Translational Neuropsychiatry Research Group
Research topics
Metabolic and epigenetic foundations of intergenerational trauma
Traumatic experiences, especially in childhood, are associated with negative physical and mental health outcomes in adulthood. Growing evidence suggests that behavioral and metabolic disturbances linked to childhood trauma may be transmitted across generations.
However, the precise mechanisms by which childhood trauma affects germ cells and enables intergenerational transmission of symptoms remain unclear. This research combines parallel analyses in a mouse model exposed to early-life trauma with studies of human cohorts from Bosnia, Pakistan, and Poland. Our current findings indicate a role for metabolic factors and associated non-coding RNAs in transferring the effects of childhood trauma to germ cells, enabling their intergenerational transmission.
Combating neurodegenerative diseases through metabolism
Neurodegenerative diseases (NDDs), such as Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and frontotemporal lobar degeneration (FTLD), are major contributors to morbidity and mortality among older adults worldwide. These diseases are characterized by the accumulation of toxic proteins in the brain—such as amyloid and tau in AD, or TDP-43 in ALS and FTLD. NDDs result from an imbalance between the overproduction and insufficient clearance of these aggregates.
Using a multimodal approach, the TREND team has uncovered complex links between cellular energy metabolism and several NDD-associated proteins, such as TDP-43, as well as microglia—the resident immune cells of the brain responsible for clearing these deposits. Our ongoing research suggests that targeted modulation of metabolic pathways can reduce TDP-43-associated toxicity. Similarly, the microglia’s ability to remove toxic amyloid deposits in AD can be enhanced through appropriate metabolic manipulations.
Immunometabolic foundations of vulnerability vs. resilience to adverse childhood experiences
Adverse childhood experiences (ACEs) are among the strongest risk factors for later neuropsychiatric disorders. However, individual vulnerability to the long-term effects of ACEs varies widely. We propose that microglia play a key role as mediators of this vulnerability, and that ACE-induced changes in serum lipid profiles and associated non-coding RNAs may modify microglial function.
We employ a unique, interdisciplinary approach combining analyses of samples from human cohorts with in vitro models of human microglia. This project has enormous potential to reduce the global health burden associated with ACEs.