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Home - Science - Scientist Directory - Towner, Rheal A.

Rheal A. Towner, Ph.D.

Director of MRI Facility

Associate Member
Advanced Magnetic Resonance Center

Associate Professor, Department of Pathology and Pharmaceutical Sciences, University of Oklahoma Health Sciences Center

Associate Member, College of Medicine, Graduate Faculty in the Department of Pathology, University of Oklahoma Health Sciences Center

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My 101

The research in my laboratory centers on developing new ways to diagnose and predict the outcome of human diseases using non-invasive imaging and spectroscopic methods. These methods also allow us to evaluate new and existing drugs and determine optimal treatment protocols for the specific disease. In our studies, we use the techniques of magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to identify and study specific conditions of injured or diseased tissues in small animal models of disease. MRI is the newest and most advanced way to visualize structures inside the body since the invention of CT (or “CAT”) scans. Unlike CT scans, however, MRI does not involve radiation, but combines the use of a large magnet and radio waves. The hydrogen atoms in the body react to the magnetic field generated by MRI, while a computer analyzes the results and turns them into a picture. The image resolution of the picture is quite detailed and can detect very small changes in structures within tissues of the body. Our experimental approach of using MRI and MRS technology with small animal models of disease has many advantages, including the ability to investigate disease processes both in vivo, which means while the animal is alive, and in real time. Currently, we are most interested in understanding the molecular events that lead to the formation and development of cancer cells as well as the processes that cause tissue injury after the ingestion of natural toxins that can be found in contaminated food or water.

Both a fundamental and key issue in the early detection of cancer is to identify and understand characteristic molecular or metabolic events that occur in malignant cells but do not occur in normal cells. One way that we study this issue in my laboratory is to investigate specific components of metabolic reactions (metabolites), or molecular indicators, in malignant cells that are different from those in normal cells. These molecular indicators of cancerous tissues can then be used to predict and understand the development of nodules and tumors, from the initiation of a malignant cell throughout the progression of the cancer. Most recently, we are using this strategy in rodent (mice and rat) models of liver and brain cancer to investigate tumor morphology, new blood vessel formation, and fatty acid metabolism. We have discovered certain MRI techniques (MRI at 7 Tesla) that can detect tumor nodules in the liver as small as the thickness of a sheet of paper, allowing in vivo assessment of nodule/tumor development during the very first stages of formation of a cancer. The MRI techniques that we use are so sophisticated that they can even detect certain changes in metabolites inside the cells of the nodules or tumors and then correlate these changes with stages of tumor progression (also called tumor grading). One metabolic change that we have detected in cancer cells is an alteration in lipid unsaturated fatty acids. Additionally, we have found that certain enzymes involved in the metabolism or breakdown of fatty acids by cells are altered during tumor formation and thus, these findings may explain the metabolic changes that we observed by MRI. In similar studies, we use the same MRI strategies and techniques to measure metabolic changes in cells that occur after exposure to food- or water-borne toxicological agents, such as toxins produced by fungus and bacteria (mycotoxins, cyanobacteria toxins, etc.). The ability to correlate metabolic information obtained by MRI with tumor development and toxin-induced tissue injury should provide new insights into critical cell processes that are involved in malignancy and toxicity, as well as lead to a better understanding of mechanisms that occur in normal cells.

Another focus in our laboratory is on the discovery of “MRI molecular targeting agents”, or agents that selectively target or pinpoint tumor antigens on cancer cells and then allow the cancer cells to be visualized by MRI in live animals. By using in vivo MRI techniques to study tumors in the liver and brain of rodent models of cancer, we can simultaneously detect changes in tumor markers on the malignant cells, measure biochemical properties of the cancer cells, and determine the pathology of the tumor. We then correlate these molecular findings with progression of the disease. In fact, my laboratory was among the first to detect nodules/tumors in experimental animal models that express a specific receptor found in many human cancers (called c-MET), using the in vivo MRI molecular-targeting approach. These same MRI methods are also used to assess anti-cancer treatments in the animal cancer models and we have found a promising drug candidate that recedes tumor growth in an experimental model of brain cancer.

The ultimate goal of our research is to develop in vivo MRI methods that can be used in the clinic as tools for tumor grading and to predict the extent of tissue injury from toxin exposure in human patients. Having the ability to use a non-invasive technique such as in vivo MRI in both the diagnosis and therapy of cancer, among other diseases, provides great benefit to both the patient and physician.

