University of California, Riverside

Division of Biomedical Sciences



Biomedical Sciences Faculty


Ameae Walker

Professor of Biomedical Sciences

Ameae M. Walker

University of California, Riverside
Riverside, CA 92521

Tel: (951) 827-5942
Fax: (951) 827-5504
E-mail: ameae.walker@ucr.edu
Office: 1255 Webber Hall

Education and Training

  • B.Sc. (Honors) Biochemistry, University of Liverpool, 1973
  • Ph.D. Cell biology, University of Liverpool, 1976
  • Postdoctoral Cell biology, Yale University Medical School, 1979

Research Summary

We have two major areas of interest in my lab: the growth-factor and cancer-promoting activities of the hormone prolactin, and the role milk immune cells play in development of the thymus in offspring.

Prolactin: Prolactin has growth factor (as well as other) activities in many tissues, including the pituitary, breast, smooth muscle-like cells, prostate, ovary, and cells of the immune system. Although most prolactin is produced by the pituitary, some is produced in these other tissues where it can act as an autocrine or paracrine growth factor. In all of these tissues, we have demonstrated antagonism between unmodified and phosphorylated prolactin (or a molecular mimic thereof) in the regulation of growth; this antagonism can be disturbed, leading to increased cell proliferation or decreased apoptosis or both. This antagonism is most dramatically demonstrated in vivo where we have, for example, shown the molecular mimic of phosphorylated prolactin to completely inhibit pregnancy- associated growth of the mammary gland, and the formation of tumors from human prostate cancer cells. The mimic of phosphorylated prolactin works in large part by altering splicing of prolactin receptors to produce a form that both acts as a dominant negative to the growth signal-transducing form, as well as itself transducing a signal leading to cell cycle arrest and apoptosis. As part of our analyses, we therefore investigate the posttranslational modification of prolactin, the regulation of prolactin release, prolactin-receptor interactions, signal transduction, and effects on gene transcription in each of these tissues. The laboratory uses a wide spectrum of techniques ranging from microscopy to molecular biology to analysis in normal and transgenic animal models.

Milk immune cells: The benefits of nursing are manifold and, beyond the delivery of nutrients, include the transfer of antibodies and the resultant passive immunization of babies. In addition, we have demonstrated the specific transcytosis of T lymphocytes in the milk across the gastrointestinal epithelium of offspring and their subsequent homing to the thymus. These transferred cells affect development of the offspring’s own thymocytes and immune responses when the offspring are adult. The long-term objectives of this project are to determine the importance of maternal milk cell transfer to immune responses in offspring, especially as such transfer might relate a) to T cell development in general, b) to sexual dimorphism both in susceptibility to immune disease and the efficacy of immunization, and c) to the possibility of safely enhancing immunity in young children.

Awards

  • Award for teaching excellence from the MD classes of 1994, 2007, 2010, 2011.
  • Fellow, Royal Society of Medicine, 2008.
  • Elected to the Academy of Distinguished Teachers, 2006.
  • Keynote Speaker at Japanese Pituitary Society Meeting, 2001.
  • Cancer Federation Research Recognition Award, 1997.
  • Recipient of Campus Distinguished Teaching Award, 1994.
  • Faculty Research Lecturer, Kitasato University, Japan, 1993.
  • Travel award from the Welcome Trust, 1976.
  • Medical Research Council (England) Predoctoral Fellowship, 1973-1976.

