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

Category: Medicine Page 1 of 16

Duke Scientists Studying the Shape of COVID Things to Come

Sticky post

The novel coronavirus pandemic has now resulted in more than 3 million confirmed cases globally and is pushing scientists to share ideas quickly and figure out the best ways to collaborate and contribute to solutions.

SARS-CoV-2 surface proteins illustrated by We Are Covert, via Wikimedia Commons

Recently, Duke researchers across the School of Medicine came together for an online symposium consisting of several short presentations to summarize the latest of what is known about the novel coronavirus, SARS-CoV-2.

This daylong event was organized by faculty in the Department of Molecular Genetics and Microbiology and researchers from different fields to share what they know about the virus and immunity to guide vaccine design. This conference highlighted the myriad new research pathways that Duke researchers are launching to better understand this pandemic virus.

One neat area of research is understanding viral processes within cells to identify steps at which antivirals may block the virus. Stacy Horner’s Laboratory studies how RNA viruses replicate inside human cells. By figuring out how viruses and cells interact at the molecular level, Horner can inform development of antivirals and strategies to block viral replication. Antivirals stop infections by preventing the virus from generating more of copies of itself and spreading to other cells. This controls damage to our cells and allows the immune system to catch up and clear the infection.

At the symposium, Horner explained how the SARS-CoV viral genome consists of 29,891 ribonucleotides, which are the building blocks of the RNA strand. The viral genome contains 14 areas where the RNA code can be transcribed into shorter RNA sequences for viral protein production. Though each RNA transcript generally contains the code for a single protein, this virus is intriguing in that it uses RNA tricks to code for up to 27 proteins. Horner highlighted two interesting ways that SARS-CoV packs in additional proteins to produce all the necessary components for its replication and assembly into new viral progeny.

The first way is through slippery sequences on the RNA genome of the virus. A ribosome is a machine inside the cell that runs along a string of RNA to translate its code into proteins that have various functions. Each set of 3 ribonucleotides forms one amino acid, a building block of proteins. In turn, a string of amino acids assembles into a distinct structure that gives rise to a functional protein.

One way that SARS-CoV-2 packs in additional proteins is with regions of its RNA genome that make the ribosome machinery slip back by one ribonucleotide. Once the ribosome gets offset it reads a new grouping of 3 ribonucleotides and creates a different amino acid for the same RNA sequence. In this way, SARS-CoV-2 makes multiple proteins from the same piece of RNA and maximizes space on its genome for additional viral proteins.

An example of an RNA ‘hairpin’ structure, which might fool a ribosome to jump across the sequence rather than reading around the little cul de sac. (Ben Moore, via Wikimedia Commons)

Secondly, the RNA genome of SARS-CoV-2 has regions where the single strand of RNA twists over itself and connects with another segment of RNA farther along the code to form a new protein. These folds create structures that look like diverse trees made of repetitive hairpin-like shapes. If the ribosome runs into a fold, it can hop from one spot in the RNA to another disjoint piece and attach a new string of amino acids instead of the ones directly ahead of it on the linear RNA sequence. This is another way the SARS-CoV-2 packs in extra proteins with the same piece of RNA.

Horner said a step-by-step understanding of what the virus needs to survive at each step of its replication cycle will allow us to design molecules that are able to block these crucial steps.

Indeed, shapes of molecules can determine their function inside the cell. Three Duke teams are pursuing detailed investigation of SARS-CoV-2 protein structures that might guide development of complementarily shaped molecules that can serve as drugs by interfering with viral processes inside cells.

Some Duke faculty who participated in the virtual viral conference. (L-R from, top) Stacy Horner, Nick Heaton, Micah Luftig, Sallie Permar, Ed Miao and Georgia Tomaras. (image: Tulika Singh)

For example the laboratory of Hashim Al-Hashimi, develops computational models to predict the diversity of structures produced by these tree-like RNA folds to identify possible targets for new therapeutics. Currently, the Laboratories of Nicholas Heaton and Claire Smith are teaming up to identify novel restriction factors inside cells that can stop SARS-CoV-2.

However, it is not just the structures of viral components expressed inside the cells that matter, but also those on the outside of a virus particle. In Latin, corona means a crown or garland, and coronaviruses have been named for their distinctive crown-like spikes that envelop each virus particle. The viral protein that forms this corona is aptly named the “Spike” protein.

This Spike protein on the viral surface connects with a human cell surface protein (Angiotensin-converting enzyme 2, abbreviated as ACE2) to allow the virus to enter our cells and cause an infection. Heaton proposed that molecules designed to block this contact, by blocking either the human cell surface protein or the viral Spike protein, should also be tested as possible therapies.

