Duke Research Blog

Following the people and events that make up the research community at Duke.

Category: Biology (Page 1 of 18)

Opportunities at the Intersection of Technology and Healthcare

What’d you do this Halloween?

I attended a talk on the intersection of technology and healthcare by Dr. Erich Huang, who is an assistant professor of Biostatistics & Bioinformatics and Assistant Dean for Biomedical Informatics. He’s also the new co-director of Duke Forge, a health data science research group.

This was not a conventional Halloween activity by any means, but I felt lucky to be exposed to this impactful research surrounded by views of the Duke forest in fall in Penn Pavilion at IBM-Duke Day.

Erich Huang

Erich Huang, M.D., PhD. is the co-director of Duke Forge, our new health data effort.

Dr. Huang began his talk with a statistic: only six out of 53 landmark cancer biology research papers are reproducible. This fact was shocking (and maybe a little bit scary?), considering  that these papers serve as the foundation for saving cancer patients’ lives. Dr. Huang said that it’s time to raise standards for cancer research.

What is his proposed solution? Using data provenance, which is essentially a historical record of data and its origins, when dealing with important biomedical data.

He mentioned Duke Data Service (DukeDS), which is an information technology service that features data provenance for scientific workflows. With DukeDS, researchers are able to share data with approved team members across campus or across the world.

Next, Dr. Huang demonstrated the power of data science in healthcare by describing an example patient. Mr. Smith is 63 years old with a history of heart attacks and diabetes. He has been having trouble sleeping and his feet have been red and puffy. Mr. Smith meets the criteria for heart failure and appropriate interventions, such as a heart pump and blood thinners.

A problem that many patients at risk of heart failure face is forgetting to take their blood thinners. Using Pillsy, a company that makes smart pill bottles with automatic tracking, we could record Mr. Smith’s medication taking and record this information on the blockchain, or by storing blocks of information that are linked together so that each block points to an older version of that information. This type of technology might allow for the recalculation of dosage so that Mr. Smith could take the appropriate amount after a missed dose of a blood thinner.

These uses of data science, and specifically blockchain and data provenance, show great opportunity at the intersection of technology and healthcare. Having access to secure and traceable data can lead to research being more reproducible and therefore reliable.

At the end of his presentation, Dr. Huang suggested as much collaboration in research between IBM and Duke as possible, especially in his field. Seeing that the Research Triangle Park location of IBM is the largest IBM development site in the world and is conveniently located to one of the best research universities in the nation, his suggestion makes complete sense.

By Nina Cervantes        

Smoking Weed: the Good, Bad and Ugly

DURHAM, N.C. — Research suggests that the earlier someone is exposed to weed, the worse it is for them.

Very early on in our life, we develop basic motor and sensory functions. In adolescence, our teenage years, we start developing more complex functions — cognitive, social and emotional functions. These developments differ based on one’s experience growing up — their family, their school, their relationships — and are fundamental to our growth as healthy human beings.

This process has shown to be impaired when marijuana is introduced, according to Dr. Diana Dow-Edwards of SUNY Downstate Medical Center.

Sure, a lot of people may think marijuana isn’t so bad…but think again. At an Oct. 11 seminar at Duke’s Center on Addiction & Behavior Change, Dow-Edwards enlightened those who attended with correlations between smoking the reefer and things like IQ, psychosis and memory.

(https://media.makeameme.org/created/Littering-and-SMOKIN.jpg)

Dow-Edwards is currently a professor of physiology and pharmacology and clearly knows her stuff. She was throwing complicated graphs and large studies at us, all backing up her primary claim: the “dose-response relationship.” Basically the more you smoke (“dose”), the more of a biological effect it will have on you (“response”).

Looking at pot users after adolescence showed that occasionally smoking did not cause a big change in IQ, and frequently smoking affected IQ a little. However, looking at adults who smoked during adolescence correlated to a huge drop of around 7 IQ points for infrequent smokers and 10 points for frequent smokers. Here we see how both age and frequency play a role in weed’s effect on cognition. So if you are going to make the choice to light up, maybe wait until your executive functions mature around 24 years old.

