Thomas A. Jongens, Ph.D.

faculty photo
Associate Professor of Genetics
Department: Genetics
Graduate Group Affiliations

Contact information
Smilow Center for Translational Research, 10th Floor
Genetics Room 10-134
3400 Civic Center Blvd., Bldg. 421
Philadelphia, PA 19104-5158
Office: 215-573-9332
Fax: 215-573-9411
B.A. (Biochem/Cell Biology)
University of California, San Diego, 1981.
Ph.D. (Molecular Biology)
University of California at Berkeley, 1989.
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Description of Research Expertise

Key Words: Autism, Intellectual Disability, Fragile X Syndrome, Drosophila, Genetics, Neuroplasticity, Neurocircuits, Pharmacology

Research Interests: Our lab is interested in defining and correcting the underlying pathophysiological defects that lead to intellectual disability (ID) and autism (ASD). The majority of our research utilizes Drosophila models of genetic diseases that lead to ID/ASD, with mouse and human cellular models being used to validate our findings. Our approach has led to a better understanding of what causes these disorders as well as the identification of treatments that are currently being tested in several ongoing clinical trials.

Research Techniques: Behavioral and memory testing, Genetics, Cell Biology, Biochemistry, Neurocircuit mapping, Pharmacology

Research Summary: Our lab utilizes Drosophila to develop and study models of intellectual disability and autism in humans. We can do this as homologues of human disease genes exist in Drosophila that have conserved sequence and biological activity. Drosophila mutants of these genes enable us to take advantage of the powerful and rapid genetic approaches that can be used with this organism. The powerful genetics in combination with well-developed behavioral and cognitive assays enables us to determine the underlying pathophysiological defects caused by loss of disease gene function and to identify potential genetic and pharmacological treatment routes for these diseases.

We pioneered this approach for Fragile X Syndrome (FXS), the leading genetic cause of autism and intellectual disability. Patients with this disorder suffer from reduced intellectual capacity, high social anxiety, as well as several other behavioral and physical symptoms. FXS is caused by the loss of FMRP protein function. FMRP and the Drosophila homologue of the protein called dFMR1, encode RNA binding proteins that associate with hundreds of mRNAs and in general, reduce the translation of these mRNA targets. By developing a Drosophila model of FXS, based on loss of function mutations of the dfmr1 gene, we have been able to model this disease. These studies have identified several behavioral and cognitive deficits in the Drosophila FXS model. Using a combination of genetics, neuroanatomy, cell biology and biochemistry we have identified several signaling pathway defects in this model that underlie the behavioral and cognitive deficits. These findings helped us identify genetic and pharmacological treatments that restore the behavioral and cognitive phenotypes. Importantly, we have shown that many of the behavioral and cognitive defects can be restored during adulthood indicating that significant plasticity still exists in the adult nervous system. These results have replicated in the mouse FXS model and have lead to ongoing clinical trials.

Selected Publications

Choi, C. H., Schoenfeld, B. P., Weisz, E. D., Bell, A. J., Chambers, D. B., Hinchey, J., Choi, R. J., Hinchey, P., Kollaros, M., Gertner, M. J., Ferrick, N. J., Terlizzi, A. M., Yohn, N., Koenigsberg, E., Liebelt, D. A., Zukin, R. S., Woo, N. H., Tranfaglia, M. R., Louneva, N., Arnold, S. E., Siegel, S. J., Bolduc, F. V., McDonald, T. V., Jongens, T. A., McBride, S. M.: PDE-4 inhibition rescues aberrant synaptic plasticity in Drosophila and mouse models of fragile X syndrome. J Neurosci 35(1): 396-408, 2015.

Gross, C., Chang, C. W., Kelly, S. M., Bhattacharya, A., McBride, S. M., Danielson, S. W., Jiang, M. Q., Chan, C. B., Ye, K., Gibson, J. R., Klann, E., Jongens, T. A., Moberg, K. H., Huber, K. M., Bassell, G. J.: Increased Expression of the PI3K Enhancer PIKE Mediates Deficits in Synaptic Plasticity and Behavior in Fragile X Syndrome. Cell Rep 11(5): 727-36, 2015.

Wolman, M. A., de Groh, E. D., McBride, S. M., Jongens, T. A., Granato, M., Epstein, J. A.: Modulation of cAMP and ras signaling pathways improves distinct behavioral deficits in a zebrafish model of neurofibromatosis type 1. Cell Rep 8(5): 1265-70, 2014.

Schoenfeld, B. P., Choi, R. J., Choi, C. H., Terlizzi, A. M., Hinchey, P., Kollaros, M., Ferrick, N. J., Koenigsberg, E., Ferreiro, D., Leibelt, D. A., Siegel, S. J., Bell, A. J., McDonald, T. V., Jongens, T. A., McBride, S. M.: The Drosophila DmGluRA is required for social interaction and memory. Frontiers in pharmacology 4: 64, 2013.

McBride SM, Sandra L. Holloway and Thomas A. Jongens: The Utility of Drosophila in identifying Pharmacological Therapies for Fragile X Syndrome. Drug Discovery Today: Technology 2013.

Berkowitz, K. M., Sowash, A. R., Koenig, L. R., Urcuyo, D., Khan, F., Yang, F., Wang, P. J., Jongens, T. A., Kaestner, K. H.: Disruption of CHTF18 causes defective meiotic recombination in male mice. PLoS genetics 8(11): e1002996, 2012.

McBride, S. M., Bell, A. J., Jongens, T. A.: Behavior in a Drosophila model of fragile X. Results and problems in cell differentiation 54: 83-117, 2012.

Bhogal, B., Jepson, J. E., Savva, Y. A., Pepper, A. S., Reenan, R. A., Jongens, T. A.: Modulation of dADAR-dependent RNA editing by the Drosophila fragile X mental retardation protein. Nature neuroscience 14(12): 1517-24, 2011.

Beerman, R. W., Jongens, T. A.: A non-canonical start codon in the Drosophila fragile X gene yields two functional isoforms. Neuroscience 181: 48-66, 2011.

Choi, C. H., Schoenfeld, B. P., Bell, A. J., Hinchey, P., Kollaros, M., Gertner, M. J., Woo, N. H., Tranfaglia, M. R., Bear, M. F., Zukin, R. S., McDonald, T. V., Jongens, T. A., McBride, S. M.: Pharmacological reversal of synaptic plasticity deficits in the mouse model of fragile X syndrome by group II mGluR antagonist or lithium treatment. Brain research 1380: 106-19, 2011.

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Last updated: 08/09/2021
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