One promising type of molecule to block this interaction is an antibody. Antibodies are “Y” shaped molecules that are developed as part of the immune response in the body by the second week of coronavirus infection. These molecules can detect viral proteins, bind with them, and prevent viruses from entering cells. Unlike several other components on our immune defense, antibodies are shaped to specifically latch on to one type of virus. Teams of scientists at Duke led by Dr. Sallie Permar, Dr. Georgia Tomaras, and Dr. Genevieve Fouda are working to characterize this antibody response to SARS-CoV-2 infection and identify the types of antibodies that confer protection.

Infectious disease specialist Dr. Chris Woods is leading an effort to test whether plasma with antibodies from people who have recovered can prevent severe coronavirus disease in acutely infected patients.

Indeed, there are several intriguing research questions to resolve in the months ahead. Duke scientists are forging new plans for research and actively launching new projects to unravel the mysteries of SARS-CoV-2. With Duke laboratory scientists rolling up their sleeves and gowning up to conduct research on the novel coronavirus, there will be soon be many more vaccine and therapeutic interventions to test.

Guest post by Tulika Singh, MPH, PhD Candidate in the Department of Molecular Genetics and Microbiology (T: @Singh_Tulika)

Duke’s Fundamental Research Can Turn Viruses Into Marvels

Sticky post

The COVID-19 epidemic has impacted the Duke research enterprise in profound ways. Nearly all laboratory-based research has been temporarily halted, except for research directly connected to the fight against COVID-19. It will take much time to return to normal, and that process of renewal will be gradual and will be implemented carefully.

Trying to put this situation into a broader perspective, I thought of the 1939 essay by Abraham Flexner published in Harper’s magazine, entitled “The Usefulness of Useless Knowledge.” Flexner was the founding Director of the Institute for Advanced Study at Princeton, and in that essay, he ruminated on much of the type of knowledge acquired at research universities —  knowledge motivated by no objective other than the basic human desire to understand. As Flexner said, the pursuit of this type of knowledge sometimes leads to surprises that transform the way we see that which was previously taken for granted, or for which we had previously given up hope. Such knowledge is sometimes very useful, in highly unintended ways.

Gregory Gray, MD MPH
Gregory Gray, MD MPH

The 1918 influenza pandemic led to 500 million confirmed cases, and 50 million deaths. In the Century since, consider how far we have come in our understanding of epidemics, and how that knowledge has impacted our ability to respond. People like Greg Gray, a professor of medicine and member of the Duke Global Health Institute (DGHI), have been quietly studying viruses for many years, including how viruses at domestic animal farms and food markets can leap from animals to humans. Many believe the COVID-19 virus started from a bat and was transferred to a human. Dr. Gray has been a global leader in studying this mechanism of a potential viral pandemic, doing much of his work in Asia, and that experience makes him uniquely positioned to provide understanding of our current predicament.

From the health-policy perspective, Mark McClellan, Director of the Duke Margolis Center for Health Policy, has been a leading voice in understanding viruses and the best policy responses to an epidemic. As a former FDA director, he has experience bringing policy to life, and his voice carries weight in the halls of Washington. Drawing on faculty from across Duke and its extensive applied policy research capacity, the Margolis Center has been at the forefront in guiding policymakers in responding to COVID-19.

Through knowledge accrued by academic leaders like Drs. Gray and McClellan, one notes with awe the difference in how the world has responded to a viral threat today, relative to 100 years ago. While there has been significant turmoil in many people’s lives today, as well as significant hardship, the number of global deaths caused by COVID-19 has been reduced substantially relative to 1918.

One of the seemingly unusual aspects of COVID-19 is that a substantial fraction of the population infected by the virus has no symptoms. However, those asymptomatic individuals shed the virus and infect others. While most people have no or mild symptoms, other people have very adverse effects to COVID-19, some dying quickly.

This heterogeneous response to COVID-19 is a characteristic of viruses studied by Chris Woods, a professor medicine in infectious diseases. Dr. Woods, and his colleagues in the Schools of Medicine and Engineering, have investigated this phenomenon for years, long before the current crisis, focusing their studies on the genomic response of the human host to a virus. This knowledge of viruses has made Dr. Woods and his colleagues leading voices in understanding COVID-19, and guiding the clinical response.

A team led by Greg Sempowski, a professor of pathology in the Human Vaccine Institute is working to isolate protective antibodies from SARS-CoV-2-infected individuals to see if they may be used as drugs to prevent or treat COVID-19. They’re seeking antibodies that can neutralize or kill the virus, which are called neutralizing antibodies.

Barton Haynes,MD
Barton Haynes, MD

Many believe that only a vaccine for COVID-19 can truly return life to normal. Human Vaccine Institute Director Barton Haynes, and his colleagues are at the forefront of developing that vaccine to provide human resistance to COVID-19. Dr. Haynes has been focusing on vaccine research for numerous years, and now that work is at the forefront in the fight against COVID-19.

