Advancing Liver Research: Insights from the UCLA Liver Institute and Beyond

The UCLA Liver Institute is at the forefront of research into liver diseases, transplantation, and innovative therapies. This article explores some of the groundbreaking work being conducted by UCLA researchers, along with contributions from the California Liver Research Institute, highlighting their commitment to advancing treatment and management of liver diseases.

Liver Transplantation: A Multidisciplinary Endeavor

The development of a successful liver transplantation program demands a multidisciplinary approach, typically found in large tertiary referral medical centers. UCLA's liver transplant program exemplifies this, requiring a special commitment from various medical, nursing, and administrative divisions, as well as the blood bank, social services, operating room personnel, and intensive care unit facilities. Preparation involves comprehensive training for all team members, both in animal laboratories and established liver transplant centers. In its early stages, UCLA's program demonstrated promising results, with 62 transplants performed in 50 patients during the first two years, achieving an overall survival rate of 72 percent and no operative deaths.

Addressing the Organ Shortage: Enhancing Liver Protection

One of the most significant challenges in organ transplantation is the nationwide shortage of donor livers, leading to high patient mortality. Researchers at UCLA are actively investigating methods to expand the donor pool by using molecular therapies to strengthen the liver's protective pathways. Hepatic ischemia-reperfusion injury (IRI), which occurs when a liver's blood supply is interrupted and then restored during transplantation, is a major cause of donor liver loss or failure. Recent research has identified proteins like CEACAM1 and Human Antigen R (HuR) that act as protective switches, preventing damage from IRI. By understanding how these proteins function, researchers aim to develop treatments that keep more donor livers healthy and suitable for transplantation. The next step involves testing whether these protective switches can be activated in human livers before transplantation.

Spotlights on Cutting-Edge Research

Unveiling Endothelial Resilience: The Role of Laminar Blood Flow

Laminar blood flow is known to promote endothelial resilience, but the specific signaling mechanisms behind this protection have been unclear. A study published in the Journal of Clinical Investigation (JCI) sheds light on a signaling mechanism in endothelial cells that protects against inflammation. Researchers discovered that laminar flow-induced endothelial cell body elongation establishes polarized mechanosensitive signaling domains. These domains facilitate focal calcium entry via TRPV4 channels to produce nitric oxide. Silencing domain activity results in spontaneous inflammation, while activating TRPV4 channels limits inflammation during exposure to an inflammatory agonist. This discovery has therapeutic potential for protecting against or treating vascular diseases.

Heart Arrhythmias: The Role of Fibroblasts

A new study published in Science reveals that heart arrhythmias are promoted by fibroblasts, scar-forming cells found in scar tissues of the injured heart. The researchers identified new mechanisms of fibroblast-myocyte communication, which have clinical implications and may be applicable to the treatment of the nervous system.

Liver-Heart Communication: The Impact of Coagulation Factor XI

Another study published in Science highlights the communication between the liver and heart, focusing on a liver-derived protein, coagulation factor XI (FXI), and its role in heart injury. These findings contribute to a better understanding of the complex interactions between these vital organs.

Mapping the Cardiac Autonomic Nervous System

Researchers at UCLA are creating a comprehensive atlas of how the cardiac autonomic nervous system controls the heartbeat. This multiscale approach provides valuable insights into the intricacies of cardiac function.

Vascular Calcification: Modifying Calcification and Outcomes

While vascular calcification is associated with a higher risk of cardiac events, the impact of modifying calcification on outcomes remains unclear. Further research is needed to determine whether interventions targeting calcification can improve patient outcomes.

UCLA Health Jonsson Comprehensive Cancer Center: Advancements in Cancer Research

The UCLA Health Jonsson Comprehensive Cancer Center is dedicated to advancing cancer research and treatments. Recent presentations at the American Association for Cancer Research (AACR) Annual Meeting showcased innovative studies in areas such as immunotherapy, organoid models, epigenetic markers, and drug resistance.

Overcoming Drug Resistance in Liver Cancer

Research presented at the AACR Annual Meeting focused on lenvatinib resistance in liver cancer and potential combination therapies to enhance its efficacy. The study identified specific drug combinations, such as SOS1 inhibitors and anti-apoptosis targeting agents, that showed promise in overcoming resistance and improving treatment outcomes for patients with advanced liver cancer.

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Personalized Treatment for Head and Neck Cancer

A high-throughput organoid-based drug screening platform has been developed to evaluate the combined effects of radiotherapy and targeted therapies on head and neck squamous cell carcinoma (HNSCC). This platform successfully identified therapeutic strategies that enhance radiosensitivity and reduce tumor invasion, with the goal of improving personalized treatment outcomes for patients with advanced HNSCC.

Enhancing Cancer Detection and Monitoring with Liquid Biopsies

A highly sensitive blood test, cfTrack-methyl, has been developed to detect minimal residual disease in patients with cancer. By combining a patient’s unique tumor methylation signatures with data from other cancer patients, this approach enhances accuracy, even in individuals with complex conditions like cirrhosis or hepatitis B.

Novel Approaches to Pancreatic Cancer Treatment

A promising new approach to treating pancreatic cancer combines JD006, a novel biguanide analogue, with CDK inhibitors. Early work shows that this combination significantly reduces cell proliferation and disrupts key molecular pathways.

Epigenetic Age as a Biomarker for Breast Cancer

Research has found that accelerated epigenetic aging, a DNA-based marker of aging, is linked to a higher risk of developing breast cancer, particularly in postmenopausal women. Measuring epigenetic age in blood could help identify high-risk individuals and guide breast cancer prevention strategies.

Thermal Ablation and NK-Cell Based Immunotherapy

Thermal ablation with NK-cell based immunotherapy may improve HCC outcomes. While thermal ablation currently provides excellent outcomes for early-stage hepatocellular carcinoma (HCC), a new study indicates that applying nonlethal hyperthermia may also improve natural killer (NK) cell cytotoxicity and effect better outcomes for multiple HCC cell lines.

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NK Cell Infusion Enhances Tumor Control

NK Cell Infusion Enhances Tumor Control after Ablation-associated Sub-lethal Hyperthermia in vitro and in vivo: Implications of MHC-I shedding.

Augmenting Microwave Ablation with Supercharged NK cells

The RSNA Research Scholar grant "Augmenting Microwave Ablation with Supercharged NK cells in an Oncopig Liver Tumor Model" was just awarded!

California Liver Research Institute: Commitment to Diversity and Research

The California Liver Research Institute is a non-profit organization dedicated to the advancement of treatment and management of liver diseases. They are committed to supporting diversity in their organization and providing care for all communities. Dr. Mena, the Medical Director of Pasadena Liver Center, serves as the Principal Investigator on all studies and has over 20 years of experience in liver disease research and management.

Supporting Research and Free Services

The California Liver Research Institute relies on donations to continue offering free services to the population and further research on all aspects of liver disease.

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