Indiana University Purdue University Indianapolis

Simon J Rhodes Ph.D.

Dean, Dean's Office
Professor, Biology
Adjunct Professor of Cellular and Integrative Physiology, IUSM
Adjunct Professor of Biochemistry and Molecular Biology, IUSM

Education

B.Sc. (Hons) Biochemistry, University of Sheffield, U.K.

Ph.D. Biochemistry/Biological Sciences, Purdue University, West Lafayette, Indiana

Postdoctoral Fellowship, Molecular Medicine, University of California, San Diego

Professional Affiliations

  • Endocrine Society USA
  • AAAS
  • American Physiological Society

Editorial

  • Journal of Molecular Endocrinology
  • Frontiers in Neuroendocrine Science

Current Research

Our research program investigates the pathways that control pituitary gland organogenesis. Through collaborations with pediatric endocrinologists, we have translated this work to the clinic, defining new forms of combined pediatric hormone deficiency diseases and developing new diagnostic and genetic counseling tools. The anterior pituitary gland secretes polypeptide hormones that are essential for human development and physiology parameters including growth, reproduction, the stress response, metabolic homeostasis, and lactation. Diseases involving pituitary dysfunction therefore can involve severe syndromes affecting many tissues and systems. During embryogenesis, the actions of transcription factors, such as the LHX3 and LHX4 homeodomain proteins, govern the establishment of the hormone-secreting pituitary cell types. Through established collaborations with clinical partners, our laboratory has demonstrated that mutations in the LHX3 and LHX4 genes cause severe pediatric combined pituitary hormone deficiency diseases and other symptoms such as nervous system defects. For example, through biochemical structure/function analyses and characterization of patient phenotypes, we have determined that mutations affecting distinct parts of the LHX3 protein are correlated with specific disease outcomes: mutations only compromising the carboxyl terminus are associated with a more restricted disease involving pituitary hormone deficiency but not nervous system problems. We have generated a novel knock-in mouse model of a unique form of pediatric hormone deficiency disease that we recently described. The resulting mice display marked dwarfism, thyroid disease, female infertility, and reduced male fertility.

Our work is funded by the NICHD/NIH.

Select Publications

  1. Gilbert, B.L., Banks, J., Houser, J.W.H., Rhodes, S.J., and Lees, N.D. (2014). Persistence, degree completion, and student development in an experiential learning program. Journal of College Student Development, 55:7, p707-713.
  2. Malik, R.E. and Rhodes, S.J. (2014). The role of DNA methylation in regulation of the murine Lhx3 gene. Gene. 2013 Oct 31. doi:pii: S0378-1119(13)01454-6. 10.1016/j.gene.2013.10.045.
  3. Park, S., Mullen, R.D., and Rhodes, S.J. (2013). Cell-specific actions of a human LHX3 gene enhancer during pituitary and spinal cord development. . Mol Endocrinol. 2013 Dec;27(12):2013-27. doi: 10.1210/me.2013-1161. Epub 2013 Oct 7.

  4. Gahete, M.D., Duran-Prado, M., Delgado-Niebla, E., Garrido, J.J., Rhodes, S.J., García-Navarro, S., Gracia-Navarro, F., Malagon, M.M., Luque, R.M., and Castaño, J.P. (2013). Porcine sst1 can physically interact with other somatostatin receptors and its expression is regulated by metabolic/inflammatory sensors. Am. J. Physiol. Endocrinol. Metab. 2013 Dec 24. [Epub ahead of print].
  5. Park, S., Mullen, R.D., and Rhodes, S.J. (2013). Cell-specific actions of a human LHX3 gene enhancer during pituitary and spinal cord development. . Mol Endocrinol. 2013 Dec;27(12):2013-27. doi: 10.1210/me.2013-1161. Epub 2013 Oct 7.
  6. Hunter, C.S., Malik, R.E., Witzmann, F., and Rhodes, S.J. (2013). LHX3 interacts with inhibitor of histone acetyltransferase complex subunits LANP and TAF-1β to modulate pituitary gene regulation. PLoS One. 2013 Jul 4;8(7):e68898. doi:10.1371/journal.pone.0068898. Print 2013.

  7. Prince, K.L., Colvin, S.C., Park, S., Lai, X., Witzmann, F.A., and Rhodes, S.J. (2013). Developmental analysis and influence of genetic background on the Lhx3 W227ter mouse model of combined pituitary hormone deficiency disease. Endocrinology. 2013. Feb;154(2):738-48. doi: 10.1210/en.2012-1790. Epub 2013 Jan 3.

