What are the genes and pathways disrupted in neurodevelopmental disorders such as autism? We are using a combination of computational and wet-bench approaches to elucidate novel signal cascades important for the pathophysiology of autism. We are focused on identifying the neural circuits and cell-type contributions of these genes to brain development. We are also developing new rodent models for testing the behavioral consequences of modifying these genes.
What are the human-specific gene expression signatures and signaling pathways? We are taking a comparative genomics approach to identify genes that have been modified in the human brain. Genes of interest are being further examined using both human neuronal cultures and animal models.
Which genes are important for human cognition from a functional standpoint? We are examining the correspondence of human brain gene expression with measurements of human brain activity. We are also examining how these correlations are disrupted in cognitive disorders.
Memory encoding is an essential step for all learning. However, the genetic and molecular mechanisms underlying human memory encoding remain poorly understood, and how this molecular framework permits the emergence of specific patterns of brain oscillations observed during mnemonic processing is unknown. Here, we directly compare intracranial electroencephalography recordings from the neocortex in individuals performing an episodic memory task with human gene expression from the same areas. We identify genes correlated with oscillatory memory effects across 6 frequency bands. These genes are enriched for autism-related genes and have preferential expression in neurons, in particular genes encoding synaptic proteins and ion channels, supporting the idea that the genes regulating voltage gradients are involved in the modulation of oscillatory patterns during successful memory encoding across brain areas. Memory-related genes are distinct from those correlated with other forms of cognitive processing and resting state fMRI. These data are the first to identify correlations between gene expression and active human brain states as well as provide a molecular window into memory encoding oscillations in the human brain.
Isabel Mendizabal, Stefano Berto, Noriyoshi Usui, Kazuya Toriumi, Paramita Chatterjee, Connor Douglas, Iksoo Huh, Hyeonsoo Jeong, Thomas Layman, Carol A. Tamminga, Todd M. Preuss, Genevieve Konopka and Soojin V. Yi Cell type-specific epigenetic links to schizophrenia risk in the brain. Genome Biology 2019 20:135. https://doi.org/10.1186/s13059-019-1747-7
Hickey, Berto, S., Konopka, G. Chromatin Decondensation by FOXP2 Promotes Human Neuron Maturation and Expression of Neurodevelopmental Disease Genes. Cell Reports, Vol.27, Issue 6, P1699-1711.E9, May 07 2019 https://doi.org/10.1016/j.celrep.2019.04.044
Co, M., Hickey, S.L., Kulkarni, A., Harper, M., Konopka, G. Cortical Foxp2 supports behavioral flexibility and developmental dopamine D1 receptor expression. BioRxiv. 05. 2019. https://doi.org/10.1101/624973.
Anderson, A.G., Kulkarni, A., Harper, M., Konopka, G. Single-cell analysis of Foxp1-driven mechanisms essential for striatal development. BioRxiv. 04.18.2019. https://doi.org/10.1101/611780.
Berto, S., Mendizabal, I., Usui N., Toriumi, K., Chatterjee, P., Douglas, C., Tamminga, C., Preuss, T.M., Yi, S.V., Konopka, G. Accelerated evolution of oligodendrocytes in human brain. BioRxiv. 04.12.2019. https://doi.org/10.1101/601062
Kulkarni A., Anderson AG, Merullo DP, Konopka G (2019) Beyond bulk: a review of single cell transcriptomics methodologies and applications. Current Opinion in Biotechnology, Volume 58, August 2019, Pages 129-136. doi: 10.1016/j.copbio.2019.03.001.
Issei S. Shimada, Bandarigoda N. Somatilaka, Sun-Hee Hwang, Ashley G. Anderson, John M. Shelton, Veena Rajaramd, Genevieve Konopka, Saikat Mukhopadhyay (2019) Derepression of sonic hedgehog signaling upon Gpr161 deletion unravels forebrain and ventricular abnormalities. Developmental Biology. Available online 23 March 2019. doi: 10.1016/j.ydbio.2019.03.011.
Richardson RB, Ohlson MB, Eitson JL, Kumar A, McDougal MB, Boys IN, Mar KB, De La Cruz-Rivera PC, Douglas C, Konopka G, Xing C, Schoggins JW. (2018) A CRISPR screen identifies IFI6 as an ER-resident interferon effector that blocks flavivirus replication. Nat Microbiol. 2018 Nov;3(11):1214-1223. doi: 10.1038/s41564-018-0244-1. Epub 2018 Sep 17.
