Duke Research Blog

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

Category: Biology Page 1 of 21

Overdiagnosis and the Future of Cancer Medicine

For many years, the standard strategy for fighting against cancer has been to find it early with screening when the person is still healthy, then hit it with a merciless treatment regimen to make it go away.

But not all tumors will become life-threatening cancers. Many, in fact, would have caused no issues for the rest of the patients’ lives had they not been found by screening. These cases belong to the category of overdiagnosis, one of the chief complaints against population-level screening programs.

Scientists are reconsidering the way to treat tumors because the traditional hit-it-hard approach has often caused the cancer to seemingly go away, only to have a few cells survive and the entire tumor roar back later with resistance to previously effective medicine.

Dr. Marc Ryser, the professor who gave this meaty talk

In his May 23 talk to Duke Surgery, “Cancer Overdiagnosis: A Discourse on Population Health, Biologic Mechanism and Statistics,” Marc Ryser, an assistant professor at Duke’s Departments of Population Health Sciences and Mathematics, walked us through how parallel developments across different disciplines have been reshaping our cancer battle plan. He said the effort to understand the true prevalence of overdiagnosis is a point of focus in this shift.

Past to Future: the changing cancer battle plan
Credit: Marc Ryser, edit: Brian Du

Ryser started with the longstanding biological theory behind how tumors develop. Under the theory of clonal sweeps, a relatively linear progression of successive key mutations sweeps through the tumor, giving it increasing versatility until it is clinically diagnosed by a doctor as cancer.

Clonal sweeps model, each shade is a new clone that introduces a mutation

With this as the underpinning model, the battle plan of screen early, treat hard (point A) makes sense because it would be better to break the chain of progression early rather than later when the disease is more developed and much more aggressive. So employing screening extensively across the population for the various types of cancer is the sure choice, right?

But the data at the population level for many different categories of cancers doesn’t support this view (point B). Excluding the cases of cervical cancer and colorectal cancer, which have benefited greatly from screening interventions, the incidence of advanced cases of breast cancer and other cancers have stayed at similar levels or actually continued to increase during the years of screening interventions. This has raised the question of when screening is truly the best option.

Scientists are thinking now in terms of a “benefit-harm balance” when mass-screening public health interventions are carried out. Overdiagnosis would pile up on the harms side, because it introduces unnecessary procedures that are associated with adverse effects.

Thinking this way would be a major adjustment, and it has brought with it major confusion.

Paralleling this recent development on the population level, new biological understanding of how tumors develop has also introduced confusion. Scientists have discovered that tumors are more heterogeneous than the clonal sweeps model would make it appear. Within one tumor, there may be many different subpopulations of cancer cells, of varying characteristics and dangerousness, competing and coexisting.

Additional research has since suggested a more complex, evolutionary and ecological based model known as the Big Bang-mutual evolution model. Instead of the “stepwise progression from normal to increasingly malignant cells with the acquisition of successive driver mutations, some cancers appear to evolve more like a Big Bang, where the malignant ability is already concentrated in the founder cell,” Ryser said.

As the first cell starts to replicate, its descendants evolve in parallel into different subpopulations expressing different characteristics. While more research has been published in favor of this model, some scientists remain skeptical.

Ryser’s research contributes to this ongoing discussion. In comparing the patterns by which mutations are present or absent in cancerous and benign tumors, he obtained results favoring the Big Bang-mutual evolution model. Rather than seeing a neat region of mutation within the tumor, which would align with the clonal sweeps model, he saw mutations dispersed throughout the tumor, like the spreading of newborn stars in the wake of the Big Bang.

How to think about mutations within a tumor
credit: NASA

The more-complicated Big Bang-mutual evolution model justifies an increasingly nuanced approach to cancer treatment that has been developing in the past few years. Known as precision medicine (point C), its goal is to provide the best treatment available to a person based on their unique set of characteristics: genetics, lifestyle, and environment. As cancer medicine evolves with this new paradigm, when to screen will remain a key question, as will the benefit-harm balance.