  8. Rhodes, S.J., Camper, S.A., and Roberson, M.S. (2012). Promotion and tenure are not your goals. Endocrine News, April 2012

  9. Dong Y, Zhang L, Zhang S, Bai Y, Chen H, Sun X, Yong W, Li W, Colvin SC, Rhodes SJ, Shou W, Zhang ZY. Phosphatase of regenerating liver 2 (PRL2) is essential for placenta development by downregulating PTEN (phosphatase and tensin homologue deleted on chromosome 10) and activating Akt. J Biol Chem. 2012 Jul 12. [Epub ahead of print] PubMed PMID: 22791713.
  10. Yusuf D, Butland SL, Swanson MI, Bolotin E, Ticoll A, Cheung WA, Zhang XY, Dickman CT, Fulton DL, Lim JS, Schnabl JM, Ramos OH, Vasseur-Cognet M, de Leeuw CN, Simpson EM, Ryffel GU, Lam EW, Kist R, Wilson MS, Marco-Ferreres R, Brosens JJ, Beccari LL, Bovolenta P, Benayoun BA, Monteiro LJ, Schwenen HD, Grontved L, Wederell E, Mandrup S, Veitia RA, Chakravarthy H, Hoodless PA, Mancarelli MM, Torbett BE, Banham AH, Reddy SP, Cullum RL, Liedtke M, Tschan MP, Vaz M, Rizzino A, Zannini M, Frietze S, Farnham PJ, Eijkelenboom A, Brown PJ, Laperrière D, Leprince D, de Cristofaro T, Prince KL, Putker M, del Peso L, Camenisch G, Wenger RH, Mikula M, Rozendaal M, Mader S, Ostrowski J, Rhodes SJ, Van Rechem C, Boulay G, Olechnowicz SW, Breslin MB, Lan MS, Nanan KK, Wegner M, Hou J, Mullen RD, Colvin SC, Noy PJ, Webb CF, Witek ME, Ferrell S, Daniel JM, Park J, Waldman SA, Peet DJ, Taggart M, Jayaraman PS, Karrich JJ, Blom B, Vesuna F, O'Geen H, Sun Y, Gronostajski RM, Woodcroft MW, Hough MR, Chen E, Europe-Finner GN, Karolczak-Bayatti M, Bailey J, Hankinson O, Raman V, LeBrun DP, Biswal S, Harvey CJ, DeBruyne JP, Hogenesch JB, Hevner RF, Héligon C, Luo XM, Blank MC, Millen KJ, Sharlin DS, Forrest D, Dahlman-Wright K, Zhao C, Mishima Y, Sinha S, Chakrabarti R, Portales-Casamar E, Sladek FM, Bradley PH, Wasserman WW. The transcription factor encyclopedia. Genome Biol. 2012;13(3):R24. PubMed PMID: 22458515.
  11. Bechtold-Dalla Pozza S, Hiedl S, Roeb J, Lohse P, Malik RE, Park S, Durán-Prado M, Rhodes SJ. A recessive mutation resulting in a disabling amino acid substitution (T194R) in the LHX3 homeodomain causes combined pituitary hormone deficiency. Horm Res Paediatr. 2012;77(1):41-51. Epub 2012 Jan 26. PubMed PMID: 22286346; PubMed Central PMCID: PMC3355643.
  12. Mullen RD, Park S, Rhodes SJ. A distal modular enhancer complex acts to control pituitary- and nervous system-specific expression of the LHX3 regulatory gene. Mol Endocrinol. 2012 Feb;26(2):308-19. Epub 2011 Dec 22. PubMed PMID: 22194342; PubMed Central PMCID: PMC3275162.
  13. Prince KL, Walvoord EC, Rhodes, S,J. (2011) The role of homeodomain transcription factors in heritable pituitary disease. Nature Rev Endocrinol. Jul 26. doi: 10.1038/nrendo.2011.119. [Epub ahead of print].
  14. Colvin, S.C., Malik R.E., Aaron D. Showalter, A.D., Sloop, K.W., and Rhodes, S.J. (2011). A model of pediatric pituitary hormone deficiency separates the endocrine and neural functions of the LHX3 transcription factor in vivo. PNAS, 2011 Jan 4;108(1):173-8. Epub 2010 Dec 13. PMC3017168.
  15. Gibau-Sanchez, G., Foertsch, F., Queener, S.F., Blum, J.S., Brutkiewicz, R.R., Roman, A., Wilkes, D.S., Sturek, M.S., Rhodes, S.J., and Broxmeyer, H.E. (2010). Diversifying Biomedical Training: A Synergistic Intervention. Journal of Women and Minorities in Science and Engineering. 16(3):215-235.
