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Ben Kelvington

Address: 2400 PBDBBen Kelvington new photo
Phone: (319) 353-4535
Email: benjamin-kelvington@uiowa.edu

Mentor: Ted Abel, PhD

Undergraduate Institution: Augustana University (SD)

Graduate Program: Pharmacology

Year Entered Into Program 2020

Research Descripton

Molecular mechanisms underlying striatal-dependent behavior changes in the 16p11.2 hemideletion mouse model of neurodevelopmental disorder

Neurodevelopmental disorders, including Autism Spectrum Disorder (ASD), create enduring challenges for those affected and their support system. Deficiencies in support for those with ASD, which is estimated to affect 1 in 54 children and is highly sex-biased, are owed in part to insufficient knowledge of the underlying neurobiological mechanisms of this diverse condition. 16p11.2 hemideletion syndrome is a genetic copy number variant with a high penetrance of neurodevelopmental disorders that is estimated to account for 0.6% of all ASD diagnoses. This deletion can be faithfully modeled in mice, who share a fully syntenic genetic locus. Our lab has shown that these mice are hyperactive and show a male-specific deficit in reward learning, which are both behaviors that depend on the function of the striatum. The striatum is a brain region that plays a critical role in movement regulation and the reward system. Furthermore, RNA sequencing of 16p11.2 mouse model brain tissue shows a robust dysregulation of gene expression specifically in the striatum of these mice compared to wild-type controls. Interestingly, genes that encode components of the complement system, important contributors to the innate immune system, are included in this striatal-specific dysregulation. The complement system plays an increasingly appreciated role in neurodevelopmental processes such as synaptic pruning as well as regulating the proliferation and migration of neural progenitors. Notably, our lab has shown that an antagonist of the complement receptor C3aR1 can partially rescue the hyperactive phenotype of 16p11.2 hemideletion mice. My work as a graduate student will investigate the molecular mechanisms by which changes in gene expression, including genes in the complement system, alter neurodevelopment and result in striatal-dependent behavior deficits in the 16p11.2 mouse model. My work will also focus on elucidating the sex dependence of these mechanisms.

Awards

  • Fellowship appointment on the Pharmacological Sciences Training Program (NIH T32 GM067795), University of Iowa, 2021-present

  • Dean’s Award for Biomedical Graduate Studies, University of Iowa, 2020

  • NCAA Postgraduate Scholarship, 2020

Publications

  • In Submission: Kelvington, B. A., Nickl-Jockschat, T., Abel, T. Neurobiological insights into twice exceptionality: Circuits, cells, and molecules. Preprints 2021, 2021110224 (doi: 10.20944/preprints202111.0224.v1).

Abstracts

  1. Kelvington, B., Cheek, T., Pohlmann, M., Gubbels, J., Larson, M. Mechanistic Connection between Ovarian Cancer and Platelets. SD BRIN/SD EPSCoR Undergraduate Research Symposium, Pierre, South Dakota, 2018 (Poster Presentation).

  2. Kelvington, B., Cheek, T., Pohlmann, M., Gubbels, J., Larson, M. Mechanistic Connection between Ovarian Cancer and Platelets. Arthur Olsen Student Research Symposium, Augustana University, Sioux Falls, South Dakota, 2019 (Poster Presentation).

  3. Kelvington, B., Coungeris, N., Sheets, J., Francis, K. Morphometric profiling of human iPSC-derived neurons using high-content imaging analyses. Sanford Summer Research Symposium, Sanford Research, Sioux Falls, South Dakota, 2019 (Poster Presentation).

  4. Kelvington, B., Coungeris, N., Sheets, J., Francis, K. Morphometric profiling of human iPSC-derived neurons using high-content imaging analyses. Annual Neurobehavioral Research Symposium, Center for Brain and Behavior Research, University of South Dakota, Vermillion, South Dakota, 2019 (Poster Presentation).

  5. Kelvington, B. Defining Genes in the 16p11.2 Region Critical for Striatal Complement Dysregulation. Neuroscience & Pharmacology Rotating Graduate Student Workshop, University of Iowa, Iowa City, Iowa, 2021 (Oral Presentation).

  6. Kelvington, B., Kim, J., Vanrobaeys, Y., Abel, T. Investigating a role for reward-dependent histone post-translational modifications in a mouse model for neurodevelopmental disorder. Biomedical Science Graduate Program Admissions Poster Session, University of Iowa, Iowa City, Iowa, 2022 (Poster Presentation).

  7. Kelvington, B. Investigating striatal cell-type contributions in a mouse model for neurodevelopmental disorder. Biomedical Science Program Graduate Student Recruitment, University of Iowa, Iowa City, Iowa, 2022 (Oral Presentation).

  8. Kelvington, B. Investigating a role for striatal histone methylation in a mouse model for neurodevelopmental disorder. Neuroscience & Pharmacology Graduate Student Workshop, University of Iowa, Iowa City, Iowa, 2022 (Oral Presentation).

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