Engineering and materials science have also advanced significantly since 1918. Ken Gall, a professor of mechanical engineering and materials science has led Duke’s novel application of 3D printing to develop methods for creatively designing personal protective equipment (PPE). These PPE are being used in the Duke hospital, and throughout the world to protect healthcare providers in the fight against COVID-19.

Much of the work discussed above, in addition to being motivated by the desire to understand and adapt to viruses, is motivated from the perspective that viruses must be fought to extend human life.

In contrast, several years ago Jennifer Doudna and Emmanuelle Charpentier, academics at Berkeley and the Max Planck Institute, respectively, asked a seemingly useless question. They wanted to understand how bacteria defended themselves against a virus. What may have made this work seem even more useless is that the specific class of viruses (called phage) that infect bacteria do not cause human disease. Useless stuff! The kind of work that can only take place at a university. That basic research led to the discovery of clustered regularly interspaced short palindromic repeats (CRISPR), a bacterial defense system against viruses, as a tool for manipulating genome sequences. Unexpectedly, CRISPR manifested an almost unbelievable ability to edit the genome, with the potential to cure previously incurable genetic diseases.

Charles Gersbach, a professor of Biomedical Engineering, and his colleagues at Duke are at the forefront of CRISPR research for gene and cell therapy. In fact, he is working with Duke surgery professor and gene therapy expert Aravind Asokan to engineer another class of viruses, recently approved by the FDA for other gene therapies, to deliver CRISPR to diseased tissues. Far from a killer, the modified virus is essential to getting CRISPR to the right tissues to perform gene editing in a manner that was previously thought impossible. There is hope that CRISPR technology can lead to cures for sickle cell and other genetic blood disorders. It is also being used to fight cancer and muscular dystrophy, among many other diseases and it is being used at Duke by Dr. Gersbach in the fight against COVID-19. 

David Ashley, Ph.D.
David Ashley, Ph.D.

In another seemingly bizarre use of a virus, a modified form of the polio virus is being used at Duke to fight glioblastoma, a brain tumor. That work is being pursued within the Preston Robert Tisch Brain Tumor Center, for which David Ashley is the Director. The use of modified polio virus excites the innate human immune system to fight glioblastoma, and extends life in ways that were previously unimaginable. But there are still many basic-science questions that must be overcome. The remarkable extension of life with polio-based immunotherapy occurs for only 20% of glioblastoma patients. Why? Recall from the work of Dr. Woods discussed above, and from our own observation of COVID-19, not all people respond to viruses in the same way. Could this explain the mixed effectiveness of immunotherapy for glioblastoma? It is not known at this time, although Dr. Ashley feels it is likely to be a key factor. Much research is required, to better understand the diversity in the host response to viruses, and to further improve immunotherapy.

The COVID-19 pandemic is a challenge that is disrupting all aspects of life. Through fundamental research being done at Duke, our understanding of such a pandemic has advanced markedly, speeding and improving our capacity to respond. By innovative partnerships between Duke engineers and clinicians, novel methods are being developed to protect frontline medical professionals. Further, via innovative technologies like CRISPR and immunotherapy — that could only seem like science fiction in 1918 (and as recently as 2010!) — viruses are being used to save lives for previously intractable diseases.

Viruses can be killers, but they are also scientific marvels. This is the promise of fundamental research; this is the impact of Duke research.

“We shall not cease from exploration
And the end of all our exploring
Will be to arrive where we started
And know the place for the first time.”

T.S. Eliot, Four Quartets

Post by Lawrence Carin, Vice President for Research

Medicine’s ‘Digital Health’ Future

Sticky post

“How often do we get to see a new field [of medicine] grow?” asked Satasuk “Joy” Bhosai (MD MPH), the chief of digital health and strategy for the Duke Clinical Research Institute.

Bhosai offered insights to the rapidly emerging and expanding field of digital health in her talk “Digital Health: How Do We Scale?” at Duke’s School of Nursing on Wednesday, March 4th.

Joy Bhosai, MD MPH

Digital health is a blanketing term that refers to a wide – and growing – array of services and products that merge digital technologies with healthcare to improve its quality, efficiency, and personalization. To put it simply: Digital health is the computerization of healthcare. Some of the largest, current digital trends of health care, according to Bhosai, are Artificial Intelligence (AI)/Machine Learning (ML), digital therapeutics, and innovations in delivery models. However, she presented a graphic (shown below) that shows the reach of the field.

Digital health is an expansive field that encompasses many types of products and services in the field of healthcare.

Bhosai focused on the challenges to digital health’s progress and the role that academia and research play in addressing these issues. “Having an idea and the technology are only the beginning,” Bhosai said.

To prove her point, Bhosai highlighted the company Proteus. Once valued at $1.5 billion, they are now struggling to stay afloat because they haven’t provided the data on effectiveness that investors needed.

