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Jose M. Teixeira, PhD

Associate Professor, Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School

Contact Info

Jose Teixeira
Massachusetts General Hospital
55 Fruit St

Boston, MA, 02114
Phone: 617-724-1616
Fax: 617-726-0561
teixeira@helix.mgh.harvard.edu

Assistant

Not Available.

DF/HCC Program Affiliation

Gynecologic Cancers

Lab Website

VCRB

Research Abstract

We are studying uterine development and function, particularly its differentiation from the primordial Müllerian ducts. We hypothesize that β-catenin plays a major role in postnatal uterine development and that its dysregulated function may be an underlying cause of leiomyomata, the most common gynecologic tumor. We are investigating the function of β-catenin in uterine development and have found that targeted deletion of β-catenin in mouse uterus leads to progressive replacement of smooth muscle with fat in the myometrium with estrous cycling. These results suggested that there is a regenerative cell in the uterus that is dependent on β-catenin function and is hormonally regulated. We propose to continue these studies by identifying the uterine smooth muscle cells that behave like the regenerative satellite cells in skeletal muscle. We will also attempt to determine the source of the cells that contribute to uterine smooth muscle. The studies will provide a better understanding of postnatal uterine development and should also provide clues to the etiology of uterine muscle pathologies such as leiomyomata, which are more commonly known as uterine fibroids and affect 25-40% of women.

Another focus of my laboratory is the in vitro maturation of human oocytes and their subsequent use for embryonic stem (ES) cell research. Human ES cells are currently derived from surplus embryos generated during in vitro fertilization (IVF) treatment. More recently, however, the technique of somatic cell nuclear transfer into unfertilized eggs offers the possibility of creating human ES cells whose genetic makeup matches that of the recipient. In addition to providing a powerful research tool for understanding human disease, this approach may eventually allow patients to be treated with an unlimited supply of new cells that will be recognized as 'self,' thereby avoiding the serious problem of rejection by the body's own immune defenses. In order for progress to be made on this front, a steady supply of human oocytes is needed. However, acquiring sufficient oocytes from donors undergoing requisite fertility treatments with no reproductive or medical benefit to themselves is problematic for both ethical and logistical reasons. Our contribution to this effort will be to isolate oocytes from the discarded ovaries of patients undergoing routine surgical procedures requiring removal of their ovaries. These isolated oocytes will be matured in vitro and stimulated to undergo parthenogenesis, with the ultimate goal of their development as recipients for somatic cell nuclear transfer.

Additionally, I have a long-standing collaboration with Dr. Patricia Donahoe to study the molecular mechanisms of MIS (also known as anti-Müllerian hormone or AMH) signaling and function. MIS is expressed shortly after differentiation of the fetal testis and is required for Müllerian duct regression during male fetal development. In females, the absence of MIS allows the Müllerian duct to develop into the female internal reproductive tract structures. By the end of puberty, the level of MIS expression has decreased substantially in males and is no longer sexually dimorphic because females have begun expressing MIS at levels that are indistinguishable from males. Why is MIS still expressed at such high levels in males well after Müllerian duct regression has occurred? Why does decreased expression of MIS herald puberty in males? Why do females begin expressing MIS? What role does MIS play in the gonad? Does MIS (or lack thereof in females) contribute to any predisposition to or protection from developmental errors in metabolism? MIS has been shown to be a strong inhibitor of ovarian, prostate, and breast cancer cell proliferation. Does MIS control proliferation of these tissues physiologically? These questions are largely unanswered and form the basis of our current and future efforts to understand the continued postnatal expression of MIS and its consequence to normal health and development, and as a possible cancer therapeutic.

Publications

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