Anita Bhattacharyya, PhD

Position title: Associate Professor, Cell and Regenerative Biology

PhD, University of Cincinnati
Co-Core Director, IDD Models
Sub-Core Director, hPSC Services

Contact Information

Waisman Center
1500 Highland Avenue
Room 623
Madison, WI 53705
608-265-6142
bhattacharyy@waisman.wisc.edu
Bhattacharyya Lab at UW-Madison

Research Statement

My research examines how the development of the cerebral cortex is altered in developmental disorders characterized by mental impairment. The cerebral cortex is the most complex area of the brain and is responsible for functions unique to humans, such as language and abstract thought. Problems in any of the crucial steps in the formation of the cerebral cortex can lead to mental impairment. Research in my lab is focused on two genetic developmental disorders, Down syndrome and Fragile X syndrome. Down syndrome is caused by an extra chromosome (Trisomy 21), while Fragile X syndrome is due to a single gene mutation (fmr1 gene). I am using human pluripotent stem cells that carry either trisomy 21 or the fmr1 mutation to study the development of the cerebral cortex in vitro. These stem cells have intrinsic characteristics that can be investigated in culture to further our understanding and treatment of developmental disorders. By defining the mistakes in neurodevelopment that lead to mental impairment, we may be able to target therapeutics for these developmental disorders.

