Rice and MD Anderson scientists are researching new methods for treating brain cancer by overcoming the blood-brain barrier. Photo via Getty Images.

Rice University chemist Han Xiao, who also serves as director of the university’s Synthesis X Center, and cancer biologist Dihua Yu of The University of Texas MD Anderson Cancer Center have received a three-year, $1.5 million grant from the Robert J. Kleberg Jr. and Helen C. Kleberg Foundation.

The funding will allow them to continue their research on treating brain metastasis by overcoming the blood-brain barrier, or the BBB, according to a news release.

Brain metastasis is the leading form of brain cancer, with survival rates below 20 percent within a year of diagnosis, according to the National Library of Medicine. It commonly originates from breast, lung and melanoma cancers.

The BBB typically acts as a protective barrier for the brain. However, it prevents most drugs from being able to directly reach the brain. According to Rice, only 2 percent of FDA-approved small molecule drugs can penetrate the BBB, limiting treatment options.

Xiao and Yu’s approach to dealing with the BBB includes a light-induced brain delivery (LIBD) platform. The advanced system employs nanoparticles that are embedded with a near-infrared dye for the transport of therapeutic agents across the BBB. The research will evaluate the LIBD’s ability to improve the delivery of small-molecule drugs and biological therapies. Some therapies have shown potential for reducing cancer growth in laboratory studies, but they have struggled due to limited BBB penetration in animal models.

“Our LIBD platform represents a novel strategy for delivering drugs to the brain with precision and efficiency,” Xiao said in a news release. “This technology could not only improve outcomes for brain metastasis patients but also pave the way for treating other neurological diseases.”

The Kleberg Foundation looks for groundbreaking medical research proposals from leading institutions that focus on “innovative basic and applied biological research that advances scientific knowledge and human health” according to the foundation.

“This research is a testament to the power of collaboration and innovation,” Xiao said in a news release. “Together, we’re pushing the boundaries of what’s possible in treating brain metastasis and beyond.”

Rice launched the Synthesis X Center, or Synth X, last spring. It was born out of what started about eight years ago as informal meetings between Xiao's research group and others from the Baylor College of Medicine’s Dan L Duncan Comprehensive Cancer Center. It aims to turn fundamental research into clinical applications through collaboration.

“This collaboration builds on the strengths of both research teams,” Xiao said in the release. “By combining SynthX Center's expertise in chemistry with Dr. Yu's expertise in cancer biology and brain metastases, we aim to create a transformative solution.”

Breakthrough research on metastatic breast cancer, a new way to turn toxic pollutants into valuable chemicals, and an evolved brain tumor chip are three cancer-fighting treatments coming out of Houston. Getty Inages

These 3 Houston research projects are aiming to fight or prevent cancer

Research roundup

Cancer remains to be one of the medical research community's huge focuses and challenges, and scientists in Houston are continuing to innovate new treatments and technologies to make an impact on cancer and its ripple effect.

Three research projects coming out of Houston institutions are providing solutions in the fight against cancer — from ways to monitor treatment to eliminating cancer-causing chemicals in the first place.

Baylor College of Medicine's breakthrough in breast cancer

Photo via bcm.edu

Researchers at Baylor College of Medicine and Harvard Medical School have unveiled a mechanism explains how "endocrine-resistant breast cancer acquires metastatic behavior," according to a news release from BCM. This research can be game changing for introducing new therapeutic strategies.

The study was published in the Proceedings of the National Academy of Sciences and shows that hyperactive FOXA1 signaling — previously reported in endocrine-resistant metastatic breast cancer — can trigger genome-wide reprogramming that enhances resistance to treatment.

"Working with breast cancer cell lines in the laboratory, we discovered that FOXA1 reprograms endocrine therapy-resistant breast cancer cells by turning on certain genes that were turned off before and turning off other genes," says Dr. Xiaoyong Fu, assistant professor of molecular and cellular biology and part of the Lester and Sue Smith Breast Center at Baylor, in the release.

"The new gene expression program mimics an early embryonic developmental program that endow cancer cells with new capabilities, such as being able to migrate to other tissues and invade them aggressively, hallmarks of metastatic behavior."

Patients whose cancer is considered metastatic — even ones that initially responded to treatment — tend to relapse and die due to the cancer's resistance to treatment. This research will allow for new conversations around therapeutic treatment that could work to eliminate metastatic cancer.

University of Houston's evolved brain cancer chip

Photo via uh.edu

A biomedical research team at the University of Houston has made improvements on its microfluidic brain cancer chip. The Akay Lab's new chip "allows multiple-simultaneous drug administration, and a massive parallel testing of drug response for patients with glioblastoma," according to a UH news release. GBM is the most common malignant brain tumor and makes up half of all cases. Patients with GBM have a five-year survival rate of only 5.6 percent.

"The new chip generates tumor spheroids, or clusters, and provides large-scale assessments on the response of these GBM tumor cells to various concentrations and combinations of drugs. This platform could optimize the use of rare tumor samples derived from GBM patients to provide valuable insight on the tumor growth and responses to drug therapies," says Metin Akay, John S. Dunn Endowed Chair Professor of Biomedical Engineering and department chair, in the release.

Akay's team published a paper in the inaugural issue of the IEEE Engineering in Medicine & Biology Society's Open Journal of Engineering in Medicine and Biology. The report explains how the technology is able to quickly assess how well a cancer drug is improving its patients' health.

"When we can tell the doctor that the patient needs a combination of drugs and the exact proportion of each, this is precision medicine," Akay explains in the release.

Rice University's pollution transformation technology

Photo via rice.edu

Rice University engineers have developed a way to get rid of cancer-causing pollutants in water and transform them into valuable chemicals. A team lead by Michael Wong and Thomas Senftle has created this new catalyst that turns nitrate into ammonia. The study was published in the journal ACS Catalysis.

