Shen-Orr Lab – Systems Immunology & Precision Medicine

VISION

Understand the origins of immune system variation and leverage it for a new era of precision medicine.

The immune system is a sensory system, a sixth sense, whose role it is to sense the environment (external or internal) and respond to changes in that environment. Immunity is based on a diffuse system of interacting cells whose net output is greater than the sum of its parts and whose complexity is encoded by over a quarter of the human genome.
Research in the lab targets three directions:

Charting the Immune Landscape

How the immune system varies over time as a function of our environment, with a particular focus on aging. Our immune systems change a lot, influenced by a whole array of things. Change starts at a young age, based - predominately - on the genes we inherited. As we grow older, our life experiences and choices play a greater and greater role in shaping our immune system. These are all factors unique to each of us as individuals. We aim to identify and map the ‘rules of the game’ for how such environmental drivers act and the molecular mechanisms that drive our immune cells to transition between different states. Our primary focus in this regard is understanding how the healthy immune system changes over your lifespan (immune-aging), how these changes in state affect immune response and how they interact with disease.

Forwarding Immune Based Precision Medicine

From identifying immune diagnostics and therapeutic directions to understanding the logistical and cost structure needed to transform healthcare. We can now broadly measure multiple data types on each human blood sample: its immune cell composition; the communication of these cells with one another, and functional traits telling us how a person's immune cells respond to cytokine messages. These technologies give us tremendous power, making it possible to see how everybody’s immune system is a little different and how small differences in biological cell-circuitry ultimately yield real-world, clinical differences in health and disease. This allows us to develop diagnostics that capture the present status of your disease risk and defenses, based not only on your genetics but also on your life history. We focus on developing a clinically relevant metric of immune-aging (IMMAGE) and in understanding the relationship of tissue cellular circuitry to clinical responses.

Bridging Data-Insight Gap

Developing next generation analytical methodologies for grappling with the high complexity of biological and clinical data. We can now generate extremely rich molecular and phenotypic data (i.e. big/deep data) but we can interpret and understand only a few percent of it. Data growth is exponential whereas insight grows at a linear pace at best. In short, there is a data revolution, but we are not getting our bang for the buck from the data we are generating. We develop computational methods aimed at a non-linear increase in insight by tackling fundamental problems in data interpretation. In recent years our focus here has been on enabling the quantitative study of biological process dynamics, especially in the context of inter-cellular communication networks and in tackling the large translational gap that exists between humans and the models used to study humans such as mice.

Shai Shen-Orr PhD, Principal Investigator. Director Tech.AI.BioMed and Zimin Institute for AI Solutions in Healthcare. Chief Scientist, CytoReason

Background: Systems and Computational Biology, Informatics, Immunology

Why: I am fascinated by how evolution and development forces shape global and emergent properties exhibited by biological systems. Torn between a love of basic science and a commitment to bettering healthcare, I found synergy in Immunology.

How: Imagining a better future, reading between the lines, overcoming obstacles.

Contact: shenorr@technion.ac.il

Timothy J. Few-Cooper PhD, Senior Staff Scientist

Background: Molecular Genetics, Developmental Biology, Computational Biology

Why: A love of mentoring students and blurring the lines between scientific disciplines, and a long-held fascination with systems that change with time (i.e. evolution, aging, development, language etc.)

How: Leading and mentoring students. Fostering student development. Lab leadership, project management, infrastructure development.

Contact: timcooper@technion.ac.il

Neta Milman PhD, Senior Staff Scientist

Background: Biochemistry and Molecular biology, Immunology

Why: I am a believer in the synergism between experimental and computational biology, and that the two combined accelerate our understanding of human biological systems.

How: By developing experimental infrastructure that integrates with computational analysis. Lab leadership, project management and designing frameworks to study human biology in Israel.

Contact: neta.milman@technion.ac.il

Jonathan Sahar MSc, Staff Scientist

Background: Bioinformatics, Neuroscience

Why: In awe of the complexity that biological systems achieved through evolution, I seek to become more intimately acquainted with them through science - hoping to advance our knowledge of the immune system to benefit patients as a result.

How: Applying computational methods to multi-omics and high resolution, spatial-omics data.

Anastasia Brodov-Nevo MSc, Staff Scientist

Background: Stem Cell Biology, Immunology, Molecular Biology

Why: Keen to understand how immune aging affects the intricate interplay between various subsets of immune cells and how this shapes overall immune function and health.

How: By developing advanced experimental platforms and investigating the interactions taking place between immune components in the context of aging.

Zoya Davidov, Lab Administrative Assistant

Background: Economics, Accounting

Why: I believe that a positive mindset creates a positive environment.

How: Assisting with the day-to-day administrative operations in the lab. By working with a great group of people, every task is possible.

Yuval Klein MSc, Research Assistant

Background: Human Biology, Biochemistry & Molecular Biology

Why: I get a kick out of tackling biological problems and seeking answers. I love gaining knowledge and meeting new people.

How: Supporting multiple biological projects, where each of them is unique and requires a different set of skills and expertise.

Naama Mor, Research Assistant

Background: Biotechnology, Biology, Immunology

Why: I am passionate about biology, and immunology in particular. Finding answers to biological questions, learning new techniques, and investigating the immune system fascinates me.

How: Providing support for many areas of biological research using variety of high dimensional and high throughput single-cell assays.

Martin Lukačišin PhD, Postdoctoral Fellow (Aly Kaufman Fellow and Rubinstein Technion Integrated Cancer Center Fellow)

Background: Systems Biology, Cancer Biology, Yeast Genomics and Quantitative Biology.

