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Center for Women’s Health Research

Center for Womens Health Research
 

Colleen Julian, PhD


​Assistant Professor
Department of Medicine

 

Research Description

 

What is your research?

 
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?
 
Although 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?

Timeline

 

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 important?

 
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.

Project Team

 

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.

http://www.ucdenver.edu/academics/colleges/medicalschool/departments/medicine/BIPM/Faculty/Pages/Colleen-Glyde-Julian.aspx
 

To learn more about the BIRCWH program at University of Colorado Anschutz Medical Campus, click here:
BIRCWH