Positions
- Professor
-
Department of Neuroscience
Baylor College of Medicine
Houston, TX US
- Professor
-
Department of Biochemistry and Molecular Pharmacology
Baylor College of Medicine
Houston, TX US
Education
- PhD from Harvard Medical School
- 05/1998 - Boston, MA US
- Cell Biology - Signal Transduction
- Post-Doctoral Fellowship at Harvard Medical School
- 09/2006 - Boston, MA US
- Neuroscience
- Post-Doctoral Fellowship at Harvard Medical School
- 09/1999 - Boston, MA US
- Cell Biology - Signal Transduction
- BS from University of Minnesota
- 05/1992 - Minneapolis, MN US
- Biochemistry
Professional Interests
- Molecular and cellular mechanisms regulating mammalian neural circuit development and plasticity in health and disease/injury
- Formation and activity-dependent remodeling of excitatory and inhibitory synapses
- Axonal and dendritic growth
- Directed cell migration
- Rho GTPase and Adhesion-GPCR signaling in the nervous system
Professional Statement
The long-term goal of our research is to understand the molecular and cellular mechanisms underlying neural circuit formation and plasticity in the mammalian central nervous system (CNS) in the context of both health and disease/injury. A major focus of our research is elucidating how neurons sense external cues and transduce intracellular signals that direct essential processes like synapse development and remodeling, dendritic/axonal growth, and cell migration. In addition to investigating how these processes are normally regulated, we examine how dysregulation of key signaling pathways (particularly those regulating cytoskeletal dynamics) contribute to neurological disorders (e.g., intellectual disabilities, autism spectrum disorder, Alzheimer’s disease, depression, anxiety, and chronic pain) and whether targeting these pathways can promote recovery following injury or disease. Our laboratory is also actively engaged in numerous collaborative projects, including examining the synaptic mechanisms underlying cognitive decline following radiation therapy and the effects of the gut microbiome on brain development and behavior. To accomplish these goals, we utilize a multidisciplinary approach, employing in vivo and in vitro rodent models and a combination of state-of-the-art genetic, molecular, cellular, biochemical, electrophysiological, and behavioral methods.Websites
Selected Publications
- Li L, Ru Q, Lu Y, Fang X, Chen G, Saifullah AB, Yao C, Tolias KF. "Tiam1 coordinates synaptic structural and functional plasticity underpinning the pathophysiology of neuropathic pain.." Neuron. 2023 Jul 5;111(13):2038-2050. Pubmed PMID: 37146610
- Ru Q, Lu Y, Saifullah AB, Blanco FA, Yao C, Cata JP, Li DP, Tolias KF, Li L. "TIAM1-mediated synaptic plasticity underlies comorbid depression-like and ketamine antidepressant-like actions in chronic pain.." J Clin Invest.. 2022 Dec 15;132(24):e158545.. Pubmed PMID: 36519542
- Cheng J, Scala F, Blanco FA, Niu S, Firozi K, Keehan L, Mulherkar S, Froudarakis E, Li L, Duman JG, Jiang X, Tolias KF. "The Rac-GEF Tiam1 Promotes Dendrite and Synapse Stabilization of Dentate Granule Cells and Restricts Hippocampal-Dependent Memory Functions.." J Neurosci.. 2021 Feb 10;41(6):1191-1206. Pubmed PMID: 33328293
