By David Robinson

June 19, 2019 | The University of Arkansas for Medical Sciences (UAMS) made history this spring with its first Master of Science graduate in biomedical informatics/translational bioinformatics.

Biomedical informatics professionals use computational tools to learn from medical and public health information to improve human health.

As one of the program’s first enrollees, Dina Elsayed was aware she would be among the first graduates but didn’t imagine she would be the first.

“Honestly, it was intimidating but exciting,” she said. “It is a great feeling to be the first graduate of the biomedical informatics program at a great university like UAMS.”

The new degree program is offered by the Department of Biomedical Informatics in the College of Medicine with support from the UAMS Translational Research Institute. Translational bioinformatics is one of four tracks developed by the Department of Biomedical Informatics offering both master’s and doctorate degrees.

Other new tracks are:

• Clinical research informatics (first in the United States)
• Imaging informatics
• Clinical informatics

“Biomedical informatics is an emerging field in health care and precision medicine, making it possible to customize treatments for individual patients,” said Christopher T. Westfall, M.D., executive vice chancellor of UAMS and dean of the College of Medicine. “I am proud of our biomedical informatics leadership because this program positions UAMS as a national leader in one of the fastest growing health research fields.”

Because of its focus on human health, the UAMS biomedical informatics program is unique to Arkansas, addressing a critical workforce need in the field, said Fred Prior, Ph.D., professor and chair of the Department of Biomedical Informatics.

“In addition to Dina’s degree, we had five certificate graduates and 22 students are currently enrolled,” Prior said. “We’re excited about the momentum we have for this new program and we look forward to its continued growth.”

Each of the four tracks are offered in the UAMS Graduate School as a 36-credit hour master’s degree with a Professional and a Master of Science option. Additionally, the doctoral program will take a minimum 55 credit hours that are inclusive of the master’s degree credit hours.

“These degrees have strengthened our curriculum and are already helping us compete for students nationally,” said Graduate School Dean Robert E. McGehee Jr., Ph.D.

Both master’s options can be completed in two years with full-time enrollment, and the Ph.D. can be completed in four years, though for most students it’s expected to take five years.

The Graduate Certificate consists of one core course, a practicum, and additional courses of the candidate’s choosing.

Elsayed earned a medical degree in Egypt and has that country’s board certification in dermatology. She hopes to use her new degree to pursue multiple research projects that use the science of genomics to help cancer patients.​

“I found that the translational biomedical informatics track will allow me to learn about the most advanced research in treating cancer through studying the genetic abnormalities in cancer patients,” she said. “I chose this program with the hope that one day I would be able to participate in the discovery of new, effective cancer therapies.”

As part of her thesis, she studied new gene abnormalities in patients with multiple myeloma and its correlation with severity and prognosis of the disease.

“We identified about 20 genetic transcripts related to multiple myeloma, some of which are probably linked to severity and prognosis of the disease,” she said. “I hope this novel information will open the door for further research projects to achieve better outcomes for this dreadful cancer.”

The program is now accepting applications for fall 2019. The deadline for applying for fall 2019 is July 1. To apply or for additional information, please visit the link below.

https://dbmi.uams.edu/education/graduate-programs/.

More information about the degree program is at https://dbmi.uams.edu/education/graduate-programs/admission-information/.

J. Paul Mounsey, M.D., Ph.D., FACC, a nationally recognized leader in electrophysiology, will join UAMS on Oct. 1 as director of the Division of Cardiovascular Medicine in the UAMS College of Medicine Department of Internal Medicine and director of the cardiovascular program at UAMS.

“Dr. Mounsey brings extensive expertise and leadership experience to our clinical, educational and research programs in cardiovascular medicine,” Executive Vice Chancellor and Dean Christopher T. Westfall, M.D., and Internal Medicine Chair James Marsh, M.D., said in a June 17 announcement to the faculty.

Current Division Director and Professor David Rutlen, M.D., will assume a new role on Oct. 1 as director of Inpatient Cardiology, leading efforts to enhance quality and efficiency in inpatient cardiology care.

“We also want to take this opportunity to express our gratitude to Dr. Rutlen for his 11 years of service and excellent leadership of the Division of Cardiovascular Medicine, as well as for his ongoing commitment to providing high-quality cardiovascular care at UAMS,” Westfall and Marsh said.

