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UTA awarded $6 million in 2016 to find new ways to identify and treat cancer

University of Texas at Arlington

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IMAGE: UTA leads in cancer research across the entire spectrum of patient experience. view more

Credit: UTA

The University of Texas at Arlington is becoming a major cancer research institute, receiving more than $6 million dollars in new grants in 2016 to strengthen its integrated cancer research program and improve outcomes across the complete spectrum of the patient experience.

"UTA's scientific expertise across basic cancer research, identification and diagnostics and non-invasive, mid-term, invasive and post-operative therapies is accelerating dramatically in order to enable substantial impact on health in Texas," UTA President Vistasp Karbhari said.

"By assembling a world-class team that works together we hope not only to make transformative advances in key areas related to cancer, but also to provide the highest level of educational and research experiences to our students, in keeping with our Strategic Plan theme of Health and the Human Condition."

Following a strong recruiting effort, UTA's cancer team now includes more than 25 faculty from across the Colleges of Science, Engineering and Nursing and Health Innovation, all focused on developing new ways to find and treat cancer.

"In 2016, UTA was named in the elite group of R1: Doctoral Universities - Highest Research Activity by the Carnegie Classification of Institutions of Higher Education, joining a distinguished group of 115 institutions including Harvard, MIT and Johns Hopkins," added Duane Dimos, UTA's vice president for research. "We also broke ground on a new $125 million Science and Engineering Innovation and Research building, which will be the University's signature research facility for multidisciplinary life and health science teaching and research. It is our moment to move forward in cancer."

UTA's cancer research is also moving out of the lab and into the commercial sector, with several companies formed around the University in key areas like immunotherapy or the development of novel chemical compounds to attack cancer.

"We are positioning UTA as the innovation hub around cancer for the North Texas region," Dr. Dimos said.

Basic cancer research to improve drug design

In 2016, UTA recruited several new biology faculty around cutting-edge fields such as the study of the genetic mutations of cancer cells, how cells respond to mitochondrial stress and the potential role of enzymes that can regulate cell death in cancer.

Among the new hires is acclaimed cell biology researcher Mark Pellegrino, who left Memorial Sloan Kettering Cancer Center in New York for UTA to study mitochondrial stress signaling in the context of cancer biology, supported by a large grant from the Cancer Prevention and Research Institute of Texas. Dr. Pellegrino's discovery that mitochondria are an important activator of innate immunity was published in the leading journal Nature in 2014.

"When the mitochondria becomes dysfunctional, a pathway is activated in an attempt to repair itself," Pellegrino said. "Down the line, I can envision that pathway being manipulated to develop new therapies for cancer."

Identification and diagnotics: treatments designed for each patient.

Big Data

Precision medicine, or the development of treatments specifically designed for each patient, is one of the fastest-growing areas of cancer research, and requires core strength in both data mining and genomics to improve diagnostics and better predict treatment outcomes.

The University, which already runs a Human Genomics Center through the Shimadzu Institute for Research Technologies as well as a Genomics Core Facility within its biology department, made several hires in 2016 to strengthen its capacity in computational modeling and the identification of biomarkers for cancer and received new large grants in this strategic focus area.

Heng Huang, a UTA professor in the Computer Science and Engineering Department, won a $1.3 million grant from the National Science Foundation in October 2016 to analyze histopathology images and cancer genomics data to yield a mechanistic understanding from gene to phenotypic markers and cancer outcomes. This comprehensive and integrative study of cancer imaging-omics will facilitate the precision medicine research that has cancer treatment as a near-term focus.

"The long-term plan for this research is to be able to treat an individual based on his or her image-omics data," Dr. Huang said. "For instance, if a patient's tissue images change, how is that related to genomics? Or, how can we use multi-omics to detect mutations? Once we find the biomarkers in the data, we can provide precision medicine strategy to treat the illness, from determining life expectancy to tailoring medicines to an individual's needs."

In related research, Junzhou Huang, an assistant professor of computer science and engineering, earned an $535,763 National Science Foundation CAREER Award in 2016 to investigate a process by which image-omics data can be combined into files that are small enough that current computing technology will allow scientists to better predict how long a patient will live and how best to treat that patient.

"We are pulling together a team that will be able to harness the power of computational modelling alongside real clinical diagnostics, to develop new screening and diagnostics tools and to better monitor treatment and individual patient outcomes," Dimos said.

Screening and Diagnostics

UTA has built up significant expertise in the screening and diagnostics of cancer in clinical settings, including the development of specific biomedical devices that improve early detection of the disease and predictive capacities around cancer metasisis.

Zui Pan, an esophageal cancer biomarker researcher, joined UTA's nursing faculty in 2016 from The Ohio State University College of Medicine. Her work has been funded by a $1.6 million grant from the National Institutes of Health - National Cancer Institute and helps develop new screening methods for early detection and prognosis in addition to novel therapeutic drugs for this deadly disease.

