Digging in the ‘Dirt’— Solving Cancer, Opioid Addiction, and Energy Challenges

By Luke Rucker, UH Technology Bridge Communications Intern

Imagine harnessing the body's natural defenses and turning them into formidable weapons that can fight not only cancer and the opioid crisis but also help the energy sector. In the ever-evolving world of scientific research, Moores Professor of Biology and Biochemistry Preethi Gunaratne has emerged as a pioneer whose work has done just that.

GeOME Analytics, a startup co-founded by Gunaratne, has created the Reservoir & Drainage Diagnostics (RDD) tool, an innovation which can be used in the oil and gas industry. Designed for monitoring oil fields throughout the entire production process, RDD uses personalized DNA biomarkers to optimize the placement of drilling and fracking wells in oil-rich shale formations. RDD employs no -invasive DNA testing to provide precise metrics for developing upstream assets, reducing environmental impact, costs, and time.

During field tests conducted in collaboration with ChevronCorp., RDD uncovered a surprising diversity of microbial life in the Permian Basin. Between 48% and 94% of the biomarkers used to predict drainage levels, geologic zone contributions, and well-to-well communication were linked with previously unknown microbes not found in public databases.

This groundbreaking work saw GeOME Analytics honored as a winner of this year's UH Energy Innovation Challenge. However, Gunaratne has continued to break new ground, with the Cancer Genome Atlas (TCGA) Project Consortium making significant strides in understanding the genetic landscape of various cancers.

The TCGA Project Consortium (2008-2019) established a comprehensive catalog of DNA and RNA changes in 33 different cancers. This monumental effort served as the cornerstone for developing targeted therapies based on actionable mutations.

Gunaratne, with her leadership roles in the microRNA and long non-coding RNA analysis working groups within TCGA, played a pivotal role in developing the "Lineage Tracing" application. This application has since been adapted to trace changes in brain regions. It does so by utilizing microRNA biomarkers released into the bloodstream.

Gunaratne's research, which started with exploring non-coding RNAs initially considered "junk," took an unexpected turn when her team embarked on a rescue mission for discordant paired-end and split reads, typically discarded to ensure high-quality sequence files.

In collaboration with Isabelle Bedrosian, surgical oncologist at the M.D. Anderson Cancer and Randa El-Zein, radiology professor at Houston Methodist Research Institute, they utilized a 300-subject Breast Cancer RNA-seq dataset to discover agents capable of harnessing the body's natural defenses and transforming them into potent weapons against cancer.

Their secret weapon? Immunogenic neoantigens, located at the fusion junctions of these chimeric RNAs. Their cutting edge work, recently published in Frontiers in Immunology in 2023, unveiled microscopic molecular peptides that hold the key to designing vaccines capable of triggering an immune response against cancer cells.

“Cancer cells are very smart, and they hide…chemotherapy is like dropping a bomb on all the cells and hoping you got them. But now if you know the genetic mutation, it’s like sending in a sniper to eliminate them,” Gunaratne said.

To unlock this potential, Micah Castillo and Sakuni Rankothgedera, lead scientists of the UH-Sequencing Core and Patient Derived Xenograft sequencing, collaborated with other doctoral students to create an advanced technology platform. This platform deciphers the genetic code of cancer cells with unparalleled precision, using tools like Next-Generation Sequencing and Single Cell Sequencing that form a bridge between neoantigens and the body's vigilant T-cells, providing the foundation for crafting vaccines that prompt the immune system to eradicate cancer cells.

This novel technology is a massive step in creating a potential cure for cancer, and, according to Gunaratne, its importance cannot be understated.

Still, Gunaratne and her team are not content with simply publishing ingenious research papers. Understanding the urgency to translate their findings into clinical and industrial practice, they have filed multiple provisional patents, ensuring their discoveries remain protected, and more importantly, accessible to those in need.

“Don’t underestimate the impact of basic science,” she said. “We still need basic breakthroughs in biomedical engineering and so on… with the technologies we have, we are truly in an amazing period of human history.”