Faculty
Thomas A. Jongens, Ph.D.

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
Genetics Room 10-134
3400 Civic Center Blvd., Bldg. 421
Philadelphia, PA 19104-5158
Office: 215-573-9332
Fax: 215-573-9411
Fax: 215-573-9411
Email:
JONGENS@MAIL.MED.UPENN.EDU
JONGENS@MAIL.MED.UPENN.EDU
Publications
Education:
B.A. (Biochem/Cell Biology)
University of California, San Diego, 1981.
Ph.D. (Molecular Biology)
University of California at Berkeley, 1989.
Permanent linkB.A. (Biochem/Cell Biology)
University of California, San Diego, 1981.
Ph.D. (Molecular Biology)
University of California at Berkeley, 1989.
Description of Research Expertise
Key Words: Autism, Intellectual Disability, Fragile X Syndrome, Drosophila, Genetics, Neuroplasticity, Neurocircuits, PharmacologyResearch 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
Fenton AR, Peng R, Bond C, Hugelier S, Lakadamyali M, Chang YW, Holzbaur ELF, Jongens TA.: FMRP regulates MFF translation to locally direct mitochondrial fission in neurons. Nat Cell Biol 261(12): 2061-2074, Dec 2024.Valencia ML, Sofela FA, Jongens TA, Sehgal A.: Do metabolic deficits contribute to sleep disruption in monogenic intellectual disability syndromes? Trends Neurosci 47(8): 583-592, Aug 2024.
Weisz ED, Fenton AR, Jongens TA.: PGC-1α integrates insulin signaling with mitochondrial physiology and behavior in a Drosophila model of Fragile X Syndrome. NPJ Metab Health Dis 2: 2, 2024.
Levy KA, Weisz ED, Jongens TA.: Loss of neurexin-1 in Drosophila melanogaster results in altered energy metabolism and increased seizure susceptibility. Hum Mol Genet 31(20): 3422-3438, Oct 2022.
Fenton AR, Jongens TA, Holzbaur ELF.: Mitochondrial adaptor TRAK2 activates and functionally links opposing kinesin and dynein motors. Nat Commun 12: 4578, Jul 2021.
Fenton AR, Jongens TA, Holzbaur ELF.: Mitochondrial dynamics: Shaping and remodeling an organelle network. Curr Opin Cell Biol 2021.
Angelakos CC, Tudor JC, Ferri SL, Jongens TA, Abel T.: Home-cage hypoactivity in mouse genetic models of autism spectrum disorder. Neurobiol Learn Mem 165: 107000, Nov 2019.
Weisz ED, Towheed A, Monyak RE, Toth MS, Wallace DC, Jongens TA.: Loss of Drosophila FMRP leads to alterations in energy metabolism and mitochondrial function. Hum Mol Genet 27: 95-106, Jan 2018.
Choi CH, Schoenfeld BP, Bell AJ, Hinchey J, Rosenfelt C, Gertner MJ, Campbell SR, Emerson D, Hinchey P, Kollaros M, Ferrick NJ, Chambers DB, Langer S, Sust S, Malik A, Terlizzi AM, Liebelt DA, Ferreiro D, Sharma A, Koenigsberg E, Choi RJ, Louneva N, Arnold SE, Featherstone RE, Siegel SJ, Zukin RS, McDonald TV, Bolduc FV, Jongens TA, McBride SM.: Multiple Drug Treatments That Increase cAMP Signaling Restore Long-Term Memory and Aberrant Signaling in Fragile X Syndrome Models. Front Behav Neurosci 10: 136, Jun 2016.
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.
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