McLean Hospital 115 Mill Street Belmont, MA 02478
Since 2018, Torsten Klengel, MD, PhD, has been the director of the Translational Molecular Genomics Laboratory at McLean Hospital. In 2014, Dr. Klengel joined the Neurobiology of Fear Laboratory, led by Kerry J. Ressler, MD, PhD, at Emory University, as a post-doctoral fellow. After the lab relocated to McLean Hospital, Dr. Klengel was promoted to instructor in psychiatry in 2016. He is the recipient of several honors and fellowships, including a scholarship from the German National Academic Foundation, a NARSAD Young Investigator Award, an EMBO Long-Term Fellowship, and a research prize from the European Psychiatric Association.
Dr. Klengel earned his MD from the University of Wurzburg, Germany, and his PhD in neurobiology from the University of Munich, Germany. His PhD work with Elisabeth Binder, MD, PhD, at the Max Planck Institute of Psychiatry in Munich focused on gene by environment interaction and the genetic/epigenetic regulation of FK506 binding protein 51 (FKBP5).
Dr. Klengel’s Translational Molecular Genomics Laboratory investigates molecular, genetic, and epigenetic mechanisms underlying psychiatric disorders. Using a combination of clinical and pre-clinical research approaches, Dr. Klengel’s team seeks to integrate data generated from animal models, in vitro studies, and clinical research to develop better preventive and therapeutic strategies.
Recent large-scale genetic studies at the lab have emphasized the role of genetics in psychiatric disorders including schizophrenia, major depression, and post-traumatic stress disorder. The work is based on the understanding that while environmental factors can strongly contribute to the development of the certain disorders, our understanding of how genetic predisposition and the environment may affect the brain on the molecular level is sparse.
With this in mind, Dr. Klengel’s team uses translational mouse and non-human primate models to investigate the effects of stress, particularly in early life, on long-term programming of epigenetic profiles. Epigenetics refers to the stable but also reversible modification of our genome—for example, by DNA methylation—leading to changes in gene expression without changing the underlying genetic code. Prior evidence suggests that many environmental factors lead to an adjustment of epigenetic profiles.
Dr. Klengel has previously shown the effects of trauma in children on the epigenetic programming of the stress response system, in particular, on the gene FKBP5. However, humans are exposed to many environmental factors, such as stress, socioeconomic factors, nutritional factors, and chemicals, that make it difficult to pinpoint causal mechanisms. In addition, it is ethically impossible to model these factors in clinical studies. In contrast, non-human primate and rodent studies are well-controlled translational models that can help to facilitate the discovery of relevant epigenetic signatures in human studies.
To this end, Dr. Klengel’s team collaborates with researchers from the Yerkes National Primate Research Center in Atlanta, Georgia, on early life stress in rhesus monkeys. Klengel and his colleagues believe that studying natural behavior in monkeys and profiling epigenetic changes across the lifespan and across generations will yield important insights into how our environment shapes the epigenome and the risk to develop psychiatric disorders.
In a second line of research, the Translational Molecular Genomics Laboratory investigates the function of the non-coding genome in psychiatric disorders. Genome-wide association studies in psychiatry and across different fields of medicine point to genetic variations in non-coding regions significantly associated with clinical phenotypes. To this end, Dr. Klengel investigates the effect of non-coding RNAs (long non-coding RNA and circular RNAs) on behavioral and clinical phenotypes. This includes the effect of long non-coding RNA and circular RNAs on amygdala-dependent fear memory formation in mice and a collaboration with McLean’s Sabina Berretta, MD, that focuses on human postmortem brain tissue and the function of non-coding RNAs in the human brain. This work is aimed at gaining a better understanding of genetic association studies implicating significant associations of genetic variants located in non-coding regions of the genome.
Klengel T, Mehta D, Anacker C, Rex-Haffner M, Pruessner JC, Pariante CM, Pace TW, Mercer KB, Mayberg HS, Bradley B, Nemeroff CB, Holsboer F, Heim CM, Ressler KJ, Rein T, Binder EB. Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nature Neuroscience 2013;16(1):33-41.
Klengel T, Binder EB. Epigenetics of stress-related psychiatric disorders and gene × environment interactions. Neuron 2015;86(6):1343-57.
Belmont campus - Mailman Research Center, Room 114