She also pointed out the collaboration between Google and Ascension.  The duo teamed up with great technological potential to work on digital healthcare, but they received major pushback because Ascension released patients’ medical records to Google without patient knowledge or consent.

In the life cycle of developing and implementing digital health tools, Bhosai said that most companies falter or fail between beta testing and scaling. “To reach scale, evidence, and the right partners are needed.”

She proposed three main challenges as current limiters to breaking through the difficult transition that crushes so many digital health companies: 1) translating ideas to action, 2) evaluation and validation, and 3) adoption and scale.

Bhosai believes that there are many ways that academia and research could play a role in addressing these issues. Academics and researchers could give insight to the applicability of products, offer guidance on clinical utility, provide networks of contacts and support, materialize solutions, and build innovations at the front of business and growth models.

Bhosai’s proposed life cycle of digital health innovations.

This could help with things such as workflow, which may not be actualized in the product design of digital health products. One venture-backed attempt at putting information into a wearable, glasses-like device caused physicians to become very dizzy and disoriented – a problem that could have been avoided if medical specialists were integrated in the design process.

One success story is the company Akili, a digital therapeutic company that addresses cognitive impairments. A team at Duke, led by Scott Kollins, PhD, conducted a controlled clinical trial using the therapeutics and proved that the software led to improvements in treatment groups. The results of the study were submitted to the Federal Drug Administration (FDA) so that Akili can make claims around these findings in support of their service. Many other digital health products could benefit from these types of trials that provide evidence of their potential impacts in healthcare.

“Providers and academics are needed in health tech,” said Bhosai. This is a crucial connection to make for the future of the digital health field. Bhosai also pointed out that digital health tool users are not always a customer. For example, hospital systems are often the intended users of digital health services, but most hospitals have technical requirements that must be met in order to adopt a service. A product may be amazing but be barred from consideration for use because it would fail system security audits.

Products that are directly consumed by customers also must integrate into a patient’s lifestyle. “When products are high-touch, you may lose engagement,” Bhosai stated, “Patients don’t want to log onto three different apps when they could just log onto one.”

As digital health grows rapidly, companies in the field should work to navigate the health policies in place, understand the landscape of healthcare, and collaborate with academics and researchers to be successful and provide the best services for this new field of medicine.

Polymath Mae Jemison encourages bolder exploration, collaboration

Photo from Biography.com

“I don’t believe that [going to] Mars pushes us hard enough.” This was just one of the bold, thought-provoking statements made by Dr. Mae Jemison, who came to speak at Duke on Monday, February 24 as part of the 15th annual Jean Fox O’Barr Distinguished Speaker Series, presented by Baldwin Scholars.

Dr. Jemison is at the pinnacle of interdisciplinary engagement—though she is most famous for serving as a NASA astronaut and being the first African American woman to go into space, she is also trained as an engineer, social scientist and dancer. Dr. Jemison always knew that she was going to space—even though there were no women or people or color participating in space exploration as she was growing up.

Dr. Jemison says that simply “looking up” brought her here. As a child, she would look up at the sky, see the stars and wonder if other children in other places in the world were looking at the same view that she had. Growing up in the 1960’s instilled into Dr. Jemison at an early age that our potential is limitless, and the political culture of civil rights, changing art and music and decolonization were all about “people declaring that they had a right to participate.” 

Photo courtesy of Elizabeth Roy

One of the biggest pieces of advice that Dr. Jemison wanted to impart on her audience was the value of confidence, and how to build confidence in situations where people are tempted to feel incapable or forget the strengths they already possess. “They told me if I wanted to lead projects I needed an M.D.,” Dr. Jemison explained. “I went to medical school because I know myself and I knew I would want to be in charge one day.” 

At 26 years old, Dr. Jemison was on call 24 hours a day, 7 days a week, 365 days a year as the Area Peace Corps Medical Officer for Sierra Leone and Liberia. She described a case where a man came back with a diagnosis of malaria from Senegal. When Dr. Jemison first took a look, the diagnosis seemed more likely to be meningitis. After making an “antibiotic cocktail,” from what she had on site, she realized this man might lose his life if they didn’t get him to a better hospital. At this point, Dr. Jemison wanted to call a military medical evacuation, and she had the authority to do it. However, another man working with her suggested calling a doctor in Ivory Coast, or a doctor at the hospital in Germany to see what he thought before making the evacuation. Dr. Jemison knew what the patient needed in this situation was to be flown to Germany regardless of the cost of the evacuation. In reflecting on this experience, she says that she could have given someone else her authority, but letting her confidence in herself and what she knew was the right thing to do would have negatively impacted her patient. 

So, how do you maintain confidence? According to Dr. Jemison, you come prepared. She knew her job was to save people’s lives, not to listen to someone else. Dr. Jemison also admonished the audience to “value, corral and protect your energy.” She couldn’t afford to always make herself available for non-emergency situations, because she needed her energy for when a patient’s life would depend on it. 

