The UAB O’Neal Comprehensive Cancer Center announced its latest O’Neal Invests grant awardees, of which two faculty from the Department of Pathology are included. O'Neal Invests funds UAB investigators initiating new cancer-related projects to do key preliminary work to enable competitive extramural applications.
Eason Hildreth, D.V.M., Ph.D., an assistant professor in the Division of Molecular and Cellular Pathology, is a pre-R01 recipient for his project, titled, “Evaluation of the role of PU.1 in clear cell renal cell carcinoma.”
Hildreth’s study targets renal cell carcinoma (RCC), an aggressive kidney cancer. Survival after a diagnosis of RCC is over 90% at 5 years, but declines to 10% once it spreads, or malignant growths are present. Up to 92% of RCC cases are clear cell (ccRCC). There is a high rate of treatment resistance in ccRCC, particularly to immunotherapy. ccRCC has the worse prognosis of all the RCC subtypes and is most likely to spread to bone. Bone metastasis from ccRCC is associated with a worse prognosis than metastasis to other organs, making the survival rate roughly half of that observed in patients without bone metastasis. PU.1 regulates osteoclasts, the function of cells that remove bone so new bone can be made. Osteoclast activity is distinctly increased in ccRCC bone metastasis, leading to bone loss, pain and fracture.
Hildreth and his research team will investigate how PU.1 drives tumor progression and evasion of the anti-tumor immune response. This could impact not only patients with primary tumors, but also those with bone metastasis.
Carlene Zindl, Ph.D., an assistant professor in the Division of Molecular and Cellular Pathology, is a pre-R01 recipient for her project, titled, “Dissecting Regional Epithelial and Immune Cell Heterogeneity in Colorectal Cancer.”
Zindl’s study focuses on investigating how anatomical location influences colorectal cancer development and immune cell responses. Colorectal tumors arising in different regions of the colon exhibit distinct clinical behaviors and outcomes, but the underlying mechanisms are still poorly understood. This project will determine whether regional epithelial identity programs influence both tumor transformation susceptibility and immune cell recruitment patterns in location-specific colorectal cancer.
The research team will characterize differences in tumor incidence, progression and immune microenvironments between proximal and distal colon tumors. This work has the potential to redefine colorectal cancer subtypes based on tissue context and cell of origin, ultimately informing precision therapies tailored to tumor location.
The O'Neal Invests program seeks to promote excellence in areas of basic, population and translational science research relevant to cancer. The program supports nascent, paradigm-shifting cancer research proposed by UAB faculty. These are novel ideas with considerable promise and potential impact in the field of cancer care; they are likely to lead extramural funding, as determined by a peer-reviewed panel of experts. Pre-R01 grants are for $160,000 distributed over two years.