NHLBI Special Report 2014: Microbiome

NHLBI Special Report

Microbiome

Department of Health and Human Services National Institutes of Health

Human Microbiome Research at the National Heart, Lung, and Blood Institute (NHLBI) A

typical healthy body is home to more than 1 trillion microbes known as our microbiome, and this number of microorganisms outnumbers human cells by about 10 to one. Until recently though, the role of the human microbiome in human physiology remained largely unstudied, which meant its influence on human health and disease states was not entirely known.

The National Institutes of Health (NIH) Common Fund Human Microbiome Project (HMP), which began in 2007 and goes through 2015, is one of the earliest efforts to break new ground in the study of the microbiome. As a community resource program, the HMP represents one of several international efforts working to generate rich, comprehensive, and publicly available datasets of the microbiome. Its ultimate goal is to develop tools and datasets for the research community to study the role of these microbes in human health and disease.

The HMP touches every component at the NIH. To this end, the Trans-NIH Microbiome Working Group (TMWG) was established in 2012 to provide a forum for coordinating NIH extramural research activities related to the human microbiome. NHLBI has played a pivotal role in this group since its formation and has increased its investments in microbiome research in areas relevant to heart, lung, and blood diseases and conditions.

The HMP has led to important cardiovascular, pulmonary, and hematologic research, and the NHLBI continues to assess the current state of knowledge on the role of microbiome in health and disease outcomes.

Recently, with the application of molecular profiling techniques to characterize a wide variety of microbes from whole blood, results indicate that sepsis infections are polymicrobial in nature and the microbiome can influence disease severity. This suggests that a microbiome approach is likely to enhance the diagnostic capabilities for severity of disease and identify targeted therapies for bacterial sepsis.

Efforts are also underway to better define which and how foreign organisms act as effectors or “seeds” for the lung microbiome along with other components of the respiratory tract, and the role they have in health and disease. New ways of thinking about respiratory and lung diseases are emerging. Studies now suggest that the microbiome may play a role in obesity. Recent observations in both animal models and humans have demonstrated that in the context of a high fat diet, there is a redistribution of gut microbiota and that this redistribution helps produce metabolites that mediate pathophysiologic conditions such as obesity, insulin resistance and atherosclerosis. Therefore, the gut flora is a newly recognized participant in cardiac and metabolic diseases. This new research has been a true revelation to the scientific community and gives just a glimpse into what we might learn in the years to come.

In this Special Report, you’ll learn much more about exciting microbiome research being supported by NHLBI—and opportunities for you to play a part in making our world healthier.

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MICROBIOME PROFILE Ronald Krauss, MD

Senior Scientist and Director of Atherosclerosis Research Children’s Hospital Oakland Research Institute (CHORI) In addition to his position at CHORI, Dr. Krauss is also

Adjunct Professor in the Department of Medicine at UCSF and in the Department of Nutritional Sciences at UC Berkeley, as well as a Guest Senior Scientist in the Department of Genome Sciences of Lawrence Berkeley National Laboratory.

Earlier in his career, he was on staff at the National Heart, Lung, and Blood Institute in Bethesda, Maryland, first as Clinical Associate and then as Senior Investigator in the Molecular Disease Branch. Over the years, he has published nearly 400 research articles and reviews on genetic, dietary, and drug effects on plasma lipoproteins and coronary artery disease. In recent years, Dr. Krauss’ work has focused on interactions of genes with dietary and drug treatments that affect metabolic phenotypes and cardiovascular disease risk.

What do you think is the greatest potential of research into microbiomes?

What impact has your specific research had on diseases of the heart, lungs, and blood?

Microbiome research opens up a major new dimension to our understanding of how interactions with our environment affect our health. Of particular interest is the role of the intestinal microbiome in human nutrition. For example, we are learning that our gut flora affects predisposition to the development of obesity and other conditions that influence cardiometabolic risk. Moreover, we are finding that we can modify the microbiome by dietary modifications, and we hope to be able to use this information to improve and individualize nutritional approaches for disease prevention.

My own research has focused on discovery of biomarkers that can be used to identify risk for cardiovascular disease and to monitor the effectiveness of dietary and drug intervention to reduce this risk. In particular, I have found that specific forms of lipoproteins in the blood that are not detected by standard tests can have a major impact on the development of coronary artery disease. In addition, my colleagues and I have developed methodologies for measuring these lipoproteins that are now being used by research laboratories around the world, as well as by thousands of clinicians who are using these tests to help

guide the prevention and treatment of heart disease in their patients.

Another of my research activities that has had significant impact is the demonstration that dietary carbohydrates have adverse effects on metabolic profiles associated with heart disease risk, and this work has contributed to an increased focus on limiting carbohydrates rather than fats in dietary recommendations aimed at maintaining cardiovascular health.

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“Hard work, intellectual curiosity, and very often serendipity, will take you down the right path.”

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What’s the most exciting finding to come out of your research?

Please talk a bit about how the funding you received from NHLBI has helped your project.

What advice do you have for a medical student who’s interested in research?

My recent studies employing genomic tools to discover new genes and pathways affecting cholesterol metabolism, as well as the efficacy of cholesterol-lowering treatment, have been particularly exciting. While this field of research is still in its early stages, it offers tremendous potential for developing new therapeutic agents, and for targeting individuals who are most likely to benefit from treatment.

I have been fortunate to have been continuously funded by NIH for nearly 40 years. This funding has been central to my research program and to the training of many scientists— particularly young scientists—in my laboratory.

Take advantage of as many opportunities as possible to work in laboratories of accomplished scientists with strong records of training young investigators. Don’t be discouraged if your initial experiences are frustrating; hard work, intellectual curiosity, and very often serendipity, will take you down the right path.

MICROBIOME PROFILE Ronald G. Collman, MD Professor of Medicine University of Pennsylvania School of Medicine

Dr. Collman joined the Penn faculty as Assistant Profes-

sor in 1990 and rose through the ranks to become Professor of Medicine and Medicine in Microbiology in 2004. In addition to his position as co-director of the Penn Center for AIDS Research (CFAR), he is the director of the Virus/ Molecular Core of the CFAR. Dr. Collman has an extensive background in HIV-related research in the areas of viral tropism, macrophage infection and viral entry, HIV/AIDS pulmonary complications and pathogenesis, as well as neuroAIDS pathogenesis.

Dr. Collman has been continuously funded through one or more NIH HIV/AIDS-related grants since 1989. He has served on various AIDS Study Sections for the NIH, private foundations and international governmental agencies. Dr. Collman serves on the Editorial Boards of the Journal of Clinical Investigation and the Journal of Virology. He is a clinician at the Hospital of the University of Pennsylvania, where he specializes in Critical Care Medicine.

What do you think is the greatest potential of research into microbiomes?

Microbiome research is focused on many different niches: gut, genital tract, oral cavity, skin, and much more recently, the respiratory tract.

For each niche the questions differ somewhat. In the gut, the normal microbiome is very rich and plays a huge role in normal physiology and health maintenance, as well as in disease. For example, the normal gut microbiome regulates immune development, and without gut bacteria the immune system does not properly develop or is not regulated correctly—not just in the gut, but also in the lung. Gut microbiome components also metabolize certain nutrients

to pro-inflammatory mediators that are then absorbed and contribute to cardiovascular disease. A great potential direction is figuring out how the microbiome can be manipulated to regulate inflammation, asthma and allergy, cardiovascular disease, not to mention obesity, diabetes and a host of other disorders.

