December 2, 2019

Andrea Edwards Student Highlight

Andrea is a Ph.D. Student in her 5th year in the Interdisciplinary Biomedical Sciences Program. She joined the laboratory of Dr. Kevin Raney in the Biochemistry and Molecular Biology Department for her research studies.

She has a B.S. in Biology from University of Arkansas at Fort Smith.

Research Interest Statement

I study G-Quadruplexes which are non-B form DNA structures present at regulatory regions in the genome, such as promoters of proto-oncogenes. Proto-oncogenes normally regulate cell proliferation and growth but transition to oncogenes when mutated or overexpressed, promoting tumorigenesis. The prominence of G-Quadruplexes in proto-oncogenes suggests they serve an important regulatory role in the cell. Interestingly, G-Quadruplexes are highly susceptible to oxidative stress. Thus, it is important that there is a repair mechanism in place to protect these important structures. Poly (ADP-ribose) Polymerase -1 (PARP-1) binds various DNA structures and responds to DNA damage. In response, PARP-1 is enzymatically activated and covalently modifies repair enzymes or chromatin-associated proteins with polymers of ADP-ribose (PAR). PAR serves as a signal in regulation of transcription, chromatin remodeling, and DNA repair. During my research studies, I found that PARP-1 binds several G-Quadruplex structures. However, only a subset of G-Quadruplexes promote PARP-1 activity. The G-Quadruplex-forming sequence found in the proto-oncogene c-KIT promoter enzymatically activates PARP-1. I found that the loop-forming characteristics of the c-KIT G-Quadruplex sequence regulate PARP-1 catalytic activity. Eliminating the loop features reduced PARP-1 activity. Interestingly, oxidized G-Quadruplexes have been shown to form unique, looped structures to signal repair and also regulate gene expression. I found that oxidized G-Quadruplexes stimulate significant PARP-1 activity. These results support a PARP-1 and G-Quadruplex interaction, potentially linked to DNA repair and gene regulatory functions.

Something Notable about Time as a Graduate Student

At this institution, I met people that have given me great advice that I will cherish and carry with me throughout life.

Career Goals

I would like to work at St. Jude for my post-doctoral research. I have interests in teaching and also have a newfound interest in precision medicine. A dream job of mine would be to develop novel cancer therapeutics or provide knowledge that could be implemented into making better therapies.

Experiment or Technique You Would Most Like to Do

I am really interested in working with animal models such as mice. I would also like to work with patient tumor samples, performing techniques such as immunohistochemistry to identify tumorigenic markers.

Fun fact

I love to cook and try new dishes. I play piano and I’m currently learning to play by ear. I love riding four-wheelers and banshees on the farm.

Publications

Jun Gao, Alicia K. Byrd, Boris L. Zybailov, John C. Marecki, Michael J. Guderyon, Andrea D. Edwards, Shubeena Chib, Kirk L. West, Zachary J. Waldrip, Samuel G. Mackintosh, Zhaofeng Gao, Andrea A. Putnam, Eckhard Jankowsky and Kevin D. Raney, “DEAD-box RNA helicases Dbp2, Ded1 and Mss116 bind to G-quadruplex nucleic acids and destabilize G-quadruplex RNA.” Chemical Communications., Vol. 55, pg. 4467-4470, 2019.
https://www.ncbi.nlm.nih.gov/pubmed/30855040

Andrea D. Edwards, Alicia K. Byrd, John C. Marecki, and Kevin D. Raney, “G-Quadruplex loops regulate PARP-1 activation.” In preparation.

Grants

Southern Regional Education Board Dissertation Fellowship

Awards

UAMS 1st place 2019 Bhuvan Award for Excellence in Biochemistry Graduate Research

ASBMB 2019 Graduate Student Travel Award for Experimental Biology Meeting Orlando, Florida

Conference Series LLC Ltd. Molecular Biology and Nucleic Acids Conference Toronto, Ontario, Canada-Student Poster award 2018