Smoking weed earlier in life also showed a strong correlation with an earlier onset of psychosis, a very serious mental disorder in which you start to lose sense of reality. Definitely not good. I’m not trynna get diagnosed with psychosis any time soon!

One perhaps encouraging study for you smokers out there was that marijuana really had no effect on long-term memory. Non-smokers were better at verbal learning than heavy smokers…until after a three week abstinence break, where the heavy smokers’ memories recovered to match the control groups’. So while smoking weed when you have a test coming up maybe isn’t the best idea, there’s not necessarily a need to fear in the long run.

(Hanson et al, 2010)

A similar study showed that signs of depression and anxiety also normalized after 28 days of not smoking. Don’t get too hyped though, because even after the abstinence period, there was still “persistent impulsivity and reduced reward responses,” as well as a drop in attention accuracy.

A common belief about weed is that it is not addicting, but it actually is. What happens is that after repetitively smoking, feeling high no longer equates to feeling better than normal, but rather being sober equates to feeling worse than normal. This can lead to irritability, reduced appetite, and sleeplessness. Up to 1/2 of teens who smoke pot daily become dependent, and in broader terms, 9 percent of people who just experiment become dependent.

In summary, “marijuana interferes with normal brain development and maturation.” While it’s not going to kill you, it does effect your cognitive functions. Plus, you are at a higher risk for mental disorders like psychosis and future dependence. So choose wisely, my friends.

By Will Sheehan

Will Sheehan

Designing Drugs Aimed at a Different Part of Life’s Code

Individual RNA molecules fluoresce inside a breast cancer cell.

Individual RNA molecules fluoresce inside a breast cancer cell. Credit: Sunjong Kwon, Oregon Health & Science University, via Flickr.

Most drugs work by tinkering with the behavior of proteins. Like meddlesome coworkers, these molecules are designed to latch onto their target proteins and keep them from doing what they need to do.

If a protein is responsible for speeding up a reaction, the drug helps slow the reaction down. If a protein serves as a gatekeeper to a cell, regulating what gets in and what stays out, a drug changes how many molecules it lets through.

But proteins aren’t the only doers and shakers in our bodies. Scientists are finding that strings of RNA — known primarily for their role in shuttling genetic information from nucleus-bound DNA to the cell’s protein-manufacturing machinery — can also play a major role in regulating disease.

A portrait of Amanda Hargrove

Amanda Hargrove is an assistant professor of chemistry at Duke University.

“There has been what some people are calling an RNA revolution,” said Amanda Hargrove, assistant professor of chemistry at Duke. “In some diseases, non-coding RNAs, or RNAs that don’t turn into protein, seem to be the best predictors of disease, and even to be driving the disease.”

Hargrove and her team at Duke are working to design new types of drugs that target RNA rather than proteins. RNA-targeted drug molecules have the potential help treat diseases like prostate cancer and HIV, but finding them is no easy task. Most drugs have been designed to interfere with proteins, and just don’t have the same effects on RNA.

Part of the problem is that proteins and RNA have many fundamental differences, Hargrove said. While proteins are made of strings of twenty amino acids that can twist into myriad different shapes, RNA is made of strings of only four bases — adenine, guanine, cytosine and uracil.

“People have been screening drugs for different kinds of RNA for quite a while, and historically have not had a lot of success,” Hargrove said. “This begged the question, since RNA has such chemically different properties than proteins, is there something different about the small molecules that we need in order to target RNA?”

To find out, graduate student Brittany Morgan and research associate Jordan Forte combed the scientific literature to identify 104 small molecules that are known interact with specific types of RNA. They then analyzed 20 different properties of these molecules, and compared their properties to those of collections of drug molecules known to interact with proteins.

The team found significant differences in shape, atomic composition, and charge between the RNA-active molecules and the protein-active molecules. They plan to use the results to compile a collection of molecules, called a library, that are chosen to better “speak the language” of the RNA-active molecules. They hope this collection of molecules will be more likely to interact with RNA in therapeutically beneficial ways.

