Page 30 - Rappaport Institute Magazine 2024

IMMUNOLOGY
Shai Shen-Orr, PhD Associate Professor of Immunology
PhD, 2007 – Harvard University, MA, USA
Systems Immunology and Precision Medicine
My current research interests are focused on systems immunology. The immune system is highly complex and at constant interplay with the environment. At present we have only a basic understanding on how its many different components join to orchestrate protective immunity. My work covers three main themes: First, I study immune variation, from evolutionary drivers to translational implication in immune based precision medicine. Particularly in the context of aging, where we have developed a clinically meaningful metric of immune health. Second, developing computational methods geared at leveraging more from immune monitoring data. Last, coupling our computational approaches with the vast amount of public data allows to study immunity at a global scale and accelerates interpretation of omics-based data in immunology. From this I launched CytoReason, a PharmaAI company building a machine learning model of immunity and leveraging it for drug development in collaboration with pharma and biotech companies.
Selected Publications
ˆ Vainberg SG, Starosvetsky E, Gaujoux R, Blatt A, Maimon N, Gorelik Y, Pressman S, Alpert A, Bar-Yoseph, Dubovik T, Perets B, Katz A, Milman N, Chowers Y*, Shen-Orr SS*. A personalized network framework reveals predictive axis of anti-TNF response across diseases. Cell Rep Med. 2024 Jan 16;5(1):101300
ˆ Frishberg A, Milman N, Alpert A, Spitzer H, Asani B, Schiefelbein JB, Bakin E, Regev- Berman K, Priglinger SG, Schultze JL*, Theis* FJ, Shen-Orr SS*. Reconstructing disease dynamics for mechanistic insights and clinical benefit. Nat Communications. 2023 Oct 27;14(1):6840.
ˆ Alpert* A, Pickman* Y, Leipold M, Rosenberg-Hasson Y, Ji X, Gaujoux R, Rabani
H, Starosvetsky E, Kveler K, Schaffert S, Furman D, Caspi O, Rosenschein U, Khatri P, Dekker CL, Maecker HT, Davis M*, Shen-Orr SS *. A clinically meaningful metric of immune age derived from high-dimensional longitudinal monitoring. Nat Med. 2019 Mar;25(3):487-495 . News and Views in Nature Medicine
Grants and Awards
2020-2024 – Israeli Science Foundation Precision Medicine Award. “Understanding the relation of cellular and immuno- senescence in aging and their relevance to the dynamics and clinical outcomes of severe infections”, With Prof. Valery Krizhanovsky and Prof. Michal Paul
2021-2025 – Israeli Science Foundation, “High Resolution Spatial Functional Map of the Aging Gut”
2021-2026 – NIH (NIAID), P01 grant. “High resolution longitudinal immune monitoring for elucidating immune aging dynamics”. With Prof. Mark Davis
2023-2026 – Helmsley Charitable Trust, ‘Leveraging microbial-nutrition-immune interactions for personalized Crohn’s disease treatment’. With Prof. Yehuda Chowers, Hagai Bar-Yosef, Naama Geva-Zatorsky
Collaborators
Mark Davis, Stanford University John Tsang, Yale
Nir Hacohen, Broad Institute Felix Meissner, Bonn
Haggi Yosef, RHCC Valery Krizhanovsky
shenorr@technion.ac.il
Shai Shen Orr Lab
A trajectory of human immune aging is captured by the IMM-AGE score. Longitudinal tracking individuals we identified a conserved process of immune aging. By measuring 150 people annually for over nine years. Every point on the trajectory is a single human sample measured in blood for the composition of 18 immune cell types. All individuals advance
on this trajectory but at different rates, one’s position on the trajectory describes one’s immune-age or state and is a predictive factor to a variety of clinical outcomes in other tested cohorts.