Cutting edge

DOs at the NIH make discoveries across the medical spectrum

Within the largest biomedical research center in the world, DOs work to uncover information that can change medicine.


Within the largest biomedical research center in the world, several DOs are unearthing information that may change the way we practice medicine and help people live healthier lives. At the National Institutes of Health, DOs work in diverse fields including reproductive endocrinology and infertility, allergy and infectious diseases, neurology, and radiology. As part of their research, they also care for patients.

The NIH is the greatest provider of medical research funding on the planet. Headquartered in Bethesda, Md., the NIH’s main clinical center employs 1,200 physicians, dentists and PhD researchers, who are working on about 1,500 clinical studies right now.

One of those physicians is Les R. Folio, DO, MPH, a staff clinician in the NIH’s radiology department and its lead radiologist for computed tomography. When he was in the Air Force, Dr. Folio analyzed ballistic fragments on CT images on patients with gunshot and blast injuries. The position of the fragments and the injury could sometimes reveal the location of the shooter.

At the NIH, Dr. Folio and his team have applied similar techniques to find better ways to identify and measure metastatic melanoma tumors and metastatic lesions using CT. They did this by building a “lesion tracking tool” within the picture archiving and communications system they use. The tool is now FDA-approved and will allow clinicians to process oncologic measurements twice as fast, according to a recent study Dr. Folio conducted.

“One button allows a radiologist in his or her workflow to take all the lesions that have been previously measured and identified, find them based on their location, and measure them again,” he says.

Dr. Folio also is also helping National Library of Medicine researchers develop programs that automatically detect tuberculosis on chest X-rays. The programs will be vital tools in the fight against multidrug-resistant TB by helping radiologists work more efficiently, and they may soon be in use internationally in areas with shortages of radiologists, Dr. Folio says.

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“The program will be able to parse the X-rays and say, ‘Here are all the negative chest X-rays.These don’t need to go to a radiologist,’ ” Dr. Folio says, noting that the positive X-rays will then go to a radiologist to be manually examined.

Advancing stroke research

John K. Lynch, DO, MPH, also works with scans in his research. As a staff clinician with the National Institute of Neurological Disorders and Stroke, Dr. Lynch and his team have been using magnetic resonance imaging for the past 10 years to examine how the brain changes following a stroke. Stroke patients often can’t pinpoint when their symptoms started. Dr. Lynch and his team are now able to use imaging to estimate the onset of the attack.

“Even if we don’t know when the patients’ symptoms started, we can use the MRI to guesstimate how long the ischemia has been going on,” Dr. Lynch says. With the MRI, clinicians no longer have to rely on patients’ accounts of their strokes to make decisions about treatment, so they can now help a much greater proportion of patients, he says.

In addition, Dr. Lynch has become an authority on the genetic factors of pediatric stroke. Drawn to the topic because of the lack of information and knowledge on causes and outcomes, he wrote several papers calling for resources to be dedicated to researching pediatric stroke.

“There was very little information that we could communicate to parents about the causes of stroke in children and what their outcomes would be,” he says. “This led to a few studies in which we were looking primarily at risk factors for stroke in children.”

In one pediatric study, Dr. Lynch found matching genetic mutations between his subjects and children in a European study. By confirming the mutations that had been identified in European populations and also identifying new risk factors, the study has led to a change in the way clinicians evaluate stroke in children, Dr. Lynch says. They now focus more on coagulation disorders as possible causes or contributors to stroke in children.

While he loves research, Dr. Lynch says performing treatments that help patients preserve their brain function and enhance their quality of life following a stroke is the most rewarding part of his job. For instance, his team recently worked with a 41-year-old woman who was transferred to their care from a local hospital after receiving tissue plasminogen activator. Dr. Lynch and his staff took images of the woman’s brain and saw that a blockage remained, that the TPA hadn’t worked. They quickly put a catheter into the artery in her brain and removed the clot.

“At the time, she was unable to speak. She couldn’t move the right side of her body, and she didn’t have any vision one side,” says Dr. Lynch. “It was a very critical situation. But in the end, by removing that clot, we salvaged a large percentage of her brain that was at risk.”

The woman is now walking and talking normally, Dr. Lynch says, and she’ll be working again soon.

“This is just one example of the importance of getting in there and removing the clot as quickly as possible, either with TPA or with some type of mechanical embolectomy,” he says.

As a stroke expert, Dr. Lynch advises primary care physicians to counsel their patients to call 911 immediately if they ever develop neurologic symptoms.

“We only have a 4.5-hour window in which to really give effective therapies, so patients have to get to the hospital immediately,” Dr. Lynch says, though he notes that his team, along with other researchers, are working to expand the window to six hours.

And because stroke treatments are so limited, emphasizing prevention is also crucial, Dr. Lynch says. Primary care physicians should encourage their patients to live a healthful lifestyle and control their blood pressure, weight and cholesterol, he says, to reduce the risk of stroke.

‘People get very excited’

Over at the National Institute of Allergy and Infectious Diseases (NIAID), Julie E. Ledgerwood, DO, is the deputy chief of the clinical trials core in the Vaccine Research Center. Dr. Ledgerwood’s team focuses on research for development of preventive HIV vaccines and new vaccines for influenza and emerging infectious diseases such as Ebola and West Nile virus. “We have published some important findings on influenza vaccine development,” she says. “We have shown that a gene-based vaccine can improve the response to traditional influenza vaccines by sixfold.”

Also with the NIAID, Todd M. Wilson, DO, has been focused on the genetics of mast cell diseases, specifically mastocytosis, as an assistant clinical investigator. His team’s studies and trials have sought to elucidate the genetic aspects of mast cell diseases and how they relate to allergy.