Mounsey currently serves as professor of medicine and director of cardiac electrophysiology and pacing in the Department of Cardiovascular Sciences at East Carolina University (ECU) and the East Carolina Heart Institute in Greenville, North Carolina.

Mounsey received his doctorate in physiology, with an emphasis in cardiac muscle biophysics, from St. Thomas Hospital Medical School in London, U.K., in 1983 and his medical degree from the University of Oxford Medical School in 1987. He completed his internship and residency in medicine at Oxford. Mounsey continued his training with a cardiology fellowship at the University of Newcastle upon Tyne in the U.K. and a cardiac electrophysiology fellowship at the University of Virginia.

Mounsey began his career in academic medicine as a lecturer in cardiology at Oxford and then as a senior lecturer in cardiology at the University of Birmingham in the U.K. He returned to the United States in 1996 and served on the faculty of the University of Virginia until 2007, when he was recruited to the University of North Carolina (UNC). He served as a professor of medicine and director of cardiac electrophysiology and pacing at UNC until 2012, when he was named Cecil Sewell Endowed Distinguished Professor of Medicine. Mounsey was recruited to Eastern Carolina University and his current posts in the ECU Brody School of Medicine and East Carolina Heart Institute in August 2017.

In addition to publishing extensively, Mounsey has served on the editorial boards of Heart Rhythm, the Journal of Cardiovascular Electrophysiology and the Journal of Electrocardiography. He has also been an ad hoc reviewer for numerous journals including Circulation and the Journal of the American College of Cardiology.

Mounsey is a Fellow of the Royal College of Physicians, the American College of Cardiologists and the American Heart Association. Among numerous honors, he received the University of Virginia Department of Internal Medicine Clinical Excellence Award and the University of Virginia Dean’s Award for Clinical Excellence in 2001. He received the Leonard S. Gettes Faculty Teaching Award in the UNC Division of Cardiology in 2008.

Arabinda Choudhary, M.D., M.B.A., FACHE, has been named chair of the Department of Radiology in the UAMS College of Medicine. He will join the faculty on August 1, following the retirement of current chair James McDonald, M.D.

“Dr. Choudhary brings extensive experience as a clinical, executive and academic leader at top tier hospitals,” UAMS Executive Vice Chancellor and College of Medicine Dean Christopher T. Westfall, M.D., FACS, said in a June 14 announcement to the faculty.

Choudhary has served as chair of pediatric radiology at Nemours/Alfred I. duPont Hospital for Children in Wilmington, Delaware, since 2013. He is internationally recognized in his subspecialty of pediatric neuroimaging and for his expertise in imaging related to pediatric abusive head trauma (AHT).

Choudhary received his medical degree from the Medical College of Calcutta in 1994. He completed residencies in pediatrics at Princess of Wales Hospital and the University of Wales and Llandough Hospital in the U.K., followed by a residency in radiology at Cambridge University. He continued his training with fellowships in pediatric radiology and pediatric neuroradiology at Cincinnati Children’s Hospital Medical Center.

Choudhary received his M.B.A. with a major in finance from the Wharton School at the University of Pennsylvania in 2017 and received Fellow of the American College of Healthcare Executives (FACHE) certification in 2018. He is board certified in clinical informatics, radiology, neuroradiology and pediatric radiology.

He began his career in academic medicine as director of pediatric neuroradiology at Penn State Milton S. Hershey University Medical Center in Hershey, Pennsylvania, from 2006 to 2013. He also served as associate program director of radiology in 2011-2012. He developed the pediatric neuroradiology section with increased specialization and a comprehensive teaching curriculum for fellows and residents. He also worked with partnering hospitals to build relationships and provide subspecialist services. He taught medical students at Penn State and mentored numerous students, residents, fellows and junior faculty members.

Choudhary’s research has centered on diagnosis of brain and spinal trauma, as well as chronic disease and surgery involving the brain. He was the lead author on a 2018 consensus statement on abusive head trauma, the leading cause of fatal head injuries in children younger than 2 years of age. The statement, supported by 15 international pediatric and radiology organizations and published in the journal Pediatric Radiology, outlines the consensus of evidence-based medical findings on AHT to serve as a tool within the legal system. Within weeks of publication it was in the top 5% of all research ever tracked by Altmetric, and it was the third most downloaded article from Springer’s pediatric and radiology journals in 2018.