- Duman JG, Mulherkar S, Tu YK, Erikson KC, Tzeng CP, Mavratsas VC, Ho TS, Tolias KF. "The adhesion-GPCR BAI1 shapes dendritic arbors via Bcr-mediated RhoA activation causing late growth arrest.." Elife. 2019 Aug 28;8:e47566. Pubmed PMID: 31461398
- Tu YK, Duman JG, Tolias KF. "The Adhesion-GPCR BAI1 Promotes Excitatory Synaptogenesis by Coordinating Bidirectional Trans-synaptic Signaling.." J Neurosci.. 2018 Sep 26;38(39):8388-8406. Pubmed PMID: 30120207
- Yao C, Fang X, Ru Q, Li W, Li J, Mehsein Z, Tolias KF, Li L. "Tiam1-mediated Maladaptive Plasticity Underlying Morphine Tolerance and Hyperalgesia." Brain. 2024 Apr 5;(awae106) Pubmed PMID: 38577773
- Sharma J, Mulherkar S, Chen UI, Xiong Y, Bajaj L, Cho BK, Goo YA, Leung HE, Tolias KF, Sardiello M "Calpain activity is negatively regulated by a KCTD7-Cullin-3 complex via non-degradative ubiquitination.." Cell Discov.. 2023 Mar 24;9(1):32. Pubmed PMID: 36964131
- Duman JG, Blanco FA, Cronkite CA, Ru Q, Erikson KC, Mulherkar S, Saifullah AB, Firozi K, Tolias KF. "Rac-maninoff and Rho-vel: The symphony of Rho-GTPase signaling at excitatory synapses.." Small GTPases. 2022 Jan 13;1:14-47. Pubmed PMID: 33955328
- Choudhury D, Autry AE, Tolias KF, Krishnan V. "Ketamine: Neuroprotective or Neurotoxic?." Front Neurosci.. 2021 Sep 10;15:672526. Pubmed PMID: 34566558
- Cadwell CR, Scala F, Fahey PG, Kobak D, Mulherkar S, Sinz FH, Papadopoulos S, Tan ZH, Johnsson P, Hartmanis L, Li S, Cotton RJ, Tolias KF, Sandberg R, Berens P, Jiang X, Tolias AS. "Cell type composition and circuit organization of clonally related excitatory neurons in the juvenile mouse neocortex.." Elife. 2020 Mar 5;9:e52951. Pubmed PMID: 32134385
- Wang L, Pang K, Han K, Adamski CJ, Wang W, He L, Lai JK, Bondar VV, Duman JG, Richman R, Tolias KF, Barth P, Palzkill T, Liu Z, Holder JL Jr, Zoghbi HY. "An autism-linked missense mutation in SHANK3 reveals the modularity of Shank3 function.." Mol Psychiatry. 2020 Oct;25(10):2534-2555. Pubmed PMID: 30610205
- Mulherkar S, Tolias KF. "RhoA-ROCK Signaling as a Therapeutic Target in Traumatic Brain Injury.." Cells. 2020 Jan 18;9(1):245. Pubmed PMID: 31963704
- Morgan, Anderson, Araç, Aust, Balenga, Boucard, Bridges, Engel, Formstone, Glitsch, Gray,Hall,Hsiao,Kim,Knierim,Kusuluri,Leon, Liebscher, Piao, Prömel, Scholz, Srivastava, Thor, Tolias, Ushkaryov,Vallon, Van Meir ,Vanhollebeke,Wolfrum,Wright, Monk, Mogha. "The expanding functional roles and signaling mechanisms of adhesion G protein-coupled receptors.." Ann N Y Acad Sci.. 2019 Nov;1456(1):5-25. Pubmed PMID: 31168816
- Duman JG, Dinh J, Zhou W, Cham H, Mavratsas VC, Paveškovic M, Mulherkar S, McGovern SL, Tolias KF, Grosshans DR. "Memantine prevents acute radiation-induced toxicities at hippocampal excitatory synapses.." Neuro Oncol.. 2018 Apr 9;20(5):655-665. Pubmed PMID: 29112734
- Mulherkar S, Firozi K, Huang W, Uddin MD, Grill RJ, Costa-Mattioli M, Robertson C, Tolias KF. "RhoA-ROCK Inhibition Reverses Synaptic Remodeling and Motor and Cognitive Deficits Caused by Traumatic Brain Injury.." Sci Rep.. 2017 Sep 6;7(1):10689. Pubmed PMID: 28878396
- Duman JG, Tu YK, Tolias KF. "Emerging Roles of BAI Adhesion-GPCRs in Synapse Development and Plasticity." Neural Plast.. 2016;8301737 Pubmed PMID: 26881134
- Duman JG, Tolias KF. "RhoGTPases Spread the Word for Synaptic Crosstalk." Dev Cell.. 2016 Oct 24;39(2):136-138. Pubmed PMID: 27780038
