Biology subjects

Waller, J.

Publications and source records attributed to Waller, J..

3 recordsLinked to original sources

bioRxiv2026

Distinct and cooperative roles of host and tumor Osteopontin in colorectal cancer liver metastasis

Osteopontin (OPN) is a secreted phosphoprotein implicated in colorectal cancer liver metastasis (CRCLM), yet the distinct spatial contributions of host-and tumor-derived OPN in driving this disease remain unclear. Using a 2 x 2 genetic knockout mouse model targeting OPN in host and tumor compartments, combined with spatial transcriptomics, we investigated compartment-specific OPN functions in CRCLM. Tumor-derived OPN promotes tumor proliferation through MEK/ERK signaling. Host OPN licenses monocyte-to-macrophage differentiation, while tumor OPN polarizes macrophages towards an M2-like state. Both host and tumor OPN suppress T cells in the tumor microenvironment, whereas loss of host OPN reveals an interferon-driven, anti-tumor niche. Translational studies using OPN-blockade immunotherapy in syngeneic and patient-derived xenograft mouse models reduced tumor burden and enhanced T cell infiltration. Together, these findings redefine the OPN-myeloid paradigm in CRC and nominate OPN as a potential therapeutic target.

immunology↗

bioRxiv2022

The Children's Brain Tumor Network (CBTN) - Accelerating Research in Pediatric Central Nervous System Tumors through Collaboration and Open Science

Pediatric brain tumors are the leading cause of cancer-related death in children in the United States and contribute a disproportionate number of potential years of life lost compared to adult cancers. Moreover, survivors frequently suffer long-term side effects, including secondary cancers. The Childrens Brain Tumor Network (CBTN) is a multi-institutional international clinical research consortium created to advance therapeutic development through the collection and rapid distribution of biospecimens and data via open-science research platforms for real-time access and use by the global research community. The CBTNs 32 member institutions utilize a shared regulatory governance architecture at the Childrens Hospital of Philadelphia to accelerate and maximize the use of biospecimens and data. As of August 2022, CBTN has enrolled over 4,700 subjects, over 1,500 parents, and collected over 65,000 biospecimen aliquots for research. Additionally, over 80 preclinical models have been developed from collected tumors. Multi-omic data for over 1,000 tumors and germline material is currently available with data generation for > 5,000 samples underway. To our knowledge, CBTN provides the largest open-access pediatric brain tumor multi-omic dataset annotated with longitudinal clinical and outcome data, imaging, associated biospecimens, child-parent genomic pedigrees, and in vivo and in vitro preclinical models. Empowered by NIH-supported platforms such as the Kids First Data Resource and the Childhood Cancer Data Initiative, the CBTN continues to expand the resources needed for scientists to accelerate translational impact for improved outcomes and quality of life for children with brain and spinal cord tumors.

cancer biology↗

bioRxiv2018

Is the blunderbuss a misleading visual metaphor for stasis and punctuated evolution?

I discuss the usefulness of the so-called \"blunderbuss pattern\" of phenotypic evolution as a visual metaphor for stasis and punctuated evolution that was originally put forward in Uyeda et al. (2011) in their highly influential paper \"The million-year wait for macroevolutionary bursts\". I argue the blunderbuss pattern is not surprising, and in some cases it is misleading. I review several publications that cite Uyeda et al. (2011) that seem to be confused about the meaning of the pattern and what it implies. I do not critique the original analysis within Uyeda et al (2011), but show the blunderbuss pattern itself would be produced even when assuming a Brownian motion (completely gradual) model of phenotypic divergence. Finally, I discuss how the interesting results of the paper have been overlooked in favor of the surprisingly powerful, but also misleading visual metaphor of the blunderbuss.

evolutionary biology↗