Studies in the lung are at a much earlier stage. What our group has shown is that the healthy lung has exceedingly low levels of bacteria, and that the types of bacteria almost exactly match those that are found at the vocal cords. For that reason, we think that the normal lung is continually exposed to upper respiratory tract bacteria through micro-aspiration (which we know occurs at low

levels in healthy people), which are very efficiently cleared, and that the low levels of bacteria normally found there are a result of that. Others have shown that these bacterial communities are different in certain lung diseases, such as COPD, and we’ve shown markedly abnormal lung microbial communities (bacterial, fungal and viral) in people who have undergone lung transplantation. And obviously the lung microbial populations are different in suppurative diseases, where chronic or recurrent infection occurs, such as cystic fibrosis.

I see important opportunities for this to help us understand the normal process that deals with microbial seeding from the upper respiratory

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tract and how that goes awry in disease states, as well as whether those interactions impact the normal respiratory immune system.

In disease states where an abnormal respiratory tract microbiome is established, we want to look at how the individual components within the microbial community interact, and how they contribute to dysfunction and damage. For example, we are investigating whether these lung microbiome communities that are established in people who have received lung transplants play a role in the high rate of transplant failure over time.

Finally, the tools that have been developed to study lung microbiome are so powerful because you do not need to be looking for any specific agent, and so we think they will be very useful for new ways to diagnose lung infections and pneumonia.

What impact has your specific research had on diseases of the heart, lungs, and blood?

Studying the respiratory tract microbiome is quite different from sites like the gut, skin, oral cavity or genital tract for two main reasons. First, sampling those sites is straightforward because they are easily accessible. In contrast, in order to sample the lung in living subjects you need to pass through the upper respiratory tract (mouth, nose, throat), which is very rich in microbes. Secondly, the gut, skin and similar sites have rich microbial communities, and so inadvertent contamination from other sources has little relative impact. In contrast, the healthy lung has very low quantities of microbes, so the smallest bit of contamination, such

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What’s the most exciting finding to come out of your research?

as carryover during sampling from the upper respiratory tract, or even microbial DNA present on sampling instruments and reagents, can have a huge impact and create serious artifact.

I think our studies have had impact in two ways. First, we have helped develop approaches—both sampling and analytical—that can overcome some of these challenges to microbiome studies of the respiratory tract and hopefully will more effectively open the field for many groups to study a variety of lung diseases. Secondly, we have been able to show very clearly what the microbiome of the normal lung is both quantitatively and qualitatively, which is the basis needed for any studies of disease states. To be honest, studies in diseases are now just beginning, and I expect that the disease-specific impact of our work and many others now working in the area is soon to come.

One of the really cool things about bacterial 16S rRNA gene sequencing (which is one of the most common approaches used in microbiome studies) is that it is highly quantitative, meaning you can compare the proportions of each bacterial sequence in different samples. We used this to determine the relative abundance of bacteria in samples from the lung compared with samples in the upper respiratory tract, in order to identify those that are higher in the lung, which means they are growing in the lung. This can be a great way to define the cause of lung infections. Not only did this let us identify some expected bacteria that cause pneumonia, but it also led us to identify bacteria causing lung infection that cannot be be cultured, and to identify infection caused by multiple bacteria together. For example, we can see a “molecular signature pattern” of aspiration pneumonia, which is caused by normal mouth bacteria that enter into the lung and instead of being cleared, replicate and cause disease. We did this using a combination of molecular sequencing approaches (“wet bench” work) and mathematical/statistical computation (“dry bench” work).

Another exciting finding was the discovery that in the lungs of some healthy people, and much more commonly in people with HIV infection, you can find a bacteria that causes a rare gastrointestinal disease (Trophyrema whipplie); it was not previously known to reside in the lung. We did this work with a multi-center collaborative group

(the Lung HIV Microbiome Program) and so we know this is true for people with HIV infection in many different cities. We don’t yet know whether this actually causes lung disease in these people, but it’s a new finding ready to be followed up on.

Finally, we’re pursuing a new discovery in lung transplantation. We have found startlingly high levels of certain viruses in the lungs of people who received a lung transplant, even though they have absolutely no symptoms. It is going to be interesting and very exciting to try and figure out whether this has an effect on the transplanted lung and its outcome.

Please talk a bit about how the funding you received from NHLBI has helped your project.

We got our start in this area through NHLBI funding. Several years ago, a very forward-looking group within NHLBI identified lung microbiome studies as an important area with great potential. It was the NHLBI

HIV/AIDS program that was particularly interested in this area at the time, and I’ve been an HIV researcher for a long time in addition to being a Pulmonary and Critical Care physician. When the NHLBI issued a request for grant applications to study the lung microbiome in healthy people and those with HIV infection, we jumped at the chance both to use it as an opportunity to develop new approaches and tools for lung microbiome studies in general and to ask whether the lung microbiome might be altered due to immune deficiency in HIV infection. The project has been very fruitful and has enabled us to generate all our data so far. I am very grateful for the foresight of the NHLBI program to recognize this potential. That grant is now in its fifth year and has led to several additional projects enabling us to study the respiratory tract microbiome in other conditions including lung transplantation, the lung disease sarcoidosis, and other areas.

“If you are sure you want to pursue a path in research, consider a combined MD/PhD degree.”

What advice do you have for a medical student who’s interested in research?

Get great clinical training and go into a field of medicine that gets you really excited. Find opportunities to collaborate on research while you are a student so you get some early experience and develop a way of thinking. If you are sure you want to pursue a path in research, consider a combined MD/PhD degree. As you go through your clinical training and learn to be a physician, be open not just to what you are being taught but also to what you are not being taught because it’s not known. This will help you recognize the questions that still need to be answered that are relevant to clinical medicine, which is a great way to focus research on what is important and what interests you. Finally, good research is a collaborative effort. The studies we’ve done have worked only because of a collaboration between my group and that of Dr. Rick Bushman, a basic microbiologist here at Penn.

This type of collaboration enables new ideas to result from two different perspectives and backgrounds, creating more than either of us alone could.

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MICROBIOME PROFILE Alison Morris, MD, MS

Associate Professor of Medicine and Immunology University of Pittsburgh Medical Center After completing residency and fellowship at the University

of California San Francisco, Dr. Morris completed an additional year of critical care training and received a master’s of clinical science at the University of Pittsburgh. She became a faculty member at the University of Pittsburgh in Pulmonary, Allergy, and Critical Care Medicine, then was on the faculty at the University of Southern California before returning to Pittsburgh in 2006.

Dr. Morris’ clinical interests focus on lung disease in HIV-infected patients and in care of intensive care unit patients. The type of studies performed by Dr. Morris’ group include large cohort epidemiologic studies of lung disease and respiratory symptoms, translational studies in which physiologic and molecular techniques are applied to patient populations, and collaborations with co-investigators utilizing non-human primate models of disease.

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What do you think is the greatest potential of research into microbiomes?

What impact has your specific research had on diseases of the heart, lungs, and blood?

What’s the most exciting finding to come out of your research?

We are thinking about human diseases from a whole different perspective based on insights from microbiome work. The fact that microbial cells and genes outnumber those of humans has tremendous implications for how we think about disease causality. There are a multitude of ways that microbes could influence health and disease, and we are just beginning to understand the complex relationships of microbes and their hosts. These insights hold potential to change not only treatment of disease, but also the prevention of disease by altering early life exposures or by modifying the microbiome in a favorable way.