Ayhan, F. and Konopka, G. (2018) Regulatory genes and pathways disrupted in autism spectrum disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2018 Aug 28;89:57-64. doi: 10.1016/j.pnpbp.2018.08.017.
Ayhan, F. and Konopka, G. (2018) Genomics of autism spectrum disorder: approach to therapy. F1000Research 2018, 7(F1000 Faculty Rev):627; doi: 10.12688/f1000research.13865.1
Fontenot MR, Berto S, Liu Y, Werthmann G, Douglas C, Usui N, Gleason K, Tamminga CA, Takahashi JS, Konopka G. (2017) Novel transcriptional networks regulated by CLOCK in human neurons. Genes Dev. 2017 Nov 1;31(21):2121-2135. doi: 10.1101/gad.305813.117. Epub 2017 Dec 1.
Usui N, Araujo DJ, Kulkarni A, Co M, Ellegood J, Harper M, Toriumi K, Lerch JP, Konopka G. (2017) Foxp1 regulation of neonatal vocalizations via cortical development. Genes Dev. 2017 Oct 15;31(20):2039-2055. doi: 10.1101/gad.305037.117. Epub 2017 Nov 14.
Escamilla CO, Filonova I, Walker AK, Xuan ZX, Holehonnur R, Espinosa F, Liu S, Thyme SB, López-García IA, Mendoza DB, Usui N, Ellegood J, Eisch AJ, Konopka G, Lerch JP, Schier AF, Speed HE, Powell CM. (2017) Kctd13 deletion reduces synaptic transmission via increased RhoA. Nature. 2017 Nov 9;551(7679):227-231. doi: 10.1038/nature24470. Epub 2017 Nov 1.
Araujo DJ, Toriumi K, Escamilla CO, Kulkarni A, Anderson AG, Harper M, Usui N, Ellegood J, Lerch JP, Birnbaum SG, Tucker HO, Powell CM, Konopka G. (2017) Foxp1 in Forebrain Pyramidal Neurons Controls Gene Expression Required for Spatial Learning and Synaptic Plasticity. J Neurosci. 2017 Nov 8;37(45):10917-10931. doi: 10.1523/JNEUROSCI.1005-17.2017. Epub 2017 Oct 4.
Stefano Berto, Guang-Zhong Wang, James Germi, Bradley C. Lega, Genevieve Konopka. (2017) Human Genomic Signatures of Brain Oscillations During Memory Encoding. Cerebral Cortex, April 2017.
Hanners NW, Eitson JL, Usui N, Richardson RB, Wexler EM, Konopka G, Schoggins JW (2016) Western Zika Virus in Human Fetal Neural Progenitors Persists Long Term with Partial Cytopathic and Limited Immunogenic Effects. Volume 15, Issue 11, 14 June 2016, Pages 2315–2322. Link
Berto, S., Usui, N., Konopka, G.*, and Fogel, B.L.* (2016) ELAVL2-regulated transcriptional and splicing networks in human neurons link neurodevelopment and autism. In press, Human Molecular Genetics. *Co-corresponding author.
Konopka, G., and Roberts, T.F. (2016) Insights into the neural and genetic basis of speech. Cell164(6):1269-76.
Konopka, G., and Roberts, T.F. (2016) Animal models of speech and vocal communication deficits associated with psychiatric disorders. Biological Psychiatry 79(1):53-61.a.
Usui, N., Co, M., Harper, M., Reiger, M.A., Dougherty, J.D., and Konopka, G. (2016) Sumoylation of FOXP2 regulates motor function and vocal communication through Purkinje cell development. In press, Biological Psychiatry, online Feb 12, doi 10.1016/j.biopsych.2016.02.008.
Wang G.-Z.*, Belgard, T. G.*, Mao, D., Chen, L., Berto, S., Preuss, T. M., Lu, H., Geschwind, D. H.,Konopka, G. (2015) Correspondence between Resting-State Activity and Brain Gene Expression.Neuron. 2015, 88 (4): 659–666.* Equal Contribution.
Wang G.-Z., Hickey S. L., Shi L., Huang HC., Nakashe P., Koike N., Tu B.P., Takahashi JS., Konopka G. (2015) Cycling Transcriptional Networks Optimize Energy Utilization on a Genome Scale. Cell Reports.2015, 13(9): 1868–1880.
