Core Expertise

Core Members of the Institute

The core members of the Taylor Family Institute for Innovative Psychiatric Research have long-standing and productive histories of effective collaboration. They bring a hierarchical and complementary set of skills and interests that span the spectrum from medicinal chemistry to animal behavior. They are recognized internationally for their work on neurosteroids and their studies have provided unique insights into how neurosteroids target their sites of actions and modulate neuronal function and anesthesia.

 

Medicinal & Computational Chemistry

Douglas Covey, PhD
Department of Developmental Biology

David Reichert, PhD
Department of Radiology

A central issue in understanding the actions of steroids and in developing novel therapeutics is to define the structures in the steroid molecule that underlie activity. Outstanding skills in medicinal chemistry are an essential element in the Institute.

Covey is a medicinal chemist and international leader in steroid synthesis whose laboratory focuses on the chemical synthesis of novel steroid analogues to probe neurosteroid function and to serve as lead compounds for clinical drug development. His work in the Institute will build on an existing library of steroid analogues generated over the past 20 years and is the cornerstone for innovative new molecules. Reichert is a structural chemist who brings expertise in medicinal chemistry, the dynamics of molecular interactions and computational analysis of protein structure.

 

Molecular Biochemistry & Target Identification

Alex Evers, MD
Department of Anesthesiology

Ziwei Chen, PhD
Department of Anesthesiology

The direct physical identification of the positions at which steroids associate with target proteins is an essential step in defining the sites of action. Evers and Chen are molecular biochemists who focus on identifying specific sites of action of neurosteroids using photoaffinity labeling and molecular probes synthesized in the Covey laboratory. Their work identifies sites of actions of molecules that inform subsequent chemical synthesis and physiological studies. Proteomic studies based on photoaffinity labeling also help to identify potential new targets for drug development. As an anesthesiologist, Evers also provides expertise in animal models of anesthesia and clinical applications.

 

Ion Channel Biophysics & Molecular Biology

Joe Henry Steinbach, PhD
Department of Anesthesiology

Gustav Akk, PhD
Department of Anesthesiology

After a steroid interacts with a target, the function of the target must be altered in some fashion to mediate the behavioral effects. Steinbach and Akk are cellular and molecular biophysicists who study the effects of novel agents on ion channels, translating protein-based sites of drug action into functional mechanistic studies at cellular and sub-cellular levels. Their work provides a detailed understanding of how steroids interact with receptors to produce physiological actions. These studies provide detailed molecular targets at the amino acid and ion channel level for drug discovery.

 

Cellular & Synaptic Physiology

Steven Mennerick, PhD
Department of Psychiatry

Yukitoshi Izumi, MD, PhD
Department of Psychiatry

Charles Zorumski, MD
Department of Psychiatry

Most common neuropsychiatric illnesses reflect synaptic dysfunction, or disorders in communication between neurons. Mennerick, Izumi and Zorumski are cellular neurophysiologists who study the effects of neurosteroids on synapses in the hippocampus, a region of the brain involved in memory processing and in the biology of several major psychiatric disorders.

This group also brings expertise in understanding how pharmacological agents alter the brain changes (plasticity) that are the basis of learning and memory. These studies provide a key functional link between chemical synthesis, molecular biochemistry, biophysical studies and behavior. As a psychiatrist, Zorumski provides expertise in potential clinical applications of new molecules.

 

Behavioral Testing & Animal Models of Illness

David Wozniak, PhD, & the Animal Behavioral Core Facility
Department of Psychiatry

A critical step in moving molecular and cellular observations towards therapeutic use involves behavioral studies of candidate compounds in animal models of human disorders. Wozniak is a neuroscientist with extensive expertise in studying the effects of pharmacological agents and genetic manipulations on rodent behavior. He leads and directs the Animal Behavioral Core Facility in the Department of Psychiatry. His studies include work in models of learning and memory and psychiatric disorders. Behavioral studies in animals are critical steps in the development of novel chemicals as potential treatments, providing an important bridge between cellular biology, synaptic studies and clinical applications.

 

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