My research and the research of the Lung HIV Microbiome program has helped contribute to the understanding of the existence of a lung microbiome which was previously unknown and has revealed unique members of the lung microbiome such as Trophyrema whipplei and Pneumocystis jirovecii. The impact of these organisms on the lung is currently being investigated and may lead to novel treatments for lung diseases such as COPD.

I think the most exciting finding to come out of our research is the evidence that fungi such as Pneumocystis are important in HIV and lung disease, which suggests potential for novel treatments. Also, as a group, the Lung HIV Microbiome program found that Trophyrema whipplei, which usually causes a GI disease, is present in the lung and is more common in people with HIV. This was a totally unexpected finding, and we are still trying to figure out what the clinical significance is.

“NHLBI funding has given me the ability to mentor junior investigators in the field.�

Please talk a bit about how the funding you received from NHLBI has helped your project.

The funding from NHLBI was instrumental in helping me start in this area. There was little work in the lung microbiome prior to the lung microbiome Request for Applications (RFA) they issued, and I think this consortium has really been fundamentally important in moving the field forward and starting to address the methodological challenges faced by lung microbiome investigators.

Without the support of NHLBI, it is unlikely that I would have been able to enter this field. The funding has also been important in giving me the ability to mentor junior investigators in the field.

What advice do you have for a medical student who’s interested in research?

I think this is an exciting field for a medical student and can be approached in many different ways.

There are opportunities for training in the sequencing and analysis aspects of microbiome work, animal studies on effects of the microbiome and interventions that alter the microbiome or the immune response, or approaching the microbiome through more clinical research on specific human populations.

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MICROBIOME PROFILE John J. LiPuma, MD

Professor of Pediatrics and Communicable Diseases, University of Michigan Medical School Professor of Epidemiology, University of Michigan School of Public Health Dr. LiPuma directs the Cystic Fibrosis Foundation Burk-

holderia cepacia Research Laboratory and Repository at the University of Michigan. Research in this laboratory focuses on infectious diseases in persons with cystic fibrosis, with an emphasis on the epidemiology, ecology, natural history, clinical microbiology, taxonomy and pathogenicity of bacteria in the Burkholderia cepacia complex.

Current studies include analyses of the population genetic structure and evolution of B. cepacia complex; the natural history of infection by B. cepacia complex and related bacterial species in cystic fibrosis; virulence factors and pathogenic mechanisms of B. cepacia complex: and molecular epidemiology of B. cepacia complex and related species.

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What do you think is the greatest potential of research into microbiomes?

What impact has your specific research had on diseases of the heart, lungs, and blood?

The increasing appreciation that the microbes that live on us and within us impact on our health in previously unimaginable ways means that there is great potential to envision new approaches to managing health and treating disease. With each passing month, microbiomic research is being applied to new areas of medicine. While gastrointestinal disease and oral health were among the first areas to recognize the potential of microbiomic research to provide new insights to age-old diseases, we are starting to see the application of microbiome research into many other diverse areas ranging from chronic lung disease to cardiovascular disease to neurologic illness.

The research in my laboratory focuses on the respiratory tract microbiome in persons with cystic fibrosis (CF), a genetic disease that predisposes people to chronic infection and inflammation of the airways. We have found that the airways of people with CF are infected with a much broader array of bacteria than was previously appreciated. We’ve also gained important insights into how

the dynamics of these complex bacterial communities relate to flares of respiratory symptoms and lung disease progression. We’re very optimistic that this new understanding will open the door to new approaches to treating airway infection in CF.

What’s the most exciting finding to come out of your research?

We have found several things that challenge the conventional wisdom of airway microbiology in CF. For

“We’re very optimistic that this new understanding will open the door to new approaches to treating airway infection in CF.”

example, it has been long thought that as people with CF age they become infected with more and more different species of bacteria. What we – and other labs – have found is that while there seems to be an increase in the diversity of the bacterial communities in CF airways early in life, this diversity actually decreases as respiratory symptoms increase and lung health declines. We also are now beginning to track changes in the structure of bacterial communities around the time of flares of respiratory symptoms. A very surprising finding in this regard is that it appears that the density of certain of the more ‘typical’ CF pathogens, e.g., Pseudomonas aeruginosa, actually decreases around the time of these flares. This is a very intriguing finding that flies in the face of logic and could provide important insight into the mechanisms of disease flares in CF.

Please talk a bit about how the funding you received from NHLBI has helped your project.

In short, the work we have accomplished simply would not have been possible without support from NHLBI. In 2009, we were fortunate to have received a “Challenge Grant” from NHLBI that provided the funding we needed to embark on this project. That support was critical in allowing us to build an infrastructure that includes not only state-of-theart equipment for next generation DNA sequencing, but also personnel skilled in bioinformatics. We continue to rely on NHLBI to enable us to leverage this infrastructure into further discovery.

A super-fine oil-and-water emulsion appears to quell the ravaging, often drugresistant infections that cause nearly all cystic fibrosis deaths.

What advice do you have for a medical student who’s interested in research?

There is nothing more rewarding than taking on a really tough question, gathering the resources needed to address the question, and discovering something novel that has potential to improve the health of people worldwide. That’s really what biomedical research is all about.

What could be better?

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MICROBIOME PROFILE David Ginsburg, MD

James V. Neel Distinguished University Professor Internal Medicine & Human Genetics University of Michigan Medical School David Ginsburg is the James V. Neel Distinguished Uni-

versity Professor of Internal Medicine and Human Genetics, Warner-Lambert/Parke-Davis Professor of Medicine, a member of the Life Sciences Institute (LSI) at the University of Michigan Medical School, and a Howard Hughes Medical Institute Investigator. At Michigan, Dr. Ginsburg’s career has been distinguished in both clinical practice and basic research. As a physician, Dr. Ginsburg is board-certified in four specialties: hematology, oncology, internal medicine and clinical genetics. In his lab at the LSI, he investigates the fundamental biology and genetics of blood clotting.

Dr. Ginsburg has identified the genes and mutations associated with many subtypes of von Willebrand disease and the specific gene mutations that bring them about. The work has scientific implications as well as impact on patients with the disease.

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What do you think is the greatest potential of research into microbiomes?

What impact has your specific research had on diseases of the heart, lungs, and blood?

From a basic science perspective, this is a fascinating problem that we’re only now able to approach due to spectacular advances in sequencing technologies. We will certainly learn a lot about how our microbiome interacts with itself and with us, how this relates to human health and disease, and what the impact of antibiotic use is on this delicate balance. These findings might well set the stage for improved diagnosis and prediction for a wide range of human diseases, as well as more rational approaches to therapy. That said, this research is still in the early stages and it’s hard to predict what will happen.

For many years, the major focus of my lab’s research has been on the blood coagulation system and how disturbances in its function lead to human bleeding and clotting diseases. Our link to the microbiome has come serendipitously from two different lines of work. In the first, we discovered a gene variant in certain mouse strains that results in markedly reduced von Willebrand factor (vWF) levels. This variant has been maintained stably in a number of types of mice, in the laboratory and in the wild, suggesting that there must be some advantage to this variant that balances out the negative effect of low vWF levels. It turns out

that this variant significantly changes the intestinal microbiome of the mouse, and we suspect that this change—or altered susceptibility to a specific group of pathogens—may explain this balancing selection. Similar microbially related selection may well underly broad genetic variation in the normal level for many human blot clotting factors.

