About Us

Our laboratory has long been interested in the neurobiological underpinnings of mood and anxiety disorders and the mechanism(s) of action of antidepressants. Much of our focus has been on the role of corticotropin-releasing factor (CRF) in the pathophysiology and treatment of depression. We were one of the first to identify elevated levels of CRF in depressed patients. Since then, our lab, among others, has been one of the driving forces in understanding the role CRF may play in the pathophysiology of depression and as a therapeutic target. We have demonstrated that chronic administration of a number of antidepressants, benzodiazepines, as well as mood stabilizers, all interact with the CRF system, particularly when the system is already dysregulated. We are currently investigating the behavioral, endocrine, and pharmacological effects associated with acute and chronic treatment of CRF1 receptor antagonists in rodents. These compounds show great potential as novel antidepressants, anxiolytics, and/or neuroimaging agents. Gene delivery studies in rodents seek to elucidate the underlying CRF pathology associated with depression and/or early life trauma.

Wavelet decomposition of the primary sequence of the human muscarinic 1 receptor

We also use analogous methodologies to explore the mechanism of action of antipsychotic drugs and the pathogenesis of schizophrenia. Currently, antipsychotic drugs are not completely effective and their ultimate mechanisms of action are obscure. Since the 1970s, many have hypothesized a role of neurotensin (NT) as an endogenous antipsychotic. Strong evidence (anatomical, biochemical, pharmacological, and behavioral) has been gathered, in our laboratory and others, suggesting that mesolimbic NT transmission is involved in both phenomena.

Currently, the lines of research in the laboratory include manipulation of the mesolimbic NT system (via knock out mice and viral vector technologies), exploration of the interaction between the estrous cycle, schizophrenia and the NT system; and the study of protein-protein interaction between NT and dopamine receptors in vitro and in vivo. In collaboration with adjunct faculty Arnold Mandell, MD and Karen Selz, PhD (Cielo Institute) we have also been investigating how hydrophobic interactions between protein motifs, as identified via mathematical analysis of the primary amino acid sequence, can be used to generate novel biologically active peptides.

The techniques currently used in our laboratory range from theoretical design of novel peptides, molecular biology, cellular biology, genetics, and behavioral pharmacology. Our lab also studies the pharmacokinetics and pharmacodynamics of psychotherapeutics. One of the most relevant applications of this has been studies from our lab investigating the effects of fetal and infant exposure to antidepressants and antipsychotics. We are currently assessing the effects of in utero drug and/or stress exposure on the long term development of the brain (epigenetics). In addition, we have developed methodologies to assess ex vivo transporter occupancy of antidepressant medications in clinical populations. This may lead to relatively simple methods to correlate pharmacokinetic parameters with treatment response and also help identify patients who are non-responders due to inadequate dosing. We collaborate closely with medicinal chemists on the pharmacological characterization of novel radiotracers for PET imaging.