Selected Publications

  • Yang NY, Lopez-Bergami P, Goydos JS, Yip D, Walker AM, Pasquale EB, Ethell IM. The EphB4 receptor promotes the growth of melanoma cells expressing the ephrin-B2 ligand. Pigment Cell Melanoma Res. 2010 Oct;23(5):684-7.
  • Terasaki Y, Yahiro K, Pacheco-Rodriguez G, Steagall WK, Stylianou MP, Evans JF, Walker AM, Moss J. Effects of prolactin on TSC2-null Eker rat cells and in pulmonary lymphangioleiomyomatosis. Am J Respir Crit Care Med. 2010 Aug 15;182(4):531-9.
  • Chen Y, Huang K, Chen KE, Walker AM. Prolactin and estradiol utilize distinct mechanisms to increase serine-118 phosphorylation and decrease levels of estrogen receptor alpha in T47D breast cancer cells. Breast Cancer Res Treat. 2010 Apr;120(2):369-77.
  • Tan D, Walker AM. Short form 1b human prolactin receptor down-regulates expression of the long form. J Mol Endocrinol. 2010 Mar;44(3):187-94.
  • Huang KT, Walker AM. Long term increased expression of the short form 1b prolactin receptor in PC-3 human prostate cancer cells decreases cell growth and migration, and causes multiple changes in gene expression consistent with reduced invasive capacity. Prostate. 2010 Jan 1;70(1):37-47.
  • Ueda EK, Soares CR, Bartolini P, DeGuzman A, Lorenson MY, Walker AM. A molecular mimic of phosphorylated prolactin (S179D PRL) secreted by eukaryotic cells has a conformation with an increased positive surface charge compared to that of unmodified prolactin. Biochemistry. 2009 Jul 28;48(29):6887-97. Erratum in: Biochemistry. 2009 Sep 15;48(36):8764.
  • Helena CV, McKee DT, Bertram R, Walker AM, Freeman ME. The rhythmic secretion of mating-induced prolactin secretion is controlled by prolactin acting centrally. Endocrinology. 2009 Jul;150(7):3245-51.
  • Deng C, Ueda E, Chen KE, Bula C, Norman AW, Luben RA, Walker AM. Prolactin blocks nuclear translocation of VDR by regulating its interaction with BRCA1 in osteosarcoma cells. Mol Endocrinol. 2009 Feb;23(2):226-36.
  • Ma LJ, Walter B, Deguzman A, Muller HK, Walker AM. Trans-epithelial immune cell transfer during suckling modulates delayed-type hypersensitivity in recipients as a function of gender. PLoS One. 2008;3(10):e3562.
  • Huang K, Ueda E, Chen Y, Walker AM. Paradigm-shifters: phosphorylated prolactin and short prolactin receptors. J Mammary Gland Biol Neoplasia. 2008. Mar;13(1):69-79.
  • Tan D, Huang KT, Ueda E, Walker AM. S2 deletion variants of human PRL receptors demonstrate that extracellular domain conformation can alter conformation of the intracellular signaling domain. Biochemistry. 2008 Jan 8;47(1):479-89. Epub 2007 Dec 15.
  • Guzmán EA, Langowski JL, De Guzman A, Muller HK, Walker AM, Owen LB. S179D prolactin diminishes the effects of UV light on epidermal gamma delta T cells. Mol Cell Endocrinol. 2008 Jan 2;280(1-2):6-12.
  • Williams VL, DeGuzman A, Dang H, Kawaminami M, Ho TW, Carter DG, Walker AM. Common and specific effects of the two major forms of prolactin in the rat testis. Am J Physiol Endocrinol Metab. 2007 Dec;293(6):E1795-803.
  • Wang Y, Chiu CT, Nakamura T, Walker AM, Petridou B, Trousdale MD, Hamm-Alvarez SF, Mircheff AK, Schechter JE. Traffic of endogenous, transduced, and endocytosed prolactin in rabbit lacrimal acinar cells. Exp Eye Res. 2007 Dec;85(6):749-61. 
  • Wu W, Zanello L, Walker AM. S179D prolactin sensitizes human prostate cancer cells such that physiological concentrations of 1, 25 dihydroxy vitamin D3 result in growth inhibition and cell death. Prostate. 2007 Oct 1;67(14):1498-506.
  • Walker AM. S179D prolactin: antagonistic agony! Mol Cell Endocrinol. 2007 Sep 30;276(1-2):1-9.
  • Ma LJ, Guzmán EA, DeGuzman A, Muller HK, Walker AM, Owen LB. Local cytokine levels associated with delayed-type hypersensitivity responses: modulation by gender, ovariectomy, and estrogen replacement. J Endocrinol. 2007. May;193(2):291-7.
  • Wang Y, Chiu CT, Nakamura T, Walker AM, Petridou B, Trousdale MD, Hamm-Alvarez SF, Schechter JE, Mircheff AK. Elevated prolactin redirects secretory vesicle traffic in rabbit lacrimal acinar cells. Am J Physiol Endocrinol Metab. 2007 Apr;292(4):E1122-34.
  • Walker AM. Therapeutic potential of S179D prolactin--from prostate cancer to angioproliferative disorders: the first selective prolactin receptor modulator. Expert Opin Investig Drugs. 2006 Oct;15(10):1257-67.
  • Wu W, Chen YH, Ueda E, Tan D, Bartolini P, Walker AM. Different forms of prolactin have opposing effects on the expression of cell cycle regulatory proteins in differentiated mammary epithelial cells. Oncol Res. 2006;16(2):75-84.

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General Campus Information

University of California, Riverside
900 University Ave.
Riverside, CA 92521
Tel: (951) 827-1012

Department Information

Division of Biomedical Sciences
UC Riverside School of Medicine
2608 School of Medicine Education Building

Tel: (951) 827-5470

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