There’s another problem, though: Overdiagnosis is incredibly hard to quantify. In fact, it’s by nature not possible to directly measure it. That’s where another area of Ryser’s research seeks to find the answers. He is working to accurately model overdiagnosis to estimate its extent and impact.

Going forward, his research goal is to try to understand how to bring together different scales to best understand overdiagnosis. Considering it in the context of the multiscale developments he mentioned in his talk may be the key to better understand it.

Post by Brian Du

Pot Not So Harmless for Teens

Marijuana is becoming legalized and decriminalized to the point that more than 63 percent of Americans have access to medical and recreational cannabis. But researchers and policy experts still don’t know very much about the long-term health effects.

The 2019 annual symposium by Duke’s Center on Addiction & Behavior Change,  “Altered States of Cannabis Regulation: Informing Policy with Science,” provided some scientific answers. Madeline Meier, assistant professor of Psychology at Arizona State University and a former Duke post-doc, spoke about her longitudinal research projects that offer critical insights about the long-term effects of cannabis use.

Meier investigates the relationship between cannabis use and IQ in a 38-year-long study that has been collecting data on a group of 1,000 people born in New Zealand since birth. Longitudinal studies like this that follow the same group of individuals across their lifespan are vital to understanding the effects of extended cannabis use on the human body, but they are difficult to conduct and keep funded. The 95 percent retention rate of this study is quite impressive and provides much-needed data.


Madeline Meier of Arizona State University

The researchers had tested the babies’ IQ at early childhood, then conducted regular IQ and cannabis use assessments between the ages of 18 and 38. They found that participants who heavily used weed for extended periods of time experienced a significant IQ drop, as well as other impairments in learning and memory skills. Specifically, users who had three or more clinical diagnoses of cannabis dependency, defined as compulsive use despite physical, legal, or social problems caused by the drug, showed an average 6-point IQ drop over the years. Those who only tried the drug a few times showed no decline, and those who never used weed showed a 1-point IQ increase.

Notably, however, the results depended on age of onset and level of use. Meier emphasized that her results do not support the common misconception that any amount of weed use can immediately lead to IQ decline. To the contrary, Meier’s team found that short-term, low-level use did not have any effect on IQ; only heavy users suffered the negative effects. The age of onset of cannabis use was critical, too: Adolescents were more vulnerable to the drug’s harms, with study participants who started using as adolescents showing an 8-point drop in IQ points. Given what we know about adolescents’ affinity for risky behavior, specifically around experimentation with drugs, this finding is particularly worrisome.

In addition to causing cognitive impairment, persistent cannabis use jeopardizes people’s psychosocial functioning as well. The Dunedin longitudinal study has also revealed that people who continued to use weed despite multiple dependency diagnoses experienced downward social mobility, relationship problems, antisocial workplace behavior, financial difficulties, and even higher numbers of traffic convictions. In short, social life is likely to be perilous for heavy weed users.

While some have suggested that the harmful effects of weed might be caused not by the drug itself but by the reduced years of education, low socioeconomic status, mental health problems, or simultaneous use of tobacco, alcohol or other drugs among weed users, Meier and her team found that the impairments persisted even when these factors were accounted for. Cannabis alone was responsible for the effects reflected in Meier’s research. In fact, there is limited evidence for the opposite causational link: weed use may be the cause of mental health problems rather than being caused by them. One study found a weak correlation between years of marijuana use and depression, but Meier was careful to point out that it would take “a lot of cannabis use to lead to clinically diagnosed depression.”

Given this data, Meier called on the policy-makers in the room to focus their efforts on delaying the onset of cannabis use in youth and encouraging cessation (especially among adolescents). In appealing to the researchers, she underlined the need for additional longitudinal studies into the mechanisms and parameters of cannabis use that produce long-term impairments.

As public and political support of marijuana legalization grows, we must be careful not to underestimate the dangers of the drug. Without knowing the full extent of the risks and benefits of weed, policy-makers cannot effectively promote public health, safety, and social equity.