Photo courtesy of Elizabeth Roy

Dr. Jemison’s current project, 100 Year Starship, is about  trying to ensure we have the capabilities to travel to interstellar space. “The extreme nature of interstellar hurdles requires we re-evaluate what we think we know,” Dr. Jemison explained. Alpha Centauri, the next closest star, is more than 25 trillion miles away. Even if we go 10% the speed of light, it will still take us 50 years to get there. We need to be able to travel faster, the vehicle has to be self-replenishing, and we have to think about space-time changes. What Dr. Jemison calls the “long pole in the tent” is human behavior. We need to know how humans will act and interact in a small spaceship setting for possibly decades of space travel. Dr. Jemison is thinking deeply about how we can apply the knowledge we already possess to fix world problems, and how we can start preparing now for problems we may face in the future. For example, how would health infrastructure in deep space look different? How would we act on a starship that contains 5,000 people when we can’t figure out how to interact with each other on the “starship” we’re on now?

Returning to the childhood love for stargazing that brought her here, Dr. Jemison discussed towards the end of her talk that a stumbling block for the majority of people is insufficient appreciation of our connection across time and space. She has worked with a team to develop Skyfie, an app that allows you to upload photos and videos of your sky to the Sky Tapestry and explore images other people in different parts of the world are posting of their sky. Dr. Jemison’s hope is this app will help people realize that we are interconnected with the rest of the universe, and we won’t be able to figure out how to survive as a species on this planet alone. 

By Victoria Priester

Man’s Best Friend, Our Relationship to Dogs

The average dog costs its human owner $10,000-20,000 over the course of its lifetime, from vet care and grooming to treats and toys to the new fad of doggie DNA testing. But what’s in it for us? Researcher Kerri Rodriguez – a Duke alum of evolutionary anthropology and current grad student with Purdue University’s College of Veterinary Medicine – explores just that.

Rodriguez is a member of the OHAIRE Lab at Purdue, which stands for the Organization for Human-Animal Interaction Research and Education. Continuing her work from undergrad, Rodriguez researches the dynamic duo between humans and dogs – a relationship some 15,000 to 40,000 years in the evolutionary making. Rodriguez returned to Duke to speak on February 12th, honoring both Darwin Day and Duke’s second annual Dog Day.

It’s well-known that dogs are man’s best friend, but they do much more than just hang out with us. Dogs provide emotional support when we are stressed or anxious and are highly attentive to us and our emotional states.

In a study of 975 adult dog owners, dogs ranked closely to romantic partners and above best friends, children, parents, and siblings when their owners were asked who they turn to when feeling a variety of ways. Dogs provide non-judgmental support in a unique way. They have also been found to reduce levels of the stress hormone cortisol, lower perceived stress in individuals, improve mood, and improve energy up to 10 hours after interactions. Therapy dogs are prevalent on many college campuses now due to these impacts and are found in hospitals for the same reasons, having been found to reduce subjective pain, increase good hormones and dampen bad ones, causing some patients to require less pain medications.

(Creative Commons)

 Along with reduced stress, dogs make us healthier in other ways, from making us exercise to reducing risk of cardiovascular disease. A study of 424 heart attack survivors found that non-dog owners were four times more likely to be deceased one year after the attack than victims who owned dogs.

The increased social interaction that dogs offer their human companions is also quite amazing due to the social facilitation effect they provide by offering a neutral way to start conversations. One study with people who have intellectual disabilities found that they received 30% more smiles along with increased social interactions when out in public with a dog. Similar studies with people who use wheelchairs have produced similar results, offering that dogs decreased their loneliness in public spaces and led to more social engagements.

Rodriguez also shared results from a study dubbed Pet Wingman. Using dating platforms Tinder and Bumble, researchers found that after one month, simulated profiles containing pictures with dogs received 38% more matches, 58% more messages, and 46% more interactions than simulated profiles without. Even just having a dog in photos makes you appear more likable, happier, relaxed, and approachable – it’s science!

 A large bulk of Rodriguez’s own work is focused on dogs in working roles, particularly the roles of a service dog. She explained that unlike therapy or emotional support dogs, service dogs are trained for one person, to do work and perform tasks to help with a disability, and are the only dogs granted public access by the American Disability Association. Rodriguez is particularly interested in the work of dogs who help American veterans with post-traumatic stress disorder (PTSD).

(Creative Commons)

 Around one out of five post-9/11 military veterans have PTSD and the disorder is difficult to treat. Service dogs are becoming increasingly popular to help combat effects of PTSD, ranking at the third highest placed type of service dog in the United States. PTSD service dogs are able to use their body weight as a grounding method, provide tactile interruption, reduce hypervigilance, and prevent crowding of their veterans. However, because of the lack of research for the practice, the Veterans Association doesn’t support the use of the dogs as a therapy option. This is an issue Rodriguez is currently trying to address.           