In a second line of work, we were exploring the action of the important human pathogen, Group A Strep (GAS). We found that this protein, which activates plasminogen to dissolve blood clots, is very important to the production of disease by GAS and that inhibiting streptokinase production by the bacteria improved the survival of infected mice. We have developed a number of compounds

that inhibit GAS expression that are now candidates for development as novel antibiotics to treat GAS and related human infections, including staph aureus.

What’s the most exciting finding to come out of your research?

That’s a tough one. The two examples described previously are certainly among them. Other areas not directly related to the microbiome include the discovery of mutations in the ADAMTS13 gene as the cause of familial Thrombotic thrombocytopenic purpura (TTP) and the discovery of mutations in LMAN1 and MCFD2 as the cause of combined deficiency of Factor V and Factor VIII. The latter finding led to a major effort in our lab focused on the mammalian ER to golgi secretory pathway. Those studies recently led us to discover a unique dependence of PCSK9 (a key regulator of cholesterol) on a specific component of the COPII coat (SEC24A). This work could conceivably lead to a new approach to the treatment of high cholesterol in people, another example of how fundamental basic research lays the groundwork for future translational work that could not be anticipated when the basic work began. I’m very grateful to the NHLBI for giving me the scientific and intellectual freedom to pursue such scientific questions, well before their translational potential was apparent.

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“Don’t pay attention to all of the grim news you hear about funding and follow your interests and excitement.”

Please talk a bit about how the funding you received from NHLBI has helped your project.

Funding from NHLBI has been instrumental in all the work our lab has done over the years. The projects described previously were supported by an Research Project grant (R01) focused on VWF, which has funded my lab since early in my career, and the bacterial work by a Research Program Project grant (P01), which also supports a former student of mine, Dr. Hongmin Sun (the PI of one of the P01 projects focused on this work), who is now an associate professor with her own lab at the University of Missouri, as well as an outstanding medicinal chemist, Dr. Scott Larsen, who is at the University

of Michigan.

What advice do you have for a medical student who’s interested in research?

Don’t pay attention to all of the grim news you hear about funding and follow your interests and excitement.

The NIH will continue to support the best research well into the future, and the current squeeze on funding will likely have passed by the time a current medical student is ready to start his or her own lab. Being a physician-scientist is a great privilege and the best career in the world. I wouldn’t trade it for anything.

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NHLBI Programs to Promote Diversity Research Supplements to Promote Diversity in Health-Related Research The Diversity Research Supplements enable principal investigators with eligible NHLBI research grants and contracts to support individuals from backgrounds underrepresented in biomedical science, including individuals from underrepresented racial and ethnic groups, individuals with disabilities, individuals from disadvantaged backgrounds, and individuals who wish to re-enter research careers, on their research projects. Research supplements are available for individuals from the high school to the junior faculty level.

For program information: http://www.nhlbi.nih.gov/research/training/application-guidelines.htm

INVESTIGATOR RESEARCH SUPPLEMENT AWARDEE PROFILE

Chiadi E. Ndumele, MD, MHS

Robert E. Meyerhoff Assistant Professor of Medicine, Division of Cardiology Johns Hopkins University School of Medicine How did you become interested in research?

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I was first motivated to pursue a health-related career as a result of some early community service experiences. I was involved in community health programs in high school and college, and was very inspired by the idea of helping improve people’s health outcomes. As I learned about illnesses and medical care during medical school, I began to realize how fundamental research was to our ability to care for patients. In my chosen field, cardiology, research has led to enormous advances in our understanding of disease processes and our ability to predict, prevent and treat illnesses. Seeing the effect research has had on improving the health and health care of so many individuals made me start to see research as an extension of the community service and clinical work that I initially found so inspiring. Because

lic health school at my institution.

I’ve also been fortunate to develop great relationships with outstanding research mentors, Drs. Josef Coresh and Gary Gerstenblith, who have provided invaluable guidance and support as I develop my research career.

What are you working on now?

of this, I decided to make research a primary focus of my career.

I realized that in order to support my goals for a research career, I would need strong training and mentorship in how to perform research.

During my cardiology fellowship, I received formal training in clinical research and epidemiology at the pub-

I’m currently an Assistant Professor of Medicine at Johns Hopkins, and I devote about 75% of my time to research. My focus is on the relationship between obesity and cardiovascular disease. Obesity is an enormous public health challenge that leads to several different kinds of cardiovascular disease. I’m particularly focused on the relationship between obesity and heart failure, both because there’s a very strong association between the two and because the pathways by which obesity leads

to heart failure are not very well understood. I perform epidemiologic research, examining large databases of individuals followed over several years in order to better understand heart failure risk, as well as clinical research studies that involve direct interactions with patients. By helping to improve our understanding of the relationship between obesity and cardiovascular disease, we hope our work will inform new strategies for predicting, preventing and treating cardiovascular disease.

What are the most exciting aspects of the research you’ve done to date?

In terms of research findings, we were very interested to recently discover an independent relationship between obesity and small levels of heart injury, measured by a novel biomarker, among asymptomatic individuals in the general community without cardiovascular disease.

Importantly, those asymptomatic individuals with both obesity and evidence of significant heart injury had a nine-fold higher risk of developing heart failure over a decade than normal weight individuals without detectable heart injury. Since the relationship between obesity and heart injury wasn’t explained by traditional risk factors like hypertension and diabetes, this has launched a whole new set of inquiries to help us understand why obesity is associated with heart injury and to determine the effects of weight loss.

More generally, it’s really exciting to develop and test new ideas, work collaboratively on research with groups of smart people, and

discover interesting new findings, all with the goals of advancing medical knowledge and hopefully improving our ability to care for people as a medical community.

How has the NHLBI supplement you received helped you?

The NHLBI supplement has been extremely helpful at this early stage of my investigative career. A large part of my salary was covered by funding from the supplement, insuring that I had “protected time” to dedicate to research as a young faculty member. The research I conducted while being supported by the supplement laid the foundation for the work I’m doing now, and also helped me to successfully apply for and receive some multi-year grants (including a K23 Career Development Award from the NHLBI) to continue to support my research. The supplement also provided additional resources to cover research project costs, as well as important networking opportunities. The NHLBI supplement is an outstanding program that provides much needed support at a critical juncture of early research career development.

“Keep your primary motivation in mind as you progress with your work.”

What advice would you give to a med student who’s interested in having research be a part of his or her career?

My first piece of advice is that there are many different kinds of research – epidemiologic, clinical, translational, basic, policy-based, educational and other kinds. If you find that you’re less inspired or excited by one kind of research, it’s a good idea to initiate an experience in another area of research to see if that’s a better fit. It’s also very important to identify good mentors who will help you develop a research career. It’s often not the case that one mentor will overlap with all of your areas of interest, and people frequently have more than one. I personally have two primary research mentors with complimentary areas of expertise.

Additionally, just like we need training to learn to take care of patients, some form of research training at some point is probably also helpful.

That training can take several forms, including research mentorship, coursework or a formal degree, and it’s an important part of research career development. Finally, in whatever kind of research you do, I would advise keeping your primary motivation, “the big picture,” in mind as you progress with your work.