“We’ve found multiple mutations that contribute to mastocytosis as well as developed therapeutics that look like they have the potential in a clinical trial for the disease,” he says.

These findings, and other discoveries, are the best part of the job for him, says Dr. Wilson, who notes that he’s thrilled to advance his understanding of disease on a daily basis.

“There’s a general excitement around here,” he says. “People get very excited about research, as they should, and everyone wants to see others succeed.”

Dr. Wilson completed nine years of training with the NIAID. He is now continuing his work with the NIH in a new post at the newly launched National Center for Advancing Translational Sciences, an institute dedicated to identifying ways to speed up the process of moving therapeutics from bench to bedside.

“This was an initiative put forward by our director to start an institute to look into where the bottlenecks were in trying to get therapeutics,” says Dr. Wilson, noting that the center opened in 2011 and involves collaboration among epidemiologists, pharmaceutical companies, patient advocacy groups and clinicians.

Practice-changing discoveries

Discovering a new research question that has the potential to change and improve practice is what Micah J. Hill, DO, finds most satisfying about his work with the NIH. Dr. Hill is finishing up a fellowship in reproductive endocrinology and infertility at the NIH. His team is interested in improving comprehension of the science of in vitro fertilization. In particular, they want to reduce the number of twins and triplets in IVF births.

“A lot of our research is focused on ways we can identify the single embryo that’s most likely to get someone pregnant,” he says.

For instance, clinicians grade the quality of an embryo by examining three components: its inner cell mass, which becomes the fetus; expansion, or size; and trophectoderm, which becomes the placenta. Historically, physicians placed more emphasis on the inner cell mass, Dr. Hill says, but his team’s research identified the quality of the trophectoderm as actually more predictive. “That’s really a practice-changing thing, and it reflects that maybe we should be transferring embryos that have a better trophectoderm grade first,” he says.

Patients who want to get pregnant don’t always realize that carrying twins is much more risky than carrying a single baby, Dr. Hill says, and he and his colleagues explain to their patients that the goal should be one healthy baby rather than twins.

“As long as we can develop ways to screen the embryos that maximize patients’ chance of getting pregnant and make it safe, we can usually get them to buy into that,” he says.

Dr. Hill has also extensively researched the ways nutrition can affect steroid receptor function and, thus, fertility outcomes. His team has been studying the CRTC2 molecule, which has a coregulatory effect on the progesterone and glucocorticoid receptors. Low energy, or not enough food, can cause the molecule to increase activity in glucocorticoid receptors, which respond to stress.

“Interestingly enough, it also looks like low energy causes the molecule to repress the progesterone, which is primarily involved in reproductive tissue,” Dr. Hill says. “The fact that low energy might be involved in repressing some of those functions hasn’t really been described before, but the data’s very preliminary.”

Life of a DO at the NIH

Like everyone else at the NIH, DOs there have proved their worth through their work. And while DOs are a rarity in the halls at the NIH, many of them say their different degree is a nonissue.

“You’re judged here on your merits and what you bring to the table in terms of research and thoughts and your qualifications as a physician,” Dr. Wilson says. “I don’t think I’ve been viewed any differently.”

Dr. Lynch does say he sees upsides and downsides for DOs at the NIH. Osteopathic medical school was not sufficient preparation for his research career, he says.

“DO institutions overall typically receive very little NIH funding for research because they don’t have the adequate infrastructure or personnel to conduct research,” he says. “Because of that, there are limited opportunities for medical students who may be interested in a career in clinical research.”

But Dr. Lynch notes that other elements of his medical education proved extremely helpful to his career.

“My experience in medical school afforded me the opportunity to learn the importance of structure and function,” he says. “And in my field of neurology, a lot of the disorders we evaluate and manage are musculoskeletal.”

Balancing patient care and research

Dr. Lynch and other DOs at the NIH also undoubtedly learned the importance of bedside manner, which has come into play for these researchers more than one might think. Many physicians at the NIH, including Dr. Hill, Dr. Lynch, Dr. Wilson and Dr. Ledgerwood, spend a lot of time working with the patients who are part of their clinical trials.

Researchers often have to explain complex concepts to worried patients, Dr. Wilson says, so they must be well-versed in the art of the bedside chat.

“I not only have to address the patient’s needs, but I also have to go back and understand from a scientific perspective what questions we should be asking, and how we should derive experiments to answer those fundamental questions,” he says. “It’s very difficult to go between the two. The physicians who do it best can see across the spectrum.”

It’s going to be a challenge for all physicians in the future to maintain bedside manner in the age of rapid-fire scientific discovery, Dr. Wilson says.

“These are very complex scientific concepts that we have to not only comprehend, but also explain to patients while we’re sitting at their bedside,” he says.

Dr. Lynch says that while patient care and research are intimately connected, they satisfy different professional goals for him—and he couldn’t imagine giving up one or the other.

“Seeing patients allows me to have that immediate feedback and the satisfaction that I’m contributing in some way directly,” he says. “And the research side provides me with the notion that I can possibly impact the field and every stroke patient in the future in some way. It’s the difference between affecting the population and affecting an individual.”

Like Dr. Lynch, Dr. Hill also enjoys rooting his work in patient care.

“I wouldn’t leave taking care of patients,” he says. “I really like that part of my job, and that’s why I got into medicine. But it’s fun to help guide practice and improve it, and unless we have people asking these questions and doing it in a scientific and systematic fashion, we won’t improve medicine. I like being part of the quest to improve medicine and the delivery of care to patients.”

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