"My team has identified a protein named Orai1 that is strongly associated with esophageal tumor progression," Dr. Pan said. "We plan to evaluate the protein as a potential biomarker for esophageal cancer detection and prognosis with a goal of developing more effective therapeutic interventions for patients suffering from the disease."

Yuze "Alice" Sun, an assistant professor of electrical engineering, also earned a $500,000 National Science Foundation CAREER award in 2016 to develop optofluidic lasers to detect biomarkers for cancer diagnosis and other genetic disorders at the molecular and cellular levels.

Most lasers are semiconductor-based and require solid material to create cavities to confine light. In optofluidic lasers, two-phase liquids are controlled using microfluidics and nanofluidics to form a highly efficient optical microcavity. The all-liquid nature makes the laser adaptive and achieves high-precision tuning in an unprecedented manner, and is uniquely positioned as a novel biosensing technology.

Dr. Sun said she initially will explore using the optofluidic laser to detect biomarkers for cancer diagnosis and possibly other genetic disorders at the molecular and cellular levels.

"This could someday lead to the creation of a point-of-care platform for clinicians to use in an office, rather than having to send samples away for analysis," Sun said.

Non-invasive therapies: important contributions from science and engineering

Imaging and Simulation

UTA has focused important efforts in 2016 on strengthening niche areas such as imaging and simulation where its expertise in science and engineering can make a real contribution improving the effectiveness of non-invasive cancer therapies.

One key success was Baohong Yuan's second large grant from the Cancer Prevention and Research Institute of Texas to optimize deep-tissue imaging technology that could allow better monitoring of tumor growth.

The bioengineering associate professor's original grant focused on the growth of blood vessels in tumors. To grow, a tumor must generate blood vessels for oxygen and nutrients. Dr. Yuan successfully created imaging technology that gave clear images of those blood vessels, which tend to be disorganized.

With this technology in place, Yuan will now focus on differentiation of cells at the molecular level, including identifying specific biomarkers that may be linked to blood vessel growth.

"There are many signal pathways that can lead to blood vessel growth," Yuan said. "Researchers have successfully stopped single pathways, but that has not proved successful in the long term. If we can simultaneously stop multiple pathways, it could significantly stop or slow growth and allow more time for treatment, but to do this we must be able to monitor the molecular receptors."

UTA physicists, led by Mingwu Jin, began working with UT Southwestern and MD Anderson Cancer Center this year on multiple projects sponsored by the National Institutes of Health to develop devices and algorithms to improve the delivery of cancer therapies to patients.

In one project, the team is working to improve the quality of image-guided radiotherapy techniques that allow for better visualization of tumors, enabling physicians to deliver radiation doses to patients with high precision. In another project, UTA researchers are developing a device that can integrate tumor imaging and photo-induced cancer therapy in a single, portable device. A third project focuses on developing a novel real-time dose-monitoring method for heavy ion therapies.

"Dr. Jin's work will employ big data analysis and physics models to improve technologies used to deliver cancer therapy and ultimately improve patient care," said UTA Physics Chair Alex Weiss. "These collaborations with UT Southwestern and MD Anderson demonstrate clearly the leading role that a scientific research institution like UTA can play to advance knowledge needed by medical institutions."

Therapeutic Nanoparticles

UTA is also gaining recognition for developing new treatment techniques using therapeutic nanoparticles and nanoseeds to target cancer cells. Nanoparticles and nanoseeds have advantages over traditional therapies, as they can directly target cancer tumors without affecting healthy surrounding tissues.

One recent success is the work of UTA physicist Wei Chen, who gained international attention in 2016 for research showing that using microwaves to activate photosensitive nanoparticles produces tissue-heating effects and reactive oxygen species that ultimately lead to cell death within solid tumors.

In prior studies, the researchers had identified a new type of photosensitive nanoparticle, copper-cysteamine or Cu-Cy. They have now demonstrated that the nanoparticle Cu-Cy can also be activated by microwaves, which can be targeted directly at the tumor itself without harming surrounding tissue.

"Our new microwave-induced photodynamic therapy offers numerous advantages, the most significant of which is increased safety," Dr. Chen said. "Our nanoparticle Cu-Cy also demonstrates very low toxicity, is easy to make and inexpensive, and also emits intense luminescence, which means it can also be used as an imaging agent."

Mid-term therapies: developing and commercializing new drugs

UTA researchers are researching and successfully commercializing next-generation cancer therapies, as well as working to improve the performance of drugs that are already in the market and used on a regular basis by cancer patients.

The University recently recruited serial entrepreneur Jon Weidanz as associate vice president for research and professor of biology. His research has focused on immuno-oncology, the emerging field of therapies and treatments aimed at harnessing a patient's immune system to combat cancer. His company AbeXXa Biologics, which recently won an award at an Innovation Day at the Massachusetts Institute of Technology, is developing next-generation antibody drugs that can target specific proteins on cancer cells. AbeXXa has also signed a significant collaboration agreement with a large pharma company to develop next generation therapeutic agents for cancer immunotherapy.