Selected Publications

Pubmed

Yan, Y., Li, X., Gao, Y., Mathivanan, S., Kong, L., Tao, Y., Dong, Y., Li, X., Bhattacharyya, A., Zhao, X., & Zhang, S. C. (2024). 3D bioprinting of human neural tissues with functional connectivity. Cell stem cell, 31(2), 260–274.e7. https://doi.org/10.1016/j.stem.2023.12.009
Martinez, J. L., Piciw, J. G., Crockett, M., Sorci, I. A., Makwana, N., Sirois, C. L., Giffin-Rao, Y., & Bhattacharyya, A. (2024). Transcriptional consequences of trisomy 21 on neural induction. Frontiers in cellular neuroscience, 18, 1341141. https://doi.org/10.3389/fncel.2024.1341141
Shen, M., Sirois, C. L., Guo, Y., Li, M., Dong, Q., Méndez-Albelo, N. M., Gao, Y., Khullar, S., Kissel, L., Sandoval, S. O., Wolkoff, N. E., Huang, S. X., Xu, Z., Bryan, J. E., Contractor, A. M., Korabelnikov, T., Glass, I. A., Doherty, D., Birth Defects Research Laboratory, Levine, J. E., … Zhao, X. (2023). Species-specific FMRP regulation of RACK1 is critical for prenatal cortical development. Neuron, 111(24), 3988–4005.e11. https://doi.org/10.1016/j.neuron.2023.09.014
Lear, B. P., Thompson, E. A. N., Rodriguez, K., Arndt, Z. P., Khullar, S., Klosa, P. C., Lu, R. J., Morrow, C. S., Risgaard, R., Peterson, E. R., Teefy, B. B., Bhattacharyya, A., Sousa, A. M. M., Wang, D., Benayoun, B. A., & Moore, D. L. (2023). Age-maintained human neurons demonstrate a developmental loss of intrinsic neurite growth ability. bioRxiv : the preprint server for biology, 2023.05.23.541995. https://doi.org/10.1101/2023.05.23.541995
Giffin-Rao, Y., Sheng, J., Strand, B., Xu, K., Huang, L., Medo, M., Risgaard, K. A., Dantinne, S., Mohan, S., Keshan, A., Daley, R. A., Jr, Levesque, B., Amundson, L., Reese, R., Sousa, A., Tao, Y., Wang, D., Zhang, S. C., & Bhattacharyya, A. (2022). Altered patterning of trisomy 21 interneuron progenitors. Stem cell reports, 17(6), 1366–1379. https://doi.org/10.1016/j.stemcr.2022.05.001
Risgaard, K. A., Sorci, I. A., Mohan, S., & Bhattacharyya, A. (2022). Meta-Analysis of Down Syndrome Cortical Development Reveals Underdeveloped State of the Science. Frontiers in cellular neuroscience, 16, 915272. https://doi.org/10.3389/fncel.2022.915272
Wu, Y., West, N. R., Bhattacharyya, A., & Wiseman, F. K. (2022). Cell models for Down syndrome-Alzheimer’s disease research. Neuronal signaling, 6(1), NS20210054. https://doi.org/10.1042/NS20210054
Murie, M., Peng, Y., Rigby, M. J., Dieterich, I. A., Farrugia, M. A., Endresen, A., Bhattacharyya, A., & Puglielli, L. (2022). ATase inhibition rescues age-associated proteotoxicity of the secretory pathway. Communications biology, 5(1), 173. https://doi.org/10.1038/s42003-022-03118-0
Fathi, A., Mathivanan, S., Kong, L., Petersen, A. J., Harder, C., Block, J., Miller, J. M., Bhattacharyya, A., Wang, D., & Zhang, S. C. (2022). Chemically induced senescence in human stem cell-derived neurons promotes phenotypic presentation of neurodegeneration. Aging cell, 21(1), e13541. https://doi.org/10.1111/acel.13541
Hunt, J., Li, M., Risgaard, R., Ananiev, G. E., Wildman, S., Zhang, F., Bugni, T. S., Zhao, X., & Bhattacharyya, A. (2021). High Throughput Small Molecule Screen for Reactivation of FMR1 in Fragile X Syndrome Human Neural Cells. Cells, 11(1), 69. https://doi.org/10.3390/cells11010069
Keen, K. L., Petersen, A. J., Figueroa, A. G., Fordyce, B. I., Shin, J., Yadav, R., Erdin, S., Pearce, R. A., Talkowski, M. E., Bhattacharyya, A., & Terasawa, E. (2021). Physiological Characterization and Transcriptomic Properties of GnRH Neurons Derived From Human Stem Cells. Endocrinology, 162(9), bqab120. https://doi.org/10.1210/endocr/bqab120
