Contact Information
Research Interests
Cell-cell signaling during hypothalamic neuron development and pituitary development
Impact of endocrine disrupting chemicals during gestation on hypothalamic-pituitary development
Research Description
The hypothalamus is a critical center for homeostasis in the body and is essential for feeding, growth and reproduction, among other things. The neuroendocrine hypothalamus arises from progenitors lining the third ventricle of the brain. Obesity, infertility and dwarfism can be linked to aberrant development of these neurons. Despite the importance of this brain region to normal physiology, little is known about the factors that are necessary to get the wide variety of peptide producing neurons.
We have a focus on the Notch signaling pathway, which we hypothesize plays an important role in the proliferation and lineage specific differentiation of hypothalamic progenitor cells. We are exploring if Notch signaling is necessary and sufficient for obtaining the full complement of cells in the Arcuate Nucleus of the hypothalamus by employing transgenic and knockout mice. These studies also take advantage of molecular genetic techniques and whole animal physiology. We have an exciting collaboration with the Underhill lab that involves isolating hypothalamic stem cells and culturing them on engineered arrays so that we can test a wide variety of tethered and secreted stimuli that may influence neuron development. We are also interested in how maternal environment, including obesity or exposure to endocrine disrupting chemicals can impact hypothalamic progenitors.
The overall goal of these studies is to define the normal complement of signals that stem cells use to make fate choices in the hypothalamus. This information will be useful in finding causes for congenital neuroendocrine disorders. It also may be possible to someday engineer new neurons to replace those that don’t develop correctly or those that are damaged by brain injury
Education
B.A. Ripon College
Ph.D. Case Western Reserve University
Awards and Honors
Faculty Recognition Award, Neuroscience Student Organization
Outstanding Advisor Award, Medical Scholars Program
Additional Campus Affiliations
Molecular and Integrative Physiology
Affiliate, Neuroscience Program
Affiliate, Institute for Genomic Biology
External Links
Recent Publications
Ge, X., Weis, K. E., & Raetzman, L. (2024). Glycoprotein hormone subunit alpha 2 (GPHA2): A pituitary stem cell-expressed gene associated with NOTCH2 signaling. Molecular and Cellular Endocrinology, 586, Article 112163. https://doi.org/10.1016/j.mce.2024.112163
Santacruz-Márquez, R., Safar, A. M., Laws, M. J., Meling, D. D., Liu, Z., Kumar, T. R., Nowak, R. A., Raetzman, L. T., & Flaws, J. A. (2024). The effects of short-term and long-term phthalate exposures on ovarian follicle growth dynamics and hormone levels in female mice. Biology of reproduction, 110(1), 198-210. Article ioad137. https://doi.org/10.1093/biolre/ioad137
Cutia, C. A., Leverton, L. K., Weis, K. E., Raetzman, L. T., & Christian-Hinman, C. A. (2023). Female-specific pituitary gonadotrope dysregulation in mice with chronic focal epilepsy. Experimental Neurology, 364, Article 114389. https://doi.org/10.1016/j.expneurol.2023.114389
De La Torre, K. M., Lee, Y., Safar, A., Laws, M. J., Meling, D. D., Thompson, L. M., Streifer, M., Weis, K. E., Raetzman, L. T., Gore, A. C., & Flaws, J. A. (2023). Prenatal and postnatal exposure to polychlorinated biphenyls alter follicle numbers, gene expression, and a proliferation marker in the rat ovary. Reproductive Toxicology, 120, Article 108427. https://doi.org/10.1016/j.reprotox.2023.108427
Gonigam, R. L., Weis, K. E., Ge, X., Yao, B., Zhang, Q., & Raetzman, L. T. (2023). Characterization of Somatotrope Cell Expansion in Response to GHRH in the Neonatal Mouse Pituitary. Endocrinology, 164(10). https://doi.org/10.1210/endocr/bqad131