Guest Post by Deniz Ariturk

How the Flu Vaccine Fails

Influenza is ubiquitous. Every fall, we line up to get our flu shots with the hope that we will be protected from the virus that infects 10 to 20 percent of people worldwide each year. But some years, the vaccine is less effective than others.

Every year, CDC scientists engineer a new flu virus. By examining phylogenetic relationships, which are based on shared common ancestry and relatedness, researchers identify virus strains to target with a vaccine for the following flu season.

Sometimes, they do a good job predicting which strains will flourish in the upcoming flu season; other times, they pick wrong.

Pekosz’s work has identified why certain flu seasons saw less effective vaccines.

Andrew Pekosz, PhD, is a researcher at Johns Hopkins who examines why we fail to predict strains to target with vaccines. In particular, he examines years when the vaccine was ineffective and the viruses that were most prevalent to identify properties of these strains.

A virus consists of RNA enclosed in a membrane. Vaccines function by targeting membrane proteins that facilitate movement of the viral genome into host cells that it is infecting. For the flu virus, this protein is hemagglutinin (HA). An additional membrane protein called neuraminidase (NA) allows the virus to release itself from a cell it has infected and prevents it from returning to infected cells.  

The flu vaccine targets proteins on the membrane of the RNA virus. Image courtesy of scienceanimations.com.

Studying the viruses that flourished in the 2014-2015 and 2016-2017 flu seasons, Pekosz and his team have identified mutations to these surface proteins that allowed certain strains to evade the vaccine.

In the 2014-2015 season, a mutation in the HA receptor conferred an advantage to the virus, but only in the presence of the antibodies present in the vaccine. In the absence of these antibodies, this mutation was actually detrimental to the virus’s fitness. The strain was present in low numbers in the beginning of the flu season, but the selective pressure of the vaccine pushed it to become the dominant strain by the end.

The 2016-2017 flu season saw a similar pattern of mutation, but in the NA protein. The part of the virus membrane where the antibody binds, or the epitope, was covered in the mutated viral strain. Since the antibodies produced in response to the vaccine could not effectively identify the virus, the vaccine was ineffective for these mutated strains.

With the speed at which the flu virus evolves, and the fact that numerous strains can be active in any given flu season, engineering an effective vaccine is daunting. Pekosz’s findings on how these vaccines have previously failed will likely prove invaluable at combating such a persistent and common public health concern.

Post by undergraduate blogger Sarah Haurin
Post by undergraduate blogger Sarah Haurin


Building a Mangrove Map

“Gap maps” are the latest technology when it comes to organizing data. Although they aren’t like traditional maps, they can help people navigate through dense resources of information and show scientists the unexplored areas of research.

A ‘gap map’ comparing conservation interventions and outcomes in tropical mangrove habitats around the world turns out to be a beautiful thing.

At Duke’s 2019 Master’s Projects Spring Symposium, Willa Brooks, Amy Manz, and Colyer Woolston presented the results of their year-long Masters Project to create this map.

You’d never know by looking at the simple, polished grid of information that it took 29 Ph.D. students, master’s students and undergraduates nearly a full year to create it. As a member of the Bass Connections team that has been helping to support this research, I can testify that gap maps take a lot of time and effort — but they’re worth it.

Amy Manz, Willa Brooks, and Colyer Woolston present their evidence map (or gap map) at the 2019 Master’s Projects Spring Symposium

When designing a research question, it’s important to recognize what is already known, so that you can clearly visualize and target the gaps in the knowledge.

But sifting through thousands of papers on tropical mangroves to find the one study you are looking for can be incredible overwhelming and time-intensive. This is purpose of a gap map: to neatly organize existing research into a comprehensive grid, effectively shining a light on the areas where research is lacking, and highlighting patterns in areas where the research exists.

In partnership with World Wildlife Fund, Willa, Amy, and Colyer’s team has been working under the direction of Nicholas School of the Environment professors Lisa Campbell and Brian Silliman to screen the abstracts of over 10,000 articles, 779 of which ended up being singled out for a second round of full-text screening. In the first round, we were looking for very specific inclusion criteria, and in the second, we were extracting data from each study to identify the outcomes of conservation interventions in tropical mangrove, seagrass, and coral reef habitats around the world.