 Working with a group called K9s for Warriors, Rodriguez’s research evaluated the mental health, social health, quality of life, and cortisol levels of veterans who have received service dogs and those who were on the wait list for dogs. Veterans with service dogs had lower PTSD symptoms, better mental health, and better social health. Rodriguez is now working on a modification to this study using both veterans and their spouses that will be able to measure these changes to their well-being and health over time, as well as assessing the dog’s health too. Unlike other organizations, K9s for Warriors uses 90% shelter dogs, most of which are mutts. Each dog is as unique as the human it is placed with, but no bond is any less special.

By Cydney Livingston

The evolution of a tumor

The results of evolution are often awe-inspiring — from the long neck of the giraffe to the majestic colors of a peacock — but evolution does not always create structures of function and beauty.

In the case of cancer, the growth of a population of malignant cells from a single cell reflects a process of evolution too, but with much more harrowing results.

Johannes Reiter uses mathematical models to understand the evolution of cancer

Researchers like Johannes Reiter, PhD, of Stanford University’s Translational Cancer Evolution Laboratory, are examining the path of cancer from a single sell to many metastatic tumors. By using this perspective and simple mathematical models, Reiter interrogates the current practices in cancer treatment. He spoke at Duke’s mathematical biology seminar on Jan. 17.

 The evolutionary process of cancer begins with a single cell. At each division, a cell acquires a few mutations to its genetic code, most of which are inconsequential. However, if the mutations occur in certain genes called driver genes, the cell lineage can follow a different path of rapid growth. If these mutations can survive, cells continue to divide at a rate faster than normal, and the result is a tumor.

As cells divide, they acquire mutations that can drive abnormal growth and form tumors. Tumors and their metastases can consist of diverse cell populations, complicating treatment plans out patient outcomes. Image courtesy of Reiter Lab

With each additional division, the cell continues to acquire mutations. The result is that a single tumor can consist of a variety of unique cell populations; this diversity is called intratumoral heterogeneity (ITH). As tumors metastasize, or spread to other locations throughout the body, the possibility for diversity grows.

Intratumoral heterogeneity can exist within primary tumors, within metastases, or between metastases. Vogelstein et al., Science, 2013

Reiter describes three flavors of ITH. Intra-primary heterogeneity describes the diversity of cell types within the initial tumor. Intrametastatic heterogeneity describes the diversity of cell types within a single metastasis. Finally, inter-metastatic heterogeneity describes diversity between metastases from the same primary tumor.

For Reiter, inter-metastatic heterogeneity presents a particularly compelling problem. If treatment plans are made based on biopsy of the primary tumor but the metastases differ from each other and from the primary tumor, the efficacy of treatment will be greatly limited.

With this in mind, Reiter developed a mathematical model to predict whether a cell sample collected by biopsy of just the primary tumor would provide adequate information for treatment.

Using genetic sequence data from patients who had at least two untreated metastases and a primary tumor, Reiter found that metastases and primary tumors overwhelmingly share a single driver gene. Reiter said this confirmed that a biopsy of the primary tumor should be sufficient to plan targeted therapies, because the risk of missing driver genes that are functional in the metastases proved to be negligible.

 In his next endeavors as a new member of the Canary Center for Cancer Early Detection, Reiter plans to use his knack for mathematical modeling to tackle problems of identifying cancer while still in its most treatable stage.  

Post by undergraduate blogger Sarah Haurin

Post by Sarah Haurin

Inventing New Ways to Do Brain Surgery

This is the sixth and final 2019 post written by students at the North Carolina School of Science and Math as part of an elective about science communication with Dean Amy Sheck.

Dr. Patrick Codd is the Director of the Duke Brain Tool Laboratory and an Assistant Professor of Neurosurgery at Duke. Working as a neurosurgeon and helping with the research and development of various neurosurgical devices is “a delicate balance,” he said.

Patrick Codd

Codd currently runs a minimally invasive neurosurgery group. However, at Massachusetts General Hospital, he used to run the trauma section. When asked about which role was more stressful, he stated “they were both pretty stressful” but for different reasons. At Mass General, he was on call for most hours of the day and had to pull long shifts in the operating room. At Duke, he has to juggle surgery, teaching, and research and the development of new technology.

“I didn’t know I was going to be a neurosurgeon until I was in college,” Codd said. Despite all of the interesting specialties he learned about in medical school, he said “it was always neurosurgery that brought me back.”

Currently, he is exclusively conducting cranial surgery.

 Neurosurgeon U.S. Air Force Maj Jonathan Forbes,looks through loupes as he performs brain surgery at the Bagram Air Field in Afghanistan, Oct. 10, 2014. 