Martinez, J. L., Zammit, M. D., West, N. R., Christian, B. T., & Bhattacharyya, A. (2021). Corrigendum: Basal Forebrain Cholinergic Neurons: Linking Down Syndrome and Alzheimer’s Disease. Frontiers in aging neuroscience, 13, 742233. https://doi.org/10.3389/fnagi.2021.742233
Dierssen, M., Herault, Y., Helguera, P., Martínez de Lagran, M., Vazquez, A., Christian, B., Carmona-Iragui, M., Wiseman, F., Mobley, W., Fisher, E., Brault, V., Esbensen, A., Jacola, L. M., Potier, M. C., Hamlett, E. D., Abbeduto, L., Del Hoyo Soriano, L., Busciglio, J., Iulita, M. F., Crispino, J., … Bhattacharyya, A. (2021). Building the Future Therapies for Down Syndrome: The Third International Conference of the T21 Research Society. Molecular syndromology, 12(4), 202–218. https://doi.org/10.1159/000514437
Martinez, J. L., Zammit, M. D., West, N. R., Christian, B. T., & Bhattacharyya, A. (2021). Basal Forebrain Cholinergic Neurons: Linking Down Syndrome and Alzheimer’s Disease. Frontiers in aging neuroscience, 13, 703876. https://doi.org/10.3389/fnagi.2021.703876
Tang, X. Y., Xu, L., Wang, J., Hong, Y., Wang, Y., Zhu, Q., Wang, D., Zhang, X. Y., Liu, C. Y., Fang, K. H., Han, X., Wang, S., Wang, X., Xu, M., Bhattacharyya, A., Guo, X., Lin, M., & Liu, Y. (2021). DSCAM/PAK1 pathway suppression reverses neurogenesis deficits in iPSC-derived cerebral organoids from patients with Down syndrome. The Journal of clinical investigation, 131(12), e135763. https://doi.org/10.1172/JCI135763
Anderson, N. C., Chen, P. F., Meganathan, K., Afshar Saber, W., Petersen, A. J., Bhattacharyya, A., Kroll, K. L., Sahin, M., & Cross-IDDRC Human Stem Cell Working Group (2021). Balancing serendipity and reproducibility: Pluripotent stem cells as experimental systems for intellectual and developmental disorders. Stem cell reports, 16(6), 1446–1457. https://doi.org/10.1016/j.stemcr.2021.03.025
Hendrix, J. A., Amon, A., Abbeduto, L., Agiovlasitis, S., Alsaied, T., Anderson, H. A., Bain, L. J., Baumer, N., Bhattacharyya, A., Bogunovic, D., Botteron, K. N., Capone, G., Chandan, P., Chase, I., Chicoine, B., Cieuta-Walti, C., DeRuisseau, L. R., Durand, S., Esbensen, A., Fortea, J., … Yi, J. S. (2021). Opportunities, barriers, and recommendations in down syndrome research. Translational science of rare diseases, 5(3-4), 99–129. https://doi.org/10.3233/trd-200090
Zhao, X., & Bhattacharyya, A. (2020). Advances in Human Stem Cells and Genome Editing to Understand and Develop Treatment for Fragile X Syndrome. Advances in neurobiology, 25, 33–53. https://doi.org/10.1007/978-3-030-45493-7_2
Li M, Shin J, Risgaard RD, Parries MJ, Wang J, Chasman D, Liu S, Roy S, Bhattacharyya A, Zhao X. (2020). Identification of FMR1-regulated molecular networks in human neurodevelopment. Genome Research, 30(3):361-374. doi: 10.1101/gr.251405.119. Epub 2020 Mar 16. PMID: 32179589; PMCID: PMC7111522.
Bhattacharyya A. (2020). Advancing Knowledge of Down Syndrome Brain Development and Function With Human Stem Cells. American Journal of Intellectual and Developmental Disabilities, 125(2):90-92. doi: 10.1352/1944-7558-125.2.90. PMID: 32058817; PMCID: PMC7169307.
Dong, Y., Xiong, M., Chen, Y., Tao, Y., Li, X., Bhattacharyya, A., & Zhang, S. C. (2020). Plasticity of Synaptic Transmission in Human Stem Cell-Derived Neural Networks. iScience, 23(2), 100829. https://doi.org/10.1016/j.isci.2020.100829
Walkley SU, Abbeduto L, Batshaw ML, Bhattacharyya A, Bookheimer SY, Christian BT, Constantino JN, de Vellis J, Doherty DA, Nelson DL, Piven J, Poduri A, Pomeroy SL, Samaco RC, Zoghbi HY, Guralnick MJ; IDDRC Directors Committee. (2019). Intellectual and Developmental Disabilities Research Centers: 50 Years of Scientific Accomplishments. Annals of Neurology, 86(3):332-343. doi: 10.1002/ana.25531.
