Michael J. Soares, Ph.D.

University of Hawaii, 1981
Postdoctoral, University of California-Santa Cruz, Baylor College of Medicine

1012 Lied Building
3901 Rainbow Boulevard
Kansas City, KS 66160-7401
Phone: (913) 588-5691
Fax: (913) 588-8287
msoares@kumc.edu

Introduction

Viviparity is a mode of reproduction that occurs within the female reproductive tract. It has necessitated the acquisition of specialized maternal and extraembryonic tissues. In primates and rodents the maternal/fetal interface includes the uterine decidua of the mother and the placenta of extraembryonic origin. Hemochorial placentation, as occurs in both primates and rodents, results in the establishment of a close connection between maternal and embryonic/fetal tissues.

This close connection provides optimal gas exchange, supply of nutrients and disposal of wastes but also inherently results in maternal immunologic challenges to the genetically disparate extraembryonic and embryonic tissues. Maternal adjustments to the demands of pregnancy are paramount and include immunologic, endocrine, metabolic, and cardiovascular adaptations. Cells situated at the maternal/fetal interface orchestrate requisite changes in maternal physiology. Specifically, decidual and placental cells produce a variety of hormones, cytokines, and growth factors targeted to key maternal tissues.

Among these various regulatory signals secreted by the decidua and placenta are a prominent family of proteins related to prolactin (PRL) and known as the PRL family. The ancestral PRL structure has proven to be a malleable template for the generation of a diverse group of regulatory factors. Most interestingly, the size and composition of the PRL family is species specific. Our laboratory is currently pursuing four related areas of research: i) prolactin family and pregnancy, ii) trophoblast cell invasion, iii) trophoblast cell differentiation, and iv) maternal adaptations to pregnancy. Identification of regulatory mechanisms controlling the establishment and maintenance of pregnancy will provide insights into the etiology of placental insufficiency, early pregnancy loss, and various disorders leading to intrauterine growth restriction.

Prolactin family and pregnancy

Prolactin (PRL) is a hormone/cytokine responsible for the coordination of a wide variety of biological processes in vertebrates. In the mouse, rat, cow, and likely other mammalian species there is a large family of paralogous genes closely related to PRL. Members of the PRL family are expressed in cell- and temporal-specific patterns in the uteroplacental compartment and anterior pituitary. An overriding theme characteristic of the PRL family is its association with pregnancy and regulatory mechanisms controlling viviparity.

Trophoblast cell invasion

The focus of this project is to understand the cellular and molecular processes involved in regulating trophoblast cell migration into the uterus. We are particularly interested in investigating the dynamic interactions of natural killer cells and trophoblast cells and the development of the uterine vasculature.

Trophoblast cell differentiation

The objective of this project is to understand cellular and molecular mechanisms regulating trophoblast cell differentiation. Signal transduction cascades impacting trophoblast cell growth, differentiation, and death are currently under investigation.

Maternal adaptations to pregnancy

The purpose of this research is to understand the molecular basis of gestational dependent changes in the mother that facilitate pregnancy. Our current efforts include identifying genes involved in pregnancy dependent adaptations in the maternal liver and spleen.

Selected Publications

Muller H, Liu B, Croy BA, Head JR, Hunt JS, Dai G, Soares MJ 1999 Uterine natural killer cells are targets for a trophoblast cell-specific cytokine, prolactin-like protein-A. Endocrinology 140, 2711-2720.

Peters TJ, Chapman BM, Wolfe MW, Soares MJ 2000 Placental lactogen-I gene activation in differentiating trophoblast cells: extrinsic and intrinsic regulation involving mitogen-activated protein kinase signaling pathways. Journal of Endocrinology 165, 443-456.

Soares MJ, Linzer DIH 2001 Rodent prolactin family and pregnancy. In Prolactin, ND Horseman (ed), Kluwer Academic Publishers, Norwell, MA pp. 139-167.

Kamei T, Jones SR, Chapman BM, McGonigle KL, Dai G, Soares MJ 2002 The phophatidlyinositol 3-kinase/akt-signaling pathway modulates the endocrine differentiation of trophoblast cells. Molecular Endocrinology 16, 1469-1481.

Wiemers DO, Shao L-J, Ain R, Dai G, Soares MJ 2002 The mouse prolactin gene family locus. Endocrinology 146, in press.

Funding:

National Institutes of Child Health and Human Development [HD20676; HD39878]