“We found that there are differences between the RNA-targeted molecules and the protein-targeted drugs, and some of them are pretty striking,” Hargrove said. “What that means is that we could start to enrich our screening libraries with these types of molecules, and make these types of molecules, to have better luck at targeting RNA.”

Discovery of Key Physicochemical, Structural, and Spatial Properties of RNA-Targeted Bioactive Ligands.” Brittany S. Morgan, Jordan E. Forte, Rebecca N. Culver, Yuqi Zhang and Amanda Hargrove. Angewandte Chemie, Sept. 18, 2017. DOI: 10.1002/anie.201707641

Kara J. Manke, PhDPost by Kara Manke

Rare Cancers and Precision Medicine in Southeast Asia

Data collected through genomics research is revolutionizing the way we treat cancer. But a large population of cancer patients are being denied the benefits of this research.

Patrick Tan MD, PhD is a professor of cancer and stem cell biology at Duke-NUS Medical School in Singapore.

In 2016, less than one percent of all the existing genomic data came from the 60% of the world population living outside of the US, Europe, and Japan. Furthermore, 70% of patients who die from cancer this year will come from Asia, Africa and Central and South America.

Patrick Tan, M.D., Ph.D., and the Duke-National University of Singapore (Duke-NUS) Medical School are key players in an effort to rectify this discrepancy, specifically as it exists in Southeast Asia.

In his talk, sponsored by the Duke Center for Applied Genomics and Precision Medicine, Tan focused specifically on his work in northeast Thailand with cholangiocarcinoma (CCA), or bile duct cancer.

Liver fluke

Liver flukes like this are parasites of fish that migrate to human hosts who eat the fish raw, leading to a form of bile duct cancer.

While CCA is rare in most of the world, it appears at 100 times the global rate in the region of Thailand where Tan and his colleagues work. Additionally, CCA in this region is of a separate and distinct nature.

CCA in this region is linked with a parasitic infection of the bile ducts called a liver fluke.  Residents of this area in Thailand have a diet consisting largely of raw fish, which can be infected by the liver fluke and transmitted to the person who eats the fish.

Because of the poverty in this area, encouraging people to avoid eating raw fish has proven ineffective. Furthermore, healthcare is not readily available, so by the time most patients are diagnosed, the disease has progressed into its later and deadly stage.

The life cycle of liver flukes. (Graphic U.S. Centers for Disease Control)

Tan’s genomic research has discovered certain factors at the gene level that make liver-fluke positive CCA different from other CCA. Thus genomic data specific to this population is vital to improve the outcomes of patients with CCA.

Duke-NUS Precision Medicine (PRISM) has partnered up with the National Heart Research Institute Singapore (NHRIS) in SPECTRA, a program designed to create a database of genomic data from the healthy Asian population. SPECTRA is sequencing the genomes of 5,000 healthy Asians in order to create a baseline to which they can compare the genomes of unhealthy individuals.

These and other programs are part of a larger effort to make precision medicine, or healthcare tailored to an individual based on factors like family history and genomic markers, accessible throughout southeast Asia.

By Sarah Haurin

 

Students Bring Sixty Years of Data to Life on the Web

For fields like environmental science, collecting data is hard.

Fall colors by Mariel Carr

Fall colors in the Hubbard Brook Experimental Forest, in New Hampshire’s White Mountains.

Gathering results on a single project can mean months of painstaking measurements, observations and notes, likely in limited conditions, hopefully to be published in a highly specialized journal with a target audience made up mostly of just other specialists in the field.

That’s why when, this past summer, Duke students Devri Adams, Camila Restrepo and Annie Lott set out with  graduate students Richard Marinos, Matt Ross and Professor Emily Bernhardt to combine over six decades of data on the Hubbard Brook Experimental Forest into a workable, aesthetically pleasing visualization website, they were really breaking new ground in the way the public can appreciate this truly massive store of information.