Choudhary has published extensively and lectured internationally on neuroimaging. He received the Society of Pediatric Radiology’s prestigious Walter E. Berdon award in 2016 for authoring the best clinical research paper in Pediatric Radiology in 2015. He received the David S. Hartman, M.D., Faculty Golden Apple Award for outstanding medical student teaching at Hershey Medical Center in 2010.

Great things are happening in the UAMS College of Medicine’s Department of Family and Preventive Medicine, with a recent research poster day as just the latest sign of the department’s “good health.”

The poster session featured 35 posters, including 20 projects by residents. Topics included residency administration and education, ethics, case reports, improvements in patient care, and research on medical conditions like anemia, HIV, COPD and chlamydia.

Event organizers were Shashank Kraleti, M.D., residency program director, and Diane Jarrett, Ed.D., assistant residency director and director of education and communications for the department. They said the poster session gave residents a chance to highlight the department’s strong commitment to research and to practice their presentation skills in a laidback environment at their home campus before showcasing their work elsewhere.

Family medicine resident Appala Suman Peela, M.D., facing camera, talks with faculty member Stephen Sorsby, M.D.

“Family medicine isn’t a field that’s necessarily thought of as a huge research-producing specialty, when in fact, our department has a lot going on,” Jarrett said. “So events like these serve a dual purpose. They show our residents that the academic projects they participate in are important and that others are interested in their results, and it showcases to the wider campus all the great things that are going on in our department.”

Kraleti said he thinks the emphasis on research results in better physicians and patient care.

“I have always believed that when residents do research, they take an extensive look at a particular topic and gain knowledge that they can use in their practice,” Kraleti said. “Research also gets residents thinking creatively and proactively about how they can contribute to improving patient care in their clinic and beyond.”

Obioma Nwaiwu, M.D., Ph.D., left, talks about his project with fellow resident Paige Beck, M.D., Ph.D., while his research partner, Brian Yuen, M.D., looks on.

For example, third-year residents Obioma Nwaiwu, M.D., Ph.D., and Brian Yuen, M.D., presented their poster on how to improve shared decision making between providers and patients for prostate cancer screening, especially given that new guidelines leave the decision on whether to screen up to the patients.

Nwaiwu and Yuen tried passive approaches like handing patients flyers in the waiting room. They also tried more direct approaches like calling the patient on the phone before their appointment and contacting providers to remind them of the new guidelines.

They found that the direct approaches significantly improved the shared decision-making process.

Research and Evaluation Division faculty member Lorraine McKelvey, Ph.D., left, listens to Program Coordinator Kisa Vaughn, MPA, near Vaughn’s poster on the Passion Project.

“What this tells us is that when you empower the patient, when you empower the provider and tell them about the changes in the guidelines and give them some of the statistics involved, then they can really talk about it and come up with the decision that is best for the patient,” Nwaiwu said.

These opportunities for resident research haven’t developed in a vacuum. The department’s Research and Evaluation Division (RED) started 10 years ago. The residency program has also developed a strong research and scholarly activity curriculum for the residents and the faculty. And across the department, Kraleti said the faculty do an amazing job on both their own work and investing time to collaborate with the residents.

“They are very strong and produce a lot of work, and the clinical side and research side are always looking for collaborations,” Kraleti said. “It’s paid off. We do posters and presentations nationally and internationally, and there are lots of publications. By the time we started thinking about a poster session on campus, it was well overdue.”

The first event was in the fall and featured 25 posters. Now in the spring, the event is intended as an annual tradition, and Kraleti said they may expand it to a research day with presentations in the future.

The Family Medicine program was also recognized at Dean’s Honor Day in the spring. Kraleti won the Residency Educator Award. Nicola Edge, Ph.D., won the Faculty Excellence in Research Award. Shalese “Fitz” Fitzgerald, M.S., won the Staff Excellence in Research Award.

“It was wonderful to see our research efforts in family medicine recognized,” Kraleti said. “Several of our faculty were promoted this year. We also have had a 100% board pass rate for our residency program for seven years, which puts us among the best in the country. We feel we have good synergy happening within the department, and we’re happy to feature it with events like this.”