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INVESTIGATOR RESEARCH SUPPLEMENT AWARDEE PROFILE

Stacey Jolly, MD, MAS Assistant Professor

Cleveland Clinic Lerner College of Medicine

Staff Physician, General Internal Medicine Cleveland Clinic

How did you become interested in research?

My initial research career started in the basic sciences with two summer programs; one at the University of California San Francisco (UCSF) and one at Harvard. ​From these experiences, I realized that although I appreciated the hard work of discovery in the sciences, my purpose was to become a physician. I became interested in clinical research based on what I was observing in my clinic: chronic diseases happening in people younger and younger, but also I noticed a need with regards to research focused on American Indian/Alaska Native populations. So after medical school and residency, I completed a research fellowship designed for physicians to become clinician investigators at UCSF. For additional faculty development, I finished the University of Colorado Denver Native Investigator program which is designed to help American Indian/Alaska Native MDs or PhDs flourish in a career in academics.

What are you working on now?

I currently have a K23 career development grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to assess chronic kidney disease knowledge (CKD) and awareness among American Indians and have 15

created a DVD of digital stories, which we will pilot as a prospective educational intervention over the next year. Additionally, I work with a multi-disciplinary group at Cleveland Clinic where we have developed a CKD registry with an active research program and were awarded an R34 grant from NIDDK entitled “Navigating the Challenges of CKD” to translate educational tools into improved patient care for those with CKD.

What are the most exciting aspects of the research you’ve done to date?

It is the people that I take care of in my clinic and the Native communities that I work with that keep me motivated and excited to continue a career in research and academic general internal medicine.

How did the NHLBI supplement you received helped you?

The NHLBI supplement allowed me to continue to work on pertinent Native health issues and specifically with the Alaska-based Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study. The supplement afforded me the time and money to transition from my research fellowship at UCSF and faculty development program with the Native Investigator Program to an NIH career development award.

“The great thing about medicine and research is there are infinite problems to be solved.”

What advice would you give to a med student who’s interested in having research be a part of his or her career?

My advice would be to seek out opportunities at your institution.

Don’t be afraid to reach out and express your interest and explore if there is a project that you might be able to collaborate on or develop your own project. Most institutions and organizations want to support student initiated scholarly work. It is important to realize that you may not find your research fit immediately, but the great thing about medicine and research is there are infinite problems to be solved and there is a significant need for good physician researchers.

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POSTDOCTORAL SUPPLEMENT AWARDEE PROFILE

Leslie O. Ofori, PhD Postdoctoral Fellow, Bogyo Laboratory Department of Pathology Stanford University School of Medicine How did you become interested in research?

As a young college student, I was very curious about the structural and biochemical properties of compounds and the roles these compounds play in our everyday lives. In particular, I was fascinated by the power of simple molecules such as antibiotics to treat various infections and ease pain. I therefore became interested in understanding mechanistically how drugs work and how to make new ones or redesign existing ones for a better treatment or for the diagnoses of diseases. After graduating with a major in chemistry, I decided to pursue graduate studies in synthetic and bioorganic chemistry. My research thesis was focused on the development of small molecules as drugs for HIV and myotonic dystrophy.

What are you working on now?

As a postdoctoral researcher in the laboratory of Dr. Matthew Bogyo at Stanford, I am currently working on the development of techniques for non-invasive imaging of solid tumors and lung fibrosis using chemical probes designed to target specific proteases that are present in macrophages. The ability to identify biomarkers for diseases such as cancer and fibrotic inflammations will allow for early and accurate diagnosis as well as prognosis of the outcome of drug treatment. Infiltration of 17

to deliver a payload of anticancer drug selectively to tumor cells with a reduction in the toxicity and other side effects associated with current chemotherapy drugs.

How has the NHLBI supplement you received helped you?

immune cells such as macrophages into tumor microenvironments constitutes one of the hallmarks of most cancers and inflammations.

What are the most exciting aspects of the research you’ve done to date?

Cancer remains the second most common cause of death in the developed world. The success rate of chemotherapy depends strongly on early detection of a tumor. Therefore, chemical probes that can be used to non-invasively image will enable early diagnosis of cancer without the need for open surgery. Our approach is based on the design of compounds that selectively target tumor associated immune cells. This is exciting because these compounds have the potential to detect and report early signs of cancer and fibrosis in a non-invasive manner. Also, these compounds can be designed

Dr. Matthew Bogyo’s lab at Stanford combines expertise in both chemistry and biology to solve complex problems in biomedicine. The lab is equipped with various facilities making it convenient to achieve research goals in a timely way. The NHLBI’s support of me in this environment has enabled me to acquire diverse sets of skills necessary to be successful as an independent scientist. In addition, Stanford University School of Medicine has one of the largest groups of scientists and clinicians focusing on cutting edge research topics. I therefore have a unique opportunity to directly interact and collaborate with scientists at various levels, from basic science to advanced clinical research, which has also rapidly enhanced my growth as an independent scientist.

What does your “dream job” look like?

I am looking forward to an exciting career as an independent scientist with a focus on the discovery of new drugs for the treatment and diagnosis of diseases that are difficult to treat.

GRADUATE RESEARCH SUPPLEMENT AWARDEE PROFILE

Valarie Blue Bird Jernigan, DrPH, MPH Assistant Professor, College of Public Health University of Oklahoma Health Sciences Center How did you become interested in research?

Growing up, I never thought of becoming a scientist. I was an artist, a writer, a photographer. I liked science, but it was never something I thought I would pursue for a job until after graduating with a degree in anthropology. I knew I wanted to go on to graduate school, but didn’t know what I wanted to do. I knew that I wasn’t interested in just observing communities; I wanted to intervene in some of the factors that were creating injustice and do something that would help create more equality.

I got interested in public health because it was one of the graduate programs that University of Oklahoma offered, and I interviewed with a researcher, Dr. Elisa Lee, who at the time was leading the largest study on Native American cardiovascular disease, the Strong Heart Study. I decided to pursue an M.P.H., and she ended up becoming one of my first mentors. On my first day of work on the study, I showed up expecting I would be surrounded by other Native American researchers, but I was the only one, and I was a student to boot. It made me committed to becoming one of the voices at the table exploring public health questions in the Native community.

going to increase the amount of fresh fruit and vegetables available and sell it at prices tribal members can afford. We’ll work with product placement and promotion, offering coupons and so forth. It seemed like a good opportunity to intervene where people are already shopping.

What are the most exciting aspects of the research you’ve done to date?

What are you working on now?

THRIVE, Tribal Health and Resilience in Vulnerable Environments, is a 5-year NHLBI - funded randomized trial of healthy makeovers of tribally owned convenience stores in the Choctaw and Chickasaw Nations of Oklahoma.

These convenience stores are business endeavors tribes have embarked on to branch out from casinos and you’ll find them throughout the Nations. Because a lot of these areas are very rural, these stores are often tribal members’ main grocery store. Rather than drive to a Wal-Mart 60 miles away, they’ll go here and shop. The problem is, they sell high-fat, high-calorie processed foods. Some have fast food restaurants attached to them. Some have drive-through smoke shops so you don’t even have to get out of your car to purchase cigarettes. Our plan is to randomize these stores and to implement healthy food makeovers. We’re

Through my training, I became really interested in participatory research, and that led me to California and UC Berkeley. That’s where I realized I could mesh the two sides of my personality and it’s where the world of science, public health and film came together for me.