Bradley RA, Shireman J, McFalls C, Choi J, Canfield SG, Dong Y, Liu K, Lisota B, Jones JR, Petersen A, Bhattacharyya A, Palecek SP, Shusta EV, Kendziorski C, Zhang SC. (2019). Regionally specified human pluripotent stem cell-derived astrocytes exhibit different molecular signatures and functional properties. Development, 8;146(13):dev170910. doi: 10.1242/dev.170910.
Li, M., Hunt, J., Bhattacharyya, A., & Zhao, X. (2019). One-Step Generation of Seamless Luciferase Gene Knockin Using CRISPR/Cas9 Genome Editing in Human Pluripotent Stem Cells. Methods in molecular biology (Clifton, N.J.), 1942, 61–69. https://doi.org/10.1007/978-1-4939-9080-1_5
Hunt, J., Li, M., Zhao, X., & Bhattacharyya, A. (2019). Using Human Neural Progenitor Cell Models to Conduct Large-Scale Drug Screens for Neurological and Psychiatric Diseases. Methods in molecular biology (Clifton, N.J.), 1942, 79–88. https://doi.org/10.1007/978-1-4939-9080-1_7
Shen M, Wang F, Li M, Sah N, Stockton ME, Tidei JJ, Gao Y, Korabelnikov T, Kannan S, Vevea JD, Chapman ER, Bhattacharyya A, van Praag H, Zhao X. (2019). Reduced mitochondrial fusion and Huntingtin levels contribute to impaired dendritic maturation and behavioral deficits in FMR1-mutant mice. Nature Neuroscience, 22(3):386-400. doi: 10.1038/s41593-019-0338-y.
Reeves, R. H., Delabar, J., Potier, M. C., Bhattacharyya, A., Head, E., Lemere, C., Dekker, A. D., De Deyn, P., Caviedes, P., Dierssen, M., & Busciglio, J. (2019). Paving the Way for Therapy: The Second International Conference of the Trisomy 21 Research Society. Molecular syndromology, 9(6), 279–286. https://doi.org/10.1159/000494231
Yin, Y., Petersen, A. J., Soref, C., Richards, W. D., Ludwig, T., Taapken, S., Berndt, E., Zhang, S. C., & Bhattacharyya, A. (2019). Generation of seven induced pluripotent stem cell lines from neonates of different ethnic backgrounds. Stem cell research, 34, 101365. https://doi.org/10.1016/j.scr.2018.101365
Sun J, Carlson-Stevermer J, Das U, Shen M, Delenclos M, Snead AM, Koo SY, Wang L, Qiao D, Loi J, Petersen AJ, Stockton M, Bhattacharyya A, Jones MV, Zhao X, McLean PJ, Sproul AA, Saha K, Roy S. (2019). CRISPR/Cas9 editing of APP C-terminus attenuates β-cleavage and promotes α-cleavage. Nature Communications, 3;10(1):53. doi: 10.1038/s41467-018-07971-8.
Zhao X, Bhattacharyya A. (2018). Human Models Are Needed for Studying Human Neurodevelopmental Disorders. American Journal of Human Genetics, 103(6):829-857. doi: 10.1016/j.ajhg.2018.10.009. Review.
Ludwig TE, Kujak A, Rauti A, Andrzejewski S, Langbehn S, Mayfield J, Fuller J, Yashiro Y, Hara Y, Bhattacharyya A. (2018). 20 Years of Human Pluripotent Stem Cell Research: It All Started with Five Lines. Cell Stem Cell, 23(5):644-648. doi: 10.1016/j.stem.2018.10.009.
Jones JR, Kong L, Hanna MG 4th, Hoffman B, Krencik R, Bradley R, Hagemann T, Choi J, Doers M, Dubovis M, Sherafat MA, Bhattacharyya A, Kendziorski C, Audhya A, Messing A, Zhang SC. (2018). Mutations in GFAP Disrupt the Distribution and Function of Organelles in Human Astrocytes. Cell Reports, 25(4):947-958.e4. doi: 10.1016/j.celrep.2018.09.083.
Mizuno GO, Wang Y, Shi G, Wang Y, Sun J, Papadopoulos S, Broussard GJ, Unger EK, Deng W, Weick J, Bhattacharyya A, Chen CY, Yu G, Looger LL, Tian L. (2018). Aberrant Calcium Signaling in Astrocytes Inhibits Neuronal Excitability in a Human Down Syndrome Stem Cell Model. Cell Reports, 24(2):355-365. doi: 10.1016/j.celrep.2018.06.033.
Huo HQ, Qu ZY, Yuan F, Ma L, Yao L, Xu M, Hu Y, Ji J, Bhattacharyya A, Zhang SC, Liu Y. (2018). Modeling Down Syndrome with Patient iPSCs Reveals Cellular and Migration Deficits of GABAergic Neurons. Stem Cell Reports, 10;10(4):1251-1266.