Great things are happening in the UAMS College of Medicine’s Department of Family and Preventive Medicine, with a recent research poster day as just the latest sign of the department’s “good health.”

The poster session featured 35 posters, including 20 projects by residents. Topics included residency administration and education, ethics, case reports, improvements in patient care, and research on medical conditions like anemia, HIV, COPD and chlamydia.

Event organizers were Shashank Kraleti, M.D., residency program director, and Diane Jarrett, Ed.D., assistant residency director and director of education and communications for the department. They said the poster session gave residents a chance to highlight the department’s strong commitment to research and to practice their presentation skills in a laidback environment at their home campus before showcasing their work elsewhere.

“Family medicine isn’t a field that’s necessarily thought of as a huge research-producing specialty, when in fact, our department has a lot going on,” Jarrett said. “So events like these serve a dual purpose. They show our residents that the academic projects they participate in are important and that others are interested in their results, and it showcases to the wider campus all the great things that are going on in our department.”

Kraleti said he thinks the emphasis on research results in better physicians and patient care.

“I have always believed that when residents do research, they take an extensive look at a particular topic and gain knowledge that they can use in their practice,” Kraleti said. “Research also gets residents thinking creatively and proactively about how they can contribute to improving patient care in their clinic and beyond.”

For example, third-year residents Obioma Nwaiwu, M.D., Ph.D., and Brian Yuen, M.D., presented their poster on how to improve shared decision making between providers and patients for prostate cancer screening, especially given that new guidelines leave the decision on whether to screen up to the patients.

Nwaiwu and Yuen tried passive approaches like handing patients flyers in the waiting room. They also tried more direct approaches like calling the patient on the phone before their appointment and contacting providers to remind them of the new guidelines.

They found that the direct approaches significantly improved the shared decision-making process.

“What this tells us is that when you empower the patient, when you empower the provider and tell them about the changes in the guidelines and give them some of the statistics involved, then they can really talk about it and come up with the decision that is best for the patient,” Nwaiwu said.

These opportunities for resident research haven’t developed in a vacuum. The department’s Research and Evaluation Division (RED) started 10 years ago. The residency program has also developed a strong research and scholarly activity curriculum for the residents and the faculty. And across the department, Kraleti said the faculty do an amazing job on both their own work and investing time to collaborate with the residents.

“They are very strong and produce a lot of work, and the clinical side and research side are always looking for collaborations,” Kraleti said. “It’s paid off. We do posters and presentations nationally and internationally, and there are lots of publications. By the time we started thinking about a poster session on campus, it was well overdue.”

The first event was in the fall and featured 25 posters. Now in the spring, the event is intended as an annual tradition, and Kraleti said they may expand it to a research day with presentations in the future.

The Family Medicine program was also recognized at Dean’s Honor Day in the spring. Kraleti won the Residency Educator Award. Nicola Edge, Ph.D., won the Faculty Excellence in Research Award. Shalese “Fitz” Fitzgerald, M.S., won the Staff Excellence in Research Award.

“It was wonderful to see our research efforts in family medicine recognized,” Kraleti said. “Several of our faculty were promoted this year. We also have had a 100% board pass rate for our residency program for seven years, which puts us among the best in the country. We feel we have good synergy happening within the department, and we’re happy to feature it with events like this.”

By Amy Widner

A University of Arkansas for Medical Sciences (UAMS) researcher who is seeking an explanation for why millions of people worldwide do not respond to the current available treatments for high blood pressure has received $1.89 million from the National Institutes of Health to continue this groundbreaking work.

Shengyu Mu, Ph.D., assistant professor in the Department of Pharmacology and Toxicology in the UAMS College of Medicine, has devoted his career to understanding the causes behind this common condition. His lab has found evidence to support an emerging theory that the salt-sensitive variety of high blood pressure may actually be an immune disorder.

“Twelve years ago, no one believed there was an immune connection behind salt-sensitive hypertension,” Mu said. “Now it’s a hot topic. My lab has found evidence to suggest this, as have labs at Vanderbilt, Wisconsin and Duke universities. A picture is coming together, and the next step is understanding exactly how it works so we can pave the way for designing immunological strategies of treatment.”

More than 1 billion people worldwide have high blood pressure. In the United States, one in every three adults is living with high blood pressure. It is the leading cause of heart disease and stroke, which are major causes of death in the United States.

