Global-thinking Scientist Revels in Individual Patients

Kjersti Aagaard, M.D., Ph.D., studies how outside factors impact babies in the womb and hopes to create a supercharged prenatal vitamin that could prevent disease.

Kjersti Aagaard, M.D., Ph.D., an Assistant Professor of Obstetrics and Gynecology at Baylor College of Medicine, thinks she has the best of all worlds.

Most of the time, she's an innovative bench scientist, seeking to understand at the most basic level how what happens in the womb and during early development affects the future lives and health of the infants—even into adulthood. It was that work that made her one of 29 recipients nationwide of the 2007 National Institutes of Health Director's New Innovator Awards.

However, she also works at Ben Taub General Hospital teaching residents and helping deliver babies. One day a week, she provides care at the Baylor Clinic to women with high-risk pregnancies.

"That's the beautiful thing about what I do," she said. "I get to take one day a week to take care of patients. I find research enjoyable, but there's never an end. There's always another grant application or a paper to write. That one day a week when I have to be in the moment with those patients is fulfilling."

She traces the genesis of her research back to research done after the Dutch Famine Winter of 1944, when babies were born smaller than normal because their mothers went hungry during the waning days of World War II. Researchers found that these children, who were well fed after birth, had a high risk of becoming obese, developing type 2 diabetes, heart disease and high blood pressure. The incidence was much higher than that of children who were of normal size at birth.

In the beginning, that led Aagaard to question whether this phenomenon applied only to children who experienced the growth restriction early or was it more general? Did obesity during pregnancy affect the lives of offspring, even in adulthood? That led to an even more basic question that guides her work.

"I never really understood how genetic transmission occurred. When you think about it, when a transcription factor (a protein that guides a gene to begin the process that results in the production of an associated protein) enters the cell nucleus, it does not first encounter DNA. It encounters chromatin."

Chromatin is the substance of chromosomes, formed when DNA wraps around a core of proteins called histones and become the building blocks of chromosomes.

How, wondered Aagaard, did the transcription factor get access physically to the DNA in that kind of set up? As she learned more about development and disease, "the two problems became inextricably linked in my mind. Is it not possible that a stress on an individual can be related to modifications of the chromatin structure, and that these modifications can be transmitted across the germline (the egg and sperm that can combine to become another organism)? To understand that better, I needed to understand the concepts of epigenetics and chromatin remodeling," she said.

NOW & LATER: Aagaard touches lives now as she cares for patients like Kim Wen each week in the clinic, yet her work in the lab promises to touch infinite lives in the future.

While your genes provide the canvas, they are not the final picture. Epigenetics refers to the host of outside influences that can change the way in which genes are expressed. For example, said Aagaard, the histones that are the backbone of the chromatin can undergo chemical changes that remain stable as cells reproduce.

"The studies I have done in rats suggest that these histone changes can be transmitted across generations and can be modified by nutrition changes," said Aagaard. "We've actually shown in rats that you can come back with nutrient supplementation and reverse these changes."

She plans to use her innovator award in an experiment to see if giving animals a supercharged prenatal vitamin can reverse the changes seen in the offspring of animals who were obese during pregnancy. Her studies indicate that the offspring of obese rats had higher likelihood of developing chronic disease such as high blood pressure, obesity and diabetes in adulthood and these events were indeed related to changes in chromatin or epigenetic events.

Offspring of rats fed a high-fat diet are more likely to have acute fatty liver, a condition similar to that seen in obese children. Her work looks at how the chromatin is changed in the liver tissue of these offspring. In collaboration with Kevin Grove, Ph.D., of the Oregon University Health and Science University, she also hopes to look at the appetite-controlling region of the brain.

Her work seeks to converge fields and put her findings on the fast track for translation into patient care.

"Within five years, we hope to go back and test what we find in the Oregon studies against human samples. The goal is to come up with the nutrient supplementation that could go into a clinical trial in humans by the end of the period of the innovator award," she said.

Aagaard came to BCM because of the opportunity to pursue her work and to collaborate with pioneers in the fields of genetics.

She did not always know she would go into science, even though her family has a definite scientific bent. Her father is an Arctic oceanographer who has led 29 expeditions. Her mother was a science teacher who became an environmentalist.

"I was never confused about whether we lived in a global community and needed to think beyond our house," she said.

When she first went to college, she considered law, but she could not pass up the chance to take a course in biology. Aagaard's professor told her, "It's best to accept your fate and be a scientist." Eventually, she decided to seek a medical degree as well.

Coming south was a difficult decision. She grew up in Seattle and went to school north of the Mason-Dixon line.

She was struggling with her choices when her father advised that the next decade would be the most productive in her career.

"Everything you do that will impact your field meaningfully will happen in the next 10 years. Which institution deserves the best 10 years of your life?" he told her.

With that advice to the fore, she decided to come to Baylor College of Medicine.