The site’s navigation shows users what kinds of data they might explore in beautiful fashion.

Spanning some 8,000 acres of New Hampshire’s sprawling White Mountain National Forest, Hubbard Brook has captured the thoughts and imaginations of generations of environmental researchers. Over 60 years of study and authorized experimentation in the region have brought us some of the longest continuous environmental data sets ever collected, tracking changes across a variety of factors for the second half of the 20th century.

Now, for the first time ever, this data has been brought together into a comprehensive, agile interface available to specialists and students alike. This website is developed with the user constantly in mind. At once in-depth and flexible, each visualization is designed so that a casual viewer can instantly grasp a variety of factors all at the same time—pH, water source, molecule size and more all made clearly evident from the structures of the graphs.

Additionally, this website’s axes can be as flexible as you need them to be; users can manipulate them to compare any two variables they want, allowing for easy study of all potential correlations.

All code used to build this website has been made entirely open source, and a large chunk of the site was developed with undergrads and high schoolers in mind. The team hopes to supplement textbook material with a series of five “data stories” exploring different studies done on the forest. The effects of acid rain, deforestation, dilutification, and calcium experimentation all come alive on the website’s interactive graphs, demonstrating the challenges and changes this forest has faced since studies on it first began.

The team hopes to have created a useful and user-friendly interface that’s easy for anyone to use. By bringing data out of the laboratory and onto the webpage, this project brings us one step further in the movement to make research accessible to and meaningful for the entire world.

Post by Daniel Egitto

New Blogger Lydia Goff: Freshman with a Passion for Science Communication

Hey! My name is Lydia Goff. I am a first-year at Duke and plan to double major in English and biology in order to pursue a career in science writing. I was born in Waukesha, Wisconsin but raised primarily in the Charlotte area. My junior year of high school I transitioned from homeschool to Gaston Day School where I developed my interest in scientific research. Neither of my parents attended college so my primary teachers were books. Homeschooling instilled my love of reading which grew into an interest in writing, but it also limited my resources.

I had no exposure to scientific research until my junior year at Gaston Day when I became involved in the International Genetically Engineered Machine (iGEM) team. We worked on genetically engineering E. coli K12 so that it would die if accidentally released into the environment through a process called a kill switch. Particularly in developing countries with restricted supplies, improper disposal of genetically engineered bacteria can lead to water supply contamination. Working with my team and amazing faculty mentor showed me not only how interesting scientific research is, but also the global benefits.

A smiling woman

Lydia Goff in front of Baldwin Auditorium.

In iGEM, I ended up taking the lead in communications. Many of my teammates could understand and perform scientific procedures with a remarkable skill but struggled to communicate their ideas. I love being able to discuss the passions of others. These interactions allow me to continuously learn and to help others express themselves. Until that leadership role in iGEM, I was unsure about a major. I enjoyed writing and reading but also the STEM world. My interests bounced from calculus to creative writing to genetic engineering to art history. As I got older and the “What do you want to major in?” question became increasingly relevant, the idea of choosing one subject to focus on was painful. I did not want to stop learning about genetic engineering and neuroscience and astronomy in order to become a writer. For me, science writing and this blog represent the opportunity to never stop learning. They allow me to bounce around from lecture to laboratory and meet experts in a variety of fields, to discover the inspirations and implications of their research, and to express their ideas and discoveries to any curious person.

Post by Lydia Goff

New Blogger Ameya Sanyal: Freshman Inspired by 'Kitchen Experiments'

Hello! My name is Ameya Sanyal and I’m an incoming Trinity Freshman. While I’ve lived in Madison, WI for the past 12 years, I was born in Roswell, NM. I use she/her/hers pronouns and live with my parents, Amit and Paulomi, my younger sister, Anika, and my goldendoodle, Zain.

When I was little, my dad used to host “Science Sundays.” From vinegar volcanoes to Dr. Seuss’s “oobleck,” I was captivated. These hands-on-activities — which I fondly called “kitchen experiments” — were only the beginning of my interest in science.

