Patient Care & Research: Inside the Lab of a Physician-Scientist

Kelle Moley, MD, is a Washington University obstetrician and gynecologist at Barnes-Jewish Hospital. Moley also is co-director of the Women’s Reproductive Health Research program at Washington University. Though much of what happens in Moley’s lab, or in any research lab for that matter, is complex and often painstakingly detailed, the
basic premise is simple: A researcher asks a scientific question, then conducts experiments to try to find an answer.

In a question-and-answer conversation, you’ll discover what happens in Moley’s lab and how it affects the patients she treats.

What motivated you to become a doctor?

When I was very young, I decided that I wanted to be a scientist because my father was a scientist, working at Pfizer. Throughout college I spent my summers in a lab, where the people I worked for were interested in developing ways to inhibit cataracts commonly seen in patients with diabetes. I enjoyed the biology of drug discovery and wanted to work in that field. But my father thought I should be a doctor so that I could help more people.

Ironically, he was the one who developed the antidepressant Zoloft, helping more people than I ever could. But I took his advice and, instead of going to graduate school for a PhD, I went to medical school at Yale. Once I completed my rotation in obstetrics and gynecology, I realized I was most interested in women’s health.

What kinds of patients do you treat?

Primarily, I see patients with fertility issues, particularly women who are obese and are having trouble conceiving.

So you became a physician, yet ended up working in a lab, too. How did that happen?

After I completed my medical training, I realized I still wanted to do research. I received a five-year training grant that allowed me to leave my clinical duties and work full-time in the lab. When I returned to the medical field, there weren’t that many physicians doing science, so I had a competitive edge when applying for grants.

What is the focus of your lab?

We look at the effects of abnormal metabolism on female reproduction and do most of our work in mice. We also look at the effects of environmental toxins on sperm in both mice and humans.

Who works in your lab?

Right now, we have 16 people in the lab with varying backgrounds, including graduate students working toward their PhDs, clinical fellows who have their MDs and want to learn lab techniques, and technicians who work in science as a career.

What projects are people working on?

One of our graduate students is studying mouse reproductive egg cells known as oocytes. She is trying to understand how the eggs develop and are fertilized, and how that process changes when a mouse has diabetes or is obese. And one of our postdoctoral researchers is looking at the offspring of these obese mice to see if the changes caused by obesity are passed from generation to generation. From what we can tell so far, that seems to be the case.

What kinds of challenges do you and others in your lab face?

We experience plenty of ups and downs. For example, it’s incredibly difficult to get oocytes from mice. And if something doesn’t work right, you have to start the complicated process all over, which can be very frustrating.

How do you keep the team motivated?

I tell them that, when things don’t work out as hoped, they need to find a new way to answer the question they are asking. My lab is large; there are lots of us working together, and we function like a family, a community. When someone’s having a bad day, the rest of us rally to help that person deal with the challenge.

Can you give me an example of research from your lab that applies directly to your patients?

We know that pregnant women who are obese tend to have polycystic ovarian syndrome, or PCOS, which increases the rate of miscarriages. We think this may be due to problems with the cells lining the uterus that prevent proper implantation of the embryo.

Using an obese mouse model, we have been studying these uterine cells. We know that they require a lot of sugar to produce the energy they need to function. And we have found that they are using this sugar through a less common metabolic pathway.

We have also found that a hormone known as DHEA (dehydroepiandrostenedione) inhibits this pathway and impairs implantation. And we know that women with PCOS have elevated DHEA. When we put all that together, a light bulb went off. We think that elevated DHEA could be causing the high rate of miscarriages in women with PCOS.

During the same research project, we also found that when we added DHEA to cells, it prevented implantation. Next we wanted to know if we could find some non-hormonal way to prevent implantation and act as a new form of contraception.

We now have a provisional patent on inhibitors of the pathway we are studying. And we are screening small molecules that may work as a new drug, one that could replace hormones in existing contraceptives such as the intrauterine device, or IUD.

How does your work in the lab influence the way you care for patients—and vice versa?

I think I explain things better to a patient when I understand the underlying biology of what’s going on with her body.

We also get some of the most important questions from our patients. For example, a number of my patients have asked: “When you insert two embryos during in vitro fertilization, why don’t both always implant?” That’s exactly the kind of question we need to answer in the lab.

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Category: Women & Infants

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Barnes-Jewish Hospital at Washington University Medical Center is the largest hospital in Missouri and the largest private employer in the St. Louis region. An affiliated teaching hospital of Washington University School of Medicine, Barnes-Jewish Hospital has a 1,800 member medical staff with many who are recognized as "Best Doctors in America." They are supported by residents, interns and fellows, in addition to nurses, technicians and other health-care professionals.

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