December 12, 2008
NIH Podcast Episode #0073
Balintfy: Welcome to the 73rd episode of NIH Research Radio with news about the ongoing medical research at the National Institutes of Health—the nation's medical research agency. I'm your host Joe Balintfy. And coming up in this episode we'll have an in-depth story about how researchers can launch their careers with help from the NIH. In this example, we'll hear from one researcher who made important discoveries regarding milk allergies during his training. But first, we have a series of reports dealing with the lung. That's next on NIH Research Radio.
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Healing Process Found to Backfire in Lung Patients
Balintfy: In our first story dealing with lung discoveries, researchers at the National Institute of Environmental Health Sciences and their collaborators, have found how a mechanism in the body which typically helps a person heal from an injury, may actually be causing patients with idiopathic pulmonary fibrosis (IPF) to get worse. In other words, the body's healing process may actually be hurting these lung patients.
Garantziotis: The blood vessels are not where they're supposed to be and therefore do more harm than good.
Balintfy: Dr. Stavros Garantziotis, a staff physician at the NIEHS, studies pulmonary fibrosis which is a disease where lung tissue becomes scarred.
Garantziotis: And the lungs therefore cannot take up the oxygen, therefore the patients get more and more short of breath, need more oxygen and in extreme cases may even die.
Balintfy: Dr. Garantziotis explains that a protein in the blood, called inter-alpha-trypsin inhibitor was found to play an important role in the response to injury, in that it helps make new blood vessels.
Garantziosis: And new vessel formation is a very important part of the response to tissue injury because new vessels are needed to deliver oxygen and nutrients to the injured site and then promote the healing of the injury.
Balintfy: Researchers found through test-tube experiments and animal models that the absence of inter-alpha-trypsin inhibitor causes less vessels to be formed. Therefore they expected more would be a good thing for lung patients.
Garantziosis: However we were surprised to find out that in patients the more inter-alpha-trypsin inhibitor we found in their blood the less ability they had to take up oxygen so it seems like it caused the reverse of what we were expecting.
Balintfy: Dr. Garantziotis adds that instead of building healthy new tissue to heal the scarring in the lungs, patients with higher inter-alpha-trypsin inhibitor levels develop vessels that are far away from where they should be, pushing the blood away from the lung and bypassing the area where the body gets its oxygen, thus causing more shortness of breath. Dr. Garantziotis emphasizes that there are at least two reasons why this research is important.
Garantziosis: The first is that for the longest time people have thought that pulmonary fibrosis is a local happening, in that the lung is injured and that everybody thought that only the lung is involved in the response. What we found, interestingly, is that that inter-alpha-trypsin inhibitor is actually produced in the liver in the case of lung injury. So the response to lung injury may be a whole body affair. The second is that new vessel formation may actually be a target for treatments for pulmonary fibrosis.
Balintfy: For more information on this study, visit www.niehs.nih.gov.
Genetic study opens door to individualized treatment strategies for Lung Cancer
Balintfy: From pulmonary fibrosis, to lung cancer. Now we turn to Wally Akinso and the genetics of the disease.
Akinso: A genetic study sheds new light on possible treatment strategies for the most common form of lung cancer.
Ozenberger: Lung adenocarcinoma, it's a non small cell lung cancer.
Akinso: Dr. Brad Ozenberger is a Program director at the National Human Genome Research Institute.
Ozenberger: About 150,000 people a year in the United States are diagnosed with it.
Akinso: A multi-institution team, part of the Tumor Sequencing Project consortium and funded by the NHGRI, charted the genetic changes involved in adenocarcinoma.
Ozenberger: Medically this study begins to show that the complexity of the disease is manageable.
Akinso: Using a systematic multi-disciplinary approach, the researchers detailed key pathways involved in the disease, and described patterns of genetic mutations among different subgroups of lung cancer patients, including smokers and never-smokers. The researchers are also using new tools and technologies to examine the complete set of DNA, or genome, found in various types of cancer.
