Periodic Reporting for period 4 - deFIBER (Dissecting the cellular and molecular dynamics of bone marrow fibrosis for improved diagnostics and treatment)
Reporting period: 2022-07-01 to 2023-12-31
Fibrosis represents the culmination of persistent inflammatory responses triggered by various factors such as ongoing infections, autoimmune reactions, chemical exposure, radiation, tissue damage, and notably, cancer. It often leads to significant impairment of organ function, or in the case of bone marrow, compromised blood production, posing a significant threat to life. Once established, fibrosis is irreversible, underscoring the importance of halting its progression at an early stage.
Myelofibrosis (MF) exemplifies an incurable blood cancer characterized by progressive bone marrow fibrosis. The evolution of MF from an initial pre-fibrotic phase to full-fledged fibrosis suggests a gradual process, yet the precise changes in the early phase remain poorly understood, lacking specific diagnostic markers. Notably, there are no targeted anti-fibrotic therapies tailored for blood cancers. Allogeneic stem cell transplant (ASCT) stands as a potentially curative option, albeit high-risk and often inaccessible to the majority of patients, with unpredictable outcomes.
Our project has taken significant strides toward enhancing both the diagnosis and treatment of fibrosis related to blood cancer, culminating in the initiation of a proof-of-concept clinical trial. Through our research, we've made pivotal advancements in understanding the underlying mechanisms driving fibrosis, identifying crucial biomarkers, and pinpointing therapeutic targets. Our efforts have paved the way for more effective diagnostic methods and promising therapeutic interventions tailored specifically for fibrosis associated with blood cancer. This milestone of commencing a proof-of-concept clinical trial underscores the tangible progress we've achieved in translating our findings into actionable solutions for patients.
Myelofibrosis (MF) exemplifies an incurable blood cancer characterized by progressive bone marrow fibrosis. The evolution of MF from an initial pre-fibrotic phase to full-fledged fibrosis suggests a gradual process, yet the precise changes in the early phase remain poorly understood, lacking specific diagnostic markers. Notably, there are no targeted anti-fibrotic therapies tailored for blood cancers. Allogeneic stem cell transplant (ASCT) stands as a potentially curative option, albeit high-risk and often inaccessible to the majority of patients, with unpredictable outcomes.
Our project has taken significant strides toward enhancing both the diagnosis and treatment of fibrosis related to blood cancer, culminating in the initiation of a proof-of-concept clinical trial. Through our research, we've made pivotal advancements in understanding the underlying mechanisms driving fibrosis, identifying crucial biomarkers, and pinpointing therapeutic targets. Our efforts have paved the way for more effective diagnostic methods and promising therapeutic interventions tailored specifically for fibrosis associated with blood cancer. This milestone of commencing a proof-of-concept clinical trial underscores the tangible progress we've achieved in translating our findings into actionable solutions for patients.
Our team has leveraged cutting-edge methodologies to delve into the intricate molecular and cellular interplay between fibrosis-causing cells and malignant hematopoietic cells in MPN. Employing state-of-the-art techniques such as genetic fate tracing experiments, conditional genetic knockout mouse models, single-cell RNA sequencing, and CRISPR/Cas9 gene editing both in vivo and in vitro, we've made significant strides in unraveling this complexity.
Now, we're translating our findings into clinical relevance by analyzing patient samples and we have even initiated a clinical trial. Our overarching goal is to enhance early disease detection and, ultimately, pioneer novel targeted therapies with curative potential.
Now, we're translating our findings into clinical relevance by analyzing patient samples and we have even initiated a clinical trial. Our overarching goal is to enhance early disease detection and, ultimately, pioneer novel targeted therapies with curative potential.
The primary objective of my research is to swiftly translate our discoveries into the development of innovative targeted therapies tailored for the expansive and increasing population of patients grappling with fibrosis and organ dysfunction stemming from chronic blood cancer, or cancer more broadly. Through my ERC StG project "deFiber," I've achieved significant milestones that have profoundly shaped my career trajectory and fueled my dedication to conducting translational research aimed at benefiting patients directly.
One of the key accomplishments is securing intellectual property (IP) for a target identified via single-cell genomics. Subsequently, I successfully licensed this IP and forged a research agreement with a pharmaceutical company. This collaboration enables us to leverage our understanding of this druggable target to make a tangible impact on patient care, with the initiation of a clinical trial. Remarkably, we've transitioned from bench to bedside in under five years, underscoring the rapid translation of our research into real-world applications.
One of the key accomplishments is securing intellectual property (IP) for a target identified via single-cell genomics. Subsequently, I successfully licensed this IP and forged a research agreement with a pharmaceutical company. This collaboration enables us to leverage our understanding of this druggable target to make a tangible impact on patient care, with the initiation of a clinical trial. Remarkably, we've transitioned from bench to bedside in under five years, underscoring the rapid translation of our research into real-world applications.