raetzman@life.illinois.edu
535 Burrill Hall
Office: (217) 244-6233
Lab: (217) 333-7913
Fax: (217) 333-1133
Mail to:
Department of Molecular and Integrative Physiology
524 Burrill Hall, MC-114
407 S. Goodwin Ave
Urbana, IL 61801
Lori T Raetzman
Assistant Professor of Molecular and Integrative Physiology and of Neuroscience
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
Teaching Interests
Notch signaling pathway in 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.
Representative Publications
Himes A.D. and L.T. Raetzman. (2008). Premature differentiation and aberrant movement of pituitary cells lacking both Hes1 and Prop1. Dev. Biol., in press.
Tang H., Brennan J., Karl J., Hamada Y., Raetzman L., and B. Capel. 2008. Notch signaling maintains Leydig progenitor cells in the mouse testis. Development 135: 3745-53.
Geffner M.E., Demay M., Raetzman L., Holm I., Diamanti-Kandarakis E., Savage M.O., Francis G., and A.D. Rogol. 2008. The 88th Annual Meeting of the Endocrine Society, June 24-27, 2006, Boston MA, USA: selected pediatric presentations. Pediatr Endocrinol Rev. 5: 789-95.
Schultz-Norton J.R., Walt K.A., Ziegler Y.S., McLeod I.X., Yates J.R., Raetzman L.T., and A.M. Nardulli. 2007. The DNA Repair Protein Flap Endonuclease-1 (FEN-1) Modulates Estrogen-Responsive Gene Expression. Mol. Endo. 21: 1569-80.
Ward R.D., Davis S.W., Cho M., Esposito C., Lyons R.H., Cheng J.-F., Rubin E.M., Rhodes S.J., Raetzman L.T., Smith T.P.L., and S.A. Camper. 2007. Comparative genomics reveals functional transcriptional control sequences in the Prop1 gene. Mamm. Genome: 18, 521-37.
Raetzman L.T., Cai, J.X., and S.A. Camper. 2007. Hes1 is required for pituitary growth and melanotrope specification. Dev. Biol. 304: 255-66.
Raetzman L.T., Wheeler B.S., Ross S.A., Thomas P.Q., and S.A. Camper. 2006. Persistent Notch2 expression delays gonadotrope differentiation. Mol. Endo. 20: 2898-2908.
Ward R.D., Stone B.M., Raetzman L.T., and S.A. Camper. 2006. Cell Proliferation and Vascularization in mouse models of pituitary hormone deficiency. Mol. Endo. 20(6):1378-90. [Abstract]
Vesper A., Raetzman L.T., and S.A. Camper S.A. 2006. Role of prophet of Pit1 (PROP1) in gonadotrope differentiation and puberty. Endocrinology 147(4):1654-63. [Abstract]
Ward, R.D., Raetzman, L.T., Suh, H., Stone, B., Nasonkin, I.O., and S.A. Camper. 2005. Role of PROP1 in pituitary gland growth. Mol. Endo. 19(3):698-710. [Abstract]
Raetzman, L.T., Ross, S.A., Cook, S., Dunwoodie, S.L., Camper, S.A. and P.Q. Thomas. 2004. Developmental regulation of Notch signaling genes in the embryonic pituitary: Prop1 deficiency affects Notch2 expression. Dev. Biol. 265(2):329-40. [Abstract]
Nasonkin, I.O., Ward, R.D., Raetzman, L.T., Seasholtz, A.F., Saunders, T.L., Gillespie, P., and , S.A. Camper. 2004. Pituitary hypoplasia and respiratory distress syndrome in Prop1 knockout mice. Hum. Mol. Gen. 13(22):2727-35. [Abstract]
Raetzman, L.T., Ward, R.D., and S.A. Camper. 2002. Lhx4 and Prop1 are required for cell survival and expansion of the pituitary primordium. Development 129(18):4229-39. [Abstract]
Cushman, L.C., Watkins-Chow, D.E., Brinkmeier, M. L., Raetzman, L.T., Radak, A.L., Lloyd, R.V., and S.A. Camper. 2001. Persistent Prop1 expression delays gonadotrope differentiation and enhances pituitary tumor susceptibility. Hum. Mol. Gen. 10(11):1141-53. [Abstract]