Araujo, D.J.*, Anderson, A.G.*, Berto, S., Runnels, W., Harper, M., Ammanuel, S., Rieger, M.A., Huang, H-C., Rajkovich, K., Loerwald, K.W., Dekker, J.D., Tucker, H.O., Dougherty, J.D., Gibson, J.R., and Konopka, G. (2015) FoxP1 orchestration of ASD-relevant signaling pathways in the striatum. Genes & Development 29(20): 2081-96. *Equal Contribution.
Frank, E., Benabou, M., Bentzley, B., Bianchi, M., Goldstein, T., Konopka, G, Maywood, E., Pritchett, D., Sheaves, B., Thomas, J. (2014) Influencing circadian and sleep-wake regulation for prevention and intervention in mood and anxiety disorders: what makes a good homeostat? Ann N Y Acad Sci1334:1-25.
Usui, N., Co, M., and Konopka, G. (2014) Decoding the molecular evolution of cognition using comparative genomics. Brain, Behavior, and Evolution 84(2):103-16.
Fontenot, M., and Konopka, G. (2014) Molecular networks and evolution of human cognitive skills. Current Opinion in Genetics & Development 29C:52-59.
Lepp, S., Anderson, A., and Konopka, G. (2013) Connecting signaling pathways underlying communication to ASD vulnerability International Review of Neurobiology: Neurobiology of Autism (ed G. Konopka), Elsevier; 113:97-133.
Miller, D.J., and Konopka, G. (2013) Evolution and Development of Language, in Advances in Evolutionary Developmental Biology (ed J.T. Streelman), John Wiley & Sons, Inc, Hoboken, NJ, USA; 173-201.
Wang, G-Z., and Konopka, G. (2013) Decoding human gene expression signatures in the brain. Transcription 4(3):1-7.
Konopka, G. (2013) FOXP2: linking language and autism, in The Autisms: Molecules to Model Systems (eds. C.M. Powell, C.M. and L.M. Monteggia), Oxford University Press, New York, NY, USA; 367-393.
Bowers, J. M., and Konopka, G. (2012) ASD-relevant animal models of the Foxp family of transcription factors. Autism Open Access S1:010. http://www.omicsgroup.org/journals/2165-7890/2165-7890-S1-010.php?aid=10082
Bowers, JM, and Konopka, G. (2012) The role of the FOXP family of transcription factors in ASD. Dis Markers 33(5):251-60.
Konopka, G., Friedrich, T., Davis-Turak, J., Winden, K., Oldham, M.C., Gao, F., Chen, L., Wang, G-Z., Luo, R., Preuss, T.M., and Geschwind, D.H. (2012) Human-specific transcriptional networks in the brain. Neuron 75(4):601-617.
Wang, G-Z., and Konopka, G. (2012) Differential Functional Constraints on the Evolution of Postsynaptic Density Proteins in Neocortical Laminae. PLOS One 7(6): e39686.
Geschwind, D.H., and Konopka, G. (2012) Neuroscience: genes and human brain evolution. Nature486(7404):481-2.
Konopka, G. (2012) The fetal brain provides a raison d’etre for the evolution of new human genes. Brain Behav Evol 79(4):213-4.
Fogel, B.L., Cho, E., Wahnich, A., Gao, F., Becherel, O.J., Wang, X., Fike, F., Chen, L., Criscuolo, C., De Michele, G., Filla, A., Collins, A., Hahn, A.F., Gatti, R.A., Konopka, G, Perlman, S., Lavin, M.F., Geschwind, D.H., and Coppola, G. (2014) Mutation of senataxin alters disease-specific transcriptional networks in patients with ataxia with oculomotor apraxia type 2. Hum Mol GenetEpub Apr 23.
Zeng, J, Konopka, G, Hunt, BG, Preuss, TM, Geschwind, D, Yi, SV. (2012) Divergent whole-genome methylation maps of human and chimpanzee brains reveal epigenetic basis of human regulatory evolution. Am J Hum Genet. 91(3):455-65.
Fogel, B.L., Wexler, E., Wahnich, A., Friedrich, T., Vijayendran, C., Gao, F., Parikshak, N., Konopka, G., and Geschwind, D.H. (2012) RBFOX1 regulates both splicing and transcriptional networks in human neuronal development. Hum Mol Genet 21(19):4171-86.