Coastal Mangroves (Photo from WikiCommons: US National Oceanic and Atmospheric Administration)

While the overall project looked at all three habitats, Willa, Amy, and Colyer’s Master’s Project focused specifically on mangroves, which are salt-tolerant shrubs that grow along the coast in tropical and subtropical regions. These shrubs provide a rich nursery habitat to a diverse group of birds and aquatic species, and promote the stability of coastlines by trapping sediment runoff in their roots. However, mangrove forests are in dramatic decline.

According to World Wildlife Fund, 35 percent of mangrove ecosystems in the world are already gone. Those that remain are facing intense pressure from threats like forest clearing, overharvesting, overfishing, pollution, climate change, and human destruction of coral reefs. Now more than ever, it is so important to study the conservation of these habitats, and implement solutions that will save these coastal forests and all the life they support. The hope is that our gap map will help point future researchers towards these solutions, and aid in the fight to save the mangroves.

This year’s team built a gap map that successfully mapped linkages between interventions and outcomes, indicating which areas are lacking in research. However, the gap map is limited because it does not show the strength or nature of these relationships. Next year, another Bass Connections team will tackle this challenge of analyzing the results, and further explore the realm of tropical conservation research.

Post by Anne Littlewood, Trinity ’21

‘Death is a Social Construct’

Of the few universal human experiences, death remains the least understood. Whether we avoid its mention or can’t stop thinking about it, whether we are terrified or mystified by it, none of us know what death is really like. Turns out, neither do the experts who spend every day around it.

Nobody who sees this guy reports back, so we can only guess.

This was the overarching lesson of Dr. Robert Truog’s McGovern Lecture at Trent Semans Center for Health Education, titled “Defining Death: Persistent Problems and Possible Solutions.”

Dr. Truog is this year’s recipient of the McGovern Prize, an award honoring individuals who have made outstanding contributions to the art and  science of medicine. Truog is a professor of medical ethics, anesthesiology and pediatrics and director of the center for bioethics at Harvard Medical School. He is intimately familiar with death, not only through his research and writings, but through his work as a pediatric intensive care doctor at Boston Children’s Hospital. Truog is also the author of the current national guidelines for end-of-life care in the intensive care unit.

In short, Truog knows a lot about death. Yet certain questions about the end of life remain elusive even to him. In his talk, he spoke about the biological, sociological, and ethical challenges involved in drawing the boundary between life and death. While some of these challenges have been around for as long as humans have, certain ones are novel, brought on by technological advancements in medicine that allow us to prolong the functioning of vital organs, mainly the brain and the heart.

The “irreversible cessation of function” of these organs results in brain and cardiac death, respectively. When both occur together, the patient is declared biologically dead. When they don’t, such as when all brain function except for those that support the patient’s digestive system is lost, for instance, the patient can be legally alive without any hope of recovery of consciousness.

Robert Truog teaching (Harvard photo)

According to Truog, it is in these moments of life after the loss of almost every brain function that we realize “death is a social construct.” This claim likely sounds counterintuitive, if not entirely nonsensical, as dying is the moment we have the least control over our biology. What Dr. Truog means, however, is that as technology continues to mend failures of biology that would have once been fatal, our social and philosophical understanding of dying, what he calls “person death” will increasingly separate from the end of the body’s biological function.  

Biologically, death is the moment when homeostasis, the body’s internal state of equilibrium including body temperature, pH levels and fluid balance, fails and entropy prevails.

Personhood, however, is not mere homeostasis. Dr. Truog cited Robert Veatch, ethicist at Georgetown University, in defining person death as the “irreversible loss of that which is essentially significant to the nature of man.” For those patients who are kept alive by ventilators and who have no hope of regaining consciousness, that essentially significant nature appears to have been lost.

Nonetheless, for loved ones, signs like spontaneous breathing, which can occur in patients in persistent vegetative state, intuitively feel like signs of life. This intuitive sign of life is what made Jahi McMath’s parents refuse an Oakland California hospital’s declaration that their daughter was dead. A ventilator kept the 13-year-old breathing, even though she had been declared brain-dead. After much conflict, McMath’s parents moved her to a hospital in New Jersey, one of just two states where families can reject brain death if it does not align with their religious beliefs. In the end, McMath had two death certificates that were five years apart.