Although there are many drugs available to treat high blood pressure, fewer than 50% of patients are able to control their blood pressure with the current options. The work of Mu and others indicates that new drugs targeting the immune system could be key.

“Hypertension is a silent killer. By the time most patients find out they have it, it’s already caused damage,” Mu said. “It is important to identify unknown mechanisms involved in the pathogenesis of high blood pressure so we have better options for treating this life-altering and deadly condition.”

Mu’s lab previously found that immune cells, white blood cells called T lymphocytes (T cells), can infiltrate the kidney and stimulate excessive salt retention, resulting in blood pressure elevation.

Mu was able to pinpoint the overall process: When too many of a major subtype of these T cells interact directly with — and actually touch — the cells located in the area of the kidneys that reabsorb salt, the kidney’s absorption of salt increases, thereby impairing the function of the kidneys to filter out excessive salt. Salt-sensitive high blood pressure is the result.

With this current five-year NIH grant, Mu aims to provide, for the first time, evidence and mechanisms of how these T cells interact with kidney cells. Specifically, he will identify the key molecules involved in the interaction between T cells and kidney cells. He will define the signaling pathways involved when the process goes wrong and results in disordered immune activity.

“Dr. Mu’s work has the potential to effect positive change for millions of people,” said Nancy J. Rusch, Ph.D., professor and chair of the Department of Pharmacology and Toxicology. “Hypertension is a common — and frustrating — condition to treat, with major impacts on global population health. Dr. Mu’s breakthroughs in this area are invaluable, and we are gratified to see that the NIH recognizes the importance of supporting his vanguard research.”

In his work, Mu has been aided by Yunmeng Liu, Ph.D., a postdoctoral research associate, and Sung Rhee, Ph.D., an associate professor, both in the Department of Pharmacology and Toxicology; and Steve Post, Ph.D., a professor in the Department of Pathology.

Before coming to UAMS in 2013, Mu received his medical degree from TianJin Medical University in China and a Ph.D. from the University of Tokyo in Japan. Previously, his work has been published in Nature Medicine, the Journal of Clinical Investigation and Nature Communications. He has received the New Investigator award and the Research Recognition award from the American Heart Association and the American Physiology Society for his contributions to research.

The UAMS Graduate School Commencement Brunch is an annual event that celebrates family — both in the traditional and non-traditional sense.

Each year, students finishing their Ph.D., M.S. and certificate programs through the UAMS Graduate School meet for a casual brunch. The food is plentiful, but the formal agenda is sparse — in contrast to the regimented affair that is commencement later in the day. Students and their families talk, laugh, reflect and look ahead.

Attendees even get a little silly with a photo booth that provides instant photos, complete with props and signs that say “it was worth the hassle” and “dream big.”

People have fun, and that’s exactly how Dean Robert E. McGehee Jr., Ph.D., intends it to be.

“I really appreciate you being here for one of my favorite events of the year,” McGehee said to the crowd of about 100 at the Embassy Suites in Little Rock. “This celebration is about family, because if it weren’t for family, these students wouldn’t be graduating. So on behalf of the Graduate School, I would really like to thank every single family member who supported our graduates during their journey.”

The 2019 Graduate School class earned 16 doctorates, nine Master of Science degrees, and eight graduate certificates. McGehee said that each student is not only leaving with a degree, they in turn have left their mark on the faculty and administrative staff who worked with them along the way.

“By the time you meet these students on paper as applicants, you matriculate them, get to know them, help them through their Graduate School programs and get them all the way to brunch and commencement, they become family,” McGehee said.

Faculty mentor Jean C. McSweeney, Ph.D., R.N., professor and associate dean for research and co-director of the Ph.D. program in the UAMS College of Nursing, was there to support Laura Helen Hayes, who was in the nursing Ph.D. program. Hayes’ dissertation was about providing long-term care to adults who survived a childhood congenital heart defect.

McSweeney said it’s true that family-like ties develop between student and adviser.

“It’s just such a rewarding experience,” McSweeney said. “You work so closely with them and invest so much time and energy with them, and it’s so wonderful to see them succeed. Dr. Hayes has a very bright future ahead of her. She has already received some funding, and she’s joining our faculty. I look forward to continuing to watch her career grow.”