Puram, S.V., Yeung, C.M., Jahani-Asl, A., Lin, C., de la Iglesia, N., Konopka, G., Jackson-Grusby, L., and Bonni, A. (2012) STAT3-iNOS signaling mediates EGFRvIII-induced glial proliferation and transformation. Journal of Neuroscience 32(23):7806-18.
DeLaForest, A., Nagaoka, M., Si-Tayeb, K., Noto, F.K., Konopka, G., Battle, M.A., and Duncan, S.A. (2011) HNF4A is essential for specification of hepatic progenitors from human pluripotent stem cells. Development 138(19):4143-53.
Mukamel, Z.*, Konopka, G.*, Wexler, E., Dong, H., Osborn, G., Levitt, P., and Geschwind, D.H. (2011) Regulation of MET by FOXP2, genes implicated in higher cognitive dysfunction and autism risk. Journal of Neuroscience 31(32):11437-42. *Equal Contribution.
Konopka, G., Wexler, E., Rosen, E., Mukamel, Z., Osborn, G. E., Chen, L., Lu, D., Gao, F., Gao, K., Lowe, J.K., and Geschwind D. H. (2012) Modeling the functional genomics of autism using human neurons. Molecular Psychiatry 17(2):202-14.
Konopka, G. (2010) Functional genomics of the brain: uncovering networks in the CNS using a systems approach. WIREs Systems Biology and Medicine, Epub Dec 31.
Konopka, G., and Geschwind, D.H. (2010) Human brain evolution: harnessing the genomics (r)evolution to link genes, cognition, and behavior. Neuron 68(2):231-44.
Konopka, G., Bomar, J.M., Winden, K., Coppola, G., Jonsson, Z.O., Gao, F., Peng, S., Preuss, T.M., Wohlschlegel, J.A., and Geschwind, D.H. (2009) Human-specific transcriptional regulation of CNS development genes by FOXP2. Nature 462 (7270):213-7.
Geschwind, D.H. and Konopka, G. (2009) Neuroscience in the era of functional genomics and systems biology. Nature 461(7266):908-15.
Oldham, M.C., Konopka, G., Iwamoto, K., Langfelder, P., Kato, T., Horvath, S., and Geschwind, D. H. (2008) Functional organization of the transcriptome in human brain. Nature Neuroscience11(11):1271-82.
de la Iglesia, N.*, Konopka, G.*, Nutt, C.L., Bromberg, J.F., Frank, D.A., Mischel, P.S., Louis, D.N., and Bonni, A. (2008) Deregulation of a STAT3-IL8 signaling pathway promotes human glioblastoma cell proliferation and invasiveness. Journal of Neuroscience 28(23):5870-8. *Equal contribution.
de la Iglesia, N.*, Konopka, G.*, Puram, S., Chan, J.A., Bachoo, R.M., You, J.M., Levy, D.E., DePinho, R.A., and Bonni, A. (2008) Identification of a PTEN-regulated STAT3 brain tumor suppressor pathway. Genes and Development 22(4):449-62. * Equal contribution.
Spiteri, E., Konopka, G., Coppola, G., Bomar, J., Oldham, M., Ou, J., Vernes, S.C., Fisher, S.E., Ren, B., and Geschwind, D.H. (2007) Identification of the transcriptional targets of FOXP2, a gene linked to speech and language, in developing human brain. American Journal of Human Genetics81(6): 1144-57.
Konopka, G., Tekiela, J., Iverson, M., Wells, C., Duncan, S.A. (2007) Junctional adhesion molecule-A is critical for the formation of pseudocanaliculi and modulates E-cadherin expression in hepatic cells. Journal of Biological Chemistry 282(38): 28137-48.
July 2019: Stefano's new paper is out in Genome Biology. "Cell type-specific epigenetic links to schizophrenia risk in the brain." More
June 2019: Congrats Dr. Marissa Co on defending your PhD thesis! pics to follow
June 2019: Welcome Haley, John and Abel! Bye Amena, good luck in med school!
April 2019: Ashley wins Best Poster at the Neuroscience Retreat!! Second year in a row!
April 2019: Ashwinikumar's review paper accepted in Current Opinion in Biotechnology "Beyond bulk: a review of single cell transcriptomics methodologies and applications." Congrats!!
April 2019: Stephanie's paper accepted in Cell Reports "Chromatin decondensation by FOXP2 promotes human neuron maturation and expression of neurodevelopmental disease genes". Congrats Steph!
