Viruses circulate quietly in animal reservoirs for years, but once they pass the human barrier, they often undergo dramatic antigenic changes that make their behavior almost unpredictable. For decades, immunology and infectious-disease research heavily relied on animal models to predict how the human body will respond to viral infection. These systems have been invaluable for studying fundamental biological questions, but they frequently fall short in capturing the complexity and heterogeneity of human immune responses.
A recent Nature article argues that it’s time to fundamentally rethink this dependence and urges the global scientific community to embrace “novel alternative methods” that more accurately reflect human biology and human disease. As a physician-scientist, I see this shift as essential step for the future of human medicine. Through my work I’m creating the tools that will make it possible. The focus of my work is to develop models that reflect real human immunity and enable the recapitulation of the human immune system directly “in the dish”.
Recent advances in human stem-cell biology, multiomics, and spatial analysis have made it possible to recreate key components of human immunity ex vivo with remarkable fidelity. In our lab we’re contributing to this transformation by developing primary human systems that model immune responses to viral infections. Using cord-blood–derived hematopoietic progenitors, we can reproducibly differentiate almost every myeloid immune cell including antigen-presenting cells that are encountering viruses. These cells form the first line of defense against viral pathogens in the lung or in the skin. By modulating virus-human interactions ex vivo, we can monitor infection dynamics, immune responses to antiviral therapies, and cell to-cell communication with high precision.
“My career has been shaped by a simple idea: to truly understand viral diseases that affect millions of people, we must study their behavior in human systems. Helping millions of lives starts with answering biology’s hardest questions and for that we need to have reliable tools in our hands.” - Dr. Victoria Zyulina, MD PhD, Assistant Professor directing this research effort.
Two viruses where this approach has been particularly revealing are Chikungunya (CHIKV) and Dengue mosquito-borne pathogens whose global case numbers continue to rise. Although several vaccines have been developed and more vaccine candidates for CHIKV are in progress of becoming available to broader population, their performance and serotype-specific efficacy require deeper investigation. The importance of this CHIKV research grew in August 2025, when New York State reported its first-ever locally acquired case of CHIKV, the first U.S. case of local transmission since 2019. A key part of our Chikungunya research focuses on how macrophages shape disease outcomes. As PhD candidate Jeury Veloz explains:
“After an infected mosquito bite, the virus spreads through skin immune cells and shows a strong tropism for joint tissues, where it can persist in macrophages in the joints and drive long-lasting inflammation. My project focuses on different macrophage subsets that continue to fuel inflammatory responses even after the virus has been cleared from the blood.”
Dengue virus (DENV) presents a different set of challenges. With four antigenically distinct serotypes, DENV causes a spectrum of outcomes from mild fever to life-threatening hemorrhagic disease – and the early immune decisions that guide these trajectories remain poorly understood. Using human primary model systems, we can pinpoint how DENV-2 and DENV-4 differentially affect immune cells, revealing serotype-specific differences in replication dynamics, cytokine induction, and interferon signaling. These insights help explain why vaccines and therapeutics perform inconsistently across serotype-something traditional animal models have struggled to predict.
To address these gaps we established collaborations with colleagues at the Black Family Stem Cell Institute and the Department of Obstetrics and Gynecology at Mount Sinai, enabling access to cord-blood hematopoietic stem cells and allowing the generation of large numbers of physiologically relevant dendritic-cell subsets that mirror those first exposed to mosquito-borne viruses in human tissue cells that are nearly impossible to study directly in patients due to their absence or low frequency in peripheral blood. Working with these human-derived subsets allows me to model early infection events and microenvironmental cues that shape systemic immunity “in the dish”. Beyond investigating mosquito-born viruses, this progenitor-based platform offers broad utility for drug- and vaccine-testing. In collaboration with Kris White laboratory, we ran a pilot study for using this model for preclinical analysis of antiviral drug potency which showed us promising results for further comprehensive profiling of antiviral therapeutics. In the future we’re planning to integrate multi-omics technologies and dive deeper into identification of biomarkers of protective immunity and investigation of mechanisms underlying immune dysregulation and severe disease.
In many ways we are witnessing a paradigm shift. Understanding and modulating the immune system “in the dish” is no longer a distant vision - it is rapidly becoming the foundation upon which next-generation therapeutics, vaccines, and precision immunology will be built.
Dr. Victoria Zyulina, MD PhD is a physician-scientist and Assistant Professor at Department of Microbiology at the Icahn School of Medicine at Mount Sinai, where she leads immunology-focused R&D initiatives at the interface of innate immunity, antiviral responses, and human primary cell modeling. She has a proven track record of developing innovative ex vivo, progenitor-based dendritic-cell platforms and primary human phenotypic assays that enable early innate immune modulation, vaccine evaluation, and drug discovery applications. Dr. Zyulina’s background spans discovery research, translational immunology, and therapeutic mechanism-of-action studies, supported by over $150K in competitive funding and multiple peer-reviewed publications. Prior to Icahn School of Medicine Mount Sinai, she conducted postdoctoral research at the Hospital for Special Surgery, where she applied multi-omics approaches and in vivo models to dissect autoimmune inflammation in the context of autoimmunity. Her PhD work at the Medical University of Graz established her foundational expertise in hematopoietic stem cell biology, multiparameter flow cytometry, and molecular immunology, leading to the discovery of a novel miRNA regulating human stem cell fate. Awarded the prestigious Erwin Schrödinger and Austrian Marshall Plan Fellowships, she is known for high-impact scientific leadership, outstanding trainee development, and the ability to execute complex cross-functional collaborations.
Jeury Veloz is a microbiology PhD candidate at the Department of Microbiology at the Icahn School of Medicine at Mount Sinai. His research focuses on how alphaviruses leverage macrophage differentiation pathways to shape inflammatory responses and promote infection. Through this work, he aims to identify the mechanisms driving arthritic disease linked to persistent alphaviral infection. After completing his PhD, Jeury intends to pursue a research career in industry, contributing to the development of innovative immunotherapies and treatments for autoimmune and infectious diseases.