Research

A critical issue regarding in vivo early detection of many cancers is to define and identify characteristic molecular or metabolic events which represent malignant tumors. I utilize in vivo magnetic resonance (MR) technology, in particular MRI and image-guided MR spectroscopy (MRS), to detect nodules and/or tumors in liver and brain cancer models and simultaneously determine the pathology and biochemical properties of the lesions which reflect disease progression.

My research is focused on the investigation of in vivo tissue metabolic indicators that can be used to predict and understand nodule and tumor development from initiation through to progression. We have found that MRI at 7 Tesla can detect hepatic nodules/tumors >100 mm in diameter, allowing in vivo assessment of nodule/tumor development during carcinogenesis. In addition, MRS can detect nodule and tumor-specific metabolic events, such as alterations in lipid unsaturated fatty acids and correlate these metabolic changes with tumor grading. We have also found that fatty acid desaturase enzymes, stearoyl-CoA desaturase 1 (Scd1) and fatty acid desaturase (FADS or 6-desaturase) are found to be altered during tumor formation which may reflect alterations in lipid metabolism that we detect with in vivoMRS. Currently we are investigating in vivo tumor morphology and angiogenesis, using MRI and MR angiography, respectively, and fatty acid metabolism using image-guided MRS, in a transgenic mouse (TGF-/c-myc) hepatocarcinogenesis model and rat glioma models.

A related area of research that we have commenced in my laboratory is to design MRI-detectable molecular targeting agents to visualize nodule and tumor antigens in vivo. We are the first to detect nodules/tumors in experimental models that express c-MET, a tyrosine kinase receptor found in many human cancers, using the in vivo MRI molecular-targeting approach. The aim is to be able to use MRS and molecular-targeted MRI as clinical diagnostic tools for in vivo tumor grading. We are also using MR methods to assess anti-cancer drugs in experimental animal cancer models.

Other areas of interest in my laboratory include studies regarding oxidative stress mechanisms associated with carcinogens, such as aflatoxin. We were the first to detect and characterize hydroxyl and arachidonyl radicals from the in vivo metabolism of aflatoxin in mammals.

Brief CV

Education
B.Sc., University of Guelph, Ontario, Canada, 1982
M.Sc., University of Guelph, Ontario, Canada, 1985
Ph.D., University of Guelph, Ontario, Canada, 1989

Memberships
International Society of Magnetic Resonance in Medicine
International Society of Magnetic Resonance
The Australian and New Zealand Society for Magnetic Resonance
The International Society for EPR (ESR) Spectroscopy
The Society for Free Radical Research
Society for Free Radical Biology and Medicine
American Association for Cancer Research
Oklahoma Center for Neurosciences

Joined OMRF Scientific Staff in 2002.

Publications

View more publications

Recent Publications

Towner RA, Gulej R, Zalles M, Saunders D, Smith N, Lerner M, Morton KA, Richardson A. Rapamycin restores brain vasculature, metabolism, and blood-brain barrier in an inflammaging model. Geroscience, 2021 April, PMID: 33846885

Towner RA, Greenwood-Van Meerveld B, Mohammadi E, Saunders D, Smith N, Sant GR, Shain HC, Jozefiak TH, Hurst RE. SuperGAG biopolymers for treatment of excessive bladder permeability. Pharmacol Res Perspect 9:e00709, 2021 February, PMID: 33540486, PMCID: PMC7861891

Towner RA, Smith N, Zalles M, Morris S, Toliver M, Saunders D, Lerner M, Kumar G, Axtell RC. ELTD1 as a biomarker for multiple sclerosis: Pre-clinical molecular-targeted studies in a mouse experimental autoimmune encephalomyelitis model. Mult Scler Relat Disord 49:102786, 2021 January, PMID: 33517175

Selected Publications

Madka V, Mohammed A, Li Q, Zhang Y, Biddick L, Patlolla JM, Lightfoot S, Towner RA, Wu XR, Steele VE, Kopelovich L, Rao CV. Targeting mTOR and p53 Signaling Inhibits Muscle Invasive Bladder Cancer In Vivo. Cancer Prev Res (Phila). 2016 Jan;9(1):53-62. Epub 2015 Nov 17. PMID: 26577454 PMCID: PMC4839263

Coutinho de Souza P, Mallory S, Smith N, Saunders D, Li XN, McNall-Knapp RY, Fung KM, Towner RA. Inhibition of Pediatric Glioblastoma Tumor Growth by the Anti-Cancer Agent OKN-007 in Orthotopic Mouse Xenografts. PLoS One. 2015 Aug 6;10(8):e0134276. eCollection 2015. PMID: 26248280 PMCID: PMC4527837