Another faculty member developing specific drugs around cancer is UTA chemistry and biochemistry Chair Frederick MacDonnell. He is a co-founder of Tuevol Therapeutics, a company which has exclusively licensed the intellectual property to TS101, a ruthenium-based metallodrug that shows effectiveness against platinum-resistant lung cancer.

Ruthenium is a rare metallic element and the drugs developed at UTA have many of the therapeutic effects of platinum-based drugs, but without the dehabilitating side effects. Rolf Brekken and Tom Wilkie of the UT Southwestern Hamon Center for Therapeutic Oncoclogy are co-founders and are working Dr. MacDonnell to advance this drug to clinical studies.

"Further facilitating the translation of our inventions into viable therapies, with investment backing from major pharmaceutical companies, corporate venture capital and angel investors, is an important strategy as we move forward," Dr. Weidanz said. "This will allow us to create an innovation hub around cancer that will integrate the University with surrounding businesses and enhance our national and international reputation."

Invasive Therapies: bioengineering devices

In solutions for invasive cancer therapies, Liping Tang's recent work has led to the creation of a cancer trap, a potentially groundbreaking technology for treating metastatic cancer.

The cancer trap can be implanted under the skin to attract circulating cancer cells by releasing cancer cell-attracting biomolecules.

"This research tries to stop the cancer before it spreads," Dr. Tang said. "We attract the cancer with these decoys, which are artificial lymph nodes made of biodegradable polymers."

"Then, when it's trapped, we can use a more targeted radiation."

Cancer traps also can be incorporated with chemotherapy drugs or immunotherapy agents to locally eliminate cancer cells with minimal systemic toxicity and have the potential to revolutionize treatment of this disease. His work is currently supported by two three-year grants from the Department of Defense and the Wilson Charitable Foundation Trust.

Post-Operative Treatment: Improving Survival Rates

UTA is also leading the way in developing therapies to improve the quality of life of cancer patients, both during and after treatment. Over the past two years, the University has made cluster hires in the Department of Kinesiology, bringing to the University a group of experts who can bring their innovative vision to improving the patient experience.

Mark Haykowsky, a professor in the College of Nursing and Health Innovation and Moritz Chair of Geriatric Nursing and Research at UTA, was recently recruited from Alberta's Faculty of Rehabilitation Medicine, one of the world's preeminent rehabilitation medicine programs.

One of his main areas of research is in cardio-oncology, with specific emphasis on the role that exercise training can play to prevent anti-cancer therapy-mediated cardiovascular dysfunction.

This year he launched UTA's FitSteps exercise program, which helps cancer patients increase mobility and boost endurance while undergoing treatment. The program, a partnership with the Cancer Foundation for Life, is structured and tailored to each individual.

"A community's greatest asset is a healthy, thriving population," said UTA College of Nursing and Health Innovation Dean Anne Bavier. "Partnerships of this kind help ensure better survival rates for cancer patients in our community. They also help ensure a better quality of life. Helping tackle such real life problems is a critically important part of our reason for being as a health-focused college and as a university."

UTA will continue this strong commitment to cancer and to the Texan community going forward, added UTA President Vistasp Karbhari.

"The National Cancer Institute reports that approximately 39 percent of men and women will be diagnosed with cancer during their lifetime," Karbhari said. "Progress is being made against the disease, but much work remains. UTA aims to make an important contribution to providing new solutions and treatments to help patients with this disease."

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CANCER Researchers

Science

Sen Xu, biology: genetic mutation of cancer cells
Mark Pellegrino, biology: mitochondrial stress signalling
Clay Clark, biology: programmed cell death
Jon Weidanz, biology: immunology
Jonghyun Yun, mathematics, integrative statistical models
Suvra Pal, mathematics: disease modelling
Mingwu Jin, physics: devices to improve treatment delivery
Wei Chen, physics: photosensitive nanoparticles
Frederick MacDonnell, chemistry and biochemistry: novel chemistries
Jongyun Heo, chemistry and biochemistry: immune response

Engineering

Baohong Yuan, bioengineering: imaging technologies
Heng Huang, computer science and engineering: cancer imaging-omics
Junzhou Huang, computer science and engineering: image-omics
Samir Iqbal, electrical engineering: cancer detection device
J.-C. Chiao, electrical engineering: microfluidic devices
Yuze "Alice" Sun, electrical engineering: optofluidic lasers
Yaowu Hao, materials science and engineering: radiotherapeutic nanoseeds
Kytai Nyguyen, bioengineering: nanoparticles, microparticles and hydrojels
Liping Tang, bioengineering: cancer traps
Hanli Liu, bioengineering: imaging
Shouyi Wang, industrial and manufacturing systems engineering: imaging
Chris Ding, computer science and engineering: cancer imaging-omics
Jia Rao, computer science and engineering: cancer imaging-omics

Nursing

Zui Pan, nursing: biomarkers cancer
Mark Haykowsky, kinesiology: cardio-oncology
Marco Brotto, kinesiology: aging
Paul Fadel, kinesiology: clinical translational science

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