Contact Information
Research Interests
Research Topics
Development, Endocrinology, Neurobiology
Disease Research Interests
Neurological and Behavioral Disorders, Reproductive Diseases, Infertility, and Menopause
Research Description
Notch signaling pathway in hypothalamic-pituitary gland development and disease
The pituitary is the master gland coordinating growth, fertility, metabolism and the body's response to stress. To exert these effects, the anterior pituitary has distinct cell types that produce thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), and prolactin (PRL). If the development or function of these cells in the pituitary gland is disrupted, two main diseases result. Hypopituitarism, defined as loss of at least one pituitary hormone, occurs in 1:4000 births. Only a small number of cases are caused by known genetic mutations. The other main category of pituitary disease, tumor formation, is very common, with an incidental prevalence of 30% at autopsy. The genetic causes of pituitary tumors are largely unknown and could result from the loss or gain of function of a normal developmental process.
Research in my laboratory is focused on understanding the role of cell-cell signaling during pituitary development. We hypothesize that the Notch signaling pathway may play an important role in the proliferation and lineage specific differentiation of progenitor cells in the embryonic pituitary. The Notch signaling pathway is an evolutionarily conserved mechanism that orchestrates cell fate choices in a broad spectrum of developmental systems. The core pathway includes two transmembrane ligands, (Delta and Jagged), a transmembrane receptor (Notch), a coactivator (CSL/Rbpsuh) and a downstream transcription factor (Hes). Many components of the Notch pathway are present in the developing pituitary, but their function in this system is unknown.
We are interested in uncovering the role of Notch signaling in the normal development of the pituitary and in pituitary disease. We are exploring if Notch signaling is necessary and sufficient for obtaining the full complement of cells in the pituitary by employing transgenic and knockout mice. These studies also take advantage of molecular genetic techniques and whole animal physiology.
Education
B.A. 1994 Ripon College, Ripon, WI
PhD. 2000 Case Western Reserve University, Cleveland, OH
Postdoc. 2000-2005 University of Michigan, Ann Arbor, MI
Awards and Honors
2010 James Heath Award for Excellence in Teaching MIP, UIUC
2015 Outstanding Advisor Award, Medical Scholars Program, UIUC
2017 Arnold O Beckman Award, University of Illinois Research Board
2018 NSO Faculty Recognition Award, Neuroscience Program, UIUC
2019 Teaching Excellence Award, UIUC School of Molecular and Cellular Biology
2019 Service Excellence Award, UIUC School of Molecular and Cellular Biology
2024 Promotion award: LAS Dean’s Distinguished Professorial Scholar, UIUC
2025 Sidney Ingbar Distinguished Service Award, Endocrine Society
Additional Campus Affiliations
External Links
Highlighted Publications
Ge X, Weis KE, Raetzman LT. (2024). Glycoprotein hormone subunit alpha 2 (GPHA2): A pituitary stem cell-expressed gene associated with NOTCH2 signaling. Mol Cell Endocrinol., May 15;586:112163. [Abstract]
Weis KE, Thompson LM, Streifer M., Guardado I, Flaws JA, Gore AC, Raetzman LT. (2023). Pre- and postnatal exposure to the polychlorinated biphenyl mixture Aroclor 1221 alters female rat pituitary gonadotropins and estrogen receptor alpha levels. Reprod Toxicol., Jun;118.108388. [Abstract]
Gonigam RL, Weis KE, Ge X, Yao B, Zhang Q, Raetzman LT. (2023). Characterization of somatotrope cell expansion in response to GHRH in the neonatal mouse pituitary. Endocrinology, Aug 28;164(10). [Abstract]
Gonzalez RVL, Weis KE, Gonsioroski AV, Flaws JA, Raetzman LT. (2021). Iodoacetic acid, as water disinfection byproduct, disrupts hypothalamic and pituitary reproductive regulatory factors and induces toxicity in the female pituitary. Toxicol Sci., Oct 27;184(1):46-56. [Abstract]
Biehl MJ and Raetzman LT. (2015). Rbpj-κ mediated Notch signaling plays a critical role in development of hypothalamic Kisspeptin neurons Dev. Biol. 406:235-46. [Abstract]
Nantie LB, Himes AD, Getz DR, Raetzman LT. (2014). Notch signaling in postnatal pituitary expansion: proliferation, progenitors, and cell specification. Mol. Endocrinol.28(5):731-44. [Abstract]
Aujla PK, Naratadam GT, Xu L, Raetzman LT. (2013). Notch/Rbpjκ signaling regulates progenitor maintenance and differentiation of hypothalamic arcuate neurons. Development 140(17):3511-21. [Abstract]
Brannick KE, Craig ZR, Himes AD, Peretz JR, Wang W, Flaws JA, Raetzman LT. (2012). Prenatal exposure to low doses of bisphenol A increases pituitary proliferation and gonadotroph number in female mice offspring at birth. Biol. Reprod. 87(4):82. [Abstract]
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
Ge, X., Weis, K., & Raetzman, L. (2024). Impact of developmental exposures to endocrine-disrupting chemicals on pituitary gland reproductive function. Reproduction (Cambridge, England), 168(6). https://doi.org/10.1530/REP-24-0072
Graham, G. J., Ibanez, E. M., Mitchell, L. J., Weis, K. E., Raetzman, L. T., Cortesi, F., & Rhodes, J. S. (2024). Generation of the First Transgenic Line of the Iconic Coral Reef Fish Amphiprion ocellaris. Marine Biotechnology, 26(5), 1067-1078. https://doi.org/10.1007/s10126-024-10357-1
Martinez-Mayer, J., Brinkmeier, M. L., O’Connell, S. P., Ukagwu, A., Marti, M. A., Miras, M., Forclaz, M. V., Benzrihen, M. G., Cheung, L. Y. M., Camper, S. A., Ellsworth, B. S., Raetzman, L. T., Pérez-Millán, M. I., & Davis, S. W. (2024). Knockout mice with pituitary malformations help identify human cases of hypopituitarism. Genome medicine, 16(1), Article 75. https://doi.org/10.1186/s13073-024-01347-y
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), 196-208. Article ioad137. https://doi.org/10.1093/biolre/ioad137