*Dong Y, Wu H, Rahman HN, Liu Y, Pasula S, Tessneer KL, Cai X, Liu X, Chang B, McManus J, Hahn S, Dong J, Brophy ML, Yu L, Song K, Silasi-Mansat R, Saunders D, Njoku C, Song H, Mehta-D’Souza P, Towner R, Lupu F, McEver RP, Xia L, Boerboom D, Srinivasan RS, Chen H. Motif mimetic of epsin perturbs tumor growth and metastasis. J Clin Invest. 2016 Mar 21. pii: 87344.[Epub ahead of print] PMID: 26999611 PMCID: PMC4811111

Rajagopalan V, Zhang Y, Ojamaa K, Chen YF, Pingitore A, Pol CJ, Saunders D, Balasubramanian K, Towner RA, Gerdes AM. Safe Oral Triiodo-L-Thyronine Therapy Protects from Post-Infarct Cardiac Dysfunction and Arrhythmias without Cardiovascular Adverse Effects. PLoS One. 2016 Mar 16;11(3):e0151413.  eCollection 2016. PMID: 26981865  PMCID: PMC4794221

Tarantini S, Hertelendy P, Tucsek Z, Valcarcel-Ares MN, Smith N, Menyhart A, Farkas E, Hodges EL, Towner R, Deak F, Sonntag WE, Csiszar A, Ungvari Z, Toth P. Pharmacologically-induced neurovascular uncoupling is associated with cognitive impairment in mice. J Cereb Blood Flow Metab. 2015 Nov;35(11):1871-81. Epub 2015 Jul 15. PMID: 26174328 PMCID: PMC4635246

* He T, Smith N, Saunders D, Pittman BP, Lerner M, Lightfoot S, Silasi-Mansat R, Lupu F, Towner RA. Molecular MRI differentiation of VEGF receptor-2 levels in C6 and RG2 glioma models. Am J Nucl Med Mol Imaging 3:300-311, 2013. PMID: 23901356 PMCID: PMC3715774

*Indicates collaborative department publication

 

Contact

Advanced Magnetic Resonance Center, MS 60
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104

Phone: (405) 271-7383
Fax: (405) 271-3980
E-mail: Rheal-Towner@omrf.org

Lab Staff

Nataliya Smith, Ph.D.
Associate Staff Scientist

Debra Saunders
Senior Research Assistant

News from the Towner lab

Dr. Towner in the Media

News from the Towner lab

OMRF brain cancer study reveals clue for treating MS
April 1, 2021

A discovery by a scientist studying brain cancer at OMRF could be key to improving MS treatment.

OMRF doctors make potential breakthrough in brain cancer treatment
September 16, 2020

Doctors at the Oklahoma Medical Research Foundation are celebrating what could become a breakthrough in brain cancer treatment.

FDA grants designations for OMRF brain tumor drug
September 2, 2020

The Oklahoma Medical Research Foundation is one step closer to beating rare forms of brain cancers.

OMRF brain tumor drug receives rare disease designations from the FDA
September 2, 2020

The drug treats fast-growing, deadly brain cancers with no effective treatment.

New use for OMRF brain cancer treatment could extend lives
December 18, 2019

In a new study, the OMRF compound OKN-007 is being combined with the current standard-of-care medication for glioblastoma.

OMRF discovers compound that could fight deadly cancer
January 21, 2019

Glioblastoma is an aggressive form of brain cancer with no cure, but a new OMRF discovery offers hope.

Oblato acquires all rights to glioblastoma drug from OMRF
October 29, 2018

Oblato, Inc., has acquired all rights from OMRF to OKN-007, an investigational drug for the treatment of a deadly form of brain cancer.

Staying alive: Can an experimental OMRF drug stop Mike Schuster’s brain cancer?
September 11, 2018

As Mike Schuster nears the three-year anniversary of his diagnosis with glioblastoma, he’s already doubled the life expectancy for patients with the deadly cancer.

OMRF hosts 2018 Loyal Donors reception
May 15, 2018

OMRF officials brought more than 110 long-time donors together from across the state to celebrate their dedicated supporters at the annual Loyal Donor Society reception.

Q BioMed Inc. finalizes license agreement with OMRF, RGCB
June 15, 2017

QBioMed has the global exclusive rights to develop and market a novel chemotherapeutic drug to treat liver cancer.

Investigating the role of obesity in arthritis
February 21, 2017

Osteoarthritis, or OA, is the most common form of disability in the U.S.

Trio of new grants brings $2.7 million to OMRF labs
May 6, 2016

Awards “a testament to the quality of research in Oklahoma”

Biotech company acquires OMRF brain cancer drug
February 15, 2016

Agreement will expand clinical trials of glioblastoma drug

Love and other drugs
February 9, 2016

Brain scans of people who are in love look similar to scans of drug addicts.

