Allie Davis and Dustyn Barnette, graduate students in Dr. Grover Paul Miller’s lab attended the Society of Toxicology National Meeting in Baltimore, MD last weekend and presented their research. Allie presented a poster entitled ” Bioactivation of Halogenated Aromatic Drugs as Precursors to Drug-Induced Hepatotoxicity” and Dusty presented a poster entitled “Determining Mechanism of Thiazole Metabolically Activated Toxic Outcome through Experimental and Computational Techniques​”.

March 14, 2019

Isabelle Racine Miousse, Ph.D.

Assistant Professor
Department of Biochemistry and Molecular Biology
UAMS College of Medicine
Research Interest Statement

Cancer cells fundamentally differ from healthy cells in the way they metabolize the amino acid and methyl donor methionine. This phenomenon is known as methionine dependence. It manifests as an increased reliance on an exogenous supply of methionine for growth and alterations in DNA and histone methylation patterns.

My work investigates these crucial differences between healthy cells and cancer cells. My expertise covers the absorption, processing and utilization of methyl groups, as well as epigenetic changes associated with cancer. I utilize metastatic melanoma models in vitroand in vivo to investigate the molecular bases of methionine dependence, relate dietary methionine levels to changes in the gut environment, and, finally, leverage this knowledge to improve the response rate in patients with metastatic melanoma receiving immunotherapy. With my work, I aim to improve the outcomes of cancer therapy for patients.

Dr. Miousse’s Grants

 Pilot Award, UAMS College of Medicine

$25,000*

01/01/19 – 12/31/19

Methionine and autophagy in metastatic melanoma

*cancer-related annual direct costs

UAMS Collaborators

Alan Tackett, Ph.D. (Biochemistry and Molecular Biology)

Igor Koturbash, M.D., Ph.D. (Environmental and Occupational Health)

Stephanie Byrum, Ph.D. (Director of Bioinformatics Core, Arkansas Children’s Research Institute)

Stepan Melnyk, M.D., Ph.D. (Director of the Core Metabolomics Laboratory, Arkansas Children’s Research Institute)

Laxmi Yeruva, Ph.D. (Pediatrics)

Alicia Byrd, Ph.D. (Biochemistry and Molecular Biology)

 External Collaborators

David Rosenblatt, M.D., Ph.D. (McGill University)

Alexandra Noel, Ph.D. (LSU School of Veterinary Medicine)

Opportunities for Collaboration

I welcome collaborations on the topics of DNA and histone modifications, as well as methyl donors such as folic acid and vitamin B12. I also have an interest in nutrition and metabolism.

You Might Not Know That …

I have two passions outside of work. I enjoy cooking, for the creative aspect (anything but desserts!) I also enjoy rock climbing for the problem-solving skills it requires and have done that for 10 years.

Cancer-related Publications

Miousse IR, Ewing LE, Kutanzi KR, Griffin RJ, Koturbash I. DNA Methylation in Radiation-Induced Carcinogenesis: Experimental Evidence and Clinical Perspectives. Crit Rev Oncog. 2018;23(1-2):1-11.

Miousse IR, Tobacyk J, Quick CM, Jamshidi-Parsian A, Skinner CM, Kore R, Melnyk SB, Kutanzi KR, Xia F, Griffin RJ, Koturbash I. Modulation of dietary methionine intake elicits potent, yet distinct, anticancer effects on primary versus metastatic tumors. Carcinogenesis. 2018 Sep 21;39(9):1117-1126.

Miousse IR, Pathak R, Garg S, Skinner CM, Melnyk S, Pavliv O, Hendrickson H, Landes RD, Lumen A, Tackett AJ, Deutz NEP, Hauer-Jensen M, Koturbash I. Short-term dietary methionine supplementation affects one-carbon metabolism and DNA methylation in the mouse gut and leads to altered microbiome profiles, barrier function, gene expression and histomorphology. Genes Nutr. 2017 Sep 6;12:22.

Miousse IR, Chang J, Shao L, Pathak R, Nzabarushimana É, Kutanzi KR, Landes RD, Tackett AJ, Hauer-Jensen M, Zhou D, Koturbash I. Inter-Strain Differences in LINE-1 DNA Methylation in the Mouse Hematopoietic System in Response to Exposure to Ionizing Radiation. Int J Mol Sci. 2017 Jul 4;18(7). pii: E1430.

Miousse IR, Tobacyk J, Melnyk S, James SJ, Cheema AK, Boerma M, Hauer-Jensen M, Koturbash I. One-carbon metabolism and ionizing radiation: a multifaceted interaction. Biomol Concepts. 2017 May 24;8(2):83-92.

Miousse IR, Kutanzi KR, Koturbash I. Effects of ionizing radiation on DNA methylation: from experimental biology to clinical applications. Int J Radiat Biol. 2017 May;93(5):457-469.

Students and postdocs from across campus participated in the 2019 Student Research Day poster presentations on March 12th.  Numerous award winners are affiliated with the Biochemistry and Molecular Biology department.  The Bhuvan Award is given to the project which makes the best use of biochemistry.  Andrea Edwards (Raney lab), Duah Alkam (Ussery and Smeltzer labs) and Joseph Rom (Smeltzer lab) were the winners.  Zach Waldrip (Burdine lab) and Alicja Urbaniak (Chambers lab) earned the top two prizes in the post-doctoral category and Zach also won the best poster overall.  Congratulations to all!