  16. Gilbert, B.L., Lees, N.D., and Rhodes, S.J. (2009). The Life-Health Sciences Internships Program: Research and Professional Experience Internships as an Undergraduate Retention Tool. In R. Hayes (Ed.), Proceedings of the 5th National Symposium on Student Retention, 2009, Buffalo. (pp. 404-410). Norman, OK, The University of Oklahoma.
  17. Sehgal, R., Sheibani, N., Rhodes, S.J., and Belecky Adams, T.L. (2009). BMP7 and SHH regulate Pax2 in mouse retinal astrocytes by relieving TLX repression. Dev Biol. 332(2):429-443. PMC2917894.
  18. Colvin., S.C., Mullen, R.D., Pfäffle, R.W., and Rhodes, S.J. (2009). LHX3 and LHX4 transcription factors in pituitary development and disease. Pediatric Endocrinology Reviews, Suppl 2:283-90.PMC Journal – In Process.
  19. Prince, K.E., Mullen, R.D., Colvin, S.C., and Rhodes, S.J. (2009). The LHX3 LIM-homeodomain factor. Transcription Factor Encyclopedia.
  20. Pfäffle, R., Savage, J., Hunter, C., Palme, C., Ahlmann, M., Kumar, P., Bellone, J., Schönau, E., Korsch, E., Brämswig, J., Stobbe, H., Blum, W., and Rhodes, S.J. (2007). Four novel mutations of the LHX3 gene cause combined pituitary hormone deficiencies with or without limited neck rotation. J. Clin. Endo. Metab., 92: 1909-1919.
  21. Pfäffle, R.W., Hunter, C.H., Savage, J.J., Duran-Prado, M., Mullen, R.D., Neeb., Z.P., Stobbe, H.M., Eiholzer, E., Haddad, N., Hesse, V., Blum, W.F., Weigel, J., and Rhodes, S.J. (2008). Three novel classes of missense mutations within the LHX4 gene cause autosomal dominantly inherited forms of hypopituitarism with variable hormonal deficiencies. J. Clin. Endocrinol. Metab., 93(3):1062-1071. PMCID2266965.
  22. Kelberman, D., Turton, J., Woods, K.S., Mehta, A., Al-Kawari, M., Greening, J., Swift, P., Otonkoski, T., Bitner-Glindicz, M., Rhodes, S.J., and Dattani, MT. (2009). Molecular analysis of novel PROP1 mutations associated with combined pituitary hormone deficiency. Clinical Endocrinology, 70(1):96-103. PMC Journal – In Process.
  23. Mullen, R.D., Colvin, S.C., Hunter, C.H., Savage, J.J., Walvoord, E.C., Bhangoo, A.P.S., Ten, T., Weigel, J., Pfäffle, R.W., and Rhodes, S.J. (2007). Roles of the LHX3 and LHX4 LIM-homeodomain factors in pituitary development. Mol. Cell. Endocrinol., 265-266: 190-195.
  24. Savage, J.J., Mullen, R.D., Sloop, K.W., Colvin, S.C., Camper, S.A., Franklin, C.L., and Rhodes, S.J. (2007). Transgenic mice expressing LHX3 transcription factor isoforms in the pituitary: effects on the gonadotrope axis and sex-specific reproductive disease. J. Cell. Physiol., 212: 105-117.
  25. Ward, R.M., Cho, M.-C., Esposito, C., Lyons, R.H., Cheng, J.-F., Rubin, E.M., Rhodes, S.J, Raetzman, L.T., Smith, T.P.L., and Camper, S.A. (2007). Comparative genomics reveal functional transcriptional control sequences in the Prop1 gene. Mamm. Genome 18(6-7):521-37. Epub 2007 Jun 8. PMCID1998882.
  26. Savage, J.J., Hunter, C.S., Jacob, T., Clark-Sturm, S.L., Pfäffle, R., and Rhodes, S.J. (2007). Mutations in the LHX3 gene cause dysregulation of pituitary and neural target genes that reflect patient phenotypes. Gene 400(1-2):44-51. Epub 2007 Jun 7. PMCID2045125.
  27. Walvoord, E., Vannerson, J., and Rhodes, S.J. (2010). Precocious Pubic Hair Development: A Team Based Learning Review of the Hypothalamic-Pituitary-Adrenal Axis and Puberty. MedEdPORTAL. http://services.aamc.org/30/mededportal/servlet/s/segment/mededportal/?subid=7953.