The type of research I do today, community-based participatory research, uses research combined with action for social change. I use research as a tool to empower communities and give communities an opportunity to tell their stories.

That’s what prompted my latest documentary project, 40 Winters.

The western world uses science to understand the world, and it’s an incredible tool. Native people have always used story as the way to understand the world. Growing up bi-racial—my mother is white, my father is Choctaw—“story” is how I learned about who I am and it was a natural progression with my work, especially as a way to speak to Native people.

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Can you talk about the path from getting a Graduate Research Supplement and now having an R01? What have you learned that could be helpful to someone who has similar goals?

Those of us who are not exposed to career development planning and training can easily get lost in the cracks. My graduate research supplement was my first major opportunity to build my career, and I took it. I was lucky that Dr. Elisa Lee, PI of the Strong Heart Study, offered it. So the first thing I would say is that you have to be open to all of the opportunities that arise in your life, which means you have to be open, you have to be looking for what life has to offer you (even if you’re not at all sure that is anything!).

The next thing I would say is that opportunities are more likely to present themselves to those who are prepared, who have passion, and who have a point of view. I believe a big reason I’ve been successful is because I am passionate about working to improve the health of Native people and that comes through in my work. I am always prepared. I do my homework. During my education and training if I had a meeting with a PI, I read his or her research, I studied what he or she worked on, and I developed my own point of view on that PI’s work. Indeed, I only approached potential mentors because I loved their work, and I always came with questions to our

meetings. This made me stand out as being prepared, curious, creative, and engaged, and people want to support students like that.

Mentoring is a two-way street.

Mentors will take you on if you have something to offer them as well, and I always did. After the diversity supplement I received when I was doing my MPH, I applied and was accepted to UC Berkeley, and I immediately got started writing an NIH pre-doc grant, which got funded through NIDDK. I was the first student in the history of UC Berkeley to come into the College of Public Health with NIH pre-doc funding. I did this by immediately meeting with faculty after I got notice I’d been accepted and planning my pre-doc grant, writing it the semester before I started at Cal. I think that this comes from a desire, again, to take advantage of opportunities. I went to Kate Lorig, another mentor of mine at Stanford, and told her I wanted to apply for the NIH pre-doc and I wanted to do the pre-doc on her diabetes self-management program, modified for Native Americans.

So again, I had an agenda and a goal, and I just needed her support.

This was exciting and appealing for her and I think people enjoy mentoring students who are already hitting the ground running. I stayed on at Stanford to do a three-year, NHLBI-funded postdoc grant.

At this point, I was beginning to get my own research funding through Robert Wood Johnson Foundation and Cal Endowment, and it was because I had a point of view; I had

specific research I wanted to do and I worked to write that up and get it funded. I would say those qualities have served me well.

Because the bottom line is this: those of us who are from diverse backgrounds come into the university system and into research to offer our diverse perspectives. That is what diversity is about. For me it was being American Indian, Choctaw, and my goal was to bring my Choctaw worldview into the academic setting, into science, and into research. I was passionate about that, about being within the academic system and offering up the reality that there are different ways of looking at this, not just one. That is what good science is. And even though I have worried many times throughout my career “Should I have spoken up then?

Should I have said that?” I never let that worry silence my genuine openness to expand my knowledge and hopefully, at least, make others think about things along the way.

“Opportunities are more likely to present themselves to those who are prepared, who have passion, and who have a point of view.”

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Graduate Research Supplement Awardee Profile

Annie Mirsoian

Laboratory of Dr. William J Murphy, PhD Department of Dermatology UC Davis School of Medicine How did you become interested in research?

My initial discovery of my interest in pursuing a career within research came in an unconventional and roundabout manner. During my undergraduate years, I pursued degrees in both biology and philosophy.

I had a long passion for acquiring skills in argumentation and, simultaneously, I was increasingly falling in love with the world of biomedical science. I pined for the ability to rationalize the world around me in a logical manner, and particularly sought out opportunities to study the causes and systems behind human health and disease. While I was initially unsure of how to bring these two worlds together, in my second year I was very fortunate to be offered a position within a research laboratory. I jumped at the opportunity and instantly realized that scientific research offered me a way to mesh my love of logical reasoning with my drive to solve biomedical questions. This early opportunity opened my eyes to a new world of possibilities and instantly taught me that a career in research was definitely for me.

What are you working on now?

My research is centered within the field of immunology, with a focus on natural killer (NK) cell biology.

NK cells have been defined based on their ability to target and kill a

variety of “stressed” cells, such as tumor cells, infected cells, and damaged cells. My current research focuses on delineating the distribution of NK cell subsets, as defined by their distribution of activating

due to the pathogenesis of blood cancer malignancies. Therefore, I am also applying my findings within both young and aged models to determine the consequences of aging upon NK cell subset distribution and function. Data gathered from this project will help lead to the discovery of novel NK cell developmental and homeostatic pathways as well as a deeper understanding of NK cell subset effector functions and immunomodulatory capabilities. My goal is for my project to foster the discovery of novel regulatory mechanisms that may enhance anti-viral responses to protect patients from secondary infections and impact overall patient outcome.

“Scientific research offered me a way to mesh my love of logical reasoning with my drive to solve biomedical questions.” and inhibitory receptors, within different viral disease states as well as post-hematopoietic stem cell transplantation (HSCT). Immediately after HSCT, patients experience a significant risk for the development of secondary viral infections that often cause post-transplant morbidity and mortality. In addition, patients undergoing HSCT are most commonly skewed as either young or elderly

What are the most exciting aspects of the research you’ve done to date?

Although NK cells have traditionally been described as effector cells due to their rapid production of Interferon-gamma and cytotoxicity, our lab is beginning to add additional effector functions to unique subsets of NK cells that have, until this point, largely gone undefined. This aspect of our research is the most exciting 20

as we are beginning to unravel the complexity of NK cell biology and function under various disease states, and we are expanding on the traditional roles of NK cells to include various immunoregulatory roles. These new and unique NK cell subset effector functions will allow for greater clinical utility of NK cells and a more robust understanding of how we may modulate these different effector functions based on the disease state and age of individual patients.

How has the NHLBI supplement you received helped you?

The NHLBI research supplement has played a central role in allowing me to further the development of my laboratory capabilities and allowed the rapid progress of my project. In addition, I feel that the NHLBI supplement has been highly supportive

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of ensuring my continual growth as a scientist by also providing support to attend conferences and to participate in career development opportunities. Through this support I have been able to take additional courses, attend training seminars, and present my research at two national meetings where I am able to interact and network with key scientists.

Overall, this fellowship has greatly enhanced my ability to be both scientifically productive as well as continue to develop and shape my path towards a career in research.

What does your “dream job� look like?

My dream job would be a faculty research position either within a university or a teaching hospital setting. As an immunologist, I hope to build a laboratory with a focus upon conducting meaningful research that can be translated from bench

to bedside. My experiences thus far within my graduate degree training at the UC Davis School of Medicine have endowed me with a deep appreciation for the importance of collaborations between clinicians and laboratory-based researchers. I am experiencing first-hand the impact that these partnerships have on the ability to quickly translate scientific advances into improved therapies for cancer patients. I hope to continue this practice of working together with both laboratory-based scientists and medical professionals and being able to make positive impacts on patient outcomes.

Graduate Research Supplement Awardee Profile

Daniel Serrano Laboratory of Dr. Silvia Muro

University of Maryland, College Park How did you become interested in research?

