Elisabeth Battinelli, M.D., Ph.D.
Since joining the Division of Hematology at Brigham and Women’s Hospital, I have focused on both research and clinical care with an expertise in platelet disorders. My clinical responsibilities are centered in Hemostasis and Thrombosis Clinic, which enables me to care for patients with clotting disorders and platelet abnormalities. My research focuses on how platelets differentially release angiogenesis regulatory proteins in the setting of malignancy. This work has immense implications for cancer as platelets play a central role in tumor growth and development of metastasis. By understanding the interaction of platelets and tumor cells, we can ultimately target the secretory mechanisms of the platelet to develop targeted cancer therapy. In addition we aim to understand how anti-platelet agents can disrupt the interaction of tumor cells and platelets ultimately for therapeutic benefit. Recently, I also expanded this research to investigate how factors released from platelets not only influence tumor growth but also “fuel the fire” by driving platelet production and regulate platelet protein content. This work demonstrates that in inflammatory states such as malignancy, factors released from platelets directly increase the production of platelets thereby amplifying their response within the tumor milieu.
Histological staining, highlighting splenic megakaryocytes from a mouse with triple negative breast cancer.
How Cancer Subverts Megakaryocytes to Alter Platelet Production and Content
We aim to determine how the presence of malignancy influences megakaryocytes within the bone marrow mileau. We believe that megakaryocytes in the setting of cancer are reprogrammed supporting not only increased platelet production leading to thrombocytosis but also upregulation of key proteins which are then packaged into platelets. In this way, megakaryocytes produce platelets that are not only more abundant but also manipulated to support tumor growth and metastasis formation.
Crosstalk Between Platelets and Tumor Cells
We aim to understand the molecular crosstalk that occurs between platelets and tumor cells to determine 1) how platelets become activated in response to tumor cells and 2) how interaction with platelets regulates the metastatic phenotype of tumor cells. Given the recent clinical trials establishing that anti-platelet agents such as aspirin can improve survival and decrease metastatic spread in cancer patients, we also aim to understand how anti-platelet therapies disrupt the platelet tumor cells interaction.
Confocal microscopy of platelets binding to a breast cancer cell
The Role of CCL5 in Breast Cancer-Driven Thrombocytosis
We have recently shown that platelet-derived CCL5 can regulate megakaryocyte maturation and platelet production. We now aim to explore the role of platelet-derived CCL5 in malignancy-driven thrombocytosis.
Immunofluorescence of human megakaryocytes containing CCL5 (green).
Differential staining of alpha granules within a megakaryocyte.
The Granular Organization of Pro-Angiogenic and Pro-metastatic Factors in Platelets
Early studies in our laboratory established that platelets differential package and secrete pro- and anti-angiogenic factors such that platelets can direct the angiogenic and metastatic response. We now aim to understand further how these factors are preferentially endocytosed by megakaryocytes and platelets.