Targeting Neutrophil Functions as a Novel Model of Psoriasis Immunotherapy

Principal Investigator: Zvi Granot, Ph.D.
Institution: Hebrew University of Jerusalem

Grant Mechanism: Discovery Grant
Funding Amount: $75,000
Project Start Date: August 1, 2024
Project End Date: July 31, 2025
Status: Active
Keywords: Psoriasis, Drug Therapy, Inflammation

Project Summary:

Neutrophils, the predominant white blood cell population in circulation, play a crucial role in psoriasis by being extensively recruited to psoriatic plaques where they release detrimental components, exacerbating symptoms. This highlights the potential of blocking specific neutrophil components as a therapeutic strategy for psoriasis. Our proposal advocates for the utilization of precision nanomedicine to investigate how inhibiting the production of these harmful mediators in neutrophils impacts the initiation and progression of psoriasis. The successful completion of this research holds the promise of introducing a novel approach to neutrophil-based immunotherapy that would benefit a diverse spectrum of patients suffering from psoriasis.

How will your project help improve the lives of the 125 million affected by psoriatic disease?

Neutrophils play a crucial role in inflammatory processes and have been implicated in both the initiation and maintenance of psoriasis. This underscores the potential of neutrophils as a therapeutic target for psoriasis. We have developed a nanoparticle-based drug delivery platform specifically tailored for neutrophils, applicable to both mouse and human cells. This novel platform allows precise modification of neutrophil function, offering a novel avenue for immunotherapy in psoriasis patients. Unlike conventional approaches, this unexplored therapeutic strategy targets specific neutrophil functions without inducing systemic immune suppression, making it particularly promising for psoriasis patients who may not respond to other therapies.

Researcher Profile:

Zvi Granot, Ph.D.
Professor, Dept. of Developmental Biology and Cancer Research, Faculty of Medicine, Hebrew University
Born in Ramat-Gan, Israel, I did my B.Sc. in biology at the Hebrew University. I then completed my M.Sc. and Ph.D. under the supervision of Prof. Joseph Orly from the department of biochemistry at the Hebrew University focusing on protein degradation in the mitochondria. I then spent two years as a postdoctoral fellow studying pancreatic beta-cell function in Prof. Yuval Dor’s lab in the faculty of medicine at the Hebrew University. In 2007, I started a postdoctoral fellowship in Dr. Robert Benezra’s lab at Memorial Sloan-Kettering Cancer Center, New York, USA. I joined the faculty of medicine as an assistant professor in August of 2012 and was appointed as an associate professor in 2019.
My research focus is neutrophils which are the most abundant white blood cell in the circulation. They are the first line of defense against microbial infections and play a key role in inflammation. In recent years, we have studied neutrophil function in health and disease and identified various neutrophil populations. These observations challenged the traditional notion that neutrophils are a homogenous population of cells and opened new avenues of research and novel diagnostic and therapeutic opportunities. With this realization, we have developed a platform for neutrophil specific drug delivery which allows the manipulation of neutrophil function in vivo. My research interests include gaining further insight into neutrophil heterogeneity, understanding of neutrophil contribution in various clinical scenarios and the utilization of our neutrophil specific drug delivery platform for the development of novel immunotherapeutic strategies.
I was invited to present our work in several prestigious scientific meetings and have authored or co-authored 63 original articles and reviews.