A man and three woman smiling.

My family and I experimenting with our camera.

Throughout elementary and middle school, I eagerly awaited science class. I loved to learn about real-life examples; projectile motion came alive with classroom rocket demonstrations and nitrogen fixation took on meaning with a field trip to a teacher’s farm.

In high school, I became frustrated as the science classes seemed to only cover core concepts. Although I recognized the importance of building a strong foundation in biology, chemistry and physics, I wanted to know more about the applications of basic scientific principles.

At this juncture, my interest in social studies began to grow. I joined various activist and leadership groups and explored the link between people and social change. In electives such as Government & Politics and Psychology, I could immediately see how skills such as knowing my rights and understanding my behavior in a nature-nurture context were valuable.

In the future, I’d like to become an activist-doctor and interact directly with patients while uniting with other physicians to pursue social change. Consequently, I hope to pursue an interdisciplinary major combining political science and medicine.

Three women in traditional Indian clothing.

My family and I celebrating Diwali, the festival of lights.

At Duke, I’d like to explore how communication across disciplines can result in increased health and wellness. As an aspiring Global Health and Biology double major, I am excited to think critically about the driving forces between social inequities and brainstorm how new scientific discoveries can be utilized in finding a solution to public health crises.

I am looking forward to writing about the impact of social determinants on health and wellness and emerging healthcare research and technologies. Apart from being a member of the research team, I hope to get involved with GlobeMed and the Hindu Students Association. If you see me volunteering in the Durham community or at Hindu celebrations, please say hi!

Post by Ameya Sanyal

Happy Patients, Healthy Lungs

Lung-shaped leaves

Evaluating a patient’s mental health before and after lung transplant surgery can help improve long-term outcomes. Source: tikyon, Flickr.

Diseases like Chronic Obstructive Pulmonary Disease (COPD) and Cystic Fibrosis (CF) are hard to treat. Lung transplant is important option for people who do not benefit from other treatments, and understanding the outcomes for these patients is crucial.

Patrick Smith, PhD, a clinical psychologist at Duke Hospital, shared his research into predictors for outcomes of lung transplant with a group of transplant physicians and surgeons at the Duke Hospital on Sept. 14.

“Patients receive transplants to live longer and to feel better,” Smith said.

Focus on the first goal has increased the median survival time after a lung transplant to six years. But Smith began his research because of an interest in the second goal.

An incredibly complex, long, and difficult procedure, transplants require extensive testing and therapies before a patient enters the operating room (OR). Among the pre-operative testing is a mental health assessment to determine if any psychological issues exist that could make recovery more difficult. Mental health issues can affect adherence, or a patient’s commitment to continuing the prescribed post-op medication after release from the hospital.

Smith’s research found that some of these tests can be incredibly useful at predicting outcomes not previously explored; patients who show cognitive impairments before surgery were found to be more likely to fall victim to delirium, a post-operative state of confusion and psychosis that has been linked to an increased risk of complications and death.

While acknowledging the usefulness of pre-operative testing, Smith also pointed out the inadequacy of this model. Failing to continue psychological assessments after the surgery and throughout the recovery means that doctors are missing important clues that could indicate how well patients will recover.

Through his research, Smith has found that the presence of depressive symptoms after transplant is actually a much more useful and accurate tool for predicting risk of mortality than symptoms exhibited before surgery.  

This point is strengthened by a previous study that found that successful treatment of depressive symptoms in liver transplant patients reduced the mortality rate of depressive patients to that of their non-depressive counterparts.

These results are promising for the possibility of improving transplant outcomes; by valuing and treating both pre-operative and post-operative signs of risk, doctors can improve the outcomes for their patients and ensure the limited supply of organs is being used in the best and most successful way possible.

Post by Sarah Haurin

 

 

Captive Lemurs Get a Genetic Health Checkup

DURHAM, N.C. — Careful matchmaking can restore genetic diversity for endangered lemurs in captivity, researchers report.

