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Thomas Biederer, PhD

Professor of Neurology
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About

Titles

Professor of Neurology

Biography

Thomas Biederer received his Ph.D. in Cell Biology from the Humboldt-Universität zu Berlin, Germany. Thomas Biederer then pursued postdoctoral training with Dr. Thomas Südhof at the UT Southwestern Medical Center at Dallas to investigate mechanisms of synapse formation. He started his research group in 2003 as faculty member at Yale University, was 2013-2019 at Tufts University, and joined the Yale faculty again in 2019.

Dr. Biederer’s multidisciplinary research is motivated by his deep-seated interest in the biology of synapses, the cellular structures that connect neurons into networks. His long-term goals are to define how synapses develop, understand their roles in cognition, and investigate the profound disease relevance of synaptic aberrations. Progress from his group is providing insights into trans-synaptic complexes and how they dynamically organize synapse formation and maturation in vitro and in vivo. Attaining these goals is of importance to human health as altered synapse formation and stability underlie devastating brain disorders, including those that are neurodevelopmental diseases and related to drugs of abuse.

Appointments

Education & Training

Postdoctoral Fellow
University of Texas Southwestern Medical Center (2003)
PhD
Humboldt University of Berlin (1998)

Research

Overview

Bridging the cleft to induce synapse formation

How do synapses form? Select trans-synaptic interactions are now known to guide synapse development and we have identified and characterized synaptogenic cell adhesion molecules. One of these molecules, the immunoglobulin protein SynCAM 1, is required and sufficient to drive excitatory synapse formation in vivo. We build on this progress and analyze the functions of different synaptogenic adhesion proteins and how they cooperate.

In addition, we map the macromolecular and topological organization of the cleft of synapses using superresolution imaging and EM approaches. Our data support the concept that the synaptic cleft is comprised of structurally and molecularly diverse nanodomains. We are now testing the idea that the cleft is not static as widely assumed but a dynamic compartment, using methodologies including single particle tracking in live neurons. These studies can reveal how the sub-synaptic organization and dynamics of the cleft contribute to synaptic functions.

Synaptogenic signaling pathways

The intracellular signaling mechanisms instructing synapse development remain incompletely understood. Our work has shown that SynCAMs have signaling roles and we are elucidating these pathways. Analyzing synaptic changes in vivo, we have applied proteomic studies of synapses in mouse models with altered synaptogenesis to dissect signaling pathways. One example is our identification of the GTPase activator Farp1 as a novel postsynaptic protein that acts downstream of SynCAM adhesion and Semaphorin/Plexin signaling to promote synapse number and dendrite differentiation. We continue to elucidate how signaling pathways are integrated to control dendrite and synapse development.

Tuning networks

Synapse-organizing proteins not only allow neurons to connect but also impact neuronal networks once they are formed. This is underlined by a wealth of studies including from our group that synaptic adhesion proteins can modulate synaptic plasticity and impact memory processes. We address how synapse-organizing proteins contribute to the remodeling of neuronal connections. On the one hand, we investigate hippocampus-dependent memory processes. On the other, we use the paradigm of visual system plasticity to determine roles of trans-synaptic interactions in the experience-dependent maturation of cortical networks. This approach is based on in vivo electrophysiological recordings. Our work has translational potential as synaptic aberrations are a hallmark of autism-spectrum disorders and schizophrenia.


Medical Subject Headings (MeSH)

Biochemistry; Central Nervous System; Neurology; Neurosciences; Parkinson Disease; Schizophrenia; Synapses

Research at a Glance

Yale Co-Authors

Frequent collaborators of Thomas Biederer's published research.

Publications

2024

2023

2021

2019

Academic Achievements & Community Involvement

  • honor

    Initiative d’Excellence Award

  • honor

    Brain Research Foundation Fellow

  • honor

    Dana Foundation Scholar Award

  • honor

    NARSAD (Natl. Alliance for Research on Schizophrenia and Depression) Young Investigator Award

  • honor

    Basil O’Connor Starter Scholar Research Award

Get In Touch

Contacts

Academic Office Number
Office Fax Number
Mailing Address

Neurology

100 College Street, Room 244

New Haven, Connecticut 06510

United States