Peipei Zhu’s research focuses on the role of neutrophils, a group of cells that comprise more than 60% of the pool of white blood cells that repair the body from infection and help heal tissue.
Zhu discovered that the pool of circulating neutrophils in the bloodstream becomes heterogeneous in inflammatory diseases, including cancer and cardiovascular diseases. In addition to “normal” neutrophils, a new type of neutrophil called NeP (Neutrophil Progenitor) appears only in tumor-bearing mice and melanoma patients — and can serve as a possible early-stage marker for melanoma.
Zhu’s work identified NeP as the earliest neutrophil progenitor cell. It resides in the bone marrow of healthy mice and humans to produce and maintain a daily supply of neutrophils. However, in incidences of cancer, NeP flow from the bone marrow to the tumor site, where it promotes tumor growth.
Conversely, “normal” neutrophils, which are produced by NePs at steady state, were found to suppress tumor growth. So, targeting NePs offers a new avenue for immunotherapy for cancer, an area of treatment that, so far, has mostly focused on T lymphocytes. Drugs that target NePs, and therefore neutrophils, could also help with neutrophil-related diseases, like neutropenia, leukemia, Kawasaki Disease or cardiovascular diseases.
Zhu’s current research includes characterizing the specific groups of neutrophils and NePs that promote immune functions for or against tumors. She also works to identify the key regulators of these functions via cutting-edge immune-profiling and epigenetic approaches; and she uses different mechanisms to improve the capacity of cells to kill tumors.
The research in Zhu lab also uses novel next-generation sequencing technologies and approaches to track the fate of neutrophils in heath and inflammatory diseases – all with the aim of identifying biomarkers and new cellular and molecular targets to improve treatments.
Beyond cancer immunology, Zhu has also studied the role of an enzyme known as AMPK in helping trigger anti-inflammatory behavior in a different kind of innate immune cells, macrophages. AMPK is present in all cells in the body and is thought to play a role in treating diseases such as obesity, type 2 diabetes and cardiovascular disease.
Macrophages can become highly specialized to help with specific types of inflammation in the body, and in some cases can worsen the inflammation. Zhu and colleagues showed that the AMPK enzyme is needed to control the way macrophages respond — a key step in the progression of many diseases.