Ozenberger: This study shows is that these technologies can reveal what's going on in these cancers. Tell us something new and that we can begin to sort out the real meaning from the genome of what's going on.
Akinso: Dr. Ozenberger says the findings should pave the way for more individualized approaches for detecting and treating the nation's leading cause of cancer deaths.
Ozenberger: So now we are going to be able as we dissect more and more cancers and understand the pieces that break the rest of the research community is going to be able to develop therapeutic strategies to fix these problems and help the cancer patients.Akinso: In addition, the genetic findings suggest that certain lung cancer patients might benefit from chemotherapy drugs currently used to treat other types of cancer. Dr. Ozenberger believes, clearly more still remains to be discovered, and researchers have just begun to realize the tremendous potential of large-scale genomic studies. This is Wally Akinso at the National Institutes of Health, Bethesda, Maryland.
Trial May Help Determine if Biomarkers Can Help Guide Treatment for Lung Cancer
Balintfy: A key to treating diseases like lung cancer, is being able to find out if and when someone might get the condition. In this next report from Wally Akinso, we hear about the importance of biomarkers: signs that can lead to identifying and treating lung cancer.
Akinso: A new large study could help guide treatment for lung cancer with the use of biomarkers, which are molecules found in the body that can signal an abnormal process or disease. A National Cancer Institute study for non-small cell lung cancer was launched to validate whether a biomarker can predict clinical benefit in the treatment of this disease.
Dr. Ullmann: What we’re trying to determine if this marker can also predict how the therapy can be effective or not based on the presence of that marker.
Akinso: Dr. Claudio Dansky-Ullmann is part of the Clinical Investigation Branch at the NCI.
Dr. Ullmann: You try to find a more direct reference in terms of what the patient has in his tumor or her tumor that you can target and the read out of that will allow you to say if the patient has this marker then that patient will benefit from that particular treatment that you’re trying to deliver.
Akinso: In this case, biomarkers would identify a target known as epidermal growth factor receptor which can be increased in some lung cancers. Dr. Ullmann explains the main objectives of the study.
Dr. Ullmann: One is to really see the role of the marker in trying to predict response to an agent that targets that particular marker. Then the other question is which way of measuring that marker is the one that is the most valid one. And then the other question is to compare in these patients with high or low activity of this marker if they would do better with a targeted therapy or they would do better or worst with the standard chemotherapeutic agent.
Akinso: Approximately 1,200 lung cancer patients will be tested for the status of the epidermal growth factor receptor, and then will be randomly assigned to treatment based on the test results. Dr. Ullmann is optimistic that this study can develop better therapies for lung cancer.
Dr. Ullmann: It would be very important to be able to pinpoint what a particular patient has in terms of these markers that may position that patient in a better way, to say well if you get this particular targeted therapy or agent you will do much better compared to receiving just nonspecific or standard therapy.
Akinso: Lung Caner is expected to claim 161,480 lives in 2008, and 215,020 people are expected to be diagnosed with the disease this year, making it the number one cancer killer. For more information on this trial visit, www.clinicaltrials.gov , and look up the MARVEL study. This is Wally Akinso at the National Institutes of Health, Bethesda, Maryland.
Balintfy: Coming up next, some insight on how scientists can start their careers in biomedical research. Stay tuned.
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NIAID Training Grant
Balintfy:More often than not, the stories in this podcast focus on the research and discoveries made here at the National Institutes of Health. We feature the NIH researchers, scientists and doctors who do the work, and with their help, get explanations of the importance of that work. In this special feature, we’re turning a little bit away from the research itself, to see how researcher can get their start. In particular, through training.
Prograis: Training mechanisms, whether it’s the institutional training grant, or an individual fellowship grant, or mentor career award…
Balintfy: Dr. Lawrence Prograis is a senior scientist at the National Institute of Allergy and Infectious Diseases.