Research brings new view of difficult urinary disorder
November 30, 2015

Contrast MRI may lead to better diagnosis for bladder pain syndrome

Scientist looks at new therapies for pancreatic, liver cancers
July 2, 2015

Scientists are developing at new ways to specifically target tumors.

OMRF scientist develops method for diagnosing bladder pain syndrome
March 6, 2015

Researcher reveals innovative approach for diagnosing interstitial cystitis.

OMRF scientists look ahead to research in 2014
January 2, 2014

A new year brings new challenges for medical researchers.

Putnam City Schools race to fund cancer research
November 13, 2013

The Cancer Classic is a fun event with a serious purpose.

Biomarkers help doctors decide how to treat brain cancers
September 10, 2013

OMRF’s biomarker discoveries could bring new therapies for beating gliomas.

Tracking ALS could open new avenues for treatment
August 15, 2013

Scientists are using MRI to follow the path of free radicals in ALS.

OMRF brain cancer drug enters clinical trials at OU cancer center
August 7, 2013

OMRF, Stephenson Cancer Center begin tests of experimental compound

Attacking cancer on multiple fronts
May 7, 2013

Cutting off avenues for growth is key to killing tumors.

OMRF discovery could change brain cancer surgeries
November 12, 2012

A biomarker will help doctors better see and treat gliomas.

Putnam City Schools top $3 million for cancer research
September 5, 2012

Since 1976, PC students, teachers and parents have given to OMRF.

OMRF pioneers new method of examining diabetes
July 5, 2012

Scientists will learn more about free radicals in diabetes with new information

OMRF events raise more than $675,000 to fight brain cancer
June 25, 2012

Rockers Alice Cooper and Shooter Jennings come out to support research

Collaboration yields new ocular disease target
May 7, 2012

Findings may help improve treatments for retinopathy and macular degeneration

OMRF’s “cyber-sleuth” hunts new genes
August 11, 2011

Scientist Jonathan Wren uses computers to predict gene functions.

For high school teacher, cancer drive is part of the lesson plan
July 1, 2010

For teacher Denise Kimbrough, Bethany cancer drive for OMRF is personal.

OMRF scientists exploring novel breast cancer treatment
November 16, 2009

New method may keep breast cancer from spreading

Seeing double: OMRF adds second research MRI
August 19, 2008

In 2004, the Oklahoma Medical Research Foundation opened the state’s first small-animal magnetic resonance imaging (MRI) facility. With an investment of $3.75 million to build the facility, recruit a director and purchase a 10,000-pound magnet, OMRF knew it was taking a chance. Four years later, that risk has paid off: Researchers from institutions across the […]

OMRF developing promising treatment for brain tumor affecting Kennedy
May 27, 2008

Compound may shrink gliomas like that affecting Sen. Kennedy

OMRF Unveils State’s First Small Animal MRI Facility
October 11, 2004

The Oklahoma Medical Research Foundation unveiled Oklahoma’s first small animal magnetic resonance imaging (MRI) facility at a ribbon-cutting ceremony today.  With a 10,000-pound magnet that is 140,000 times stronger than the earth’s magnetic field, the facility – one of only about a dozen in the U.S. – will allow scientists to study the cells and […]

OMRF Receives $10 Million Grant
September 30, 2003

The Oklahoma Medical Research Foundation announced today that it has received a $10 million grant from the National Institutes of Health. “This is yet another important step in the emergence of Oklahoma as a center of biomedical excellence,” said OMRF President Dr. J. Donald Capra. “Five years ago, this state had never seen a $10 […]

Dr. Towner in the Media

Presbyterian Health Foundation awards grants to OMRF, OUHSC
Oklahoman.com

Presbyterian Health Foundation awards $3.9 million in grants
JournalRecord.com

OMRF discovers drug that fights aggressive brain cancer
KFOR.com

OMRF discovers cancer-fighting drug for aggressive brain cancer
5NewsOnline.com

OMRF reports cancer research
JournalRecord.com

Licensing deal paves way for wider trial of OMRF glioblastoma therapeutic
NewsOK.com

Oblato acquires glioblastoma drug from OMRF
PipelineReview.com

Oblato acquires glioblastoma drug from OMRF
APNews.com

Oblato acquires rights to glioblastoma drug
P&T Community

Can an experimental drug from OMRF stop Mike Schuster's brain cancer?
OKNursingTimes.com

Staying alive: Can an experimental drug stop Mike Schuster's brain cancer? 
NewsOk.com

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