April 2019: Yuxiang presents at Texas Society for Circadian Biology & Medicine meeting, and Ana has poster at NIMH conference!
March 2019: Ashley collaborates on paper, out now: "Derepression of sonic hedgehog signaling upon Gpr161 deletion unravels forebrain and ventricular abnormalities"
January 2019: Welcome new graduate student Emre Caglayan!
December 2018: Konopka lab outing! Pics in the gallery.
October 2018: Welcome rotation student Lauretta!
October 2018: Ana and Newaz pass quals & are PhD candidates. Congrats!
September 2018: Welcome rotation students Yoheilly and Emre!
August 2018: Trevor heads off to UT; Bye Trevor!
July 2018: Stephanie's Public PhD Defense! Congrats Dr. Lepp Hickey!
July 2018: Shelly presents at STARS poster session. Bye Shelly!
June 2018: Welcome to our summer high school students Trevor and Shelly!
April 2018: Stephanie wins Best Talk and Ashley wins Best Student Poster at the UTSW Neuroscience retreat! Konopka lab sweep!
March 2018: Congrats on all the new papers!
February 2018: Welcome to our new graduate student Ana!
January 2018: Welcome to our new green fellow Amena!
November 2017: O’Donnell Brain Institute at UT Southwestern joins global effort to map human cells. Read More
October 2017: Welcome to our new graduate student Newaz!
Spetember 2017: Congrats Ashley on winning a travel award to present her research at the Basal Ganglia Gordon Conference in March 2018!
July 2017: DJ is officially a PhD neuroscientist! Good luck at UC Berkeley in the Saijo Lab!
June 2017: North Texas Researchers Identify More Than 100 Genes Linked To Human Memory. More at KERA Radio.
June 2017: STAR Student Trevor joins the lab for the summer! Welcome!
April 2017: Gena is promoted to Associate Professor with tenure! Congrats fearless leader!
April 2017: Stefano's paper "Human Genomic Signatures of Brain Oscillations During Memory Encoding" is published in Cerebral Cortex!
March 2017: Miles passed his dissertation defense entitled "The Evolution and Function of the Genomic Landscape of the Human Brain"! Congrats and good luck!
March 2017: Welcome to our new post-docs Fatma and Yuxiang!
March 2017: Our rotation student Emily joins the lab! Welcome Emily!
January 2017: Connor joins the lab! Welcome Connor!
November 2016: Marissa wins a Keystone Symposia Travel Award! Congrats!
September 2016: Konopka Lab wins the golden brain in the 2016 Summer Lab Olympics! Congrats to Team Dragon-Thunder!
August 2016: Aarin finishes her rotation in the Konopka Lab- good luck with your future studies!
August 2016: The new lab website goes live! Thanks for checking it out!
June 2016: STAR Student Yosiah joins the lab for the summer! Welcome!
May 2016: Nori teams up with members of the Schoggins lab to publish a study on Zika virus in Human Neural Progenitors in Cell Reports!
April 2016: Stefano's paper, "ELAVL2-regulated transcriptional and splicing networks in human neurons link neurodevelopment and autism", is accepted at Human Molecular Genetics. Congrats Stefano!
(Sep 2011-Sep 2012)
Mike Bowers, Ph.D.
(Jan 2012-Mar 2013)
(Jun 2012-Mar 2013)
Steven Wen Qi, M.S.
(Jun-Aug 2012, Jun-Aug 2013)
(Jun 2013-Aug 2014)
(Jun 2014-Aug 2014)
(Jun 2014-Jul 2015)
Enrique De Alba
Hanqing (Kathy) Shang
(Oct 2015-Jan 2016)
Guang-Zhong Wang, Ph.D.
(Aug 2011-Mar 2016)
Kazuya Toriumi, Ph.D.
(Mar 2015-Mar 2017)
Noriyoshi Usui, Ph.D.
(Oct 2012-Mar 2017)
Miles Fontenot, Ph.D.
MD/PhD Neuroscience Graduate Student
(Jul 2013-Mar 2017)
(Jun 2016-Apr 2017)
Daniel Araujo, Ph.D.
PhD Neuroscience Graduate Student
(Jan 2012-Jul 2017)
Trevor Thai Nguyen
(Jun-Aug 2017; Jun-Aug 2018)
UTD Green Fellow
UTD Green Fellow
(Jan 2018-June 2019)