BBT/BCB Seminar
“The Patient as Host: The Effects of Tissue Environmental Factors on Disease"
Dr. Risa Burr
Postdoctoral Researcher, Mass General Hospital Cancer Center
Thursday January 26th @ 12pm
Gateway 1002
Pizza will be served!
Abstract: The historical focus on cell-intrinsic genetic mechanisms for cancer development and progression has recently given way to a holistic appreciation of the tissue and patient as an active host within which the cancer develops, constantly interacting with environmental factors like the immune system. These environmental interactions change both the cancer and the environment, producing effects that can only be observed when considering the system as a whole. In this seminar, Dr. Burr will describe two vignettes exemplifying the value of considering the patient beyond the tumor, spanning tumor initiation and metastasis. In the first story, whole exome sequencing of tumor and normal lung tissue followed by lineage tracing discovered somatic mosaicism as a new mechanism to explain why some patients develop multiple primary lung tumors at once. This discovery has implications for how clinicians treat this complex disease. In the second story, a mouse model of metastatic prostate cancer was used to evaluate changes that occur in the cancer cell and metastatic microenvironmental fibroblasts as the cell transitions from dormant to outgrowing into a visible metastasis. One such change leads to upregulation of a paracrine signaling pathway in which prostaglandin E2 expression by the cancer cell induces prolactin expression by nearby fibroblasts, which binds to upregulated prolactin receptor on the cancer cell, ultimately resulting in proliferation of the metastatic cancer. Interruption of this signaling with an FDA-approved drug reduced metastasis in mice. Without consideration of the tumor environment, neither of these important findings would have been discovered. In the future, Dr. Burr will continue to study the role of the microenvironment in determining the outcome of colonization, focusing on cancer metastasis while bringing insights from conditions such as pregnancy and fungal infection.