- Lai KO, Jordan BA, Ma XM, Srivastava DP, Tolias KF. "Molecular Mechanisms of Dendritic Spine Development and Plasticity." Neural Plast.. 2016;2078121 Pubmed PMID: 27127656
- Cadwell, C.R., Palasantza, A., Jiang, X., Berens, P., Deng, Q., Yilmaz, M., Reimer, J., Shen, S., Bethge, M., Tolias, K. F., Sandberg, R., Tolias, A.S. "Electrophysiological, transcriptomic and morphologic profiling of single neurons using Patch-seq." Nat Biotechnol.. 2015 Dec 21;
- Duman, JG, Mulherkar, S., Tu, YK., Cheng, J., Tolias, K.F. "Mechanisms for spatiotemporal regulation of Rho-GTPase signaling at synapses." Neurosci Lett.. 2015 Aug 5;601:4-10. Pubmed PMID: 26003445
- Um, K., Niu, S., Duman, J. G., Cheng, J., Tu, Y-K., Schwechter, B., Liu, F., Hiles, L., Narayanan, A., Ash, R. T. Mulherkar, S., Alpadi, K., Smirnakis, S. M., Tolias, K. F. "Dynamic control of excitatory synapse development by a Rac1 GEF/GAP regulatory complex." Dev Cell. 2014;29(6):701-715. Pubmed PMID: 24960694
- Mulherkar, S., Uddin, M.D., Couvillon, A., Sillitoe, R., Tolias, K. F. "The small GTPases RhoA and Rac1 regulate cerebellar development by controlling cell morphogenesis, migration and foliation.." Dev. Biol.. 2014 Aug 14;Epub ahead of p. Pubmed PMID: 25128586
- Schwechter, B., Rosenmund, C., Tolias, K. F. "RasGRF2 Rac-GEF activity couples NMDA receptor calcium flux to enhanced synaptic transmission." Proc. Natl. Acad. Sci. USA. 2013 Aug 27;110(35):14462-14467. Pubmed PMID: 23940355
- Mulherkar, M., Liu, F., Chen, Q., Narayanan, A. S., Couvillon, A., Shine, H. D., Tolias, K. F. "The Small GTPase RhoA is Required for Proper Locomotor Circuit Assembly." PLoS One. 2013 Jun 25;8(6):e67015. Pubmed PMID: 23825607
- Narayanan, A. S., Reyes, S. B., Um, K., McCarty, J. H., Tolias, K. F. "The Rac-GAP Bcr is a novel regulator of the Par Complex that controls cell polarity." Mol Biol Cell.. 2013 Dec;24(24):3857-3868. Pubmed PMID: 24152735
- Duman, J. G., Tzeng, C. P., Tu, Y-K., Munjal, T., Schwechter, B., Ho, T., Tolias, K. F. "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):6964-6978. Pubmed PMID: 23595754
- Schwechter, B. and Tolias, K. F. "Cytoskeletal Mechanisms for Synaptic Potentiation." Commun Integr Biol.. 2013 Nov 1;6(6):e27343. Pubmed PMID: 24505509
- Reyes, S. B., Narayanan, A. S., Lee, H.S., Tchaicha, J. H., Aldape, K.D., Lang, F. F., Tolias, K. F., McCarty, J. H. "β8 Integrin Associates with RhoGDI1 to Suppress Activation of Rac1 and Cdc42 in Invasive Glioblastoma Cells." Mol. Biol. Cell.. 2013 Feb;24(4):472-482. Pubmed PMID: 23283986
- Tolias KF, Duman JG, Um K "Control of synapse development and plasticity by Rho GTPase regulatory proteins.." Prog. Neurobiol.. 2011 Jul;94(2):133-48. Pubmed PMID: 21530608
- Tolias, K. F., Bikoff, J. B., Kane, C. G., Tolias, C. S., Hu, L., Greenberg, M. E. "The Rac1 guanine nucleotide exchange factor Tiam1 mediates EphB receptor-dependent dendritic spine development." Proc. Natl. Acad. Sci. USA. 2007 Apr 24;104(17):7265-7270. Pubmed PMID: 17440041
- Zhou, P., Porcionatto, M., Pilapil, M., Chen, Y., Choi, Y., Tolias, K. F., Bikoff, J. B., Hong, E.J., Greenberg, M. E., Segal, R. A. "Polarized Signaling Endosomes Coordinate BDNF-induced Chemotaxis of Cerebellar Precursors." Neuron. 2007 Jul 5;55(1):53-68. Pubmed PMID: 17610817