Best Minds Best Medicine

Features

Spotlight

Briefs

Volume 4, Issue 1, Summer 2008


	Global-thinking Scientist Revels in Individual Patients by Ruth SoRelle, M.P.H. Kjersti Aagaard, M.D., Ph.D., studies how outside factors impact babies in the womb and hopes to create a supercharged prenatal vitamin that could prevent disease. Kjersti Aagaard, M.D., Ph.D., an Assistant Professor of Obstetrics and Gynecology at Baylor College of Medicine, thinks she has the best of all worlds. Most of the time, she's an innovative bench scientist, seeking to understand at the most basic level how what happens in the womb and during early development affects the future lives and health of the infants—even into adulthood. It was that work that made her one of 29 recipients nationwide of the 2007 National Institutes of Health Director's New Innovator Awards. However, she also works at Ben Taub General Hospital teaching residents and helping deliver babies. One day a week, she provides care at the Baylor Clinic to women with high-risk pregnancies. "That's the beautiful thing about what I do," she said. "I get to take one day a week to take care of patients. I find research enjoyable, but there's never an end. There's always another grant application or a paper to write. That one day a week when I have to be in the moment with those patients is fulfilling." She traces the genesis of her research back to research done after the Dutch Famine Winter of 1944, when babies were born smaller than normal because their mothers went hungry during the waning days of World War II. Researchers found that these children, who were well fed after birth, had a high risk of becoming obese, developing type 2 diabetes, heart disease and high blood pressure. The incidence was much higher than that of children who were of normal size at birth. In the beginning, that led Aagaard to question whether this phenomenon applied only to children who experienced the growth restriction early or was it more general? Did obesity during pregnancy affect the lives of offspring, even in adulthood? That led to an even more basic question that guides her work. "I never really understood how genetic transmission occurred. When you think about it, when a transcription factor (a protein that guides a gene to begin the process that results in the production of an associated protein) enters the cell nucleus, it does not first encounter DNA. It encounters chromatin." Chromatin is the substance of chromosomes, formed when DNA wraps around a core of proteins called histones and become the building blocks of chromosomes. How, wondered Aagaard, did the transcription factor get access physically to the DNA in that kind of set up? As she learned more about development and disease, "the two problems became inextricably linked in my mind. Is it not possible that a stress on an individual can be related to modifications of the chromatin structure, and that these modifications can be transmitted across the germline (the egg and sperm that can combine to become another organism)? To understand that better, I needed to understand the concepts of epigenetics and chromatin remodeling," she said. NOW & LATER: Aagaard touches lives now as she cares for patients like Kim Wen each week in the clinic, yet her work in the lab promises to touch infinite lives in the future. While your genes provide the canvas, they are not the final picture. Epigenetics refers to the host of outside influences that can change the way in which genes are expressed. For example, said Aagaard, the histones that are the backbone of the chromatin can undergo chemical changes that remain stable as cells reproduce. "The studies I have done in rats suggest that these histone changes can be transmitted across generations and can be modified by nutrition changes," said Aagaard. "We've actually shown in rats that you can come back with nutrient supplementation and reverse these changes." She plans to use her innovator award in an experiment to see if giving animals a supercharged prenatal vitamin can reverse the changes seen in the offspring of animals who were obese during pregnancy. Her studies indicate that the offspring of obese rats had higher likelihood of developing chronic disease such as high blood pressure, obesity and diabetes in adulthood and these events were indeed related to changes in chromatin or epigenetic events. Offspring of rats fed a high-fat diet are more likely to have acute fatty liver, a condition similar to that seen in obese children. Her work looks at how the chromatin is changed in the liver tissue of these offspring. In collaboration with Kevin Grove, Ph.D., of the Oregon University Health and Science University, she also hopes to look at the appetite-controlling region of the brain. Her work seeks to converge fields and put her findings on the fast track for translation into patient care. "Within five years, we hope to go back and test what we find in the Oregon studies against human samples. The goal is to come up with the nutrient supplementation that could go into a clinical trial in humans by the end of the period of the innovator award," she said. Aagaard came to BCM because of the opportunity to pursue her work and to collaborate with pioneers in the fields of genetics. She did not always know she would go into science, even though her family has a definite scientific bent. Her father is an Arctic oceanographer who has led 29 expeditions. Her mother was a science teacher who became an environmentalist. "I was never confused about whether we lived in a global community and needed to think beyond our house," she said. When she first went to college, she considered law, but she could not pass up the chance to take a course in biology. Aagaard's professor told her, "It's best to accept your fate and be a scientist." Eventually, she decided to seek a medical degree as well. Coming south was a difficult decision. She grew up in Seattle and went to school north of the Mason-Dixon line. She was struggling with her choices when her father advised that the next decade would be the most productive in her career. "Everything you do that will impact your field meaningfully will happen in the next 10 years. Which institution deserves the best 10 years of your life?" he told her. With that advice to the fore, she decided to come to Baylor College of Medicine.		Search all issues: Best Minds Best Medicine BCM Campaign Seeks to Raise $1 Billion Attracting Stars: McNairs Give $100 Million To Recruit Top Scientists Lester and Sue Smith Gift Tackles Breast Cancer in the Clinic and Lab Two Alumni Share Commitment to Scholarship Support Features Taking Personalized Medicine to New Heights Creating Culture While Building Walls Changing Complexion of Medicine Spotlight Click for your Doctor: New eVisits Trade Exam Room for Inbox Kjersti Aagaard: 2007 Winner of NIH New Innovator Award Getting World-Class Breast Cancer Care...With or Without Insurance James Lupski's Tenacity Founds New Field of Genomic Medicine Briefs BCM Named National Diabetes Research Center DeBakey Takes the Gold The Trash is no Place for Expired Medication Removing Brain Tumors Through the Nose SPORE Spawns New Lymphoma Efforts The Coffee-Cholesterol Connection BCM Campaign puts Personalized Medicine on the Fast-Track

	Volume 4, Issue 1, Summer 2008



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