Alan Tackett, Ph.D., Professor of Biochemistry and Scharlu Family Endowed Chair in Cancer Research, was named as the Arkansas Biosciences Institute Established Investigator of the Year for his work on histone epigenetic mechanisms that regulate gene transcription and that are coupled to melanoma progression.  He is also the director of the Center for Translational Pediatric Research and the IDeA National Resource for Proteomics.  Congratulations Dr. Tackett!

Nov. 15, 2018 | A team of University of Arkansas for Medical Sciences (UAMS) research scientists recently was awarded a $1.8 million, five-year grant by the National Institute on Aging to investigate common pathways that contribute to the aging of various tissues.

Robert Shmookler Reis, D. Phil, professor in the UAMS College of Medicine’s Donald W. Reynolds Department of Geriatrics, and Srinivas Ayyadevara, associate professor in same department, are the co-principal investigators leading the study. Co-investigators are Steve Barger, Ph.D., professor in the Departments of Geriatrics and Neurobiology & Developmental Sciences, and Alan Tackett, professor in the Department of Biochemistry & Molecular Biology.

The goal of the research is to identify what different neurodegenerative diseases like Alzheimer’s disease have in common with other age-progressive diseases and conditions such as heart disease, muscle wasting, kidney disease, and type 2 diabetes.

Protein aggregation — clustering or clumping of protein molecules — has long been recognized as a hallmark of neurodegenerative diseases like Alzheimer’s and Parkinson’s.

“We were the first ones to show that protein aggregation happens not just in the brain, but also in the heart, skeletal muscle and kidney with age and age-associated diseases,” Ayyadevara said.  Reis added, “The misfolding of proteins, which contributes to protein aggregation, is promoted by stress and inflammation, accumulating with age.”

Reis said the team has looked at protein aggregation for nearly a decade, funded by grants from the U.S. Department of Veteran Affairs.  For the last two years, it has also been supported as part of a multi-investigator National Institutes of Health (NIH) grant led by Sue Griffin, Ph.D., professor and vice chair of research at the UAMS Donald W. Reynolds Institute on Aging.  Peter Crooks, Ph.D., D.Sc., chair and professor of the Department of Pharmaceutical Sciences in the UAMS College of Pharmacy, developed novel derivatives of anti-inflammatory drugs.

As part of the NIH grant, Crooks, Reis, Ayyadevara, and graduate student Samuel Kakraba tested these drugs for their ability to inhibit protein aggregation and to extend life. One drug, PNR502, was the main subject of a recently awarded patent covering several bioactive compounds.

“It not only inhibits further protein aggregation but even appears to reverse it,” Ayyadevara said. “Working with Dr. Barger, we will examine whether it can preserve youthful functions in the hearts and brains of normal mice, and in a mouse model of Alzheimer’s.”

“We have shown that protein aggregation accompanies aging of all tissues, and probably contributes causally to most or all age-associated diseases,” said Reis. “This fundamental molecular process may underlie most of the deterioration that defines aging. It’s a Pandora’s box that holds all the things that go wrong as we get older, so it offers an unprecedented opportunity to finally understand how and why so many disparate factors contribute to aging.”

Oleg Karaduta from Boris Zybaylov’s lab was invited to give an oral talk at the Second Global Summit and EXPO on Proteomics in Dallas, TX. His presentation highlighted the basics of metaproteomics data processing pipe-line, its application to the study of function of gut microbiome in chronic kidney disease and current results of their research.

Researchers at the University of Arkansas for Medical Sciences (UAMS) have received a $604,208 grant to study how an abnormal protein found in ovarian cancer and some brain tumors helps tumors grow.

The National Institutes of Health (NIH) awarded the three-year grant to Karen Abbott, Ph.D., assistant professor in the UAMS College of Medicine’s Department of Biochemistry and Molecular Biology, and Analiz Rodriguez, M.D., Ph.D., assistant professor in the UAMS College of Medicine’s
Department of Neurosurgery. Abbott is principal investigator for the grant, and Rodriguez is co-investigator.

The pair are researching glycosylation changes, which are found in both ovarian cancer and glioblastoma, an aggressive brain tumor. Glycosylation is the enzymatic process that attaches glycans (a series of carbohydrates, including the sugars) to proteins, or other organic molecules.

In her previous research, Abbott developed an antibody that targets glycosylation on proteins covering the surface of ovarian cancer cells. The new project involves adapting that protein into a new type of therapy for the disease and examining if it also could serve as an effective therapy for glioblastoma, which shares the same type of glycosylation.

“This research can help us understand the proteins that carry this glycosylation change and how this change promotes signals to keep cancer cells alive. Studying those pathways may lead to new methods to kill the cancer cells but leave the normal ones alone,” said Rodriguez, a neurosurgeon
and researcher.

“With this grant, we will be developing a new type of therapeutic by modifying the current antibody to allow destruction of the cancer cells,” Abbott said.

In their work, Rodriguez’s lab, which focuses on glioblastoma, will provide tumor samples from patients to test this novel therapy.

Rodriguez and Abbott, whose labs are next door to each other, decided to team up after learning of each other’s research and discovering it intersected.

“We decided it would be a good idea to join forces and work on something together,” Rodriguez said.

Congratulations to the Wahls lab for their recent publication in Epigenetics & Chromatin.

Chromatin-mediated regulators of meiotic recombination revealed by proteomics of a recombination hotspot

Congratulations to Binyam Balachew on winning first place in the Graduate Student Association Research Symposium Poster presentation!

Dr. Wayne Wahls’ study on disparities in NIH funding is featured in the Nature Daily Briefing today.

Andrea Edwards recently present her work at a conference on Molecular Biology & Nucleic Acids in Toronto Canada.  Andrea presented a poster entitled “G-Quadruplex in PARP1-Mediated DNA Damage Response”.  Her work is aimed at addressing the role of PARP-1 in DNA damage repair, in particular with regards to G-quadruplex DNA.  Andrea earned first prize in the poster competition and was chosen to present her work to the conference attendees as a short talk.  Her talk was well-received by the audience.  Congratulations Andrea!!

Two graduate students in the Raney lab, Andrea Edwards and Binyam Belachew, attended a Molecular Biology & Nucleic Acids meeting in Toronto, Canada. Andrea presented a poster entitled “G-Quadruplex in PARP1-Mediated DNA Damage Response.”  Binyam presented a poster entitled “Function and Mechanism of Hepatitis C Virus Non-structural Protein 3 (HCV NS3) Unfolding of Viral  G-quadruplex RNA Structures.”