Overview
MOLECULAR AND BIOPHYSICAL PRINCIPLES OF SYNAPTIC FUNCTION
The focus of this lab is the study of the molecular basis of synaptic transmission in the mammalian brain. Our primary interests lie in understanding the regulation of vesicle traffic in presynaptic terminals, and how this traffic impacts presynaptic function. Synaptic terminals are specialized cellular structures that carry out carefully orchestrated vesicle trafficking through the interplay of molecular machines. Modulation of synaptic function almost certainly relies on changing the efficiency of one of many of these trafficking steps. Similarly, synaptic dysfunction could easily arise from loss of proper regulation of these steps. We use biophysical tools to characterize the molecular machinery as it functions in living synapses, ultimately always asking the question of how synapses work. We use many types of optical assays in combination with molecular, genetic and chemical tools to determine the molecular basis of various steps of the vesicle cycle as well as the roles of specific proteins that are enriched in the presynaptic terminal. In recent years we have been addressing how endocytosis is regulated at nerve terminals as well as how vesicles are clustered and mobilized for secretion upon action potential firing. The lab continuously develops new assays and approaches to address these questions.Through these studies, we hope to gain insight into how information is controlled at the synaptic level in both normal and diseased states of brain function. For more information see: Dr. Ryan's lab
Dr. Ryan is a faculty member in the Tri-Institutional PhD Program in Chemical Biology.
Highlights
- 1Proceedings of the National Academy of Sciences of the United States of America · 2024
- 2Science advances · 2021
- 3Science advances · 2024
Publications
Funding
Active
8 grants- PISFI-AN-NC-BE-00034663-18Simons Collaboration on Brain Energetics (SCOBE)Simons Foundation · 2026–2031
- PIR01NS036942-27Physiology of single synaptic CNS terminalsNational Institute of Neurological Disorders and Stroke · 2011–2029· 2 renewals
- KPK08GM148935-01Metabolic impact of Intralipid on synaptic function as a mechanism of resuscitation in local anesthetic systemic toxicityNational Institute of General Medical Sciences · 2023–2028
- PISFI-AN-NC-BE-00033889Simons Collaboration on Brain Energetics (SCOBE) - EquipmentSimons Foundation · 2026–2027
- Sub-PIASAP-025173Impaired integration of organelle function in Parkinson's diseaseMichael J. Fox Foundation for Parkinson's Research · 2024–2027 · via Yale University
- PISPARK 245930-02 DiscretionaryA Better PGK-1 Activator for PDSPARK NS, Inc. · 2024–2027No publications yet
- Co-IR01GM058055-22Synaptic Mechanisms of General Anesthetic ActionNational Institute of General Medical Sciences · 2010–2026· 3 renewals
- PIR01NS117139-05Metabolic Vulnerability of Synapses in Neurodegenerative DiseaseNational Institute of Neurological Disorders and Stroke · 2020–2026
Completed grants (13)
- Sub-PIYU 203691-04Impaired integration of organelle function in Parkinson's diseaseMichael J. Fox Foundation for Parkinson's Research · 2020–2025 · via Yale University
- PIR37NS036942-24Physiology of single synaptic CNS terminalsNational Institute of Neurological Disorders and Stroke · 1997–2024· 4 renewals
- PIAddgene 700216Addgene 700216Addgene, Inc. · 2022–2023
- Co-IR01HD090132-03Investigation of the Roles for CaV1.2 in Non-Excitable Tissue During DevelopmentEunice Kennedy Shriver National Institute of Child Health and Human Development · 2016–2021
- PIR01MH085783-10Quantitative Mapping of Molecules and Release Properties at Nerve TerminalsNational Institute of Mental Health · 2009–2020· 2 renewals
- PITISCI 2016-001Role of Tet and Chromatin Remodeling Genes in Human Cerebellar Neuron Synapse Formation and FunctionTri-Institutional Stem Cell Initiative (Weill Cornell) · 2016–2020
- PITISCI 2016-023Role of Presenilins in Axon ER Calcium Handling and Human Synaptic FunctionTri-Institutional Stem Cell Initiative (Weill Cornell) · 2016–2018
- Sub-PIR01NS060809-10Molecular Mechanism of LRRK2 Biology and Pathology in Parkinson's DiseaseNational Institute of Neurological Disorders and Stroke · 2013–2018 · via Mount Sinai School of Medicine
- PIR21NS083355-02Identification of Synaptic Alpha2delta Binding PartnersNational Institute of Neurological Disorders and Stroke · 2013–2015
- PIP01DA010154-15The Presynaptic Vesicle Cycle for the Slow Acting Neurotransmitter SecretionNIDA · 2006–2011 · via NIH RePORTER
- PIT32GM070369-05Tri-Institutional Training Program in Chemical BiologyNIGMS · 2004–2009 · via NIH RePORTER
Honors & distinctions
- Fellow · American Academy of Arts and Sciences · 2024
- Sloan Research Fellowship · Alfred P. Sloan Foundation · 1999
- Member · National Academy of Sciences
Available technologies
News mentions
- Aging Midbrain Neurons Face Energy Crisis Linked to Parkinson’sDecember 5, 2025
Dopamine neurons in a part of the brain called the midbrain may, with aging, be increasingly susceptible to a vicious spiral of decline driven by fuel shortages, according to a study led by Weill Cornell Medicine investigators.