Andrea Edwards, 1st place Bhuvan Award

Duah Alkam, 2nd place Bhuvan Award

Joseph Rom, 3rd place Bhuvan Award

Dr. Zach Waldrip, 1st place postdoctoral category and 1st place overall

Dr. Alicja Urbaniak, 2nd place post-doctoral category

Proteomic Characterization of the Arsenic Response Locus in S. cerevisiae.

The melanocortin pathway and control of appetite-progress and therapeutic implications.

Congratulations to Lauren Davis who successfully defended her dissertation entitled “Histone Posttranslational Modifications as Diagnostic Markers for Melanoma” on February 20th.  Lauren is a student in Alan Tackett’s lab.

Oleg Karaduta was selected to receive a Young Investigator Educational Grant to study clinical application of mass spectrometry during the MSACL 11^th Annual Conference.

Curriculum includes short courses, practical training sessions and a variety of workshops.  Congratulations Dr. Karaduta!

Feb. 5, 2019 | Researchers at the UAMS Winthrop P. Rockefeller Cancer Institute received a funding boost thanks to the efforts of two volunteer groups.

One small grant award of $50,000 and three pilot awards of $15,000 each were presented to UAMS cancer researchers at a reception and research poster showcase hosted by the Envoys volunteer advocacy group Jan. 31.

Volunteers from the Hot Springs Village Walk for Cancer Research present funds for the Seeds of Science small grant award to Samantha Kendrick, Ph.D. (second from right). Also pictured (from left) are Cancer Institute Interim Director Laura Hutchins, M.D.; Christy Etheridge; Donna Aylward; Bob Hebert; Lynne Border; and Melanie Pederson. Kendrick’s co-investigator Brendan Frett, Ph.D., is not pictured.

The small grant award was funded by proceeds from the 17^th annual Village Walk for Cancer Research, held Sept. 29, 2018 in Hot Springs Village. Organized by volunteers, the walk unites the community, which is located one hour southwest of Little Rock, in support of cancer research.

“Knowing the money we raise is used to advance cancer research right here in Arkansas is very satisfying for those of us who organize the walk and participate in it,” said Melanie Pederson, event chair. Donna Aylward serves as co-chair.

Since 2002, the Village Walk for Cancer Research has raised about $500,000 for research programs at the UAMS Cancer Institute. The 2019 walk is scheduled for Sept. 28 at Balboa Pavilion in Hot Springs Village.

A team of two researchers received the small grant award for their work addressing drug resistance to aggressive lymphoma.

Brendan Frett, Ph.D., assistant professor in the Department of Pharmaceutical Sciences in the UAMS College of Pharmacy, and Samantha Kendrick, Ph.D., assistant professor of Department of Biochemistry and Molecular Biology in the UAMS College of Medicine, are collaborators on the project. They are exploring using a proteolysis targeting chimera molecule along with targeted therapies to break down the cancer-promoting protein Nek2

found in aggressive lymphoma. This dual treatment approach has the potential to reduce drug resistance and lead to better patient outcomes.

Jenny Long, president of the UAMS Cancer Institute Foundation Envoys, and Laura Hutchins, M.D., Cancer Institute interim director, were on hand to congratulate the Seeds of Science award recipients.

Three $15,000 pilot awards were presented to researchers for their work in a variety of areas. Funding for the awards was made possible by RockStar Lounge, an annual fundraising event hosted by the Envoys.

This year’s RockStar Lounge is set for April 5 at Cajun’s Wharf in Little Rock and will feature a performance by Memphis-based band Doctor Zarr’s Amazing Funk Monster. One-hundred percent of the net proceeds from RockStar Lounge is used to fund cancer research projects at UAMS.

“We are always excited and pleased to present grants to our very worthy scientists for their innovative projects,” said Jenny Long, Envoys president.

Recipients of the pilot awards were:

• Alicia Byrd, Ph.D., and Stephanie Byrum, Ph.D., assistant professors in the Department of Biochemistry and Molecular Biology in the UAMS College of Medicine

Byrd and Byrum’s project aims to identify new targets for cancer therapy by investigating the regulation of the DNA damage response pathway in cancerous and normal cells.

• Robert Eoff, Ph.D., associate professor in the Department of Biochemistry and Molecular Biology in the UAMS College of Medicine

Eoff’s project attempts to determine if a regulatory pathway normally associated with immune suppression in brain tumors also plays a role in resistance to the anti-cancer drug Temodar. Results of this study could increase understanding of how the elements involved in treatment resistance are regulated in malignant brain tumors.

• Zhiqiang Qin, M.D., Ph.D., associate professor in the Department of Pathology in the UAMS College of Medicine

The subtype of lung cancer known as non-small cell lung cancer (NSCLC) is a leading cause of cancer death in Arkansas. Qin’s project examines the use of the gene EIF4G1 as a therapeutic target for NSCLC and could provide the framework for the development of a clinical trial evaluating EIF4G1-targeted therapy.