Chris Bolden — a graduate from the Interdisciplinary Biomedical Sciences Ph.D. program who worked with Eric Peterson, Ph.D., in the Department of Pharmacology and Toxicology on developing a vaccine against methamphetamine addiction — provided the keynote remarks.

Bolden acknowledged the important support he received from his family and mentor, but also thanked his peers.

“I have an amazing group of friends as a result of this journey,” Bolden said. “They became like a family while I was here. During our first year, we would study late at night, we would create study groups and study guides — we would do whatever it took to help each other pass.”

Surveying the crowd, Bolden concluded: “We all made it together.”

By David Robinson

An international research collaboration that includes the University of Arkansas for Medical Sciences (UAMS) has discovered that aging in nematodes (worms) can be slowed and even reversed by a number of Food and Drug Administration (FDA)-approved drugs, findings that have the potential to extend human lifespan.

The study findings are published in Scientific Reports.

The collaboration was led by Robert J.S. Reis, D.Phil., at UAMS, and Peter Fedichev, Ph.D., a founder of the longevity biotech startup Gero. Other collaborators are from the Skolkovo Institute of Science and Technology (SIST) and Moscow Institute of Physics and Technology (MIPT).

The research team identified 10 FDA-approved drug compounds that slowed the aging process in nematodes.

“This gives us a chance to find drugs that could be used in some combination to optimize human lifespan,” said Reis, a professor in the departments of Geriatrics, Biochemistry and Molecular Biology, and Pharmacology and Toxicology in the UAMS College of Medicine.

Reis brought extensive experience to the project, including expertise in lifespan research, genetics and model systems to study aging. He led a team of UAMS researchers who created the necessary C. elegans strains for the study and performed the drug testing. A nonparasitic roundworm, C. elegans is one of the most intensively studied animals on the planet. Its genome was the first to be sequenced among multicellular organisms. C. elegans adults typically live just 15-25 days, but their lives can be extended by a variety of mutations and gene-silencing interventions.

Srinivas Ayyadevara, Ph.D., in the Reis group, made a key discovery that mutations in one particular gene extend worm lifespan tenfold ― a world record for any animal. They created a panel of worm strains varying in lifespan across that 10-fold range, which were all genetically identical apart from one or two mutations. They determined the “expression profile” of each strain at several ages, by sequencing their RNA contents, to see if there were features that change predictably with age or lifespan.

Using these data, Fedichev’s group used novel methods to extract an “RNA signature of aging,” which they cross-checked and expanded using previous expression patterns from aging worm strains. They used this signature to search for drugs that tended to reverse the RNA-expression changes that accompany aging by screening the Connectivity Map (CMAP), a database created by scientists at the Broad Institute of MIT and Harvard University. CMAP contains information about the effects on gene activity in human cells of almost all available FDA-approved drugs. From the 1,309 drugs in the CMAP database, the researchers found 10 that alter human gene expression in a way opposite to the age-related changes observed for corresponding genes in nematodes.

Six of these drugs had been previously documented to have anti-aging potential, while four had never been studied in that context. All of the tested drugs slowed aging in nematodes. The most efficient compound extended nematode lifespan by 30%.

Reis emphasized how extraordinary these results are. “Previous studies of several thousand pharmacologically active compounds had found less than one in 20 that were able to extend C. elegans lifespan, in striking contrast to our observation of life extension by all 10 drugs predicted to oppose aging, including four drugs for which there were no previous aging data,” he said. “This is remarkably compelling evidence that the expression profile of aging must be conserved from nematodes to humans, and is likely to be fundamental to all animals.”

By Amy Widner

Roger D. Pechous, Ph.D., studies the bacteria that caused the infamous black death of the Middle Ages, shedding light on something old to potentially protect against something new: bioterrorism. The University of Arkansas for Medical Sciences (UAMS) researcher’s latest work has been published in Infection and Immunity.

Pechous is an assistant professor in the Department of Microbiology and Immunology in the UAMS College of Medicine. The article, titled “Modeling Pneumonic Plague in Human Precision-cut Lung Slices Highlights a Role for the Plasminogen Activating Protease in Facilitating Type 3 Secretion,” has been published online in advance of the August print edition of the journal.