- Fat May Play an Important Role in Brain MetabolismJuly 1, 2025
While glucose, or sugar, is a well-known fuel for the brain, Weill Cornell Medicine researchers have demonstrated that electrical activity in synapses—the junctions between neurons where communication occurs—can lead to the use of lipid or fat droplets as an energy source.
- Weill Cornell Medicine Researcher Wins the SPARK NS 2025 Immersive Translational Research GrantApril 3, 2025
Dr. Timothy Ryan has been named one of eight academic principal investigators to participate in the SPARK NS Translational Research Program, 2025 cohort.
- The Role of an Energy-Producing Enzyme in Treating Parkinson’s DiseaseAugust 21, 2024
An enzyme called PGK1 has an unexpectedly critical role in the production of chemical energy in brain cells, according to a preclinical study led by researchers at Weill Cornell Medicine.
- New Molecular Sensor Tracks Energy Use at the Subcellular LevelMay 16, 2024
A team led by researchers at Weill Cornell Medicine and the Howard Hughes Medical Institute (HHMI) Janelia Research Campus has developed and tested a high-resolution sensor for tracking the real-time dynamics of ATP levels in cells and within subcellular compartments.
Show 3 more mentions
- Dr. Timothy Ryan Elected to National Academy of SciencesMay 1, 2024
Dr. Timothy Ryan, professor of biochemistry in anesthesiology at Weill Cornell Medicine, has been elected to the prestigious National Academy of Sciences, one of the highest honors a scientist can receive.
- Brain Drain: Scientists Explain Why Neurons Consume So Much Fuel Even When at RestDecember 3, 2021
Pound for pound, the brain consumes vastly more energy than other organs, and, puzzlingly, it remains a fuel-guzzler even when its neurons are not firing signals called neurotransmitters to each other. Now researchers at Weill Cornell Medicine have found that the process of packaging neurotransmitters may be responsible for this energy drain.
- Scientists Discover a Key Metabolic Tuning Mechanism for NeuronsDecember 17, 2019
Neurons have a special mechanism that allows them to quickly boost energy production to support bursts of brain activity, according to a new study from scientists at Weill Cornell Medicine.
Mentoring
PhD · 2
- MNMarianne NavalPhysiology, Biophysics & Systems Biology (PhD) · Class of 2024
- NANimra AsiCell & Developmental Biology (PhD) · Class of 2021
MD-PhD · 1
- KBKirsten BredvikMD-PhD WGS Biochemistry & Structural Biology (MD-PhD)
Postdoc · 7
- ZKZhanat KoshenovPostdoc mentee · 2023–2025
- ANAndrew NelsonPostdoc mentee · 2021–2023
- RFRyan FarrellPostdoc mentee · 2022–2022
- GAGhazaleh AshrafiPostdoc mentee · 2014–2019
- JDJaime de Juan SanzPostdoc mentee · 2013–2019
External relationships
Advisory/Scientific Board Member
Howard Hughes Medical Institute
Other Interest
Howard Hughes Medical Institute