![Winston E. Thompson, Ph.D., M.S.](/about_us/FacultyDirectory/Physiology/images/winston-e-thompson.jpg)
Winston E. Thompson, Ph.D., M.S.
Professor & Chair
Physiology
Director of Research, Obstetrics & Gynecology and Director, Mentoring Academy
Location: Medical Education Building 350
Phone: (404) 752-1715
E-mail: wthompson@msm.edu
Education
POSTGRADUATE:Marine Biological Laboratory
Certificate: Embryology
Harvard Medical School
Fellowship: Reproduction
GRADUATE:
Rutgers University and the University of Medicine & Dentistry
Degree: Doctor of Philosophy in Cell and Developmental Biology
Rutgers University
Degree: Master of Science in Endocrinology
UNDERGRADUATE:
Lafayette College
Degree: Bachelor of Art in Biology
Research Interests
In the Thompson laboratory, a team of researchers are committed to the study of women
reproductive health.
Reduced DNA Repair Capacity Leads to Increased Risk of Uterine Fibroids (UFS) in African
Americans
Uterine Fibroids (UFs, AKA: leiomyoma) are the most important benign neoplastic threat
to women's health. They are the most common cause of hysterectomy causing untold personal
consequences and hundreds of billions of health care dollars worldwide. Currently,
there is no long term effective FDA-approved medical treatment available, and surgery
is the mainstay. The etiology of UFs is not fully understood. In this regard, we and
others have recently reported that somatic mutations in the gene encoding the transcriptional
Mediator subunit MED12 are found to occur at a high frequency (~85%) in UFs. UFs likely
originate when a Med12 mutation occurs in a myometrial stem cell converting it into
a tumor-forming stem cell leading to a clonal fibroid lesion. UFs do not affect all
races equally. Increased prevalence of UFs in African- American (AA) women has been
consistently observed for >120 years. The molecular attributes behind UFs ethnic disparity
are not fully realized; however, a growing body of literature implicates unfavorable
early life environmental exposures as potentially important contributors. Environmental
exposures during sensitive windows of development can reprogram normal physiological
responses and alter disease susceptibility later in adult life. Compelling preliminary
data from our laboratory further identified that such exposure exerts two alterations
in exposed rat myometrium: (1) permanently expands myometrial stem cell compartment
and, (2) decreases DNA damage repair capacity. Quantitative PrimePCR array indicated
that several DNA damage repair genes are significantly down regulated including RAD50,
Sirt, and TP53 in myometrium from rats neonatally exposed to xenoestrogens. Importantly,
in the human equivalent, we have encountered similar observations. MyoF (high risk
myometrium from fibroid uteri) exhibited expanded myometrial stem cell compartment
as well as a decrease in DNA damage repair capacity as compared to MyoN (normal myometrium
from healthy fibroid-free uteri). This was significantly more noticeable in AA women.
Importantly, key DNA repair genes of RAD50, Sirt1, MLH1, and MLH3 were markedly decreased
in MyoF vs MyoN. Our central Hypothesis: Early life exposure, during the sensitive
period of uterine development, to environmental toxicants, which is more prevalent
in AA, permanently expands the number of myometrial stem cells as well as permanently
reprograms and attenuates key DNA damage repair genes leading to reduced myometrial
DNA damage repair capacity. Chronic reduction in DNA repair capacity eventually leads
to the emergence of mutations such as Med12 in myometrial stem cells converting them
into fibroid tumor-forming stem cells and subsequently leads to the development of
UFs. We will address this hypothesis using the following three specific aims; Specific
Aim 1: Determine whether a small but distinct myometrial stem cell population serves
as pre-fibroid tumor progenitors in AA versus Caucasian (C) women. Specific Aim 2:
Identify PcG/ TrxG (histone methylation regulators) regulated DNA repair target genes
that contribute to developmental reprogramming in UF development. Specific Aim 3:
Characterize whether Vitamin D3 is capable of increasing DNA repair capacity via reversing
disrupted epigenetic programming in myometrial stem cells. Impact: These paradigm
shifting concepts will enable us to identify genomic and epigenomic risk profiles
associated with increased susceptibility to UFs in AA women. Such knowledge will inform
an efficient precision medicine approach towards the development of novel preventative
and therapeutics strategies for this common health disparity challenge.
