06/10/2025
By Irma Silva

The Kennedy College of Sciences, Department of Biological Sciences, invites to you attend a Ph.D. Thesis Proposal Defense in Applied Biology by Michelle Downing entitled "Neutrophil Development and Their Role in Adaptive Immunity."

Candidate: Michelle Downing
Degree: Doctoral
Date: Tuesday, June 24
Time: 1 – 3 p.m.
Location: Cumnock Hall Trustees Room

Committee Members:

  • Peter Gaines, (Advisor) Professor, Chair, Biological Sciences, University of Massachusetts Lowell
  • Natalie Steinel, Associate Professor, Biological Sciences, University of Massachusetts Lowell
  • Rachel Melamed, Assistant Professor, Biological Sciences, University of Massachusetts Lowell
  • Chia Chi Sun, Principal Scientist, EMD Serono Research and Development Institute, Inc.

Title: Neutrophil Development and Their Role in Adaptive Immunity

Brief Abstract:
Autoimmune diseases affect approximately 10% of the global population with pathogenesis often intricately linked to both adaptive and innate immune systems, complicating drug discovery efforts aimed at treating these disorders. Neutrophils, as the predominant leukocytes in the body, are essential in innate immunity, executing critical functions such as NETosis, degranulation, and reactive oxygen species (ROS) production. However, these same functions have been implicated in the progression of autoimmune diseases and cancer, highlighting the need for more refined models to study neutrophil behavior in these diseases. Given the dual roles of neutrophils as both defenders against pathogens and potential contributors to autoimmune pathology, there is a need to develop effective in vitro models that accurately reflect their roles in both innate and adaptive immune responses. We propose utilizing ex vivo cultured bone marrow-derived CD34+ stem cells to generate large populations of neutrophils that more closely mimic peripheral blood neutrophils, the field standard for human studies. We will characterize these neutrophils through flow cytometry comparing their surface markers to those of peripheral blood neutrophils and assess effector functions such as ROS and NETosis. Additionally, we will establish a neutrophil/T cell co-culture system to evaluate the impact of neutrophils on T cell activation and differentiation, using various priming methods to assess cytokine production and T cell responses. This research aims to elucidate the immunogenic potential of neutrophils and their ability to influence adaptive immune responses. By developing a robust model of neutrophil differentiation and function, these studies will facilitate the identification of specific therapeutic targets that can mitigate disease pathogenesis in autoimmune conditions while preserving the innate immune functions of neutrophils. This approach could lead to novel therapeutic strategies that address the challenges associated with treating autoimmune diseases and cancer.