Prograis: One of our central training mechanisms is the institutional training grant for which senior investigator at a major institution or institutions can apply for and if successful, they are awarded this training grant.
Balintfy: One such senior investigator is Dr. Robert Wood, professor of pediatrics at the Johns Hopkins University School of Medicine.
Wood: Our pediatric allergy and immunology fellowship program has had NIAID funding for 25 consecutive years now. And have been able to train some of the leaders in pediatric allergy and immunology in that time period.
Skirpak: My name is Justin Michael Skripak, and I’m working as a clinical faculty member at Mt. Sinai Medical Center in New York.
Balintfy: Dr. Skirpak is an example of a researcher who has recently benefited from NIH funding.
Skirpak: The training grant basically provided me with an opportunity to train at Johns Hopkins with Dr. Robert Wood as my mentor. And with that training experience I was able to find a position here at Mt. Sinai as a clinical faculty member.
Balintfy: NIAID’s Dr. Prograis, explains the details of Dr. Skirpak’s training.
Prograis: This particular institutional training grant was specific for young investigators, specifically pediatricians, those individuals who are training pediatrics, who want to go into an academic career in pediatrics, and Dr. Wood’s grant is specific for that.
Balintfy: Drs. Wood and Skirpak describe how they worked together.
Wood: Justin followed our usual path of clinical training with a substantial emphasis on research as well.
Skirpak: There were two big projects that I really worked on during my fellowship. The first one was a chart review looking at the milk allergic patients that had been seen there at Hopkins by Dr. Wood over the past 15 years. The second project was a clinical trial using a treatment with milk powder to treat children with milk allergy.
Wood: This was one of the first studies of its kind in the world and has now resulted in a publication in the Journal of Allergy and Clinical Immunology showing that most children with severe persistent milk allergy can be effectively treated with immunotherapy.
Skirpak: Essentially what we found is that the treatment with the increasing does of milk was effective to at least some degree in all children who were treated. And the side effect profile of the treatment was also within an acceptable range. So these children who were treated were initially reacting to as little as a quarter of a teaspoon of milk before the treatment, and afterwards were not reacting on average until they took five ounces of milk.
Balintfy: In addition to helping make this important research discovery about milk allergies, Dr. Skipak has, like other candidates, benefited from this kind of training grant in unique ways.
Skirpak: The training grant definitely provided me with the environment at Johns Hopkins where I could really do some research projects that probably couldn’t be done in many other places in the country.
Balintfy: Dr. Prograis says another benefit of programs like the NIAID training grant is that they lead to an intense training experience, which in turn has other positive results:
Prograis: Publications, as well as grant writing skills, as well as an in depth knowledge of how to go about doing research. And ultimately we would hope that these candidates once they’ve completed their training experience and enter into an academic research career, they then in turn will write a research grant and become successful in getting that grant themselves.
Balintfy: And Dr. Prograis adds that the individuals who receive these training opportunities are crucial to the continued progress of medical research.
Prograis: One could look at these individuals as representing the seed-corn for that next generation of researchers. They can be looked at as the new investigators that will enter into academic research or enter into the research world. Some may wind up teaching some may wind up going into biotech, some will go into academic medicine. A few may decide to go into becoming physicians to take care of patients. But that research experience that they’ve gotten, they represent the next generation of research and teachers and biologists who will take the lead in doing research for not only NIH but for America.
Balintfy: For more information on the specifics on NIAID training grants, or milk allergies, visit the website www.niaid.nih.gov.
Balintfy: For now, that's it for this episode of NIH Research Radio. Please join us again on Friday,December 26 when our next edition will be available for download. I'm your host, Joe Balintfy. Thanks for listening. NIH Research Radio is a presentation of the NIH Radio News Service, part of the News Media Branch, Office of Communications and Public Liaison in the Office of the Director at the National Institutes of Health in Bethesda, Maryland, an agency of the US Department of Health and Human Services.