Muslim cemetery at sunset in Marrakech Morocco.
(Mohamed Boualam via Wikimedia commons)

The emotional toll of such an ordeal is immense, as the media outcry around McMath made more than clear. There are more concrete, quantifiable costs to extending biological function beyond the end of personhood: the U.S. is facing an organ shortage. As people are kept on life support for longer periods, it is going to become increasingly difficult for patients who desperately need organs to find donors.

In closing, Dr. Truog reminded us that “in the spectrum between alive and dead, we set the threshold… Death is not a binary state, but a complex social choice.” People will likely continue to disagree about where we should set the threshold, especially as technology develops.

However, if we want to have a thoughtful discussion that respects the rights, wishes, and values of patients, loved ones, and everybody else who will one day face death, we need to first agree that there is a choice to be made.

Guest Post by Deniz Ariturk, Science & Society graduate student

Science Gets By With a Little Help From Its Friends

There are many things in life that are a little easier if one recruits the help of friends. As it turns out, this is also the case with scientific research.

Lilly Chiou, a senior majoring in biology, and Daniele Armaleo, a professor in the Biology Department had a problem. Lilly needed more funding before graduation to initiate a new direction for her project, but traditional funding can sometimes take a year or more.

So they turned to their friends and sought crowdfunding.

Chiou and Armaleo are interested in lichens, low-profile organisms that you may have seen but not really noticed. Often looking like crusty leaves stuck to rocks or to the bark of trees, they — like most other living beings — need water to grow. But, while a rock and its resident lichens might get wet after it rains, it’s bound to dry up.

If you’re likin’ these lichens, perhaps you’d like to support some research…

This is where the power of lichens comes in: they are able to dry to a crisp but still remain in a suspended state of living, so that when water becomes available again, they resume life as usual. Few organisms are able to accomplish such a feat, termed desiccation tolerance.

Chiou and Armaleo are trying to understand how lichens manage to survive getting dried and come out the other end with minimal scars. Knowing this could have important implications for our food crops, which cannot survive becoming completely parched. This knowledge is ever more important as climate becomes warmer and more unpredictable in the future. Some farmers may no longer be able to rely on regular seasonal rainfall.

They are using genetic tools to figure out the mechanisms behind the lichen’s desiccation tolerance[. Their first breakthrough came when they discovered that extra DNA sequences present in lichen ribosomal DNA may allow cells to survive extreme desiccation. Now they want to know how this works. They hope that by comparing RNA expression between desiccation tolerant and non-tolerant cells they can identify genes that protect against desiccation damage.  

As with most things, you need money to carry out your plans. Traditionally, scientists obtain money from federal agencies such as the National Science Foundation or the National Institutes of Health, or sometimes from large organizations such as the National Geographic Society, to fund their work. But applying for money involves a heavy layer of bureaucracy and long wait times while the grant is being reviewed (often, grants are only reviewed once a year). But Chiou is in her last semester, so they resorted to crowdfunding their experiment.

This is not the first instance of crowdfunded science in the Biology Department at Duke. In 2014, Fay-Wei Li and Kathleen Pryer crowdfunded the sequencing of the first fern genome, that of tiny Azolla. In fact, it was Pryer who suggested crowdfunding to Armaleo.

Chiou (left) and Armaleo in a video.

Chiou was skeptical that this approach would work. Why would somebody spend their hard-earned money on research entirely unrelated to them? To make their sales pitch, Chiou and Armaleo had to consider the wider impact of the project, rather than the approach taken in traditional grants where the focus is on the ways in which a narrow field is being advanced.

What they were not expecting was that fostering relationships would be important too; they were surprised to find that the biggest source of funding was their friends. Armaleo commented on how “having a long life of relationships with people” really shone through in this time of need — contributions to the fund, however small, “highlight people’s connection with you.” That network of connections paid off: with 18 days left in the allotted time, they had reached their goal.

