The Laboratory of Translational Psychiatry utilizes clinically relevant animal models of psychiatric pathology combined with data from human subjects to better understand the neurobiology underlying psychiatric pathologies. Ultimately, we seek to develop lines of investigation with high potential for translation into treatments for psychiatric patient populations.
Existing treatments for psychiatric pathologies are inadequate for many of our patients. As a practicing psychiatrist, I have been fortunate to share in the sense of relief that patients feel when the appropriate treatment is found, finally bringing mitigation of their symptoms and restoring their lives to a semblance of normalcy. Unfortunately, I have also felt the frustration of so many for whom this relief remains elusive. A major difficulty in developing new treatments for patients with psychiatric disease is rooted in our incomplete understanding of the brain and its function. The neurobiology of behavior is tremendously complex and involves interplay of neural circuits, glial function, endocrine and immune function among others. Work in the laboratory is focused on clarifying the underlying molecular causes of mental illness, while always keeping in mind the ultimate goal of improving the health and well-being of patients with mental illness.
Our current lines of research focus on the role of neuroimmune interactions and the gut microbiome in the propagation and development of addictive disorders, depression, and autism spectrum disorder. In recent years, it has become clear that brain-immune system interactions in psychiatric pathology are more complex and important than previously understood. As one of the key effectors of immune system development and function, the gut microbiome is a significant player in these interactions via the so-called gut-immune-brain axis. While modulators of inflammation or the gut microbiome have not yet been translated into tractable treatment strategies for patients, we believe there is tremendous therapeutic potential of immunomodulatory agents and these lines of research will seek to clarify how they may be utilized.
Drew D Kiraly, MD, PhD
Assistant Professor, Psychiatry
Assistant Professor, Neuroscience
Dissecting the role of granulocyte-colony stimulating factor in cocaine-mediated behavioral plasticity
We have recently discovered granulocyte-colony stimulating factor (G-CSF) as an innate immune mediator that is upregulated by cocaine treatment, and correlates with the behavioral response to cocaine. Further studies have demonstrated that treatment of rodents with G-CSF results in enhanced neuronal and behavioral plasticity in response to cocaine. Our goal is to investigate whether manipulations in G-CSF function represent a tractable strategy for reducing the symptoms of drug addiction in human populations. Future efforts will work to clarify mechanistic details of how G-CSF affects brain reward circuitry to drive these changes. We are developing cell-specific manipulations of G-CSF function, using proteomics techniques to characterize synaptic changes, and applying an array of molecular biology and epigenetics methods to clarify the signaling pathways that are altered by this important signaling molecule.
Examination of the role of the gut microbiome in propagation and development of addictive disorders
In recent years there has been a growing appreciation that the resident bacteria of the gut (the gut microbiome) can have profound effects on brain function and behavior. Recently, we demonstrated that alterations in the composition of the gut microbiome can affect the behavioral response to cocaine in animal models of addiction (Kiraly et al. Scientific Reports, 2016). Ongoing studies are examining the effects of antibiotics, prebiotics, and probiotics in animal behavioral models of opiate and psychostimulant addiction. These behavioral studies are being done in parallel with work characterizing how microbiome manipulations affect the molecular, cellular, and epigenetic response of limbic reward circuitry to drugs of abuse.
In addition to this animal work, the lab is beginning a series of studies examining how opiate or cocaine use affects changes in the gut microbiome in human patients. The hope is that these studies will ultimately lead to clinical trials targeting manipulations of the gut microbiome to limit the propagation or development of addictive disorders.
Investigating interactions between the gut microbiome and a single gene cause of autism spectrum disorder
Of all the psychiatric disorders, there is perhaps the strongest evidence for a role of the gut microbiome in the development of autism spectrum disorder. The gut microbiota undergo large-scale changes during the first years of life on a similar timescale to the development of the symptoms of autism. Children with ASD have been reported to have changes in their gut flora, frequently have gastrointestinal symptoms, and there are even anecdotal reports of some symptoms improving after treatment with antibiotics. To investigate the mechanistic role that the gut microbiome might be playing in the development of autism, we are performing manipulations of gut bacteria in an animal model of Phelan-McDermid Syndrome (Shank3KO mouse). These studies will allow us to directly investigate a gene x microbiome effect on behavior and neurobiology.
Through the Seaver Autism Center we are also actively recruiting patients with Phelan-McDermid Syndrome to see how their gut flora may differ from that of non-affected children. These studies may pave the way for development of therapeutics targeting the gut microbiome to alleviate the symptoms of this often debilitating condition.
Meet the Team
Research Associate / Lab Manager
Before joining the Kiraly Lab Nick received his bachelor’s degree in Psychology from The George Washington University. When he is not keeping things in the lab running smoothly Nick likes to challenge himself by seeing how many grapes he can fit into his mouth at once.
ACNP Memorial Travel Award, 2016
Seaver Autism Center Postdoctoral Fellowship, 2016
NIMH Brain Camp Awardee, 2016
Society for Neuroscience “Hot Topic” Presentation, 2016
Leon Levy Foundation Fellowship in Neuroscience, 2015
NIMH Outstanding Resident Award Program Travel Fellowship, 2015
Bloomberg Award UConn School of Medicine for excellence in Psychiatry, 2013
Ruth Kirchstein National Research Service Award Fellowship, 2010
NIMH Travel Award to NIMH MD-PhD Student Conference in Neuroscience and Psychiatry, 2008
UCHC Annual Neuroscience Symposium – Outstanding Scientific Presentation, 2008
Phi Beta Kappa, 2003
βββ Biological Honor Society, 2002
Nous Kai Sofia Neuroscience Honor Society, 2002
Drew University Presidential Scholar, 1999
The Kiraly Lab is expanding! We are actively seeking postdoctoral fellows, graduate students and research staff. If you are interested in performing cutting edge work dissecting the roles of neuroimmune interactions and the gut microbiome in psychiatric diseases please contact email@example.com.
Our lab utilizes a broad range of models and techniques, we are looking for a highly motivated individual with a PhD or MD (or both!) with background in Neuroscience, Cellular or Molecular Biology, Biochemistry, or any related fields.
For inquiries please contact the PI directly. To apply please send a full CV, three professional references, and a brief statement of scientific interest to firstname.lastname@example.org.
Any PhD or Masters degree candidates at Mount Sinai who might have interest in working in the lab should contact the PI directly (email@example.com) to discuss rotation projects.
Please email firstname.lastname@example.org if you would like to talk about current opportunities to join the Kiraly Lab.