ASU study shows positive lab environment critical for undergrad success in research

Undergraduate researchers with LEAP Scholars program publish findings

August 14, 2019

Getting involved in research as an undergraduate can have significant benefits, such as enhancing a student’s ability to think critically, increasing their understanding of how to conduct a research project and improving the odds that they’ll complete a degree program in science, technology, engineering and math (STEM).

And, for students who participate in research over several years, the benefits are even greater. They often develop greater confidence in their research skills along with an ability to solve problems independently, and they are more likely to pursue a career in STEM. Undergraduate students work with a faculty mentor Undergraduate students work in a neuroscience lab with faculty member Janet Neisewander. Photo by Samantha Lloyd/ASU VisLab

But many undergraduates drop out of their research experience before graduation or even during their first year working in a biology lab. Until now, there has been no research as to why.

In a study published today in PLOS ONE, a group of 14 undergraduate Arizona State University co-authors addressed this question as part of a class project. Led by School of Life Sciences Associate Professor Sara Brownell, graduate student Logan Gin and University of Central Florida Assistant Professor Katelyn Cooper, students with the LEAP Scholars program surveyed more than 750 life sciences undergraduates doing research in 25 public institutions across the U.S. They found that 50% of students who participated in the study had considered leaving their undergraduate research experience more than 50% of those students ultimately decided to leave. 

They also found that the most important factors that influence whether a student decides to continue working in research included a positive lab environment and enjoying their everyday research tasks, as well as flexible schedules, positive social interactions and feeling included. Students also persisted with their research when they felt they were learning important skills and perceived the work was important to their career goals.

“We often assume that all undergraduate research experiences are positive for students, but this study shows that this is not the case. If 50% of students consider leaving their undergraduate research experience, then that means that we have a structural problem with how we are integrating students in undergraduate research,” senior author Brownell said. “We can empower students with more knowledge about undergraduate research to help them choose a suitable lab, but we also need to find ways to make our research labs more positive environments for all students.”

Other factors, such as race, gender, GPA and college generation status, also play a role in what factors influence students to persist in their research experiences. Men were more likely than women to stay in research because they consider it important for their future careers. Men were also more likely to leave their research experience because they didn’t enjoy their specific lab tasks, while women were more likely to consider leaving because of a lack of flexibility in the lab. 

Underrepresented minority students were more likely to leave their research work because they felt they were not learning important skills, while white students were more likely to stay in research because they enjoyed their everyday lab tasks. And, students with lower GPAs were more likely to stay in research because they were unsure about future research opportunities, while those with higher GPAs were more likely to leave research because they did not enjoy the everyday lab tasks. 

“We were excited to identify factors that disproportionately affected underrepresented and marginalized students’ decisions to leave research. It will be challenging to identify solutions, but identifying these issues is a critical step in developing a more diverse and inclusive scientific community,” Gin said. 

ASU LEAP Scholars

LEAP Scholar students present their research findings on undergraduate persistence in a research lab at a spring SOLUR Symposium. Left to right: Leilani Pfeiffer, Barierane Akeeh, Deanna Elliott, Luis Guiterrez, Rebecca Mello, Carolyn Clark, Rachel Scott. (Not all researchers pictured.)


For faculty members who invest time and resources to train undergraduates to work in their labs, this study provides important insight that can be used to shape their student lab experiences, develop support policies and improve mentor and mentee relationships. 

“What was most surprising to us was the importance of the lab environment and the interactions among people in the lab,” lead author Katelyn Cooper said. “When we hire faculty members to run research labs, we often are looking for the smartest people with the best research ideas. However, this study highlights that if we want to maximize the success of undergraduates in research, we need to be selecting for supportive faculty who can create positive working environments.”

Brownell and her co-instructors lead ASU’s LEAP Scholars program, a four-semester scholarship program funded by the National Science Foundation to help community college transfer students get involved in undergraduate science research. Because many transfer students need to work a job while attending college, the LEAP program provides scholarships and mentors so they can work in a research lab instead and focus full time on their coursework.

