Our Researchers

The Anne Stirba Cancer Foundation supports the research of husband and wife team Dr. Alana Welm and Dr. Brian Welm.

Alana L. Welm, Ph.D.

Assistant Professor, Department of Oncological Sciences

Alana Welm, Ph.D., is an investigator at Huntsman Cancer Institute, an assistant professor in the Department of Oncological Sciences at the University of Utah, and a member of the Cell Response and Regulation Program. Alana Welm’s laboratory at Huntsman Cancer Institute studies breast cancer and metastasis.

Death from breast cancer is largely attributed to metastasis—when the disease spreads to other tissues. In order to metastasize, cancer cells must be able to invade the local tissue; escape from the primary site; enter into and survive in the bloodstream or lymphatic system; pass from the blood vessels into other organs; and adapt to or modify the new site to create a new tumor. The molecular mechanisms that facilitate these steps are largely unknown and are the focus of Alana Welm’s research. Her lab has developed new in vitro and in vivo approaches to better understand breast cancer and metastasis. Using 3D culture techniques and a new model system, they discovered that macrophage stimulating protein (MSP) is an important facilitator of breast cancer metastasis in mice and in humans. Current projects include studying the mechanisms that lead MSP to promote the escape of cancer cells from the primary tumor, and exploring the mechanisms by which MSP induces metastasis to bone. The lab also works to develop better models for preclinical breast cancer drug testing.

Alana Welm received her BS from the University of Montana in 1996 and her Ph.D. from Baylor College of Medicine in 2000. She then carried out postdoctoral studies in J. Michael Bishop’s lab at the University of California, San Francisco, which were funded in part by the Susan G. Komen Breast Cancer Foundation. She joined Huntsman Cancer Institute in January 2007.

Last Modified: Wednesday, August 5, 2009

See http://www.huntsmancancer.org/research/bios/welm_a.jsp

 

Bryan Welm, Ph.D.

Positions: Assistant Professor, Department of Surgery

Adjunct Assistant Professor, Oncological Sciences

Research Description:

Research in my laboratory is focused on understanding both the normal processes regulating cell fate determination in the breast, and the relationship between cellular differentiation and cancer. Based on the regenerative capacity of enriched cell populations, it is clear that in breast cancer a cellular hierarchy exists. Studies using FACS sorted tumor cells have shown that a limited cell population, distinguished by the expression of the cell surface proteins CD44 and CD24, contains the full regenerative potential of the tumor and can reproduce its cellular heterogeneity upon transplantation. These data suggest that tumors are derived from a multi-potential tumor-initiating cell, or cancer stem cell, that controls the growth and cellular homeostasis of the cancer.

Breast cancer can be categorized into distinct subtypes based on the pattern of genes expressed by the tumor. These gene expression signatures correlate with clinical outcome and provide insight into the complex molecular pathways driving the disease. The question remains whether specific molecular pathways establish the subtype or whether different cell types within the mammary hierarchy become transformed and give rise to each tumor subtype. These questions are difficult to address using existing models of breast cancer since cell lines may not retain the same cell population as the original tumor, and transgenic mouse models of breast cancer utilize promoters that are preferentially expressed in more differentiated cells. Therefore, my laboratory is developing new model systems that more appropriately mimic the cellular heterogeneity observed in breast cancer. Using these breast cancer models we are performing the following projects:

Determination of the cellular origin of breast cancer

Breast cancer is a disease with significant diversity in histology, cellular composition and clinical outcome. This diversity may result from either specific genetic mutations or transformation of different cell populations. We are performing experiments to determine whether oncogenes targeted to different mammary epithelial cells can affect the cellular composition and pathology of tumors.

Chemical library screen to identify cancer-subtype-specific therapeutics

The heterogeneous nature of breast cancer may reflect both its cellular origin and activation of specific signaling pathways. The complex etiology of breast cancer is not appropriately reproduced with established cell lines, making them of limited use in drug discovery screens. Therefore, we are developing a chemical library screen using primary tumor cells that embody the diversity of the signaling pathways activated, and the cellular variation of the original tumor. Primary tumor cells, representing both basal and luminal cancer subtypes, have been generated using an oncogene-induced mouse model of breast cancer. Tumor cells are pre-screened by both gene expression profiling and histology to identify the cancer subtype that they represent. The tumor cells representing specific subtypes are grown as 3D organoids within a laminin-rich extracellular matrix and screened using different chemical libraries. We anticipate that this screening process should increase the number of lead compounds that succeed in validation studies due to the close relationship between the cells in the assay and the originating tumor.

Research Keywords:

Stem Cells, breast cancer, chemical genetics, mammary, mouse models, differentiation

See http://medicine.utah.edu/oncsci/faculty/bwelm.htm