Why: Never ceases to be amazed how lifeless molecules come together to form life. The immune system is a formidable use-case for methods tackling emergence.

How: Computational inference of i) cytokine signaling from multi-omic data, ii) immune memory formation and recall from single-cell data and iii) quantitative changes in central dogma components in immune cells during aging.

Erik Feldman MSc, MD/PhD Candidate (Israel Presidential Award for Excellence in Research, Impetus Longevity Award)

Background: Medicine

Why: Driven by the enormous potential of hypothesis-driven data analysis and the impact it could have on a patient's life and well-being.

How: Development of scalable assays to monitor immune aging in the clinic and its relevance to different clinical conditions, leveraging both molecular and real world data.

Ornit Nahman, Direct PhD Candidate (VATAT Data Science Scholar, Medicine Excellence Program)

Background: Electrical Engineering

Why: Keen to understand the dynamics that turn a healthy tissue into a sick one.

How: High resolution tissue modelling for spatial-omic methods and applications aimed at increasing our understanding of disease progression.

Benny Perets, Direct PhD Candidate (co-mentored with Prof. Shie Mannor)

Background: Electrical Engineering & Data Science

Why: Passionate about building advanced methods for solving difficult biological (and medical) questions.

How: Focusing on novel methods for fusing knowledge into machine- and deep-learning pipelines.

Merav Birk-Bachar MD, PhD Candidate

Background: Pediatrics (Physician at Schneider Children’s Medical Center)

Why: Passionate about understanding/cracking mechanisms of inflammation, to push forward truly tailored treatment for inflammatory diseases.

How: Utilizing computational and experimental biological models to explore the mechanisms of response/non-response to biologic agents in inflammatory diseases such as psoriasis.

Tslil Regev-Paska MD, PhD Candidate (co-mentored with Dr. Dan Eytan)

Background: Pediatric Physician and aspiring Intensive Care Clinician

Why: I am driven to understand why some kids get very sick from simple bugs, and how we can help them heal.

How: Combining clinical experience and passion with biological experimentation and computational analyses I focus on the maturation of the infant immune system and its relationship with viral respiratory diseases causing critical illness.

Yochay Tzur MSc, PhD Candidate

Background: Computer Science, Computer Vision/AI & Image Analysis

Why: Driven by the desire to employ my experience into new and meaningful domains, I returned from industry (Intel/IBM) to academy - replacing Computer Vision with Biology.

How: Computational methods for cross-species translation and the application of these to drug development.

Aviv Barak, Direct PhD candidate

Background: Molecular Biochemistry

Why: Driven by the idea that the key to mastering an understanding of the immune system is the combination of clinical, experimental, and computational approaches.

How: Focused on characterizing immune aging in the context of cellular functionality and metabolism with the hope of identifying modulators of aging and improving our prognostic capabilities.

Paul Kalnitz, PhD Candidate

Background: Computer Science, Bricks and Mortar Architecture, experience in the MTRL lab

Why: I glimpse at the miraculous mechanisms of evolution, and I'm inspired to reuse the code - applied to architecture.

How: Pursuing a PhD in the MTRL lab at the Technion, inventing evo-devo architectural algorithms which regulate 3D printed concrete forms.

Noa Shechter MSc, PhD Candidate

Background: Biotechnology Engineering, Bioinformatics

Why: I am driven to solve complex, multidisciplinary challenges using computational tools to address critical questions in medicine.

How: Studying immune aging from a computational perspective, across multiple tissues.

Natalie Mendelson, MD/PhD Candidate

Background: Biomedical Engineering, Medicine

Why: The intersection of computational and biological sciences is fascinating, and has exciting potential for clinical impact.

How: I plan to deepen my knowledge in both fields and learn how to connect the dots. While still refining the exact approach, I am eager to explore methods that integrate these areas meaningfully and innovatively.

Afnan Suleiman MSc, PhD Candidate

Background: Pharmacy, Drug Sciences, Immunology

Why: Motivated by a strong curiosity about immunology and a commitment to uncovering new insights, I strive to deepen our understanding of immune system mechanisms and their implications for immune aging.

How: Experimental and computational approaches to unravel mechanistic pathways in T cells that contribute to immune cell aging and identify potential strategies for intervention.

Kohav Tal-Porath, MSc Candidate

Background: Computer Science, Bioinformatics

Why: A passion for solving biological challenges from a computational view point.

How: Developing models and algorithms aimed at acquiring a better understanding of biological clocks and metrics of aging.

Nadav Golden, MSc Candidate

Background: Computational Biology

Why: Inspired by the potential to transform today's abundance of biological data into insights that make a meaningful impact on healthcare.

How: Applying immune aging signatures to cohort datasets to expand our understanding of the roles immune aging plays in diseases, treatments and clinically relevant outcomes.

Neta Nevo MD, PhD

Neta led efforts to discover and unravel new drivers of B-cell development in order to accelerate immune system recovery in patients post chemotherapy.

Mayan Briller, PhD

Mayan led our efforts to understand how an individual's immune-age determines how well they respond to a vaccine.

https://il.linkedin.com/in/mayanbriller

Shiran Vainberg, PhD

Shiran led our investigations into drug response/mechanisms of resistance in IBD, and developed disruption networks – a new method for sample level network analysis.

Ayelet Alpert MD, PhD

Ayelet led the development and discovery of immune-age, and built innovative new algorithms to compare developmental processes across multiple trajectories.