. Engin hopes that this knowledge will form the basis for innovative prevention and treatment efforts that specifically target key disruptions in inhibitory neurotransmission and provide effective, side-effect-free relief of symptoms.
Engin E, Zarnowska ED, Benke D, Tsvetkov E, Sigal M, Keist R, Bolshakov VY, Pearce RA, Rudolph U. Tonic inhibitory control of dentate gyrus granule cells by α5-containing GABAA receptors reduces memory interference. The Journal Neuroscience 2015;35(40):13698-712.
Engin E, Smith KS, Gao Y, Nagy D, Foster RA, Tsvetkov E, Keist R, Crestani F, Fritschy JM, Bolshakov VY, Hajos M, Heldt SA, Rudolph U. Modulation of anxiety and fear via distinct intrahippocampal circuits. Elife 2016;5:e14120.
Engin E, Benham RS, Rudolph U. An Emerging Circuit Pharmacology of GABAA Receptors. Trends in Pharmacological Sciences 2018;39(8):710-732.
Belmont campus - Mailman Research Center, Room 123