After their experience, they would recommend crowdfunding as an option for other scientists. Having to create widely understood, engaging explanations of their work, and earning the support and encouragement of friends was a very positive experience.

“It beats writing a grant!” Armaleo said.

Guest Post by Karla Sosa, Biology graduate student


Dolphin Smarts

Imagine you are blindfolded and placed into a pool of water with a dolphin. The dolphin performs a movement, such as spinning in a circle, or swimming in a zig-zag pattern, and your task is to imitate this movement, without having seen it. Ready, go. 

Sound impossible? While it may not be possible for a human to do this with any accuracy, a dolphin would have no problem at all. When cognitive psychologist and marine mammal scientist Kelly Jaakkola gave this task to the dolphins at the Dolphin Research Center in Florida, they had no problem at all copying a human’s behavior. So how did they do it? Jaakkola thinks they used a combination of active listening and echolocation.

How smart are dolphins? (Photo from Wikimedia Commons: Stuart Burns)

Humans love to claim the title of “smartest” living animal. But what does this mean? How do we define intelligence? With a person’s GPA? Or SAT score? By assigning a person a number that places him or her somewhere on the scale from zero to Einstein? 

Honestly, this is problematic. There are many different types of intelligence that we forget to consider. For example, Do you know that five is less than seven? Can you remember the location of an object when you can’t see it? Can you mimic a behavior after watching it? Are you capable of cooperating to solve problems? Can you communicate effectively? All of these demonstrate different intelligent skills, many of which are observed in dolphins.

Needless to say, dolphins and humans are entirely different creatures. We have different body plans, different ways of interacting with the world, and different brains. It has been 90 million years since we shared a common ancestor, which is why the things we do have in common are so fascinating to researchers. 

Like us, dolphins understand ordinality. When presented with two novel boards with different numbers of dots, dolphins at the Dolphin Research Center chose the smaller number 83 percent of the time. But unlike us, they weren’t counting to solve this problem. When they were shown boards that represented consecutive numbers, the dolphins struggled, and often failed the task.

Similar to humans, dolphins understand that when objects are hidden from view, they still exist. At the Dolphin Research Center, they could easily remember the location of toy when a trainer hid it inside a bucket. However, unlike humans, dolphins couldn’t infer the movement of hidden objects. If the bucket was moved, the dolphins didn’t understand that the toy had moved with it.

Dr. Jaakkola presents to a packed room of Duke students

While they may not be physicists, Jaakkola has shown that dolphins are stellar cooperators, and amazing at synchronous tasks. When asked to press an underwater button at the same time as a partner, the dolphins pushed their buttons within 0.37 milliseconds of each other, even when they started at different times. As the earlier example shows, dolphins can also imitate incredibly well, and this skill is not limited to mimicking members of their own species. Even though humans have an entirely different body plan, dolphins can flexibly use their flipper in place of a hand, or their tail in place of legs, and copy human movements.

It is believed that dolphins evolved their smarts so that they could navigate the complex social world that they live in. As the researchers at the Dolphin Research Center have shown, they possess a wide array of intelligent abilities, some similar to humans and others entirely different from our own. “Dolphins are not sea people,” Jaakkola warned her audience, but that’s not to discount the fact that they are brilliant in their own way. 

We Can’t Regrow Limbs Like Deadpool, But This Creature Can

Try as we might, humans can’t regrow limbs. But losing your left leg isn’t such a problem for axolotls.

Image result for axolotl

Last Wednesday, Dr. Jessica Whited gave a fascinating talk about the importance of studying these strange little salamanders. Axolotls are capable of regenerating lost limbs so well that once a limb has fully grown back, you can’t tell the difference. No scars, no deformities. This genetic phenomenon serves as a powerful model for uncovering what mechanisms might be required for stimulating regeneration in humans.

The limb regeneration process goes through a few stages. Within hours after amputation, a wound epidermis forms around the injury. Next, a blastema grows – a big clump of cells that will be the basis for future growth. After that, a new limb just kind of sprouts out as you might imagine.

