Phone: (608) 265-6142
RESEARCH INTERESTS - How the development of the cerebral cortex is altered in developmental disorders characterized by mental impairment
B.S., 1986, University of Wisconsin – Madison, Zoology
Ph.D., 1993, University of Cincinnati College of Medicine, Anatomy and Cell Biology
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.
- 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. Aberrant Calcium Signaling in Astrocytes Inhibits Neuronal Excitability in a Human Down Syndrome Stem Cell Model. Cell Rep. 2018 Jul 10;24(2):355-365. doi: 10.1016/j.celrep.2018.06.033.PMID:29996097.
- Huo HQ, Qu ZY, Yuan F, Ma L, Yao L, Xu M, Hu Y, Ji J, Bhattacharyya A, Zhang SC, Liu Y. Modeling Down Syndrome with Patient iPSCs Reveals Cellular and Migration Deficits of GABAergic Neurons. Stem Cell Reports. 2018 Apr 10;10(4):1251-1266. doi: 10.1016/j.stemcr.2018.02.001. Epub 2018 Mar 8. PMID:29526735.
- Li M, Zhao H, Ananiev GE, Musser MT, Ness KH, Maglaque DL, Saha K, Bhattacharyya A, Zhao X. Establishment of Reporter Lines for Detecting Fragile X Mental Retardation (FMR1) Gene Reactivation in Human Neural Cells. Stem Cells. 2017 Jan;35(1):158-169. doi: 10.1002/stem.2463. Epub 2016 Jul 27. PMID:27422057.
- 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.
- Bhattacharyya A, Zhao X. (2015) Human pluripotent stem cell models of Fragile X syndrome. Molecular and Cellular Neurosciences. 73:43-51. PubMed PMID: 26640241; PubMed Central PMCID: PMC4867245.
- 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.