"Agricultural fertilizer runoff is contaminating ground and surface water, which causes ecological effects such as algae blooms as well as significant adverse effects for humans, including cancer, hypertension and developmental issues in babies," says Wong, professor and chair of the Department of Chemical and Biomolecular Engineering in Rice's Brown School of Engineering, in a news release. "I've been very curious about nitrogen chemistry, especially if I can design materials that clean water of nitrogen compounds like nitrites and nitrates."

The ability to transform these chemicals into ammonia is crucial because ammonia-based fertilizers are used for global food supplies and the traditional method of creating ammonia is energy intensive. Not only does this process eliminate that energy usage, but it's ridding the contaminated water of toxic chemicals.

"I'm excited about removing nitrite, forming ammonia and hydrazine, as well as the chemistry that we figured out about how all this happens," Wong says in the release. "The most important takeaway is that we learned how to clean water in a simpler way and created chemicals that are more valuable than the waste stream."

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Houston doctor wins NIH grant to test virtual reality for ICU delirium

Virtual healing

Think of it like a reverse version of The Matrix. A person wakes up in a hospital bed and gets plugged into a virtual reality game world in order to heal.

While it may sound far-fetched, Dr. Hina Faisal, a Houston Methodist critical care specialist in the Department of Surgery, was recently awarded a $242,000 grant from the National Institute of Health to test the effects of VR games on patients coming out of major surgery in the intensive care unit (ICU).

The five-year study will focus on older patients using mental stimulation techniques to reduce incidences of delirium. The award comes courtesy of the National Institute on Aging K76 Paul B. Beeson Emerging Leaders Career Development Award in Aging.

“As the population of older adults continues to grow, the need for effective, scalable interventions to prevent postoperative complications like delirium is more important than ever,” Faisal said in a news release.

ICU delirium is a serious condition that can lead to major complications and even death. Roughly 87 percent of patients who undergo major surgery involving intubation will experience some form of delirium coming out of anesthesia. Causes can range from infection to drug reactions. While many cases are mild, prolonged ICU delirium may prevent a patient from following medical advice or even cause them to hurt themselves.

Using VR games to treat delirium is a rapidly emerging and exciting branch of medicine. Studies show that VR games can help promote mental activity, memory and cognitive function. However, the full benefits are currently unknown as studies have been hampered by small patient populations.

Faisal believes that half of all ICU delirium cases are preventable through VR treatment. Currently, a general lack of knowledge and resources has been holding back the advancement of the treatment.

Hopefully, the work of Faisal in one of the busiest medical cities in the world can alleviate that problem as she spends the next half-decade plugging patients into games to aid in their healing.

Houston scientists develop breakthrough AI-driven process to design, decode genetic circuits

biotech breakthrough

Researchers at Rice University have developed an innovative process that uses artificial intelligence to better understand complex genetic circuits.

A study, published in the journal Nature, shows how the new technique, known as “Combining Long- and Short-range Sequencing to Investigate Genetic Complexity,” or CLASSIC, can generate and test millions of DNA designs at the same time, which, according to Rice.

The work was led by Rice’s Caleb Bashor, deputy director for the Rice Synthetic Biology Institute and member of the Ken Kennedy Institute. Bashor has been working with Kshitij Rai and Ronan O’Connell, co-first authors on the study, on the CLASSIC for over four years, according to a news release.

“Our work is the first demonstration that you can use AI for designing these circuits,” Bashor said in the release.

Genetic circuits program cells to perform specific functions. Finding the circuit that matches a desired function or performance "can be like looking for a needle in a haystack," Bashor explained. This work looked to find a solution to this long-standing challenge in synthetic biology.

First, the team developed a library of proof-of-concept genetic circuits. It then pooled the circuits and inserted them into human cells. Next, they used long-read and short-read DNA sequencing to create "a master map" that linked each circuit to how it performed.

The data was then used to train AI and machine learning models to analyze circuits and make accurate predictions for how untested circuits might perform.

“We end up with measurements for a lot of the possible designs but not all of them, and that is where building the (machine learning) model comes in,” O’Connell explained in the release. “We use the data to train a model that can understand this landscape and predict things we were not able to generate data on.”

Ultimately, the researchers believe the circuit characterization and AI-driven understanding can speed up synthetic biology, lead to faster development of biotechnology and potentially support more cell-based therapy breakthroughs by shedding new light on how gene circuits behave, according to Rice.

“We think AI/ML-driven design is the future of synthetic biology,” Bashor added in the release. “As we collect more data using CLASSIC, we can train more complex models to make predictions for how to design even more sophisticated and useful cellular biotechnology.”

The team at Rice also worked with Pankaj Mehta’s group in the department of physics at Boston University and Todd Treangen’s group in Rice’s computer science department. Research was supported by the National Institutes of Health, Office of Naval Research, the Robert J. Kleberg Jr. and Helen C. Kleberg Foundation, the American Heart Association, National Library of Medicine, the National Science Foundation, Rice’s Ken Kennedy Institute and the Rice Institute of Synthetic Biology.

James Collins, a biomedical engineer at MIT who helped establish synthetic biology as a field, added that CLASSIC is a new, defining milestone.

“Twenty-five years ago, those early circuits showed that we could program living cells, but they were built one at a time, each requiring months of tuning,” said Collins, who was one of the inventors of the toggle switch. “Bashor and colleagues have now delivered a transformative leap: CLASSIC brings high-throughput engineering to gene circuit design, allowing exploration of combinatorial spaces that were previously out of reach. Their platform doesn’t just accelerate the design-build-test-learn cycle; it redefines its scale, marking a new era of data-driven synthetic biology.”