Positions
- Associate Professor
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Department of Neuroscience
Baylor College of Medicine
Houston, TX, US
Education
- BS from University of Notre Dame
- 05/1997 - Notre Dame, Indiana, United States
- PhD from University of California, Berkeley
- 12/2002 - Berkeley, California, United States
- Post-Doctoral Fellowship at University of Washington
- 06/2007 - Seattle, Washington, United States
- Post-Doctoral Fellowship at Baylor College of Medicine
- 02/2013 - Houston, Texas, United States
Professional Statement
A dizzying array of highly specialized cell types comprise metazoans, each a masterwork of form and function. Work in my group probes the macromolecular assemblies, organelles, and signals that give rise to these cellular specializations, seeking to understand the development of complex cells and their responses to injuries. Our current efforts are focused on neurons and astrocytes, though previous work has included epithelia and neuroendocrine cells as well.
We use the techniques of molecular and cellular neuroscience, with an emphasis on microscopy and protein and lipid biochemistry. Much of our work makes use of primary cultures of cells obtained from rodent CNS, though we also use in vivo models.
Our current efforts are centered on the following projects:
1. Molecular and cellular etiology of neurocognitive survivorship after CNS radiotherapy. Brain cancer is relatively common in children, but recent clinical advances have greatly increased long-term survival and cure rates. Unfortunately, these survivors experience long-lasting damage to multiple cognitive domains. With our collaborators at The University of Texas MD Anderson Cancer Center, we have demonstrated that the decades-long prevailing hypothesis that radiation-mediated damage is restricted to undifferentiated cells is incorrect and that radiation directly damages terminally differentiated neurons. We are extending these investigations in order to fully understand the nature of radiation-mediated injuries to neurons and astrocytes and to develop strategies for clinical intervention. These studies have relevance to other modes of radiation exposure and to neurodegenerative disease.
2. Biology of adhesion-GPCRs. Adhesion-GPCRs comprise the 2nd largest family of GPCRs in the brain, yet their complex structures and the dearth of information as to their ligands has caused our understanding of their biology to lag considerably behind that of other GPCRs. We have studied the roles the brain-specific angiogenesis inhibitors (BAIs), an adhesion-GPCR subfamily, on neuronal development. These cell surface receptors contain a number of ligand-binding domains and couple to multiple intracellular signaling pathways. We hypothesize that they serve as molecular signal integrators, thereby coordinating multiple aspects of neuronal development. To test this hypothesis, we use cellular and in vivo models to dissect BAI-dependent signaling pathways and effects. We have made particular progress with BAI1, elucidating several different pathways involving Rho-GTPases that impact diverse domains of neuronal function. We hope to ultimately identify clinical strategies to improve mental and neurological health, as BAIs and other A-GPCRs have proven to have many roles in orchestrating the development and function of the CNS. This research is conducted in collaboration with our collaborators at Stanford University.
We use the techniques of molecular and cellular neuroscience, with an emphasis on microscopy and protein and lipid biochemistry. Much of our work makes use of primary cultures of cells obtained from rodent CNS, though we also use in vivo models.
Our current efforts are centered on the following projects:
1. Molecular and cellular etiology of neurocognitive survivorship after CNS radiotherapy. Brain cancer is relatively common in children, but recent clinical advances have greatly increased long-term survival and cure rates. Unfortunately, these survivors experience long-lasting damage to multiple cognitive domains. With our collaborators at The University of Texas MD Anderson Cancer Center, we have demonstrated that the decades-long prevailing hypothesis that radiation-mediated damage is restricted to undifferentiated cells is incorrect and that radiation directly damages terminally differentiated neurons. We are extending these investigations in order to fully understand the nature of radiation-mediated injuries to neurons and astrocytes and to develop strategies for clinical intervention. These studies have relevance to other modes of radiation exposure and to neurodegenerative disease.
2. Biology of adhesion-GPCRs. Adhesion-GPCRs comprise the 2nd largest family of GPCRs in the brain, yet their complex structures and the dearth of information as to their ligands has caused our understanding of their biology to lag considerably behind that of other GPCRs. We have studied the roles the brain-specific angiogenesis inhibitors (BAIs), an adhesion-GPCR subfamily, on neuronal development. These cell surface receptors contain a number of ligand-binding domains and couple to multiple intracellular signaling pathways. We hypothesize that they serve as molecular signal integrators, thereby coordinating multiple aspects of neuronal development. To test this hypothesis, we use cellular and in vivo models to dissect BAI-dependent signaling pathways and effects. We have made particular progress with BAI1, elucidating several different pathways involving Rho-GTPases that impact diverse domains of neuronal function. We hope to ultimately identify clinical strategies to improve mental and neurological health, as BAIs and other A-GPCRs have proven to have many roles in orchestrating the development and function of the CNS. This research is conducted in collaboration with our collaborators at Stanford University.
Websites
Selected Publications
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Y-K Tu, JG Duman & KF Tolias. " The adhesion-GPCR BAI1 promotes excitatory synaptogenesis by coordinating bidirectional trans-synaptic signaling. " J. Neuroscience.. 2018 ; 38 : 8388-3406.
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K Um, S Niu, JG Duman, JX Cheng, Y-K Tu, B Schwechter, F Liu, L Hiles, AS Narayanan, RT Ash, S Mulherkar, K Alpadi, SM Smirnakis & KF Tolias. " Dynamic Control of Excitatory Synapse Development by a Rac1 GEF/GAP Regulatory Complex. " Dev. Cell. 2014 ; 29 : 701-715.
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JG Duman, J Dinh, W Zhou, H Cham, VC Mavratsas, M Pacešković, S Mulherkar, SL McGovern, KF Tolias & DR Grosshans. " Memantine prevents acute radiation-induced toxicities at hippocampal excitatory synapses. " Neuro-Oncol. 2018 ; 20 : 655-665.
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JG Duman, CP Tzeng, Y-K Tu, T Munjal, B Schwechter, TS Ho & KF Tolias. " The Adhesion-GPCR BAI1 Regulates Synaptogenesis by Controlling the Recruitment of the Par3/Tiam1 Polarity Complex to Synaptic Sites. " J. Neurosci.. 2013 Apr 17; 33 (16) : 6964-78.
Pubmed PMID: 23595754.
Memberships
- International Society for Neurochemistry
- Member (06/2011)
- Adhesion-GPCR Consortium
- Associate member (03/2017)
Funding
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(PQ9) Directed and unbiased studies of synaptic injuries as sequelae of radiotherapy: mapping, sex-dependence, and reversal
#R01CA219667 - $2,191,796.00 (09/01/2017 - 08/31/2022)
- Grant funding from NIH-NCI
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Molecular and cellular mechanisms of neuronal damage caused by anticancer therapies
#CA283569 - $2,469,120.00 (03/01/2024 - 02/28/2029)
- Grant funding from NIH-NCI
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