Aletheia Burrell: Toward Non-Surgical Treatments for Uterine Fibroids

Sep 24 2011 Published by under Duke University, Summer Research Experiences

Dr. Friederike Jayes, Aletheia Burrell, Dr. Phyllis Leppert, and Dr. Darlene Taylor after Aletheia's summer research presentation, 26 August 2011. Photo credit: DJ Kroll/NCCU RISE

Today's NCCU RISE Scholar perspective comes from Aletheia Burrell. Aletheia has been conducting her research project with Dr. Darlene Taylor, Assistant Professor of Chemistry at North Carolina Central University. Dr. Taylor is a fellow of the Duke University BIRCWH program of the NIH Office of Research on Women's Health, a collaborative NIH K12 program aimed at developing the careers of junior faculty dedicated to the study of women's health.

Aletheia benefits from Dr. Taylor's own mentorship by Phyllis Leppert, MD, PhD, a recognized Duke physician-scientist researcher in the Department of Obstetrics and Gynecology and the Department of Pathology. As Dr. Leppert transitions toward retirement, we at NCCU RISE are particularly grateful for the continued mentoring by Friederike Jayes, PhD, and her commitment to the mission of the NCCU Eagles RISE program. What's been most exciting to me as a RISE program director is just how involved Dr. Jayes and Dr. Leppert have been in Aletheia's development toward doctoral training. 

Well, perhaps I should let Aletheia tell you. . . - DJK

Toward non-surgical treatments for uterine fibroids
by Aletheia Burrell, North Carolina Central University

Hola Scientopia; ¿Como estas?

I’m Aletheia Burrell, a junior biology major, with a Spanish minor, from Sanford, North Carolina via Athens, Alabama (originally ). My current aspirations involve obtaining a MD/PhD…. I’m not entirely sure about what I want my PhD in yet, but Obstetrics and Gynecology is a definite interest as far as the MD is concerned!

This summer was an invaluable whirlwind of knowledge, techniques, writing, and cell cultures!! I stayed at NCCU this summer to continue my research from the academic year on uterine fibroids under Dr. Darlene Taylor and to start working with her collaborators at Duke University, Dr. Phyllis Leppert and Dr. Friederike Jayes in the Department of Obstetrics and Gynecology.

My project was/does deal with studying a nanocarrier loaded with an antifibrotic drug and their effects on fibroid and myometrial cells.  Dr. Taylor specializes in polymer chemistry and has recently developed a proprietary drug delivery system with a colleague of mine, Melony Ochieng. As I stated, she works in collaboration with Dr. Leppert, Professor in the Department of Obstetrics and Gynecology and Pathology at Duke University, and Dr. Jayes, Assistant Professor also in the OB/GYN and Pathology departments at Duke University; two women (in my opinion) you should know when trying to understand the biology of uterine fibroids, collagen, and collagenase.

But my summer actually started with a molecular biology techniques workshop at Duke…

The workshop was a 9-day crash course / nurturing introduction to valuable techniques and molecular biology principles, some of which I hadn’t heard before, which included: cloning and protein expression, gene expression, genotyping,  siRNA and silencing genes, Western Blotting, Reverse-Transcriptase and Real-Time PCR (beforehand, I didn’t know there was a difference!). There were lectures before the actual experiments to make sure that we understood the concepts before putting them to use, like primers and primer design before the PCR reaction. AND to top it all off, all of the procedures and lectures were conveniently printed out and placed in a binder, which I affectionately call my “Bio Lab Bible” and on a CD for future reference. I learned more than I could express on this blog and this little snap shot really doesn’t do the workshop justice!

 I should mention that the whole purpose of me participating in the workshop was to understand and become familiar with biology techniques that I would use prior to doing research with  fibroid cells at Duke…

Back to fibroids and my research…

Uterine fibroids (also called leiomyomas) can cause pain, bleeding, and infertility and are diagnosed in one-fourth of all women and contribute $2.1 billion annually to health care costs. Despite the high cumulative incidence of fibroids, their etiology is elusive. Clearly, more fundamental knowledge is needed regarding the molecular biology of fibroids.

Hysterectomy is the only treatment available that permanently eliminates fibroids. It is obvious but rarely stated that hysterectomies lead to irrevocable loss of fertility. Furthermore, even without hysterectomy, fibroids, particularly subserosal fibroids can lead to infertility. More effective treatment options are needed.

Current treatment options for uterine fibroids are inadequate. Invasive procedures resulting in fibroid destruction exist (myomectomy, uterine artery embolization, and MRI guided focused ultrasound) but while these procedures preserve the uterus, they are lengthy, often painful, complicated, expensive, and fibroids can reappear. Medical therapies are either short-lived or have significant side effects. Other medical therapies have been suggested in the recent past such as Selective Estrogen Receptor Modulators (SERMs) but clinical trial results have been disappointing. Effective drug molecules exist but despite the intensive developmental efforts by several pharmaceutical companies and clinical trials they are not approved due to their side effects when administered systemically. Selective progesterone receptor modulators (SPRMs), which demonstrated significant shrinkage of fibroids and symptomatic improvement, have not yet received FDA approval due to concerns over the effect of these agents on the endometrium.

My ultimate goal then, is to find a minimally invasive treatment for women with chronic uterine fibroids; this is how I came to work with Dr Taylor, Dr. Leppert, and Dr. Jayes and their collaborative efforts to develop this drug delivery system into a minimally invasive uterine fibroid treatment.

The nanocarrier drug delivery system is a thermo-responsive, biocompatible, multifunctional polymer that is liquid at temperatures below 30 °C but gels at physiological temperatures; this is the mechanism by which drugs or other desired substances become entrapped inside the nanocarrier. It is capable of protecting a specific amount of drug against thermal, chemical, and/ or physical degradation, while disintegrating in the desired environment to release the drug(s) in a controlled manner.

Being more specific, I worked on the release kinetics of the nanocarrier this summer to determine the degree of drug release, or if whether all or most of what we are loading into the nanocarrier is actually being released as it degrades over time and how long it takes for that amount to be released.

We did these studies with two drugs in particular, indomethacin and pirfenidone. Pirfenidone is a known antifibrotic drug that has serious potential to be a drug treatment uterine fibroids if it could be delivered locally to reduce its side effects, however indomethacin was chosen because of its hydrophobic nature to show that the nanocarrier is capable to deliver either hydrophilic materials like pirfenidone or hydrophobic as with indomethacin.  First we created calibration curves for each drug through a dilution line and then measured drug concentrations with UV-Vis spectroscopy. Then we loaded both drugs at known concentrations into the nanocarrier in triplicate and placed the series for each drug in a stirrer at 37°C to simulate natural body conditions. Aliquots were taken at various time points for 14 days and read with UV-Vis to measure drug concentrations.

Whew…. That was a mouthful!!

For the sake of trying NOT to sound like I’m a politician filibustering, I’ll try to summarize the rest of my summer:

At Duke is where I worked on the more biological side of my project, such as growing up fibroid and myometrial cells for gene expression to make sure that our cell lines resemble progenitor tissues in such a way that any in vitro findings we encounter through experimentation actually resemble the in vivo fibrotic disease. I also got a taste of IRB writing, a consent form actually, so that we can receive and use donated tissues from women who are scheduled to have hysterectomies due to their chronic uterine fibroids.

I know it was a lot, and also left out quite a bit, but I am very excited with the research that I did and am continuing to do with these amazing women, RISE, and Dr. Kroll!!

So, until my next entry…

Yours truly,

Aletheia

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