Address: 2310 PBDB
Phone: (319) 467-4941
Email: valentina-botero@uiowa.edu
Mentor: Seth Tomchik, PhD
PhD Institution: The Scripps Research Institute
Research Description
Neuronal mechanisms of neurofibromin-mediated modulation of metabolic homeostasis
Neurofibromatosis type 1 is a common neurodevelopmental disorder caused by mutations in the NF1 gene, which encodes for the protein neurofibromin (Nf1). Neurofibromatosis type 1 patients are predisposed to developing multiple complications such as peripheral nerve-associated neurofibromas, malignant tumors, and neurocognitive deficits. These complications significantly affect patients’ quality of life and contribute to the overall decreased life expectancy of those with the disease. In addition, emerging studies suggest that mutations in NF1 may alter metabolism; as patients exhibit multisystemic symptoms and abnormalities (e.g., short stature, pituitary growth hormone deficiencies, and reduced body mass indexes). However, the mechanism by which Nf1 modulates metabolism is unknown. Our research suggests that Nf1 regulates metabolism via discrete neuronal circuits. Leveraging the well-established Drosophila model of neurofibromatosis type 1, its highly conserved signaling pathways, and the organism’s experimental and genetic power, we are studying the novel interactions between Nf1, neuronal circuit activity, and metabolism. Our research aims to identify the key signaling pathway activated by Nf1 to regulate metabolism within neurons and test the effects of Nf1 on neuronal and circuit physiology, leading to metabolic dysregulation.
Awards
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Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship (F31) National Institute Of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) (2022-2024)
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Neuroscience Scholars Program (NSP) Associate, Society for Neuroscience (SfN) (2020-2022)
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Diversity Supplement, National Institutes of Health (2018-2022)
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Lynk UAF Funding for Research, Mount Holyoke College (2016)
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Harap Scholarship Fund for Independent Research, Mount Holyoke College (2016 & 2017)
Publications
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Aaron Stahl, Nathaniel C. Noyes, Tamara Boto, Valentina Botero, Miao Jing, Jianzhi Zeng, Lanikea B. King, Yulong Li, Ronald L. Davis, Seth M. Tomchik. Associative learning drives longitudinally-graded presynaptic plasticity of neurotransmitter release along axonal compartments. eLife. 11:e76712, 2022. PMCID: PMC8956293
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Amy E. Clipperton-Allen, Hannah Swick, Valentina Botero, Massimiliano Aceti, Jacob Ellegood, Jason P. Lerch, Damon T. Page. Pten haploinsufficiency causes desynchronized growth of brain areas involved in sensorimotor processing. iScience. 25(2):103796, 2022. PMCID: PMC8844819
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Valentina Botero, Bethany A. Stanhope, Elizabeth B. Brown, Eliza C. Grenci, Tamara Boto, Scarlet J. Park, Lanikea B. King, Keith R. Murphy, Kenneth J. Colodner, James A. Walker, Alex C. Keene, William W. Ja, Seth M. Tomchik. Neurofibromin regulates metabolic rate via neuronal mechanisms in Drosophila. Nature Communications. 12(1):4285, 2021. PMCID: PMC8277851
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Lanikea King, Tamara Boto, Valentina Botero, Ari M. Aviles, Breanna M. Jomsky, Chevara Joseph, James A. Walker, Seth M. Tomchik. Developmental loss of neurofibromin across distributed neuronal circuits drives excessive grooming in Drosophila. PLOS Genetics. 16(7):e1008920, 2020. PMCID: PMC7398555
Abstracts
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Neurofibromin regulates metabolic rate via neuronal mechanisms. Valentina Botero, Bethany A. Stanhope, Elizabeth B. Brown, Eliza C. Grenci, Tamara Boto, Scarlet J. Park, Lanikea B. King, Keith R. Murphy, Kenneth J. Colodner, James A. Walker, Alex C. Keene, William W. Ja, Seth M. Tomchik. Genetics Society of America Annual Drosophila Research Conference, Virtual Meeting, 2021 (Poster Presentation).
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Neurofibromin regulates metabolic rate via neuronal mechanisms. Valentina Botero, Bethany A. Stahl, Eliza C. Grenci, Tamara Boto, Scarlet J. Park, Lanikea B. King, Keith R. Murphy, Kenneth J. Colodner, James A. Walker, Alex C. Keene, William W. Ja, Seth M. Tomchik. Scripps Research Graduate Student Symposium, La Jolla, CA, 2019 (Poster Presentation).
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Neurofibromin regulates metabolic rate via neuronal mechanisms. Valentina Botero, Bethany A. Stahl, Eliza C. Grenci, Tamara Boto, Scarlet J. Park, Lanikea B. King, Keith R. Murphy, Kenneth J. Colodner, James A. Walker, Alex C. Keene, William W. Ja, Seth M. Tomchik. Cold Spring Harbor Neurobiology of Drosophila, Cold Spring Harbor, NY, 2019 Poster Presentation).
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Loss of Neurofibromin function leads to increased metabolic expenditure in Drosophila. Valentina Botero, Keith R. Murphy, Kenneth J. Colodner, William W. Ja, Seth M. Tomchik. The South Florida Drosophila Research Consortium, Flies on the Beach Meeting. Miami, FL, 2018 (Poster Presentation).
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Loss of Neurofibromin function leads to increased metabolic expenditure in Drosophila. Valentina Botero, Keith R. Murphy, Kenneth J. Colodner, William W. Ja, Seth M. Tomchik. Western Massachusetts Chapter Meeting, Society for Neuroscience. Amherst, MA, 2017 (Poster Presentation).
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Loss of Neurofibromin function leads to increased metabolic expenditure in Drosophila. Valentina Botero, Keith R. Murphy, Kenneth J. Colodner, William W. Ja, Seth M. Tomchik. Northeast Undergraduate Research on Neuroscience (NEURON) Conference. North Haven, CT, 2017 (Poster Presentation).