Sandra Leander

Assistant Director of Media Relations, ASU Knowledge Enterprise


New drug targets early instigator of Alzheimer’s disease

August 14, 2019

More than a hundred years after they were first identified, two ominous signposts of Alzheimer’s disease remain central topics of research — both formed by sticky accumulations of protein in the brain. Amyloid beta solidifies into senile plaques, which congregate in the extracellular spaces of nerve tissue, while tau protein creates tangled forms crowding the bodies of neurons.

Plaques and tangles, considered classic hallmarks of Alzheimer’s, have been the objects of fierce debate, sustained research and many billions of dollars in drug development. Yet therapeutic efforts to target these pathologies, which are consistently associated with cognitive decline in both humans and animal models, have met with dispiriting failure. DYR219 is a powerful new drug developed by Travis Dunckley and his colleagues and described in the new study. Its strength lies in the fact that it can target both of the leading pathologies associated with Alzheimer's disease — plaques (caused by the protein amyloid beta) and tangles (caused by the tau protein). Further, DYR219's activity can occur early in the progression of the disease, before the formation of these pathologies, offering a better chance of preventing the advance of Alzheimer's and its destruction of cognitive function. DYR219 inhibits a kinase known as DYRK1. In Alzheimer's and other neurodegenerative diseases, DYRK1 phosphorylates both the tau and amyloid beta proteins—key steps in the formation of plaques and tangles in the brain. Graphic by Shireen Dooling Download Full Image

Travis Dunckley, a researcher at the ASU-Banner Neurodegenerative Disease Research Center, and Christopher Hulme, medicinal chemist at the Arizona Center for Drug Discovery based at the UA College of Pharmacy, are exploring a small molecule drug known as DYR219. The promising therapy, while still in the experimental stages, may succeed where other treatments have failed and could be effective against a range of neurodegenerative illnesses in addition to Alzheimer’s. 

Rather than directly attacking the visible hallmarks of Alzheimer’s, namely the plaques and tangles caused by the disease’s relentless progression, the new drug acts by inhibiting an early pathway believed to be critical in the formation of both plaques and tangles.

Dunckley says that targeting the early-stage events leading to plaque and tangle formation represents an important advance in the field. “If you can block that process early, you can delay the downstream aggregation and formation of the pathologies.”

By preventing or delaying the development of Alzheimer’s disease pathologies, DYR219 or a similar drug may halt the progression of Alzheimer’s in its tracks, before it damages the brain beyond repair.

The new small molecule acts by inhibiting DYRK1, a particular neuroactive enzyme known as a kinase. Researchers like Dunckley and Hulme have been studying DYRK1 and exploring its crucial importance not only in Alzheimer’s disease but a broad range of neurodegenerative maladies.

The new study recently appeared in the journal Molecular Neurobiology.

Two faces of DYRK1

Although the activity of DYRK1 is believed to be a key factor in the formation of plaques and tangles, it is vital to the brain during early embryonic development, where it is involved in a host of processes, including signaling pathways linked with cell growth and proliferation, as well as the differentiation of cells into mature neurons and the formation of dendritic spines essential for the transmission of nerve impulses. 

Christopher Hulme, graduate assistant Chris Foley and Travis Dunckley.

From left: Christopher Hulme, graduate assistant Chris Foley and Travis Dunckley. Hulme and Dunckley's recently formed company Iluminos has developed compounds that may help treat neurodegenerative diseases like Alzheimer’s. A new study describes a small molecule kinase inhibitor that has shown effectiveness in blocking or delaying the development of plaques and tangles — pathologies caused by accumulations of amyloid and tau proteins in the brain.

In the mature brain, however, DYRK1’s activities can turn hostile, initiating pathologies associated with Alzheimer’s, dementia with Lewy bodies and Parkinson’s disease. The dysfunction of DYRK1 is also a central feature of Down syndrome. Patients with this disorder are highly prone to developing Alzheimer’s early in life, often in their 40s or 50s.

The DYRK1 kinase carries out its harmful role in the brain through a process known as phosphorylation. When DYRK1 encounters a protein known as APP (amyloid precursor protein), it attaches a cluster of oxygen and phosphorus atoms, known as a phosphate group. DYRK1 also phosphorylates tau.