Alisch RS, Van Hulle C, Chopra P, Bhattacharyya A, Zhang SC, Davidson RJ, Kalin NH, Goldsmith HH. (2017). A multi-dimensional characterization of anxiety in monozygotic twin pairs reveals susceptibility loci in humans. Translational Psychiatry, 7(12):1282. PMCID: PMC5802687. DOI: 10.1038/s41398-017-0047-9
Li M, Zhao H, Ananiev GE, Musser MT, Ness KH, Maglaque DL, Saha K, Bhattacharyya A, Zhao X. (2017). Establishment of Reporter Lines for Detecting Fragile X Mental Retardation (FMR1) Gene Reactivation in Human Neural Cells. Stem Cells, 35(1):158-169. doi: 10.1002/stem.2463.
Rovozzo R, Korza G, Baker MW, Li M, Bhattacharyya A, Barbarese E, Carson JH. (2016). CGG Repeats in the 5’UTR of FMR1 RNA Regulate Translation of Other RNAs Localized in the Same RNA Granules. PLoS One, 11(12):e0168204. doi: 10.1371/journal.pone.0168204.
Bhattacharyya A, Zhao X. (2016) Human pluripotent stem cell models of Fragile X syndrome. Molecular and Cellular Neurosciences. 73:43-51. PubMed PMID: 26640241; PubMed Central PMCID: PMC4867245.
Li Y, Stockton ME, Bhuiyan I, Eisinger BE, Gao Y, Miller JL, Bhattacharyya A, Zhao X. (2016) MDM2 inhibition rescues neurogenic and cognitive deficits in a mouse model of fragile X syndrome. Science Translational Medicine. 27;8(336):336ra61. doi: 10.1126/scitranslmed.aad9370.
Li M, Pehar M, Liu Y, Bhattacharyya A, Zhang SC, O’Riordan KJ, Burger C, D’Adamio L, Puglielli L. (2015) The amyloid precursor protein (APP) intracellular domain regulates translation of p44, a short isoform of p53, through an IRES-dependent mechanism. Neurobiology of Aging. 36(10):2725-36. doi: 10.1016/j.neurobiolaging.
Yuan F, Fang KH, Cao SY, Qu ZY, Li Q, Krencik R, Xu M, Bhattacharyya A, Su YW, Zhu DY, Liu Y. (2015) Efficient generation of region-specific forebrain neurons from human pluripotent stem cells under highly defined condition. Scientific Reports. 5:18550. doi: 10.1038/srep18550.
Doers ME, Musser MT, Nichol R, Berndt ER, Baker M, Gomez TM, Zhang SC, Abbeduto L, Bhattacharyya A. (2014) iPSC-derived forebrain neurons from FXS individuals show defects in initial neurite outgrowth. Stem Cells and Development. 1;23(15):1777-87.
Weick JP, Held DL, Bonadurer GF 3rd, Doers ME, Liu Y, Maguire C, Clark A, Knackert JA, Molinarolo K, Musser M, Yao L, Yin Y, Lu J, Zhang X, Zhang SC, Bhattacharyya A. (2013) Deficits in human trisomy 21 iPSCs and neurons. Proceedings of the National Academy of Sciences of the United States. 110(24):9962-7.
McMillan EL, Kamps AL, Lake SS, Svendsen CN, Bhattacharyya A. (2012) Gene expression changes in the MAPK pathway in both Fragile X and Down syndrome human neural progenitor cells. American Journal of Stem Cells. 30;1(2):154-162.
Cairney CJ, Sanguinetti G, Ranghini E, Chantry AD, Nostro MC, Bhattacharyya A, Svendsen CN, Keith WN, Bellantuono I. (2009) A systems biology approach to Down syndrome: identification of Notch/Wnt dysregulation in a model of stem cells aging. Biochim Biophys Acta. 1792(4):353-63.
Bhattacharyya A, McMillan E, Chen SI, Wallace K, Svendsen CN. (2009) A critical period in cortical interneuron neurogenesis in down syndrome revealed by human neural progenitor cells. Developmental Neuroscience. 31(6):497-510 .
Bhattacharyya A, McMillan E, Wallace K, Tubon TC Jr, Capowski EE, Svendsen CN. (2008) Normal neurogenesis but abnormal gene expression in human fragile x cortical progenitor cells. Stem Cells and Development. 17(1):107-17.
Kelley, DJ, Bhattacharyya A. Lahvis G, Yin JCP, Malter JS and Davidson RJ. (2008) The cyclic AMP phenotype of fragile X and autism. Neuroscience & Biobehavioral Reviews. 32(8):1533-43.
Kelley DJ, Davidson RJ, Elliott JL, Lahvis GP, Yin JC, Bhattacharyya A. (2007) The cyclic AMP cascade is altered in the fragile X nervous system. PLoS One. 26;2(9):e931.