Professor, Department of Biochemistry and Biophysics
Cancer Cell Biology
Area of Interest
I am a professor of biochemistry and biophysics and a member of the UNC Blood Research Center. My research aims at a better understanding of the signaling mechanisms regulating megakaryocyte (MK) and platelet function in health and disease. We use mouse genetics, cell biological, biochemical and biophysical approaches to identify signaling molecules/ pathways critical for MK and platelet function in health and disease. Our long-term goal is to devise new strategies to diagnose and treat people at risk for bleeding or thrombosis.
Several lines of investigation in my laboratory are of great relevance for cancer:
- Studies on small GTPase signaling: a main focus of our studies is on Rap1 small GTPase signaling in platelets and the interplay between Rap1 and other small GTPases. Various studies demonstrated a critical role of Rap1 signaling in carcinogenesis, metastasis, chemoresistance and immune evasion. This relevance to cancer is due to Rap1 expression in tumor cells or blood cells. Our work in platelets, and planned studies in T cells, may provide important new information on how to best interfere with Rap1 signaling in combating cancer.
- Studies on platelet number and function: another key area of research in my lab is focused on a better understanding of the molecular mechanisms underlying acquired platelet disorders, such as found in cancer. For example, cancer patients undergoing chemotherapy often require platelet transfusions to prevent bleeding. Also, certain cancers (such as pancreatic cancer) can lead to both thrombotic and bleeding complications. In collaborative work with Dr. Nigel Mackman, we have shown that tissue factor-positive microvesicles (MVs) derived from pancreatic cancer cells are powerful activators of platelets, and that this MV-platelet axis is relevant for the enhanced risk of thrombosis, at least in the mouse model. However, consistent with the clinical literature, we now find that chronic platelet activation in a murine pancreatic cancer model leads to platelet exhaustion and bleeding. In future studies we will investigate the mechanism(s) underlying this platelet dysfunction, and how to optimize platelet transfusions in situations of low platelet count or platelet dysfunction. We also collaborate with Drs. Flick and Wolberg, members of the Cancer Cell Biology Program at the LCC, on the interplay of platelets and the coagulation system, the latter also being dysregulated in various cancers.
- Studies on vascular integrity: our work also investigates how platelets secure vascular integrity in inflammation, with a particular focus on agonist receptor signaling and integrin-mediated adhesion processes. This work is highly relevant for cancer as it has been shown that low platelet count or inhibition of select platelet signaling pathways leads to intra-tumor hemorrhage and increased cytotoxic activity of anti-cancer drugs.
Awards and Honors
- Outstanding Investigator Award, National Heart, Lung and Blood Institute, NIH, 2019
- Chair of 9th Symposium of Hemostasis, Chapel Hill, North Carolina, April 2018
- Vice Chair of the Gordon Research Conference on the Cell Biology of Platelets and Megakaryocytes, 2017
- Associate Editor for the Journal of Thrombosis and Hemostasis
- American Heart Association, ATVB Special Recognition Award in Thrombosis, 2016
- American Association of Clinical Chemistry, 2015
- Outstanding Speaker Award, American Association of Clinical Chemistry, 2014
- Established Investigator Award, American Heart Association, 2014
- Investigator Recognition Award from the International Society on Thrombosis and Haemostasis, 16th Biennial Awards for Contributions to Hemostasis (BACH), 2013
News and Stories
UNC Lineberger and UNC researchers discuss latest research at American Society of Hematology Annual Meeting
UNC Lineberger researchers will present the latest findings from studies and lead educational sessions at the 64th American Society of Hematology Annual Meeting in New Orleans, Dec. 10-13.