Washington University School of Medicine
Dr. Schwarz is a graduate of the MSTP training program here at Washington University where she worked with former BIRCWH mentor Dr. Helen Piwnica-Worms on cell cycle proteins and their roles in cancer. Dr. Schwarz completed her fellowship training in Radiation Oncology and joined the faculty as an Assistant Professor. For her BIRCWH studies, she focused on novel imaging modalities targeting the premetastic niche in cervical cancer. These studies are performed in a clinically relevant model of human cervical cancer in the mouse. In this model, bioluminescent tumors can be monitored non-invasively by bioluminescence, microPET and microMRI. Dr. Schwarz is using this model to explore new therapeutic strategies, including biologics, in the treatment of cervical cancer. She is Principal Investigator on an RO1 to optimize radiation therapy in cervical tumors by manipulating glucose metabolism of the tumors.
BIRCWH Scholar from 07/01/2009 until 06/30/2014
Imaging sites of metastasis before they happen: Targeting the premetastatic niche
Metastasis is a complex biologic process that allows tumor cells to escape the primary site, invade the circulation and establish new tumors at distant sites. Recent work has established a role for bone marrow-derived hematopoietic progenitor cells (HPCs) in this process. HPCs that express VEGFR1 and the integrin α4β1 arrive at sites of metastasis and form a receptive environment for tumor cells known as the premetastatic niche. In this proposal, we target α4β1 as an in vivo biomarker of the premetastatic niche using a high affinity ligand labeled with 64Cu (T1/2 = 12.7 h; β+ (17.8%)) for imaging with positron emission tomography (PET). 64Cu-CB-TE2A-LLP2A will be evaluated for its affinity to α4β1 in an isolated integrin binding assay, its specific internalization and binding affinity to tumor cells and bone marrow-derived cells, and its ability to image sites of metastasis in mouse tumor models.
Hypothesis: Targeting α4β1 with 64Cu-CB-TE2A-LLP2A is an in vivo biomarker for hematopoietic progenitor cells (HPCs) implicated in the early formation of metastasis.
- To evaluate 64Cu-CB-TE2A-LLP2A for its affinity and specificity to α4β1 in an isolated integrin binding assay.
- To evaluate 64Cu-CB-TE2A-LLP2A for its affinity to tumor cells and bone-marrow derived HPCs implicated in premetastatic niche.
- To validate the presence of HPCs and upregulation of α4β1 in mouse tumor models of metastasis.
- To visualize changes in the pattern of metastatic disease using circulating factors from primary tumor cells