cSTAR: Transforming Biomedical Research

Research Spotlight

January 2025

SBI researchers, Profs. Boris Kholodenko, Walter Kolch and Dr. Oleksii Rukhlenko developed a novel approach, termed cSTAR (cell State Transition Assessment and Regulation) to distinguish between pathological (“diseased”) and healthy states of human cells. First published in (opens in a new window)Nature in 2022, cSTAR is a powerful tool that leverages molecular data to map cellular states, model transitions, and even control these processes for therapeutic benefit. This innovation marked a significant leap in understanding diseases like cancer, tuberculosis, and vascular disorders, with promising implications for personalised medicine.

Cells in the human body exhibit remarkable plasticity, enabling tissue repair and regeneration. However, in diseases such as cancer, this plasticity can turn harmful, leading to abnormal growth and metastasis. cSTAR uses machine learning and computational modeling to identify key molecular markers distinguishing healthy from diseased states. By uncovering the mechanisms driving these transitions, SBI researchers aim to manipulate cell states, such as halting cancer cell proliferation or accelerating tissue repair.

“Controlling cell state transitions is a holy grail in biology and biomedicine,” says SBI Director, Prof Kolch. “cSTAR functions like a universal tool, much like the microchip revolutionised smart tool technologies, cSTAR can enable precise control over cellular processes.”

Major Milestones

Protecting the invention (2021-2022)

University College Dublin were proactive in protecting the intellectual property behind cSTAR. A UK patent application (GB202107576D0) was filed in 2021. A European patent application ((opens in a new window)EP4348652A1), US patent application ((opens in a new window)US20240274226A1) and WIPO patent application were filed in 2022 ((opens in a new window)WO2022248728A1). 

(opens in a new window)Tackling Tuberculosis (Science Advances, 2023)

In collaboration with Boston University and Altius Institute, SBI researchers applied cSTAR to identify small molecule therapies for tuberculosis (TB). Their work revealed immune cell states that either resist or succumb to Mycobacterium tuberculosis. By identifying compounds that shift TB-susceptible cells to resistant states, they demonstrated the potential for host-directed therapies, as highlighted in their Science Advances publication. Prof. Kholodenko, lead researcher, noted, “This novel approach delivers new targets and therapeutics to empower the immune system against TB infection.”

(opens in a new window)Advancing Vascular Research (Science Advances, 2025)

Working with Yale School of Medicine, SBI researchers explored the role of cSTAR in helping to understand vascular biology, focusing on fluid shear stress (FSS) and its effects on endothelial cells (ECs). cSTAR identified three axes of endothelial states—stability, inward remodeling, and outward remodeling—each driven by distinct FSS patterns. Low FSS triggers inflammation and vessel narrowing, while high FSS induces vessel expansion. cSTAR pinpointed the role of cyclin-dependent kinases (CDKs) in stabilising vessels under normal FSS, offering new therapeutic targets for vascular diseases.

Going Forward

Through the Precision Oncology Ireland network, SBI researchers are linking in with clinicians, patient samples and a wide network of expertise. The cSTAR platform is being applied to cancer research with the goal of creating digital twins—computational replicas of patients’ cellular environments—to predict how patients will respond to specific drug interventions. The ultimate aim is to improve treatment outcomes and minimise side effects.

A Universal Tool for Biomedical Innovation

Since 2009, SBI researchers have published over 600 papers and identified therapeutic targets for cancers such as breast cancer, melanoma, and neuroblastoma. cSTAR builds on this legacy, integrating omics data to decode complex cellular behaviours. Its applications span from cancer to infectious and vascular diseases, making it a transformative platform for precision medicine.

“cSTAR is just the beginning,” says the SBI Director, Prof Kolch. “The ability to control cell states reliably and precisely opens doors to treatments we could only imagine before—halting disease progression, accelerating healing, and even creating personalised cures.”

With ongoing research, SBI aims to refine cSTAR to tackle some of humanity’s most pressing health challenges, ensuring a future where cellular behaviour is not just understood but purposefully directed.