Department of Medicine
What is your
The title of my BIRCWH project is “Hypoxia-associated impairment of fetal growth: epigenomic perspectives.” For
successful pregnancy outcomes, the developing fetus needs both adequate oxygen
and nutrient delivery. This depends largely on the ability of the mother’s body
to adapt to pregnancy by increasing the amount of blood delivered to the fetus.
Fetal growth is frequently impaired in cases where maternal oxygen
supply is reduced, such as at high altitude or as a result of pulmonary
disease. My main interest is to understand the mechanisms by which this happens,
and to determine the long-term effects of fetal growth on disease
susceptibility in later life. There are two phases to my project 1) why does
maternal hypoxia cause IUGR? and 2) what is the link between IUGR and an
elevated risk of pulmonary disease in later life?
it is known that the low-oxygen environment at altitude reduces blood flow and
oxygen delivery to the infant, the mechanisms underlying these responses are
not known. Hypoxia,
or lack of oxygen, and other exposures are thought to modify epigenetic
patterns or, in other words, cause long-lasting changes to gene activity not by
altering the genetic code, but by making certain areas of the genome more
accessible so that specific genes can be "turned on" and by making
other areas less accessible so that those genes are effectively "turned
off". Using various laboratory and analytic techniques we can assess
epigenetic patterns. In this way, epigenetics provides an opportunity to
understand how the environment affects human physiology and disease. We think
that maternal hypoxia disrupts normal gene behavior during pregnancy by
altering epigenetic patterns and that this influences fetal growth. To explore this idea, I will compare gene
expression and epigenetic patterns during pregnancy at high and low altitude in
maternal cells (peripheral blood mononuclear cells), and determine their
relationship to fetal growth.
Specifically, for the BIRCWH project, my hypothesis is that
chronic maternal hypoxia is causing durable epigenetic changes and that this is
related to lasting effects for the offspring.
How does hypoxia modify gene expression?
Is that due to epigenetic mechanisms?
Over the next two years, I plan to complete my BIRCWH
project and, in the process, generate preliminary data and accompanying
manuscripts to support my goal of obtaining independent research funding to facilitate
the continuation of my work.
Why is your research
Fetal growth is important not only with respect to immediate
health outcomes just after birth, but also in later life. Using hypoxia as a
model for these studies has several advantages. Most prominently, since high-altitude
increases the incidence of fetal growth restriction three-fold, it allows us to
study the effect of hypoxia on fetal growth in the absence of confounding
disease. The clinical implications of fetal growth restriction are not trivial;
it is associated with an 8 to 20-fold increase in perinatal mortality depending
on the severity. My overarching pot-of-gold hope is that by understanding of
the mechanisms underlying fetal growth restriction in more depth we will
eventually be able to identify therapeutic targets to reduce the negative
short- and long-term effects of fetal growth restriction.
Dr. David Schwartz is my primary mentor and I am working in
the Division of Biomedical Informatics and Personalized Medicine in the
Department of Medicine. My project team also includes Dr. Lorna Moore, Dr.
Tasha Fingerlin, Dr. Mark Geraci, and Dr. Judy Regensteiner.
How did you become
interested in this work?
My interest in this area of research has developed over
several years. For whatever reason, I am innately interested in understanding
how the environment influences human physiology and disease. I started out in
integrative physiology at the University of Colorado Boulder, and received my
doctorate from the Department of Health and Behavioral Sciences at UCD Health
Sciences. Since that time I have been fortunate to have opportunities to
incorporate genomics methods into my work and to apply these skills to an issue
of importance for women’s health.
To learn more about the BIRCWH program at University of Colorado Anschutz Medical Campus, click here: