News

Alicia Byrd, Ph.D.

Assistant Professor
Department of Biochemistry and Molecular Biology
UAMS College of Medicine

Research Interest Statement

DNA damage occurs tens of thousands of times per day in human cells from both endogenous and environmental sources. In order to preserve the genetic material, cells have evolved multiple mechanisms to detect and repair DNA damage. Mutations in genes encoding proteins involved in the DNA damage response result in a variety of DNA repair syndromes, which have increased risks of cancers, often in childhood. However, inaccurate DNA repair can also cause genomic instability such as chromosomal rearrangements and expansion of repetitive sequences, which can lead to the development of cancer.

My research focuses on the enzymes that regulate the DNA damage response, in particular, a family of enzymes called helicases that remove secondary structures from DNA. These proteins have critical roles in DNA repair and loss of activity results in genomic instability and predisposition to many types of cancer. The molecular mechanisms of these proteins, both individually and as components of multi-protein complexes, are of interest, as are the effects of posttranslational modifications on their activity. Increased understanding of the regulation of these DNA repair processes that are critical for maintaining genomic integrity could ultimately lead to the design of better cancer therapies.

Dr. Byrd’s Grants

Winthrop P. Rockefeller Cancer Institute

Seeds of Science Pilot Award

Regulation of the DNA Damage Response in Breast Cancer

2/1/19 – 1/31/20

$15,000*

 

NIGMS – 3 R35 GM122601-03S1

Functions and Mechanisms of Helicases and G-Quadruplex Nucleic Acids

5/01/2017-4/30/2022

Role: Co-I (Kevin Raney, PI)

$129,583*

*cancer-related annual direct costs

Dr. Byrd’s UAMS Collaborators

Stephanie Byrum, Ph.D. (Department of Biochemistry and Molecular Biology)

Robert Eoff, Ph.D. (Department of Biochemistry and Molecular Biology)

Kevin Raney, Ph.D. (Department of Biochemistry and Molecular Biology)

Samantha Kendrick, Ph.D. (Department of Biochemistry and Molecular Biology)

Justin Leung, Ph.D. (Department of Radiation Oncology)

Nirmala Parajuli, DVM, Ph.D. (Department of Pharmacology and Toxicology)

Dr. Byrd’s External Collaborators

Mark Dillingham, Ph.D. (University of Bristol)

Opportunities for Collaboration

I am just beginning my independent research program at UAMS and welcome new collaborations. My primary area of interest is the DNA damage response, but anything related to genome maintenance interests me. My lab has expertise in enzymology, protein-DNA interactions, and G-quadruplex DNA, and we are particularly interested in breast cancer.

You May Not Know That …

I have visited 48 of the 52 Arkansas State Parks with my family on a geocaching adventure. Petit Jean is my favorite so far, but stay tuned; we have four parks left to see.

Recent Cancer-Related Publications

Gao J, Byrd AK, Zybailov BL, Marecki JC, Guderyon MJ, Edwards AD, Chib S, West KL, Waldrip ZJ, Mackintosh SG, Gao Z, Putnam AA, Jankowsky E, Raney KD. (2019) DEAD-box RNA helicases Dbp2, Ded1 and Mss116 bind to G-quadruplex nucleic acids and destabilize G-quadruplex RNA. Chem Commun (Camb). 55, 4467-4470.

Marecki, JC, Aarattuthodiyil S, Byrd AK, Penthala NR, Crooks PA, Raney KD (2019) N-Naphthoyl-substituted indole thio-barbituric acid analogs inhibit the helicase activity of the hepatitis C virus NS3. Bioorg Med Chem Lett. 29, 430-434.

Byrd AK, Bell, MR, Raney KD (2018) Pif1 helicase unfolding of G-quadruplex DNA is highly dependent on sequence and reaction conditions. J Biol Chem. 293, 17792-17802.

Byrd AK and Raney KD (2017) Structure and function of Pif1 helicase. Biochem Soc Trans. 15, 1159-1171.

Griffin WC, Gao J, Byrd AK, Chib S, Raney KD. (2017) A biochemical and biophysical model of G-quadruplex DNA recognition by positive coactivator of transcription 4. J Biol Chem. 292, 9567-9582.

Byrd AK, Zybailov BL, Maddukuri L, Gao J, Marecki JC, Jaiswal M, Bell MR, Griffin WC, Reed MR, Chib S, Mackintosh SG, MacNicol AM, Baldini G, Eoff RL, Raney KD. (2016) Evidence that G-quadruplex DNA Accumulates in the Cytoplasm and Participates in Stress Granule Assembly in Response to Oxidative Stress. J Biol Chem. 291, 18041-57.

By Susan Van Dusen

A grant of almost $764,000 from the National Institutes of Health (NIH) will allow the University of Arkansas for Medical Sciences (UAMS) to purchase biomedical research equipment with new capabilities unavailable elsewhere in Arkansas.

UAMS scientist Samuel G. Mackintosh, Ph.D., received the NIH S10 High-End Instrumentation Award totaling $763,971 to fund the purchase of a mass spectrometer, a piece of equipment used to identify and compare proteins essential for the development of new therapies for cancer and other diseases.

Mackintosh, an Associate Professor in Biochemistry and Molecular Biology, serves as co-director of the UAMS Proteomics Core, a shared resource at the UAMS Winthrop P. Rockefeller Cancer Institute that provides access to technologies, services and scientific consultation for scientists throughout the university, across the country and in Puerto Rico.

“Our goal is to identify new avenues for diagnosis and treatment by comparing proteins present in diseases to proteins present in healthy individuals. The UAMS Proteomics Core supports this research by identifying and quantifying large numbers of proteins from cells, tissues, blood and other biological sources,” said Mackintosh, who also is an associate professor in the UAMS College of Medicine Department of Biochemistry and Molecular Biology.

The core facility is co-directed by Rick Edmondson, Ph.D., associate professor of medicine and director of proteomics. Core staff members include Renny Lan, Aaron Storey, Lisa Orr and Robert Brown.

“Investments by the College of Medicine and Winthrop P. Rockefeller Cancer Institute in the rapidly developing field of mass spectrometry have allowed us to keep up with the advances in the field, ensuring that state-of-the-art technology is available to UAMS researchers,” Mackintosh said.

Three NIH instrument grants have been awarded in Arkansas since 2015, with two going to Mackintosh.

The NIH grant also builds on recent efforts at UAMS to strengthen collaboration between research programs funded by the NIH Institutional Development Award (IDeA) program, which seeks to expand scientific research in 23 historically underfunded states and Puerto Rico.

It also will support proteomics research through three Centers for Biomedical Research Excellence (COBRE), IDeA research centers at UAMS and Arkansas Children’s Hospital that focus on career development for young scientists and expansion of institutional research capabilities.

The COBRE research centers the grant will support focus on three areas:

• The Center for Translational Pediatric Research at Arkansas Children’s Research Institute directed by Alan Tackett, Ph.D., associate director of basic research at the UAMS Winthrop P. Rockefeller Cancer Institute and professor in the UAMS College of Medicine Department of Biochemistry and Molecular Biology;
• The Center for Microbial Pathogenesis and Host Inflammatory Responses at UAMS directed by Mark Smeltzer, Ph.D., professor in the UAMS College of Medicine Departments of Microbiology and Immunology and Orthopaedics;
• The Center for Musculoskeletal Disease Research at UAMS directed by Charles O’Brien, Ph.D., professor in the UAMS College of Medicine Department of Internal Medicine-Endocrinology.

Other UAMS researchers supporting the instrument grant application include Kevin Raney, Ph.D.; Maria Almeida, Ph.D.; and Srinivas Ayyadevara, Ph.D.

The Bioinformatics and Systems Biology Core, directed by Stephanie Byrum, Ph.D., will play a key role in analyzing data generated by the new mass spectrometer.

This federal grant will bolster the Cancer Institute’s ongoing efforts to receive National Cancer Institute Designation.

To achieve designation, cancer centers undergo a highly competitive assessment process that demonstrates an outstanding depth and breadth of research in three areas: basic laboratory, patient/clinical and population-based. The designation brings with it many benefits, including expanded access to federal funding for researchers and improved access to clinical trials for patients.

By Amy Widner

Learning by doing and reinforcing concepts through presentation — those practices were the core lessons on display at the eighth annual Central Arkansas Undergraduate Summer Research Symposium at UAMS.

About 115 undergraduate students from across Arkansas and the nation gathered in the I. Dodd Wilson Education Building to give poster presentations and oral presentations on summer research projects. The projects were the culmination of weeks — sometimes years — of work with various programs, some at UAMS and others at colleges and universities across the state, as well as the U.S. Food and Drug Administration National Center for Toxicological Research at Jefferson.

“Doing research is the best way to understand research and that’s why we’ve spent so much time and effort making these opportunities available,” said Grover P. Miller, Ph.D., professor in the Biochemistry and Molecular Biology Department in the UAMS College of Medicine.

“If you’re like me, you went into science thinking it was all about doing experiments,” Miller said. “Well, it’s about more than that. Over the summer, you’ve learned a lot of techniques, you’ve learned a lot about your project, but science is really about stories. And so today, you’re going to be telling us your stories. This is part of your journey: to pause, reflect on all you were able to achieve, and tell others about that experience.”

Miller asked how many students had conducted summer research for the first time and about 80 percent of the room raised their hands.

That was the case for Mason Archer, a senior from Ouachita Baptist University in Arkadelphia who worked with the Arkansas INBRE program (IDeA Network of Biomedical Research Excellence).

Archer studied six strains of bacteria that are developing resistance to antibiotics and are problematic in nursing home and hospital settings. They are known as ESKAPE — Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species. Archer also worked with bacteria commonly found in soil and tested about 14 of these to see if any had antibacterial properties effective against the ESKAPE group.

“I was excited to find that almost all of them were able to inhibit more than one of the ESKAPE pathogens,” Archer said. “So we would hope to use this data in the future to possibly use some of the bacteria to test them against other pathogens as well and potentially produce a new antibiotic from one of them.”

Archer hopes to become a pharmacist. He said the summer research will help him enter pharmacy school in the fall with a deeper understanding of concepts he’ll be studying.

“The research was perfect for me because I was able to work directly with antibiotics, which are — of course — really important for the pharmaceutical industry,” Archer said. “To do research with antibiotics and see firsthand how antibiotics work and how each one effects different pathogens was great.”

Alexis Baker — a senior from Hendrix College in Conway who worked with the Hendrix Odyssey Program for the second year in a row — also thinks her participation in summer research and the Summer Research Symposium will help with her career goals. She wants to be a neurosurgeon and just took the Medical College Admission Test (MCAT).

Baker worked with pain-sensing neurons and clarifying how they develop during the embryonic process.

“I definitely felt like doing summer research was worthwhile,” Baker said. “I learned so much by working in the lab that when I went back into the classroom, I felt like I was way ahead of the other students. I also feel like it helped me prepare for the MCAT.”

Baker said it’s been important for her to learn to talk about science. Last year, she didn’t present, she just observed her teammates. This year, she was on her own.

“I’ve been practicing on my family,” she said. “I’m the first one to go to college, so they don’t have any idea what I’m talking about. It challenges me to think about it and come up with a way to explain it so that they’ll understand. It will be the same someday when I’m interacting with patients, plus, when I have to really break it down and think about it, it helps me understand it better, too.”

Miller said experiences like Archer’s and Baker’s are by design. He hopes the symposium is realistic and practical for the students, who will encounter similar situations throughout their scientific careers. In addition, the symposium gives them a chance to network with faculty and fellow students and find out more about their future educational and career options.

The symposium was hosted by the Graduate School and Department of Biochemistry and Molecular Biology at UAMS as well as the National Institutes of Health-supported INBRE program and the UAMS Summer Undergraduate Research Program (SURP) to Increase Diversity in Research.

By Susan Van Dusen

A rising college senior, Huddoy Walters’ sights are set on a career in biomedical research.

“I want to be a scientist, most definitely,” said Walters, a native Jamaican and biochemistry major at the University of Arkansas at Pine Bluff.

That dream of a future in the research field was cemented by Walters’ two-time participation in a summer fellowship at UAMS sponsored by Arkansas INBRE, a program funded by the National Institutes of Health (NIH) and designed to promote biomedical research capacity and support for promising undergraduate students.

Larry Cornett, Ph.D., associate vice chancellor for research at UAMS, serves as principal investigator for Arkansas INBRE and has worked on the Summer Research Fellowship Program since its inception in 2002.

“The summer program is one of the most exciting parts of my job. It opens doors for students, many of whom are the first person in their family to attend college, and shows them firsthand what it takes to be part of a research team,” Cornett said.

In addition to pairing rising juniors and seniors with scientists at UAMS, students in the 10-week program also are placed at the University of Arkansas in Fayetteville and the University of Arkansas at Little Rock, which participate in Arkansas INBRE as research-intensive lead institutions. In 2019, a total of 13 students participated at UAMS, and three took part at the University of Arkansas.

During his first stint in the program during summer 2018, Walters conducted biochemistry research in a lab at the University of Arkansas. He spent the following summer at UAMS working alongside Antino Allen, Ph.D., associate professor in the UAMS College of Pharmacy Department of Pharmaceutical Sciences.

“My first research experience was in a program much like the INBRE Summer Research Fellowship. Now, by serving as a mentor, I can provide the same type of opportunities to the next generation of scientists,” said Allen, whose research examines how inflammation and oxidative stress affect neuronal anatomy and cognitive function after exposure to X-rays, heavy ion irradiation or traumatic brain injury.

For participant Madison Blue, the program provided the chance to experience graduate-level research before completing her biochemistry degree at Hendrix College in Conway.

“The fellowship program helped prepare me for what I’ll encounter in graduate school, and I didn’t have to leave Arkansas to participate,” said Blue, a Jonesboro native.

Blue, Walters and the additional fellows also participated in weekly workshops addressing topics such as research ethics and science writing. To wrap up their experience, they presented their research at the Central Arkansas Undergraduate Research Symposium, held July 26 at UAMS. A travel award offered to each summer fellow gives them an additional opportunity to present their research at an upcoming symposium or conference of their choice.

Robert Eoff, Ph.D., a cancer researcher who served as Blue’s mentor, said working with undergraduates brings a renewed energy to his lab and helps him improve his own teaching skills.

“For many of the students, this is their first exposure to biomedical research, so we have to break things down to be sure that the rationale for the study design and experimental details are clear and understandable,” said Eoff, associate professor in the UAMS College of Medicine Department of Biochemistry and Molecular Biology.

Eoff’s research team studies what happens when DNA damage is not repaired in a timely manner and ends up blocking the ability to replicate cells.

The fellowship program also serves the important function of connecting UAMS to undergraduate institutions across the state, where up-and-coming researchers begin their training.

The UAMS-based Arkansas INBRE program manages the initiative for partners that include the University of Arkansas at Pine Bluff, Arkansas State University, Hendrix College, Ouachita Baptist University, John Brown University and others.

“From my perspective, there’s a great cooperative spirit between UAMS and the colleges we work with across the state. It’s our goal to provide students with opportunities and experiences that elevate them to a level where they know first-hand what it means to perform biomedical research, which helps them become better advocates for science and more competitive applicants for grad school or other educational opportunities in the future,” Eoff said.

Cornett agreed, stating that he and the mentors grow attached to their students and continue to monitor their educational process. Two Summer Research Fellows have even gone on to become UAMS faculty members: Lindsey Dayer, Pharm.D., associate professor in the UAMS College of Pharmacy, and Stephanie Byrum, Ph.D., assistant professor in the UAMS College of Medicine.

“It’s always satisfying to see our fellows succeed in their chosen field,” Cornett said.

INBRE (IDeA Network of Biomedical Research Excellence) is funded by a grant from the National Institutes of Health under the Institutional Development Award (IDeA) Program of the National Institute of General Medical Sciences.