I first became interested in research during my undergraduate studies in environmental science. One semester, I took a course on phytoremediation, which refers to the use of plants for pollution clean up. This exposed me to the potential of understanding biological processes in order to harness them for the benefit of society.

Around this time, I applied for a National Science Foundation summer Research Experience for Undergraduates where I got to experience first-hand the world of research by going to the field and collecting data, writing a mock scientific journal article, and presenting my findings orally. Partly by coincidence, the project I worked on was related to understanding the ecology of a plant that can be used for phytoremediation.

This consolidated my excitement for the potential of understanding how biological systems work, and I decided to pursue my career in research.

What are you working on now?

Right now, I’m writing my dissertation, so I’m working on synthesizing all the work I’ve done during the last five years. However, the last project I worked on involved the improvement of pharmaceutical drug delivery to specific organs or sites of disease by using nanotechnology. During my grad school career, I’ve also focused on understanding the interactions between immune cells and blood

graduate student, I have focused on understanding the basic biology of blood vessels in order to improve the targeted delivery of pharmaceutical drugs.

How has the NHLBI supplement you received helped you?

vessels and also the behavior of blood clots, both of which have relevance in the clinical field, since inflammation and coagulation underlie a diverse set of pathologies.

What are the most exciting aspects of the research you’ve done to date?

The most exciting aspect of all my research projects has been their tangible applicability for improvement of society. As an undergraduate, I worked on understanding the ecological properties of a group of plants that can be exploited for phytoremediation. I also studied the molecular assembly of a group of enzymes to allow for the biosynthesis of anti-cancer compounds. As a

The NHLBI supplement has helped me focus on my research during my last year of studies. I have been able to fully concentrate on wrapping up experiments and writing my dissertation. I was also able to attend a few conferences, which has been a great way to improve my presentation skills.

What does your “dream job” look like?

As I’ve gone through the experience of graduate school, I have gained an appreciation for the idea of improving the way science works. This includes science funding, publishing, and keeping the public informed about how their tax contributions are used.​I would eventually like to be in a position that allows me to think about and enact how we can make science funding and/or publishing more efficient (and also more transparent to the public).

“The most exciting aspect of all my research projects has been their tangible applicability for improvement of society.”

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​ iomedical Research Training Program B for Individuals from Underrepresented Groups Profiles The NHLBI established the Biomedical Research Training Program for Individuals from Underrepresented Groups (BRTPUG) to offer opportunities for underrepresented post-baccalaureate individuals to receive training in basic, translational, and clinical research. The purpose of the program is to enhance career opportunities in biomedical sciences, including clinical and laboratory medicine, epidemiology, and biostatistics as applied to the etiology and treatment of heart, blood vessel, lung, and blood diseases.

BRTPUG offers each participant the opportunity to work closely with leading research scientists in the Division of Intramural Research and extramural scientists in the Division of Cardiovascular Sciences -Prevention and Population Sciences Program. The program provides participants with handson training in a research environment, which will prepare them to continue their studies and advance their careers in clinical and basic research.

Ashlea Morgan Mentor: Dr. Herbert Geller (PI) Lab: Developmental Neurobiology Section of the Cell Biology and Physiology Center of NHLBI How did you become interested in research?

I have always been very curious about why things are the way they are. This curiosity swelled during my first biology class in high school. Our very enthusiastic biology teacher would explain the scientific method and encourage us to explore life processes through collaborative science projects and in class assignments. I found this class and the material amazing! I believe my interest in the brain stems even earlier to a talk I attended in middle school. The lecturer, a neurologist from a local medical school, talked about the brain and identified it as the next frontier in medicine. He asked us provocative questions about the power of the mind and introduced the term “metacognition.” After the talk, I was able to touch the brain and explore the sulci and gyri. I was hooked! This amazement influenced my decision to become a biology/pre-professional major at my previous institution and, after transferring, a neuroscience major. I began seeking out different opportunities for research. In the spring of 2012, I began in a developmental biology lab working on the expression of a family of genes important for development, primarily of the nervous system in Xenopus laevis embryos. It was a steep learning curve for me, but I truly enjoyed being in the lab and learning new techniques. It encouraged me to seek out more research experiences after graduation.

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How did you learn about the Biomedical Research Training Program for Individuals from Underrepresented Groups supported by the NHLBI? As a way of coming full circle, I learned about this program from a friend who read about it in an earlier edition of this journal. After reading the online description, I thought it would be a wonderful opportunity for me to continue doing research and I decided to apply.

How has your internship helped you and how do you think it will help you with your goals for the future?

There are several ways this internship has helped me. I have had the opportunity to learn exponentially more about research than I previously knew in undergrad; first, because I have more time to learn and practice lab skills or gain scientific knowledge (give or take 40 hours during the week) and secondly, because I am allowed and encouraged to explore the fields of my interest through easily-accessible literature, on-campus seminars and workshops, and off-campus conferences. I have become more confident in my scientific abilities and have even displayed and defended my work in poster presentations, both on campus and at an international meeting. All this is surrounded by the ample support offered by my mentors, particularly Dr. Geller, Dr. Mishoe, and Dr. Katagiri. My mentors are always available when I have questions or concerns and each one is personally invested in my success. I have been given the opportunity to make this experience my own and develop individually as a researcher. My experience in the BRTPUG program and doing research at NIH in NHLBI will propel me towards my future goals.

As I begin planning for my next steps, I feel fortunate that I have been able to have this experience.

Georgina Kemeh Mentor: Dr. A ​ lan Remaley Lab: Cardiovascular and Pulmonary Branch How did you become interested in research?

During my sophomore year in college, I took a genetics class and my professor introduced some things he was working on in his lab. It was pretty interesting, so I asked to work with him. I started working on a project in his lab, and I became even more interested in research.

How did you learn about the Biomedical Research Training Program for Individuals from Underrepresented Groups supported by the NHLBI? During the fall 2012 semester, I presented results from my research at the Annual Biomedical Research Conference for Minority Students (ABRCMS) in California. While I was there, I visited the NIH booth to find out about the programs available for students who want to enter the medical field. I gained valuable information on becoming a post-bac and applying to the post-bac program.

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How has your internship helped you and how do you think it will help you with your goals for the future?

My internship at the NIH has been an amazing experience. My lab is very nurturing, and I started learning new things right away. My PI is a physician-scientist, and he has some clinical trials going and he keeps me in the loop. He knows that I want to go to medical school and become a physician, so he encourages me to come with him on patient rounds, and I have learned a lot from his clinical trials. My current project focuses on ways to reduce LDL cholesterol levels in patients with Familial Hypercholesterolemia, and I must say it is an intense project. This project means a lot to me and I am passionate about it since it has a potential for finding alternate ways to cure patients with elevated cholesterol level and prevent heart disease.

On a personal level, I have learned a lot about planning and organization. I have experienced growth as an individual, and I have also learned a lot about financial security and other essential social skills through the educative series of post bac lectures. Being in this program also helped me prepare for the MCAT. I have met and interacted with other students who have similar goals, which keeps me encouraged.

All the things I have experienced and learned from my internship at the NIH will be with me everywhere I go in life. I believe I have gained skills that will make me a great physician someday.

Joshua Okonkwo Mentors: Dr. Iain Scott and Dr. Michael Sack Lab: Center Molecular Medicine How did you become interested in research?

