Health University of Utah
Salt Lake City, Utah
Professor, Department of Oncological Sciences Senior Director of Basic Science Ralph E. and Willia T. Main Presidential Endowed Chair in Cancer Research Huntsman Cancer Institute
Developing strategies to improve the efficacy of immunotherapy in metastatic breast cancer.
Breast cancers can evade the body’s immune system, resulting in tumor resistance to therapy leading to recurrence, or metastasis. Many researchers are focused on harnessing the power of the immune system to eliminate breast cancer. Through laboratory studies, Dr. Welm has found a promising novel target for immunotherapy called sfRON a truncated or short form of the RON receptor tyrosine kinase and a key mediator of breast cancer metastasis. It acts on the immune system not the tumor itself and allows the tumor cells to escape immune surveillance and metastasize. Blocking sfRON prevented metastasis in laboratory models by increasing the recruitment of tumor promoting immune cells in early metastatic lesions. The team is now deciphering the mechanism of sfRON action and hopes their findings lead to a novel strategy to prevent metastasis.
The immune system is comprised of several types of immune cells that perform different functions, both tumor promoting and tumor fighting. Dr. Welm and her colleagues are testing the hypothesis that sfRON plays an important role in suppressing anti-tumor immunity by interfering with immune cell differentiation and the production of “T-helper cells” that enhance host immunity. In laboratory experiments, the combination of currently available RON kinase inhibitors and immunotherapy agents shifted immune cell differentiation to more favorable T-helper cells. Dr. Welm has developed laboratory models that recapitulate the metastatic tumor environment for use in ongoing studies.
Dr. Welm and her colleagues will utilize their laboratory models to continue to decipher the role of sfRON in blocking T-helper cell differentiation. If these laboratory studies confirm sfRON’s role, they would provide support for the combination of existing clinical RON kinase inhibitors with immune checkpoint blockade as the right strategy to help boost T cell priming and differentiation to more favorable T-helper cell subsets. Based on her findings, Dr. Welm’s team will design future studies to translate this therapeutic approach into the clinic for treating metastatic breast cancer.
Alana Welm, PhD holds the Ralph E. and Willia T. Main Presidential Endowed Chair in Cancer Research and is Senior Director of Basic Science at the Huntsman Cancer Institute. In addition, she serves on the Clinical Trials Protocol Development Committee to ensure inclusion of strong scientific correlative endpoints in all investigator-initiated clinical trials. She is also the principal investigator of an NCI U54 PDX Development and Trial Centers (the only one focused on breast cancer) and chairs the Scientific Advisory Board for the PDX-Integrator Group at the European Molecular Biology Laboratory, European Bioinformatics Institute in the United Kingdom.
Dr. Welm received her undergraduate degree in Microbiology from the University of Montana and completed a PhD in Cell and Molecular Biology at Baylor College of Medicine under the supervision of Gretchen Darlington. She then went on to conduct postdoctoral training in J. Michael Bishop’s laboratory at the University of California, San Francisco, where her work focused on developing new models of breast cancer metastasis.
In 2007, Dr. Welm established a laboratory at the University of Utah’s Huntsman Cancer and was subsequently promoted to associate professor with tenure (2013) and to full professor (2019). Her research focuses on metastatic breast cancer, investigating mechanisms by which cancer cells transition from a period of latent disease to metastatic outgrowth, and how the immune system controls that process. She also develops and utilizes patient-derived tumor models to understand breast tumor evolution during metastasis, to identify new therapeutic vulnerabilities in metastatic tumors, and to personalize therapy for breast cancer patients using functional drug testing in their tumor models. Dr. Welm has generously made these models available to the breast cancer research community at large.
2022
The Delta Air Lines Award
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