Ring-tailed lemurs born at the Duke Lemur Center have seen a recent infusion of new genetic material at key genes involved in the immune response, finds a new study.

Thanks to a long-term collaborative breeding program that transfers animals between institutions to preserve genetic diversity, genetic variation at one region was restored to levels seen in the wild.

The findings, published in the journal Ecology and Evolution, are important for the ability of future generations to fight disease.

Baby lemur twins Nemesis and Narcissa were the product of a breeding program developed by the American Association of Zoos and Aquariums to preserve the future genetic health of North America’s captive ring-tailed lemurs. Their mother Sophia was among 62 ring-tailed lemurs recommended for breeding across 20 institutions nationwide in 2016. Photo by David Haring, Duke Lemur Center.

Baby lemur twins Nemesis and Narcissa were the product of a breeding program developed by the American Association of Zoos and Aquariums to preserve the future genetic health of North America’s captive ring-tailed lemurs. Their mother Sophia was among 62 ring-tailed lemurs recommended for breeding across 20 institutions nationwide in 2016. Photo by David Haring, Duke Lemur Center.

Distant primate cousins with long black-and-white striped tails, ring-tailed lemurs live on the African island of Madagascar and nowhere else except in zoos and other captive facilities.

Some studies suggest that as few as 2,500 ring-tailed lemurs live in the wild today. Habit loss, hunting and the illegal pet trade have reduced their numbers by at least 50 percent in recent decades.

An additional estimated 2,500 ring-tailed lemurs live in zoos around the world, where experts work to maintain their genetic health in captivity.

The researchers studied DNA sequence variation at a region of the major histocompatibility complex, or MHC, a part of the genome that helps the immune system identify disease-causing bacteria, viruses and parasites.

Because different MHC gene variants recognize different types of pathogens, greater MHC diversity means animals are able to fend off a wider array of invaders.

The researchers estimated the number of MHC variants in 121 captive individuals born at the Duke Lemur Center and the Indianapolis and Cincinnati Zoos between 1980 and 2010.

They also compared them with 180 wild individuals from southwestern Madadgascar at the Bezà Mahafaly Special Reserve, where the animals regularly interbreed with lemurs from nearby forests.

Not surprisingly, MHC diversity was lower in captivity than in the wild.

Today’s captive ringtails came from a small group of ancestors that carried only a small fraction of the total genetic variation found in the larger wild population. Since their establishment, gene flow between captive populations and wild lemurs has been restricted.

Overall, the researchers found 20 unique MHC variants in the captive population, fewer than half the number in their wild counterparts.

However, efforts to identify good genetic matches across dozens of institutions have helped to preserve and even improve upon the diversity that is left.

For infants born at the Duke Lemur Center, MHC gene diversity remained low but stable for three decades from 1980 to 2010, then increased significantly from 2010 to 2013, researchers found.

Genetic contributions from several transplants contributed to the comeback.

An arranged marriage between ring-tailed lemurs at the Duke Lemur Center in North Carolina produced healthy twins Griselda and Hedwig in 2016. The infants are among 40 to 60 ring-tailed lemur infants born in North American zoos and other facilities each year. Photo by David Haring, Duke Lemur Center.

An arranged marriage between ring-tailed lemurs at the Duke Lemur Center in North Carolina produced healthy twins Griselda and Hedwig in 2016. The infants are among 40 to 60 ring-tailed lemur infants born in North American zoos and other facilities each year. Photo by David Haring, Duke Lemur Center.

The American Association of Zoos and Aquariums (AZA) tries to maintain a genetically healthy population by moving animals between institutions as potential mates. A team of experts uses computer software to help pick the best pairs for breeding.

Between 1980 and 2013, more than 1,160 ring-tailed lemurs were transferred between 217 institutions in North America alone.

In 2009, a male named Randy was transferred from the Saint Louis Zoo to the Duke Lemur Center for pairing with Sprite, a resident female. Experts also brought a mother-daughter pair, Schroeder and Leisl from the Zoo at Chehaw in Georgia, as potential mates for a resident male named Aracus.

