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Opinion: The National Institutes of Health needs to better balance funding distributions among US institutions

Wahls WP

PNAS 2019

 

 

 

 

A Time-Embedding Network Models the Ontogeny of 23 Hepatic Drug Metabolizing Enzymes.

The Translational Research Institute (TRI) announced today that five early career UAMS researchers will receive KL2 Mentored Research Career Development Program Scholar Awards.

The program provides two years of didactic and mentored research training. Scholars receive 75% salary support and up to $25,000 per year for research, tuition, travel expenses and education materials.

The KL2 Scholars were chosen from 11 applicants. Below are the new scholars, their college, department and title of their KL2 project:

• Tara Johnson, M.D.; College of Medicine, Department of Pediatrics, Neurology; Implementation and Quantification of the General Movement Assessment for Early Detection of Neurodevelopmental Disabilities in Infants
• Stephanie Kennon-McGill, Ph.D.; College of Public Health, Department of Environmental and Occupational Health; Fetal Exposure to Cannabinoids: Exposure, Methylation and Neurodevelopmental Effects
• Pearman Parker, Ph.D., M.P.H., RN; College of Nursing, Department of Nursing Science;  An exploration of the mental health needs of young women with breast cancer and implications for developing patient educational materials
• Isabel Racine-Miousse, Ph.D.; College of Medicine, Department of Biochemistry; Decreasing Methionine Intake to Improve Survival in Patients with Metastatic Melanoma
• Jennifer Vincenzo, Ph.D., M.P.H., P.T.; College of Health Professions, Department of Physical Therapy; Development of a Falls Prevention Self-Management Plan to Improve Older Adults Adherence to Prevention Strategies after Community-Based Falls Risk Screenings

Four UAMS postdoctoral trainees recently became the inaugural recipients of the Translational Research Institute (TRI) Health Science Innovation & Entrepreneurship (HSIE) Postdoctoral Scholars Program Awards.

Funded by TRI’s Clinical and Translational Science Award (CTSA) TL1 Program, the 15-credit graduate entrepreneurship training includes a significant new partnership with the University of Arkansas, Fayetteville, Sam M. Walton College of Business, which will provide distance education courses to the scholars. The scholars will work with MBA student teams at the UA to develop commercialization plans for health-science technologies conceived at UAMS.

The program spans two years as a complement to the scholars’ existing mentored research training.

The scholars and their research mentors are:

• Samir Jenkins, Ph.D., (mentor, Robert Griffin, Ph.D., Department of Radiation Oncology); interests in nanomaterials and stem cell differentiation.
• Astha Malhotra, Ph.D., (mentor, Jay Mehta, M.D., Ph.D., Department of Internal Medicine, Cardiology); interests in 3-D printing and tissue regeneration.
• Melody Penning, Ph.D., (mentor, Fred Prior, Ph.D., Department of Biomedical Informatics); interests in algorithms to predict adverse events in health care.
• Aaron Storey, Ph.D., (mentor, Ricky Edmondson, Ph.D., Department of Biochemistry and Molecular Biology, Cancer Institute – Proteomics); interests in mass spectrometry to identify bacteria in synovial fluid.

Andrea Edwards, a graduate student in Kevin Raney’s lab was selected to give both an oral and a poster presentation at the NAD+ Metabolism and Signaling Conference in Dublin, Ireland.

Effect of Sulforaphane and 5-Aza-2′-Deoxycytidine on Melanoma Cell Growth.

 

Dr. Robert Eoff has received a new, four-year grant award from the NSF.  The award is for ~1.2 million to study “Replication of G-quadruplex DNA by translesion polymerases”.  Dr. Julie Gunderson of Hendrix College is co-Investigator on the grant.

Andrea Edwards, a graduate student in Kevin Raney’s lab was selected as a Southern Regional Education Board SREB-Doctoral Scholars Program recipient for 2019-2020.   Her graduate studies will be funded through a partnership arrangement between SREB, the State of Arkansas, and the University of Arkansas for Medical Services.  She will also have her expenses paid to attend the annual Institute on Teaching and Mentoring.  Congratulations Andrea!

Dr. Magdalena Delgado who recently completed her Ph.D. in Dr. Tim Chamber’s lab has been awarded the Alan D. Elbein Award for Research Excellence.  The award is named in honor of Dr. Alan D. Elbein, who was Chair of the Department of Biochemistry & Molecular Biology from 1991 until 2009 and is given to graduate students that have shown extraordinary research performance during their graduate career. Areas of evaluation include but are not limited to fellowships, manuscripts, and presentations of research.  Congratulations Dr. Delgado!

Ten undergraduate students who are spending their summer in the UAMS Biochemistry and Molecular Biology Department doing research projects presented their work at the SURF Mid-Summer Symposium.

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

Research Interest Statement

The Raney laboratory is interested in the mechanisms and functions of nucleic acid enzymes called helicases. Helicases play central roles in all aspects of DNA and RNA metabolism; therefore they are key enzymes in maintaining genomic stability. Genetic mutations in many helicases have been correlated with numerous cancers. The Pif1 helicase is a major focus of study. Mutations in Pif1 have been linked to increased incidence of breast cancer. We are studying how such mutations alter the biochemical mechanism and ultimately biological function of the enzyme, thereby leading to cancer.