Role of Exosome-Encapsulated Microrna in the Pathogenesis of Endometriosis
Endometriosis, accounts for 10-15% of pelvic pain and infertility in women of reproductive
age. Endometriosis is also the single major cause for hysterectomy in that age group
in the USA, with an annual estimated societal cost of ∼$69.4 billion. Currently definitive
diagnosis of endometriosis requires surgery. Surgical removal of lesions, hormone
suppression, and anti-inflammatory agents are the current gold standards of therapy,
but these approaches are associated with serious side effects and a high incidence
of relapse. The invasive nature of surgery, coupled with the lack of a conclusive
laboratory biomarker for the disease, results in a mean latency of 7–11 years from
onset of symptoms to definitive diagnosis. Therefore, identification of mechanisms
involved in the early pathogenesis of endometriosis and non-invasive diagnosis and
strategic therapies for treatment are critical. Our long-term goal is to develop a
feasible diagnostic tool based on the findings here while examining the role of the
exosomal uptake that results in modulation of gene expression in recipient cells leading
to inflammation, proliferation and differentiation through this mechanism of cellular
communication, yet to be explored in the context of endometriosis. Our central hypothesis
is that specific exosomal miRNA contribute to the chronic inflammatory condition of
endometriosis. We formulated this hypothesis based on the literature and our research
on exosomes as well as our preliminary data showing exosomes derived from patients
with endometriosis had both pro-angiogenic and proinflammatory effects all factors
that are associated with the pathophysiology of endometriosis. We were the first to
report that disease stromal derived exosomes promoted pro-angiogenesis and inflammation
and here we expand to mechanistic aspects of exosomal biology and miRNA manipulation
in endometriosis. Furthermore, we identified that specific miR-199a-3p and miR-4286, are significantly over-represented in exosomes derived from endometrial stromal
cells (ESC) from endometriosis patients compared to controls. Gene prediction software
and literature search show that these miRNAs directly or indirectly target the STAT3
and ±·¹óÒ¡µþ signaling pathways and have been shown to play a role in several diseases including
ovarian cancer. A major goal of this application is to elucidate the function of
exosome encapsulated miRNAs as it relates to target cell response (inflammation, proliferation
and cell differentiation) and will be addressed in these two aims. Our research team
includes experts in the following areas: minimally invasive surgical treatment of
endometriosis, molecular imaging, molecular biology, organoid development, exosome
encapsulated miRNA engineering, gene therapy and reproductive endocrinology. This
qualified group of investigators will ensure that our discoveries are linked to basic
concepts of the pathogenesis of endometriosis and role of secreted exosomes as natural
carriers of functional miRNAs from endometrial stromal cells and their interplay with
epithelial cells.
Publications
- Hoda Elkafas, Mohamed Ali, Engy Elmorsy, Rehab Kamel, Winston E. Thompson, Osama Badary, Ayman Al-Hendy, Qiwei Yang. Vitamin D3 Ameliorates DNA Damage Caused by Developmental Exposure to Endocrine Disruptors in the Uterine Myometrial Stem Cells of Eker Rats. Cells. 2020 Jun; 9(6): 1459. PMCID: PMC7349254
- Kelsey KM, Zigo M, Thompson WE, Kerns K, Gaurishankar Manandhar G, Sutovsky M, Sutovsky P. Reciprocal surface expression of arylsulfatase A and ubiquitin in normal and defective mammalian spermatozoa. Cell Tissue Res 2020 Mar;379(3):561-576.
- Indrajit Chowdhury, Saswati Banerjee, Adel Driss, Wei Xu, Sherifeh Mehrabi, Ceana Nezhat, Neil Sidell, Robert N Taylor, Winston E Thompson. Curcumin attenuates proangiogenic and proinflammatory factors in human eutopic endometrial stromal cells through the NF-κB signaling pathway. Cell Physiol 2019 May;234(5):6298-6312.
- Djana Harp, Adel Driss, Sharifeh Mehrabi, Indrajit Chowdhury, Wei Xu, Dong Liu, Minerva Garcia-Barrio, Robert N Taylor, Bert Gold, Samantha Jefferson, Neil Sidell, Winston Thompson. Exosomes derived from endometriotic stromal cells have enhanced angiogenic effects in vitro. Cell Tissue Res 2016 Jul;365(1):187-96.
- Indrajit Chowdhury, Kelwyn Thomas, Anthony Zeleznik, Winston E Thompson. Prohibitin regulates the FSH signaling pathway in rat granulosa cell differentiation. J Mol Endocrinol. 2016 May; 56(4): 325–336. PMCID: PMC5064770
Honors and Awards
- 2012: Certificate of Teaching Excellence, Frontiers in Stem Cells in Cancer, Advanced Lab Course at Howard University
- 2012: Elected to the Board of Directors, Society for the Study of Reproduction
- 2011: NIH R15 Grant Reviewer, NIH