As a young kid, I enjoyed studying natural science, but it wasn’t until I went to college that I was formerly introduced to areas of research that appealed to both my creative and scholarly tendencies.

How did you learn about the Biomedical Research Training Program for Individuals from Underrepresented Groups supported by the NHLBI? I contacted the director of education at the NHLBI to discuss doing a post-baccalaureate year at the NIH, and he made mention of the program. I was particularly struck by the unique opportunities for mentorship and also the chance to be part of small community of like-minded scholars so I decided to apply.

How has your internship helped you and how do you think it will help you with your goals for the future?

Working at the NIH has been a rewarding experience. In addition to conducting my own research, I was afforded the opportunity to listen and network with researchers from across the county and world who come to the NIH to present their work. Thanks to the continued support and guidance from the BRTPUG program director and the many mentors I have been fortunate enough to have at the NIH, I feel I am better prepared to pursue a career in academic medicine.

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Research Training and Career Development Programs The NHLBI supports training and career development programs to prepare individuals to become productive researchers in the prevention and treatment of heart, lung, and blood diseases and sleep disorders.

The following is a list of some of the research training and career development opportunities at the NIH and NHLBI-funded institutions.

NIH Undergraduate Scholarship Program Offers competitive scholarships and research training at the NIH to exceptional students from disadvantaged backgrounds who are committed to biomedical, behavioral, and social science research careers.

NIH Summer Internship Program in Biomedical Research Open to students with strong research interest demonstrated through coursework, from high school through the graduate level, as well as medical and dental students. Research training takes place at NHLBI laboratories for 8 weeks or more during the summer.

NIH Postbaccalaureate Intramural Research Training Award (IRTA) Fellowship Supports one year of research training at the NHLBI for college graduates, within two years of graduation, who have plans to attend graduate or medical school immediately following the fellowship. Students apply to medical school or graduate school during the training period.

Short-Term Research Education Program to Increase Diversity in Health-Related Research (R25) Promotes diversity in health-related research by providing short-term support to undergraduate and health-professional students from diverse backgrounds.

T32 Training Program for Institutions That Promote Diversity This program provides training to predoctoral and health professional students and individuals in postdoctoral training at non-research intensive institutions with an institutional mission focused on serving minority and other health disparity populations not well represented in scientific research, or institutions that have been identified by federal legislation as having an institutional mission focused on these populations, with the potential to develop meritorious training programs in cardiovascular, pulmonary, and hematologic diseases, and sleep disorders. The NHLBI’s T32 Training Program for Institutions That Promote Diversity is designed to expand the capability for biomedical research by providing grant support to institutions that have developed successful programs to promote diversity and that offer doctoral degrees in the health professions or in health-related sciences.

NIH NRSA Individual Predoctoral MD/PhD or Other Dual-Doctoral Degree Fellowship (Parent F30)

MENTORING The NHLBI eMentoring Initiative is a valuable resource that provides mentorship to students and junior faculty in science-related fields. The goal is to provide Protégés with mentoring to enhance their skills and intellectual growth in science-related fields, to facilitate their successful entry into related research careers, and to promote interdisciplinary collaborations and training and career development. The NHLBI eMentoring Initiative places emphasis on mentoring individuals at less-research intensive institutions.

Sign Up TODAY! http://www.nhlbi.nih.gov/research/ training/e-mentoring/index.htm NIH NRSA Individual Predoctoral Fellowship to Promote Diversity in Health-Related Research (Parent F31-Diversity) Supports individuals from backgrounds underrepresented in biomedical science, including individuals from underrepresented racial and ethnic groups, individuals with disabilities, and individuals from disadvantaged backgrounds enrolled in programs leading to a PhD, MD/PhD, or other combined degree in the biomedical or behavioral sciences.

NIH NRSA Individual Predoctoral Fellowship (Parent F31) Supports predoctoral students in obtaining individualized mentored research training from outstanding faculty sponsors while conducting dissertation research.

Loan Repayment Programs (LRP) Information regarding the eligibility requirements and benefits for these programs may be obtained through the LRP Website: www.lrp.nih.gov/

The NHLBI supports individual predoctoral fellowships for combined MD/PhD training in research areas relevant to the mission of the NHLBI.

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K-Award Series for Career Development Provides research development opportunities for basic and clinical research scientists with varying levels of research experience who are committed to developing into independent investigators. http://grants.nih.gov/training/careerdevelopmentawards.htm

Mentored Research Scientist Development Award (Parent K01) This award supports individuals who have a research or health-professional doctoral degree and provides “protected time” (3-5 years) for an intensive, supervised career development experience. The candidate’s research project proposed must be relevant to the mission of the NHLBI and must be focused on one or more target areas specified by the NHLBI.

Mentored Career Development Award to Promote Faculty Diversity/Re-Entry in Biomedical Research (K01) Supports investigators from diverse backgrounds underrepresented in research areas of interest to the NHLBI or those who wish to re-enter their research careers (e.g., after a hiatus due to family circumstances). It is targeted toward individuals whose basic and clinical research interests are grounded in the advanced methods and experimental approaches needed to solve problems related to cardiovascular, pulmonary, and hematologic diseases in the general and health disparities populations. This program provides research development opportunities for non-tenured science faculty from diverse backgrounds underrepresented in research areas of interest to the NHLBI and for non-tenured re-entry science faculty with varying levels of research experience. The award will enable suitable faculty members holding doctoral degrees, such as the PhD, MD, DO, DVM, or an equivalent, to undertake special study and supervised research under a mentor who is an accomplished investigator in the research area proposed and has experience in developing independent investigators.

Mentored Clinical Scientist Research Career Development Award (Parent K08) This award supports postdoctoral individuals and junior faculty members who undertake three to five years of mentored research. Candidates must have clinical doctoral degrees or equivalent.

NHLBI Career Transition Award for Intramural Fellows (K22) Provides highly qualified postdoctoral fellows with an opportunity to receive mentored research experience in the NHLBI Division of Intramural Research and to facilitate their successful transition to an extramural institution as new investigators.

Mentored Patient-Oriented Research Career Development Award (Parent K23) To provide support for the career development of investigators who have made a commitment to focus their research endeavors on patient-oriented research. This mechanism provides support for a 3-year minimum up to a 5-year period of supervised study and research for clinically trained professionals who have the potential to develop into productive, clinical investigators.

FOR ADDITIONAL INFORMATION ON NHLBI TRAINING PROGRAMS NHLBI Research Training and Career Development http://www.nhlbi.nih.gov/research/training/

NHLBI Intramural Office of Education http://www.nhlbi.nih.gov/research/intramural/education/

NIH Intramural Research and Training Opportunities www.training.nih.gov

Special Report Editorial Contributions Center for Translation Research and Implementation Science, NHLBI Dr. Helena Mishoe Dr. Nara Gavini Janita Chicquelo-Coen Leslie Bassett

Additional Contributions Staff from the Division of Blood Diseases & Resources Staff from the Division of Cardiovascular Sciences Staff from the Division of Lung Diseases 27

Contacts for NHLBI Programs Academic Institutions:

Helena O. Mishoe, PhD, MPH National Heart, Lung, and Blood Institute Phone: (301) 451-5081 mishoeh@nhlbi.nih.gov

The NIH Campus, Bethesda, MD:

Herbert Geller, PhD National Heart, Lung, and Blood Institute Phone: (301) 451-9440 gellerh@nhlbi.nih.gov