A related interest of the Raney lab is in non-canonical structures of DNA and RNA that form in guanine-rich sequences termed G-quadruplex. Over 500,000 potential G-quadruplex sequences exist in the human genome but their function is largely unknown. We have identified a novel function for G-quadruplex sequences that appears to be fundamental to cellular responses to reactive oxygen species. In response to DNA damage due to oxidative stress, G-quadruplex sequences are removed from the genome, then interact with a variety of proteins. Telomeric and mitochondrial DNA are particularly susceptible to oxidative stress and contain many sequences that readily fold into quadruplex structures. We and others have found that the excised DNA quadruplexes can modulate multiple cellular activities including cell death. We hypothesize that such mechanisms involving G-quadruplexes are important to carcinogenesis. G-quadruplex structures have emerged as a target for developing anti-cancer therapies.

Dr. Raney’s Grants

National Institute of General Medical Sciences

Functions and mechanisms of helicases and g-quadruplex nucleic acids

05/01/2017 – 04/30/2022

$360,000*

*cancer-related annual direct costs

Dr. Raney’s UAMS Collaborators

• Robert Eoff, Ph.D., Biochemistry and Molecular Biology
• Guilia Baldini, Ph.D., Biochemistry and Molecular Biology
• Angus MacNicol, Ph.D., Neurobiology and Developmental Sciences
• Alicia Byrd, Ph.D., Biochemistry and Molecular Biology
• Boris Zybailov, Ph.D., Biochemistry and Molecular Biology
• Stephanie Byrum, Ph.D., Biochemistry and Molecular Biology
• Peter Crooks, Ph.D., D.Sc., Pharmaceutical Sciences

Dr. Raney’s External Collaborators

• Craig Cameron, Ph.D., Pennsylvania State University
• Maria Spies, Ph.D., University of Iowa
• Nayun Kim, Ph.D., University of Texas Health Science Center

Opportunities for Collaboration

New ideas emerge from discussions with scientists outside of one’s field. We welcome discussions and will gladly pursue opportunities in areas closely or loosely related to DNA damage response mechanisms. Other areas of interest include drug discovery.

You May Not Know That …

My wife, Veronica, and I have been married for 33 years. We have three children and two grandchildren. I was raised in north Arkansas where I enjoyed canoeing, hiking and caving.

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. “DEAD-box RNA helicases Dbp2, Ded1 and Mss116 bind to G-quadruplex nucleic acids and destabilize G-quadruplex RNA.” Chem Commun (Camb). 2019, Apr 11;55(31): 4467-4470. doi: 10.1039/c8cc1009h. PMID: 30855040
• Marecki JC, Aarattuthodiyil S, Byrd AK, Penthala NR, Crooks PA, Raney KD. “N-Naphthoyl-substituted indole thio-barbituric acid analogs inhibit the helicase activity of the hepatitis C virus NS3”. 2019. Bioorg Med Chem Lett. 2019 Feb 1;29(3):430-434. doi: 10.1016/j.bmcl.2018.12.026. Epub 2018 Dec 13. PMID: 30578035PMCID: PMC6377802 [Available on 2020-02-01]
• Griffin, W.C., Gao, J., Byrd, A.K., Chib, S., and Raney, K.D. (2017) “A Biochemical and Biophysical Model of G-quadruplex DNA Recognition by Positive Coactivator of Transcription 4.” J. Biol. Chem. June 9;292(23):9567-9582. PMID: 28416612. PMCID: PMC5465483.
• Lopez, C.R., Singh, S., Hambarde, S., Griffin, W.C., Gao, J., Chib, S., Yu, Y., Ira, G., Raney, K.D., and Kim, N. (2017) “Yeast Sub1 and human PC4 are G-quadruplex binding proteins that suppress genome instability at co-transcriptionally formed G4 DNA.” Nucleic Acids Res. 45:5850-5862. PMID: 28369605. PMCID: PMC5449603.
• Byrd, A.K., Zybailov, B.L., Maddukuri, L., Gao, J., Marecki, J.C., Jaiswal, M., Bell, M.R., Griffin, W.C., Reed, M.R., Chib, S., Mackintosh, S.G., MacNicol, A.M., Baldini, G., Eoff, R.L., and Raney, K.D., (2016) “Evidence that G-quadruplex DNA Accumulates in the Cytoplasm and Participates in Stress Granule Assembly in Response to Oxidative Stress” J. Biol. Chem. Aug. 19; 291:18041-18057. Doi: 10.1074/jbc.M116.718478. Epub 2016 Jul. 1. PMID: 27369081. PMCID: PMC5016190.
• Byrd, A.K. and Raney, K.D., “Structure and function of Pif1 helicase.” 2017. Biochem Soc. Trans. Oct 15;45(5):1159-1171. doi: 10.1042/BST20170096. Epub 2017 Sep 12. Review. PMID: 28900015. PMCID: PMC5870758. DOI: 10.1042/BST20170096