Image result for axolotl limb regeneration

So what gives the axolotl this seemingly magical ability? In attempt to answer that question, Whited’s lab looked at how the process starts – specifically at the creation of the blastema, something mammals do not form post-injury. They found that a single amputation causes an activation of progenitor cells throughout the axolotl’s body. Cells in the heart, liver, spinal cord, and contralateral limb all reenter circulation. Essentially an activation signal is sent throughout the whole body, indicating a systemic response to the injury rather than a local one.

Another question Whited sought to answer was if the same limb could regenerate multiple times. She had her student Donald Bryant carry out an experiment on a group of axolotls. Bryant would repeatedly amputate the same limb, letting it fully regrow for ten weeks between amputations. The results of the experiment show that after five amputations only 60 percent of the limb would regenerate. This percentage decreased with the number of amputations. So while axolotls may seem like they have super powers, they aren’t exactly invincible. They decline in their regenerative capabilities after repeated amputation.

Protein EYA2 PDB 3GEB.png

A key finding in this experiment was that repeated amputation led to a decrease in the EYA2 gene (Eyes Absent 2). This particular gene was deemed necessary for the blastema cells to progress through different growth checkpoints. It is required during the cell cycle “to execute decisions about whether the cells will continue to proliferate or not.” So while we don’t exactly know why, we do know that EYA2 plays an important role in the axolotl’s regenerative powers.

Although Whited and her team were able to uncover some important findings, several questions still linger. How is the activation of EYA2 induced following amputation? Why is repeated amputation linked to less EYA2 genes? If cells are poised to anticipate injury / DNA damage, why is it that repeated amputation leads to less regeneration?

Image result for deadpool baby hand

Humans and other mammals are not quite as lucky as the axolotl. Amputation is a relevant and serious issue, yet no biological solution has been devised. Thankfully, the research conducted around axolotl regenerative properties could provide us with knowledge on natural cellular reprogramming. Maybe one day we’ll be able to regrow limbs just like Deadpool.

Will Sheehan
Post by Will Sheehan

Using Genetic Clues to Reform Cardiac Care

Experiencing cardiac arrest can be compared to being in a hot air balloon in a room that is rapidly filling with water. You are trapped, desperately aware of the danger you are in, and running out of time.

Andrew Landstrom, PHD, MD, shared this metaphor with his audience in the Duke Medicine Pavilion last Thursday, and a wave of empathy flooded through his listeners. He works as an Assistant Professor of Pediatrics in Duke University’s School of Medicine, and devotes his time and energy to studying the genetic and molecular causes of sudden cardiac death in the young.

Andrew Landstrom, PHD, MD (Photo from Duke Center for Applied Genomics and Precision Medicine)

For families of children who have died suddenly and unexpectedly, the worst thing of all is hearing their doctors say, “we have no idea why.” A third of sudden death cases in children have negative autopsies, which means these children die with no explanation.

When faced with an inconclusive autopsy, everyone wants answers. Why did these children die? How do we know it’s a problem with the heart? What can be done about it? What does it mean for the siblings of the child who died?

It has since been discovered that many of these unexplained deaths are actually the result of cardiac channelopathies, which are DNA mutations that cause ion channel defects in heart cell proteins. These mutations can mess up the electrical activity of the heart and cause a heart to beat in an irregular rhythm, which can have fatal consequences. Since this is a molecular problem, and not a structural one, it cannot be identified with a conventional autopsy, and requires a deeper level of genetic and molecular analysis.

One type of channelopathy is a condition known as CPVT, which is short for catecholaminergic polymorphic ventricular tachycardia. This potentially life-threatening genetic disorder is the result of a point mutation in the genome, which means that one tiny nucleotide being changed in the DNA can lead to the single most fatal arrhythmia (irregular heart rhythm) known.

Sixty percent of children suffering from CPVT have a mutation in their RYR2 gene. This gene encodes for a protein that is found in cardiac muscle, and is a key player in how calcium is processed in heart cells. The mutated version of this gene results in proteins that let way too much calcium flood the cell, which can cause fatal changes in heart rhythm.

