Rice University scientists are pioneering two technologies to better diagnose and treat complex lymphatic anomalies. Photo via Getty Images.

An arm of the U.S. Department of Health and Human Services has awarded $18 million to scientists at Rice University for research that has the potential to revolutionize how lymphatic diseases are detected and help increase survivability.

The lymphatic system is the network of vessels all over the body that help eliminate waste, absorb fat and maintain fluid balance. Diseases in this system are often difficult to detect early due to the small size of the vessels and the invasiveness of biopsy testing. Though survival rates of lymph disease have skyrocketed in the United States over the last five years, it still claims around 200,000 people in the country annually.

Early detection of complex lymphatic anomalies (CLAs) and lymphedema is essential in increasing successful treatment rates. That’s where Rice University’s SynthX Center, directed by Han Xiao and Lei Li, an assistant professor of electrical and computer engineering, comes in.

Aided by researchers from Texas Children’s Hospital, Baylor College of Medicine, the University of Texas at Dallas and the University of Texas Southwestern Medical Center, the center is pioneering two technologies: the Visual Imaging System for Tracing and Analyzing Lymphatics with Photoacoustics (VISTA-LYMPH) and Digital Plasmonic Nanobubble Detection for Protein (DIAMOND-P).

Simply put, VISTA-LYMPH uses photoacoustic tomography (PAT), a combination of light and sound, to more accurately map the tiny vessels of the lymphatic system. The process is more effective than diagnostic tools that use only light or sound, independent of one another. The research award is through the Advanced Research Projects Agency for Health (ARPA-H) Lymphatic Imaging, Genomics and pHenotyping Technologies (LIGHT) program, part of the U.S. HHS, which saw the potential of VISTA-LYMPH in animal tests that produced finely detailed diagnostic maps.

“Thanks to ARPA-H’s award, we will build the most advanced PAT system to image the body’s lymphatic network with unprecedented resolution and speed, enabling earlier and more accurate diagnosis,” Li said in a news release.

Meanwhile, DIAMOND-P could replace the older, less exact immunoassay. It uses laser-heated vapors of plasmonic nanoparticles to detect viruses without having to separate or amplify, and at room temperature, greatly simplifying the process. This is an important part of greater diagnosis because even with VISTA-LYMPH’s greater imaging accuracy, many lymphatic diseases still do not appear. Detecting biological markers is still necessary.

According to Rice, the efforts will help address lymphatic disorders, including Gorham-Stout disease, kaposiform lymphangiomatosis and generalized lymphatic anomaly. They also could help manage conditions associated with lymphatic dysfunction, including cancer metastasis, cardiovascular disease and neurodegeneration.

“By validating VISTA-LYMPH and DIAMOND-P in both preclinical and clinical settings, the team aims to establish a comprehensive diagnostic pipeline for lymphatic diseases and potentially beyond,” Xiao added in the release.

The ARPA-H award funds the project for up to five years.

Rice University's SynthX Center, a collaborative lab focused on cancer treatments, named its inaugural seed grant recipients. Photo via Getty Images

3 Houston cancer-focused research projects receive seed grants from new innovative initiative

funding the future

Three groundbreaking projects have just received seed grants from a new Houston-based source.

This spring, Rice University launched its Synthesis X Center with the goal of fostering the growth of cancer technologies and medications. Now, the SynthX, as it is known, and Baylor College of Medicine’s Dan L Duncan Comprehensive Cancer Center have announced joint awards of grants to promising teams, all of which have principals at either Rice or Baylor.

The teams include:

  • A project from Drs. Pabel Miah of Baylor and Lei Li of Rice that involves the development and optimization of high-resolution imaging technology that’s intended for use in removing breast cancer from patients. The researchers combine ultrasound with photoacoustic technology to produce real-time imaging that allows surgeons to spot hard-to-locate tumors. This could reduce or eliminate tumor localization procedures which are invasive and costly.
  • A leukemia treatment profiting from molecular jackhammers, a type of molecule invented in the Rice University lab of Dr. James Tour. He’s joined in the project by Drs. Xin Li and Yongcheng Song, both of Baylor. Molecular jackhammers vibrate more than a trillion times per second when activated by a specific light frequency. Doing this can kill nearby cancer cells. The new treatment is intended to disrupt the activity of a transcription protein called ENL that helps fuel the growth of leukemia cells in several acute forms of the disease.
  • A project that could discover how to inspire cancer cells to kill themselves, using a cancer-associated enzyme called lysine demethylase 4A. Baylor’s Dr. Ruhee Dere and Rice’s Dr. Anna Karin-Gustavsson are studying the KDM4A with the process of apoptosis, or programmed cell death, in mind for the aberrant cells.

The seed grants are managed by Rice’s office for Educational and Research Initiatives for Collaborative Health (ENRICH). Each of the three grants is intended to last two years and includes funds of up to $80,000.

The goal is to allow research teams to collect preliminary data that can be used to apply for more substantial grants from bodies like the Cancer Prevention and Research Institute of Texas (CPRIT) or the National Institute of Health (NIH).

Three quarters of the funds will be provided in the first year. Teams that produce grant submissions with multiple principal investigators in that first year will be eligible to collect the additional quarter.

Researchers at the new SynthX Center will aim to turn fundamental research into clinical applications and make precision adjustments to drug properties and molecules. Photo via Rice University

Houston organizations launch collaborative center to boost cancer outcomes

new to HOU

Rice University's new Synthesis X Center officially launched last month to bring together experts in cancer care and chemistry.

The center was born out of what started about seven years ago as informal meetings between Rice chemist Han Xiao's research group and others from the Baylor College of Medicine’s Dan L Duncan Comprehensive Cancer Center at the Baylor College of Medicine. The level of collaboration between the two teams has grown significantly over the years, and monthly meetings now draw about 100 participants from across disciplines, fields and Houston-based organizations, according to a statement from Rice.

Researchers at the new SynthX Center will aim to turn fundamental research into clinical applications and make precision adjustments to drug properties and molecules. It will focus on improving cancer outcomes by looking at an array of factors, including prevention and detection, immunotherapies, the use of artificial intelligence to speed drug discovery and development, and several other topics.

"At Rice, we are strong on the fundamental side of research in organic chemistry, chemical biology, bioengineering and nanomaterials,” Xiao says in the statement. “Starting at the laboratory bench, we can synthesize therapeutic molecules and proteins with atom-level precision, offering immense potential for real-world applications at the bedside ... But the clinicians and fundamental researchers don’t have a lot of time to talk and to exchange ideas, so SynthX wants to serve as the bridge and help make these connections.”

SynthX plans to issue its first merit-based seed grants to teams with representatives from Baylor and Rice this month.

With this recognition from Rice, the teams from Xiao's lab and the TMC will also be able to expand and formalize their programs. They will build upon annual retreats, in which investigators can share unpublished findings, and also plan to host a national conference, the first slated for this fall titled "Synthetic Innovations Towards a Cure for Cancer.”

“I am confident that the SynthX Center will be a great resource for both students and faculty who seek to translate discoveries from fundamental chemical research into medical applications that improve people’s lives,” Thomas Killian, dean of the Wiess School of Natural Sciences, says in the release.

Rice announced that it had invested in four other research centers along with SynthX last month. The other centers include the Center for Coastal Futures and Adaptive Resilience, the Center for Environmental Studies, the Center for Latin American and Latinx Studies and the Rice Center for Nanoscale Imaging Sciences.

Earlier this year, Rice also announced its first-ever recipients of its One Small Step Grant program, funded by its Office of Innovation. The program will provide funding to faculty working on "promising projects with commercial potential," according to the website.

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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.”