The bacterium is called Yersinia pestis. Pechous and Srijon Banerjee, a postdoctoral fellow in Pechous’ lab, study pneumonic plague, the severe lung infection caused by Yersinia pestis as it spreads from human to human through inhalation. The World Health Organization (WHO) classifies pneumonic plague among the world’s deadliest infectious diseases. When the bacterium is spread by fleas, it is known as bubonic plague. Plague in the bloodstream is called septicemic plague.

“Y. pestis was responsible for three major pandemics in recorded history and continues to be a potential threat worldwide, primarily due to concerns of its release as a weapon of bioterror,” Pechous said. “Human-to-human transmission of plague occurs via the lungs, and is almost always lethal in the absence of timely treatment.”

Banerjee said death from pneumonic plague typical occurs in four to seven days. If antibiotics are not administered within 24 hours of symptom development, it is nearly 100% fatal. It is one of the deadliest bacteria known to man.

“What was unique about this study was its use of real human donor lung tissue, prepared to maintain realistic lung function in the laboratory setting,” Banerjee said. “This allowed us to observe the way Y. pestis would behave in a living human lung and see what makes it so successful at overwhelming its human host.”

Human lung tissue is cut into slices for the experiments in the Lung Cell Biology Laboratory at the Arkansas Children’s Research Institute by coauthor Richard C. Kurten, Ph.D., a professor of physiology & biophysics and pediatrics at UAMS. Kurten routinely acquires lungs from organ transplant donors and processes them for use in research in his laboratory and those of collaborators at UAMS and across the country.

From watching the behavior of Y. pestis in the lung slices in the lab, the researchers were able to pinpoint exactly how the bacteria quickly gains the upper hand.

“We show that Y. pestis hones in on a key cell type and delivers key proteins that interfere with its ability to control infection and initiate an immune response,” Pechous said. “We identify a protein on the surface of Y. pestis that is critical for directing Y. pestis to specifically target this cell type to establish infection.”

“All of this happens quickly,” Banerjee said. “By the time other signals alert the immune system to the severity of the infection, it’s too late. Ultimately, your own immune response is what ends up compromising lung function and leading to death.”

Understanding this process has applications for pneumonic plague and beyond.

For one, it’s important to better understand how Y. pestis functions, so scientists can develop better treatments for the highly contagious infectious disease. While rare today in humans, plague continues to be carried in animals and fleas, from which it can spread to humans.

For example, a 2016 outbreak in Madagascar infected 62 people, killing 26, according to the WHO. Another Madagascar outbreak in 2017 infected 2,348 people, causing 202 deaths. In the United States, the Centers for Disease Control reports an average of 1-17 cases per year, mostly in the West, where the disease is carried by rodents.

In addition, the progression of Y. pestis infection in the lungs mimics other lung infections, like severe pneumonia, but on a much faster scale. More broadly, understanding the bacterium helps scientists and public health officials plan for containing disease outbreaks. The research could also lead to the development of alternative treatments, which could be useful if the bacterium ever becomes resistant to antibiotics.

Pechous earned his doctorate from the Medical College of Wisconsin and completed postdoctoral training at the University of North Carolina at Chapel Hill. He has been studying bacterial infection since 2001. Banerjee earned his Ph.D. from the University of Calcutta in India.

The Pechous lab is another successful example from the UAMS Center for Microbial Pathogenesis and Host Inflammatory Responses, directed by Mark Smeltzer, Ph.D. The center has earned $21 million in funding through the NIH’s Centers of Biomedical Research Excellence (COBRE) program, which aims to provide funding and mentoring to researchers who are early in their careers. Its participants are studying viruses, malaria, cancer, Lyme disease and chlamydial infection. Pechous’ work is funded by the center and a grant from the NIH National Institute of Allergy and Infectious Diseases.

UAMS has six COBRE centers, which are launching new scientific careers, attracting top talent and creating concentrations of expertise on topics like neuroscience, cancer therapy, childhood obesity prevention and pediatrics.

In order to study Y. pestis at UAMS, the Pechous lab uses strict containment facilities and security procedures.

Infection and Immunity is a prestigious peer-reviewed journal published by the American Society for Microbiology that reports key discoveries that help microbiologists, immunologists, epidemiologists, pathologists and clinicians gain new insights into the underlying mechanisms of host-pathogen interactions and develop novel strategies to prevent or treat infectious diseases.