Dr. Landstrom has been using genome research to identify and explain sudden cardiac death in children, but the human genome doesn’t always provide straightforward answers. The problem is, a mutation in the RYR2 gene doesn’t always mean a person will have CPVT, and having an incidental RYR2 gene is much more common than being diagnosed with CPVT. Dr. Landstrom is studying this gene to try to figure out which variants are pathologic, and which are physiological.

“The human genome is a lot more confusing than I think I gave it credit for, and we’re just learning to deal with that confusion now,” he admitted to his audience Feb. 14.

The Components of the Human Genome (photo from NHS National Genetics and Genomics Education Centre)

If a variant is falsely identified as pathologic, a patient will be given incorrect therapies, and suffer through unnecessary procedures. However, if a variant is falsely identified as physiological, and the patient isn’t given the necessary treatment, there will be no mitigation of the patient’s life threatening disease. Neither of these are good outcomes, so it’s very important to get it right. The current models for predicting pathogenicity are poor, and Dr. Landstrom is looking to design new model that will be able to avoid the personal, subjective opinions of human doctors and determine if a variant is pathologic or not.

Could serotonin levels be used to predict an infant’s vulnerability to SIDS? (photo from Elmedir, Wikimedia Commons)

Another area that is of interest to Dr. Landstrom is the problem of Sudden Infant Death Syndrome (SIDS), which affects about six in every 10,000 infants, and cannot be diagnosed before death. He is on the search for a biomarker that would be able to predict an infant’s vulnerability to SIDS, and thinks that these deaths may be related to elevated levels of serotonin. Finding a marker like this would allow doctors to save many healthy infants from unexplained death. Dr. Landstrom knows its not easy research and admitted “we have to fail — we are meant to fail,” on the path to success. He is very aware of both the ethical complexity and the exciting implications of genome research at Duke, and committed to converting his research into patient care.

Post by Anne Littlewood

Meet New Blogger Anna Gotskind: Science and Gilmore Girls

Hello! My name is Anna Gotskind. I’m a first year originally from Chicago. I plan to double major in biochemistry and environmental science and policy with a certificate in innovation and entrepreneurship (I know it’s a mouthful).

I fell in love with science in seventh grade, inspired by a great teacher named Mark A. Klein. He wore a different tie every day of the year, had tarantulas as pets and frequently refused to say anything but “9” until 9:00 am. He also taught me to appreciate research and discovery, guiding me as I conducted my first independent experiment on the caffeine content in tea which helped me win my middle school science fair.

One of my other role models is Rory Gilmore from the T.V. show Gilmore Girls (yes, I am aware that she is a fictional character). Inspired by watching her write for the Yale Daily News I decided to join the Duke Chronicle when I got to campus. I quickly learned that I loved writing for a publication but more specifically that I loved writing about science. It was incredibly exciting for me to read a study, interview the researchers who conducted it and then translate the information into a story that was understandable to the public. Beyond this, it was also incredible to be exposed to groundbreaking research that had real-world impacts. Essentially, it made me feel like a “Big Girl” and when you’re only 5’0” tall, sometimes that’s necessary.

Rory Gilmore

My love for science does not end in the classroom. My greatest passion is travel and I’ve been fortunate enough to travel around the world with my family exploring some of nature’s greatest wonders. We’ve hiked Bryce Canyon in Utah, Ali San in Taiwan and Masada in Israel. In December 2018 we ventured to the Galapagos, which as an aspiring environmentalist was an incredible experience. We go to see tortoises, iguanas, penguins, sharks and sea lions mere feet away. Right now I’m working with Duke Professor Stuart Pimm on a Big Cats Conservation Initiative sponsored by SavingSpecies, analyzing camera trap data of species in Sumatra, Brazil, and Ecuador. So who knows, I may be off there next. For more pictures check out my Instagram page @annagotskind (shameless plug).

A Parrot my little brother Avi photographed in the Amazon Rainforest in Ecuador

I’m very excited to continue exploring and writing about the research being done on Duke’s campus!

By Anna Gotskind

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