Though Dr. Codd has earned many leadership positions in his career, he said he was never focused on advancement. He simply enjoys working on topics which he loves, such as improving minimally invasive surgical techniques. But being in leadership lets him unite other people who are interested in working towards a common goal in research and development. He has been able to skillfully bring people together from various specialties and help guide them. However, it is difficult to meet everyone’s needs all of the time. What is important for him is to be a leader when he needs to be.

Dr. Codd said there are typically five to eight research papers necessary in to lay the groundwork for every device that is developed. However, some technologies are based on the development of a single paper. He has worked on devices that make surgery more efficient and less minimally invasive and those that help the surgical team work together better. When developing technologies, he tries to keep the original purpose of the devices the same. However, many revisions are made to the initial design plans as requirements from the FDA and other institutions must be met. Ironically, Dr. Codd can’t use the devices he develops in his own operating room because it would be a conflict of interest. Typically other neurosurgeons from across the country will use them instead.

Post by Andrew Bahhouth, NCSSM 2020

Working Through Frustrations to Understand Nature Better

This is the fifth of six posts written by students at the North Carolina School of Science and Math as part of an elective about science communication with Dean Amy Sheck.

Research is a journey full of uncertainty in which scientists have to construct their own path, even if they’re unsure of what the end of the journey actually is. Despite this unpredictability, researchers continue their journey because they believe their work will one day drive their fields forward. At least, that’s why Kate Meyer Ph.D. says she has investigated something called m6A for several years.

Kathryn Meyer, Ph.D.

“Virtually every study that I have ever been part of had some frustrations involved because everything can fall apart in just one night,” Meyer said. “Despite all the frustrations you might have, you are still in the research because you know that at the end of the day, you will get new knowledge that is worthy to your field, or perhaps to the world.”

N6-methyladenosine (or m6A) is a modification to one of the four main bases of RNA – adenosine. Because RNA plays a significant role as a bridge between genetic information and functional gene products, modifications in RNA can alter how much of a certain product will be produced, which then controls how our cells and eventually our whole body functions.

The idea of this tiny but powerful modification was first proposed in the 1970s. But scientists struggled to find where m6A was located in the cell before research Meyer made a major contribution to as a trainee was published in 2012. Combining a newly developed antibody that could recognize m6A and gene sequencing techniques that became more accessible to the researchers, Meyer’s work led to the first method that can detect and sequence all of the m6A regions in a cell.

m6A’s interaction with a neuron, as depicted on Dr. Meyer’s laboratory site.

Meyer’s work was transformative research. Her method allowed laboratories around the world to investigate what regulates m6A and what its consequences are. Meyer said this first study which ignited m6A field is one of her most prideful moments as a researcher. 

Significant progress has been made since 2012, but there are still lots of questions that need to be answered. Currently, Meyer’s research team is investigating the relationships between m6A and various neurological issues. She believes that regulation of m6A controls the expression, or activity level, of various genes in the brain. As such, m6A may play an important role in neurodegenerative diseases and memory.

Author Jun Hee Shin, left, and Kate Meyer in her lab.

As an assistant professor of both biochemistry and neurobiology at Duke, Meyer is definitely one of the most important figures in the m6A field. Despite her many accomplishments, she said she had experienced and overcome many frustrations and failures on her way to the results.

Guest Post by Jun Shin, NCSSM 2020

Infants, Immunity, Infections and Immunization

This is the fourth of several posts written by students at the North Carolina School of Science and Math as part of an elective about science communication with Dean Amy Sheck.

Dr. Giny Fouda’s research focuses on infant immune responses to infection and vaccination.

Her curiosity about immunology arose during her fourth year of medical school in Cameroon, when she randomly picked up a book on cancer immunotherapy and was captivated. Until then, she conducted research on malaria and connected it to her interest in pediatrics by studying the effects of the parasitic disease on the placentas of mothers.

Genevieve Giny Fouda M.D., Ph.D.

As a postdoctoral fellow at Duke, she then linked pediatrics and immunology to begin examining mother to child transmission of disease and immunity.

Today she is an M.D. and a Ph.D. and a member of the Duke Human Vaccine Institute. She’s an assistant professor in pediatrics and an assistant research professor in the Department of Molecular Genetics and Microbiology at Duke University School of Medicine.

Based on the recent finding that children of HIV-positive mothers are more susceptible to inheriting the disease, Fouda believes that it is important to understand how to intervene in passive immunity transmissions in order to limit them. Children and adults recover from diseases differently and uncovering these differences is important for vaccine development.

This area of research is personally important to her, because she learned from her service in health campaigns in Central Africa that it is much easier to prevent disease than to treat.

Babies!

However, she believes that it is important to recognize that research is a collaborative experience with a team of scientists. Each discovery is not that of an individual, but can be accredited to everyone’s contribution, especially those whose roles may seem small but are vital to the everyday operations of the lab.