“They saw an immediate improvement in the diversity of the offspring that were born,” said lead author Kathleen Grogan, who conducted the study while working on a doctorate with co-author Christine Drea at Duke University.

Grogan and colleagues are now examining whether MHC gene diversity helps the animals live longer or produce more offspring, as has been shown for other species.

“Not only do these lemurs serve as an assurance against extinction of their Malagasy counterparts, but maintaining as many variations of genes is important for keeping the individual lemurs, as well as the population healthy for any future challenges it may face,” said AZA Species Survival Plan Coordinator Gina Ferrie, a population biologist at Disney’s Animal Kingdom.

Conserving genetic diversity in captive populations over multiple generations is challenging due to their small size and relative isolation, but careful breeding can stem the loss, said Grogan, now a postdoctoral fellow at Pennsylvania State University.

Other authors include Michelle Sauther of the University of Colorado-Boulder and Frank Cuozzo at LaJuma Research Centre in South Africa.

This research was supported by Duke University, the International Primatological Society, Primate Conservation Inc., the University of Colorado-Boulder, the University of North Dakota, the National Science Foundation (BCS 0922465, BCS-1232570, IOS-071900), the Margot Marsh Biodiversity Foundation, the St. Louis Zoo and the American Society of Primatologists.

CITATION:  “Genetic Wealth, Population Health: Major Histocompatibility Complex Variation in Captive and Wild Ring-Tailed Lemurs (Lemur Catta),” Kathleen Grogan, Michelle Sauther, Frank Cuozzo and Christine Drea. Ecology and Evolution, Date. DOI: 10.1002/ece3.3317

Not Your Basic Bench: Zebrafish Reveal Secrets of the Developing Gut

Our intestine is a highly complex organ – a tortuous, rugged channel built of many specialized cell-types and coated with a protective, slimy matrix. Yet the intestine begins as a simple tube consisting of a central lumen lined by a sheet of epithelial cells, which are smooth cells that lie on the surface of the lumen. These intestinal epithelial cells are central players in many human diseases.

A portrait of Daniel Levic

Daniel Levic, a postdoctoral research associate in the department of cell biology at the Duke University Medical Center.

Daniel Levic of the Bagnat Lab is using zebrafish as experimental models to understand how intestines are formed in hopes of finding new ways to combat disease. He wants to learn how the intestinal lumen forms during early development, and how intestinal epithelial cells take on their physiological functions.

Levic, a postdoctoral research associate in the department of cell biology at the Duke University Medical Center, focuses on projects in both basic and translational science. Daniel uses zebrafish to analyze the formation of the lumen and the polarity of epithelial cells — how specialized they are for carrying out different functions —  at the genetic and cellular level. He focuses on how membrane proteins are sorted into different, specialized domains of the cell surface and how this process affects intestinal formation. Additionally, Daniel studies how inflammation is evaded in intestinal epithelial cells in Crohn’s disease using a combination of patient biopsy samples and animal studies in zebrafish. This project is a collaborative effort aided by clinicians and human geneticists at the Duke University Medical Center.

A microscope image of a zebrafish gut

The developing gut of a zebrafish, magnified.

Though complex human diseases can’t be fully mimicked in animal models like zebrafish, this type of research can be extremely useful. These model organisms can be used to study the basic, fundamental cellular mechanisms that ultimately underlie disease. An example is Daniel’s work on Crohn’s disease, where he is trying to understand how inflammatory signaling networks become activated, specifically in intestinal epithelial cells. This problem is difficult, if not impossible, to address using exclusively human biopsy samples.

Overall, Daniel hopes that his translational research will provide new knowledge of the role of intestinal epithelial cells in Crohn’s disease and provide biomarkers that will aid clinicians in predicting how patients will respond to therapeutic interventions. Daniel’s research and basic science research are rapidly changing the way we diagnose disease, treat patients, and interact with the world around us.

Guest post by Vaishnavi Siripurapu

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