Too much phosphorylation of these critical proteins can have disastrous effects in the brain. The hyperphosphorylation of APP is believed to increase the formation of amyloid plaques, while tau hyperphosphorylation leads to neurofibrillary tangles. Inhibition of these processes could interrupt the sequence of events leading to plaque and tangle formation and block or delay the onset of Alzheimer’s.

“The reason I’m excited about this, especially in the face of a lot of the recent high-profile clinical trial failures, is that this is really a different approach to treating the disease,” Dunckley said, noting that previous efforts to target plaques and tangles directly have failed to provide any benefit to cognitive function. “What we’re trying to do is restore the normal phosphorylation of APP and tau, so that you don’t get those downstream pathologies.”

Working upstream

In earlier research, Dunckley, Hulme and colleagues showed that using a small molecule drug to inhibit DYRK1 in hybrid mice bred to develop AD-like symptoms reduced the load of amyloid plaque in their brains and improved cognitive performance.

The new study explores early DYRK1 inhibition as a potential preventive measure against Alzheimer’s, with impressive results. “We showed a robust and significant delay in the onset of amyloid and tau pathology,” Dunckley said.

Researchers speculate that one reason anti-plaque and anti-tangle therapies have shown promise in mice yet consistently failed in humans is the nature of disease progression in the two very different brains. In hybrid mice, plaques and tangles can develop quickly, before Alzheimer’s has caused significant neurodegeneration and cell loss in the brain. Treating plaques and tangles in this case can help the remaining healthy neurons resume normal function. In human Alzheimer’s, however, plaques and tangles are typically accompanied by advanced neuronal devastation. It’s simply too late in the course of the disease to derive any benefit from targeting the amyloid and tau pathologies alone.

Connection with Down syndrome

Inhibition of DYRK1 has also shown promise in the treatment of Down syndrome. The DYRK1 gene is localized on chromosome 21, in the Down syndrome critical region. Overexpression of DYRK1 appears intimately involved with the learning defects characteristic of this disease and its inhibition has been shown to improve cognitive performance in mice.

Dunckley believes a DYRK1 inhibitor like the one described in the new study could first be used to treat pathology and cognitive impairment in Down syndrome patients, before its eventual application for Alzheimer’s.

Those living with Down syndrome carry a gene defect on chromosome 21 that allows for rapid and definitive diagnosis. The fact that this pool of patients will go on to develop Alzheimer’s with high probability makes them ideal subjects for clinical trials involving DYRK1-inhibiting drugs. Such an approach promises to avoid the pitfalls currently involved in testing preventive treatments for Alzheimer’s disease, which would need to be administered years or even decades before the onset of symptoms in patients of uncertain prognosis.

Targeting an enigmatic killer

The ability of DYRK1 inhibitors to halt or significantly delay both major Alzheimer’s-associated pathologies caused by amyloid beta and tau offers renewed hope for effective treatment of Alzheimer’s and may hold the key to addressing other devastating afflictions linked to hyperphosphorylation by DYRK1.

Hulme expresses excitement about rapid advancements in this area.

“A challenging in-house design effort driven by several UA graduate students over the last seven years, most recently Christopher Foley, has successfully unearthed newer drugs that are incredibly selective, much more stable and much more potent,” he said. “If such drugs deliver on their early promise, they may eventually be used as a common prophylactic against neurodegenerative diseases, perhaps like current medications for the prevention of heart disease.”

The pressing need for an effective Alzheimer’s disease therapy could not be more acute. Dementia currently affects nearly 50 million people, striking a new victim somewhere in the world every three seconds. The majority fall victim to Alzheimer’s disease, the most common form of dementia, which accounts for around 75% of cases. Barring major advances in treatment, the number of cases is projected to skyrocket to 131.5 million by mid-century.

On a more hopeful note, because Alzheimer’s is primarily a disease of old age, it has been estimated that a therapy capable of delaying the onset by just five years would cut the number of cases globally by half. The research outlined in the current study offers an innovative approach to this urgent medical crisis. 

Richard Harth

Science writer, Biodesign Institute at ASU