- Tolias, K. F.*, Bikoff, J.B.*, Burette, A., Paradis, S., Harrar, D., Tavazoie, S., Weinberg, R.J., Greenberg, M. E. "The Rac1-GEF, Tiam1, Couples the NMDA Receptor to the Activity-Dependent Development of Dendritic Arbors and Spines.." Neuron. 2005 Feb 17;45(4):525-538. Pubmed PMID: 15721239
- Saito, K.*, Tolias, K. F.*, Saci, A., Koon H.B., Humphries, L.A., Scharenberg, A., Rawlings, D.J., Kinet, J-P and Carpenter, C. L. "BTK Regulates PtdIns-4,5-P2 Synthesis: Importance for Calcium Signaling and PI3K Activity." Immunity. 2003 Nov;19(5):669-78. Pubmed PMID: 14614854
- Tolias, K. F., Hartwig, J. H., Ishihara, H., Shibasaki, Y., Cantley, L. C., Carpenter, C. L. "Type I alpha phosphatidylinositol-4-phosphate 5-kinase mediates Rac-dependent actin assembly." Curr. Biol.. 2000;10(3):153-156. Pubmed PMID: 10679324
- Tolias, K. F. and Carpenter, C. L. "In vitro interaction of phosphoinositide-4-phosphate 5-kinases with Rac." Methods Enzymol.. 2000;325:190-200. Pubmed PMID: 11036604
- Kost, B., Lemichez, E., Spielhofer, P., Hong, Y., Tolias, K. F., Carpenter, C. L., Chua, N-H. "Rac homologues and compartmentalized phosphatidylinositol 4,5-bisphosphate act in a common pathway to regulate polar pollen tube growth." J. Cell Biol.. 1999;145:317-330. Pubmed PMID: 10209027
- Tolias, K. F. and Cantley, L. C. "Pathways for Phosphoinositide Synthesis." Chem. Phys. Lipids. 1999;98:69-77. Pubmed PMID: 10358929
- Carpenter CL, Tolias KF, Van Vugt A, Hartwig J. "Lipid kinases are novel effectors of the GTPase Rac1." Adv Enzyme Regul.. 1999;39:299-312. Pubmed PMID: 10470380
- Tolias, K. F., Rameh, L. E., Ishihara, H., Shibasaki, Y., Chen, J., Prestwich, G. D., Cantley, L. C., Carpenter, C. L. "Type I phosphatidylinositol-4-phosphate 5-kinases synthesize the novel lipids phosphatidylinositol-3,5-bisphosphate and phosphatidylinositol-5-phosphate." J. Biol. Chem.. 1998;273:18040-18046. Pubmed PMID: 9660759
- Tolias, K. F., Couvillon, A. D., Cantley, L. C., Carpenter, C. L. "Characterization of a Rac1- and RhoGDI-associated lipid kinase signaling complex." Mol. Cell Biol.. 1998;18:762-770. Pubmed PMID: 9447972
- Rameh, L. E., Tolias, K. T., Duckworth, B., Cantley, L. C. "A new pathway for phosphatidylinositol-4,5-bisphosphate synthesis." Nature. 1997;390:192-196. Pubmed PMID: 9367159
- Berditchevski, F, Tolias, K. F., Wong, K, Carpenter, C. L., Hemler, M. E. "A novel link between integrins, transmembrane-4 superfamily proteins (CD63 and CD81), and phosphatidylinositol 4-kinase." J. Biol. Chem.. 1997 Jan 31;272(5):2595-258. Pubmed PMID: 9006891
- Carpenter CL, Tolias KF, Couvillon AC, Hartwig JH. "Signal transduction pathways involving the small G proteins rac and Cdc42 and phosphoinositide kinases.." Adv Enzyme Regul.. 1997;37:377-90. Pubmed PMID: 9381982
- Kolluri, R., Tolias, K. F., Carpenter, C. L., Rosen, F. S., Kirchhausen, T. "Direct interaction of the Wiskott-Aldrich syndrome protein with the GTPase Cdc42.." Proc Natl Acad Sci U S A.. 1996;93(11):5615-8. Pubmed PMID: 8643625
- Tolias, K. F., Cantley, L. C., and Carpenter, C. L. "Rho family GTPases bind to phosphoinositide kinases." J Biol Chem.. 1995;270(30):17656-9. Pubmed PMID: 7629060
- Fuchs KR*, Shekels LL, Bernlohr DA. "Analysis of the ACP1 gene product: classification as an FMN phosphatase." Biochem Biophys Res Commun. 1992 Dec 30;189(3):1598-605. Pubmed PMID: 1336375
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