Lieber Institute for Brain Development

Division One: Brain Development

Ronald McKay, Ph.D., Director

The development of novel therapeutic targets for brain disease requires a clear understanding of how the nervous system is assembled. By perturbing the biology of cells, genetic variation influences the function of brain circuits accounting for the symptoms of mental illness. It has been a startling realization that many of the genes implicated in the causation of disorders like schizophrenia and autism control fundamental aspects of cell growth and differentiation. Clinical epidemiology of most serious psychiatric disorders also shows that early steps in the maturation of the nervous system are altered. This means that studying the early life of human cells will help us understand how the stage is set for the late appearance of clinical disorders. The science in this division is structured in four sections focused on human brain development, from pluripotency to circuit formation. Our research will define the cellular and molecular mechanisms that cause psychiatric disease.

Stem Cell Biology & Genetics: Josh Chenoweth, Ph.D., Investigator;
Kazuya Ogawa, Ph.D., Fellow
Cell Imaging & Assays: Amritha Jaishankar, Ph.D., Fellow
Circuit Activation: Marcelo Bustamante, Ph.D., Fellow 

Division Two: Developmental Neurobiology and Functional Genomics

Director to be appointed

To understand how variation in a genetic sequence related to risk impacts on the biology of risk, it is critical to determine how genes are processed in the human brain and how this processing is affected by development and by genetics. High quality postmortem human brain is thus an invaluable resource for understanding how risk genes affect brain development and function. Recent evidence indicates that most genes undergo unique processing in the human brain, leading to the expression of unexpected and previously unknown forms not found in peripheral tissues. Thus, it is critical for the ultimate goals of the Institute to collect and study human brain tissue, including fetal brain tissue, and to characterize all variants of the genes and proteins that are relevant to psychiatric illness.

Developmental Electrophysiology: Brady Maher, Ph.D., Investigator;
Feng Yang, Ph.D., Investigator
Neuropathology: Thomas M. Hyde, M.D., Ph.D., Investigator;
Michelle Mighdoll, Research Assistant
Genome informatics: Carlo Colantuoni, Ph.D., Investigator;
Andrew Jaffe, Ph.D., M.S., Postdoctoral Fellow

Division Three: Genetics, Pharmacogenetics and Cognitive Neuroscience

Daniel R. Weinberger, M.D., Director

Genetics is a core discipline related to all activities of the LIBD. The genetics project maintains a state of the art facility for genetic and epigenetic analysis in human and animal tissues. The genetics project focuses on moving genetic association to the clinical level. This is an end-stage functional genetics project, that maintains and expands a unique clinical dataset comprising over 1000 families with both schizophrenic offspring and a large normal control sample (>1000 individuals). All these individuals have detailed developmental histories with extensive clinical, cognitive, and biological assessments. This is the only sample in the world with this level of comprehensive characterization and clinical detail.

Disorders such as schizophrenia and autism ultimately represent abnormalities in how cognitive, perceptual, and emotional information is processed by the brain. Thus, to translate genetic and molecular discoveries into understanding the clinical nature of these disorders, it is critical to understand how these genetic factors affect brain information processing. The only way to do this directly in a living human being is using modern cognitive assessment and neuroimaging techniques. The LIBD has acquired a massive database of neuroimaging and cognitive data in over 3000 extensively studied individuals, including patients with schizophrenia, their healthy siblings and normal volunteer subjects. New imaging programs are being initiated at JHU and in collaboration with other institutions. New technologies are being developed across multiple neuroimaging domains to link our growing scientific understanding to clinical pharmacology.

Bioinformatics, Genetics & Epigenetics: Yuan Gao, Ph.D., Investigator;
Bin Xie, Research Assistant; 
Joo Heon Shin, Ph.D., Fellow; 
Richard Straub, Ph.D., Investigator;
Cognitive Neuroscience & Clinical Investigations: Kristin Bigos, Ph.D., Investigator;
John Meyers, BS, Database Manager, Director of Information Technology

Division Four: Drug Discovery

Solomon Snyder, M.D., Director

One of the underlying premises of the LIBD is that advances within the LIBD and elsewhere will have reached a point that, in the 21st century, translational efforts will yield new therapeutic agents for schizophrenia and other major mental disorders. The drug discovery unit has established a partnership with comparable activities of the Johns Hopkins Brain Science Institute's translational center to leverage the resources of both Institutes. We will share personnel, equipment and space to optimize efficiency and cost. The Lieber Institute efforts will be focused on drugs for the major psychiatric illnesses. It is recognized that it will be important to balance targets with a high probability of leading to an agent that will “produce something”, contrasted with riskier targets which are more innovative and whose successful exploitation may lead to major breakthroughs in therapy. The principal rationale for the LIBD drug discovery unit and the university-associated research facility is to attack targets not addressed by large pharmaceutical concerns. The LIBD drug development project is currently developing agents based on three novel targets with promising preclinical and early clinical results.

James Barrow, Ph.D., Investigator;
Glen Ernst, M.S., Senior Research Chemist;
Martha Kimos, M.S., Biochemist