At the Duke Human Vaccine Institute, Fouda enjoys collaborating as a team and contributing her time as a mentor and trainer of young scientists in the next generation.

Outside of the lab, Fouda likes to spend time reading books with her daughter, traveling, decorating and gardening. If there was one factor that improve how science in immunology is conducted, she would stress that preventing disease is significantly cheaper than treating those that become infected by it.

Dr. Fouda has made some remarkable progress in the field of disease treatment with her hard working and optimistic personality, and I know that she will continue to excel in her objectives for years to come.

Post by Vandanaa Jayaprakash NCSSM 2020

Understanding and Addressing Vaccine Hesitancy

In the midst of increasing outbreaks of vaccine-preventable disease, Duke global health researcher Lavanya Vasudevan (PhD, MPH, LPH) is investigating the reasons for vaccine hesitancy with focus on America and Tanzania.

Vaccine hesitancy refers to the refusal of or delay in accepting vaccinations, despite their availability. Vasudevan hopes to figure out what interventions will change the minds of target populations on such a heated topic.

She presented at Duke’s Global Health Institute on November 15th about her “big 5 research areas:” identification of sub-optimal vaccine uptake, contextualization of barriers to uptake, measuring parental concern, debunking misinformation, and developing and testing strategies aimed at addressing vaccine hesitancy.

Lavanya Vasudevan presenting at Duke’s Global Health Institute.

Globally, Vasudevan says that there are too many kids playing catch-up with their vaccines, meaning that even when children are getting vaccinated, the vaccinations they receive are not on time with the scheduled progression of immunizations, putting them at risk for contracting disease. Different countries measure vaccination coverage in different ways and on different timelines, which makes it harder to understand where sub-optimal vaccine uptake is happening. A better standard for assessing timeliness of vaccines is crucial. Vasudevan is working to confront this issue to gain better understanding of who and where hesitancy is coming from.

Identification of specific regions of vaccine hesitancy is crucial to navigating interventions, she added. Vasudevan wants to be able to pinpoint areas and understand the context-specific issues that vary across time, place, and vaccine type in order to be most effective.

She said that her work in Tanzania has provided insight to the problem of geographic accessibility and lack of proper supplies in the country, prompting delayed and missed vaccinations among 72% of children, according to self-reporting by their mothers. Tanzanian mothers expressed their frustrations during interviews. They frequently arrange to go to a clinic where vaccinations are offered on specific dates and travel long distances to get there. However, if there are not enough kids who come to be vaccinated, the facilities just won’t vaccinate those who did manage to show up for immunizations.  

Though the qualitative data gained through extensive interviewing and group discussions has been extremely useful and rich, Vasudevan says there is a need for quantitative tools that can rapidly screen for parent’s concerns when it comes to the vaccination of their children. Qualitative data is simply not informative on a large scale.

A review of pre-existing measures evaluated 159 studies, but the quantitative scales found were often complex and context-specific, as well as designed and validated for high-income settings. On this basis, Vasudevan and her larger research team decided to design a scale for use in Tanzania because of its specificity in addressing the contexts of the region. Tailored counseling is also being used to address the local concerns and issues.

Another parallel research project that Vasudevan is involved with aims to identify common vaccine myths, creating a taxonomy to tag these myths and developing and testing an intervention that will highlight and debunk misinformation found on the internet. The current end-goal for the work being done is a “vaccine fact-checker” that could be used on web browsers to identify the myths in vaccine-related information found online.

A common example of needles and vials containing immunization products (Creative Commons).

In closing, Vasudevan identified three main areas for developing and testing intervention strategies. She says these are behavioral nudges, educational strategies, and vaccination policy and legislation.

There is a need for parent-focused strategies that recognize parental concern for their child’s safety on all sides of the vaccination issue, she said. Stringent policies are likely to alienate hesitant parents rather than increasing vaccine uptake. This is why Vasudevan is so focused on understanding and contextualizing issues specific to hesitancy among parents. It seems that increase of vaccinations and improvement of immunization timeliness lies in hearing and reconciling with parental apprehensions and underlying root causes of these hesitations.

One area of focus that Vasudevan feels is underutilized is pre-natal care. Reduction of the divide between obstetrician/gynecologists (OBGYNs) and pediatric care may be a crucial component to educate parents and enrich their understanding about vaccinations following the birth of the child.

Beyond everything else, she said, building trust is essential; simply providing information to parents is not enough. It takes time and empathy to be enable parents to make healthy vaccination choices. Providing credible resources in a safe environment while tuning in to the causes of hesitancy may be the next step to the reduction of vaccine-preventable disease, a current top ten threat to global health.

Post by Cydney Livingston

Page 1 of 16

Powered by WordPress & Theme by Anders Norén