Sergey Ovchinnikov uses phylogenetic inference, protein structure prediction/determination, protein design, deep learning, energy-based models, and differentiable programming to tackle evolutionary questions at environmental, organismal, genomic, structural, and molecular scales, with the aim of developing a unified model of protein evolution.
Ferroptosis is an iron-dependent form of cell death with profound implications in human health and disease. In the context of cancer, the use of ferroptosis inducers to target subpopulations of highly metastatic and therapy-resistant cancer cells has garnered much excitement over the last few years. However, to gain a comprehensive understanding of the full therapeutic potential of ferroptosis, our research focuses on (i) uncovering the molecular factors affecting ferroptosis susceptibility, (ii) studying its impact on the tumor microenvironment, and (iii) developing innovative ways to modulate ferroptosis resistance in vivo. We employ a multidisciplinary approach, combining functional genomics, metabolomics, bioengineering, and a range of in vitro and in vivo models to advance our understanding in this domain and to translate our findings into effective therapies.
We use the tiny, transparent jellyfish, Clytia hemisphaerica, to ask questions at the interface of nervous system evolution, development, regeneration, and function. Our foundation is in systems neuroscience, where we use genetic and optical techniques to examine how behavior arises from the activity of networks of neurons. Building from this work, we investigate how the Clytia nervous system is so robust, both to the constant integration of newborn neurons and following large-scale injury. Lastly, we use Clytia’s evolutionary position to study principles of nervous system evolution and make inferences about the ultimate origins of nervous systems.
Our bodies are tuned to detect and respond to cues from the outside world and from within through exquisite collaborations between cells. For example, the cells lining our airways communicate with sensory neurons in response to chemical and mechanical signals, and evoke key reflexes such as coughing. This cellular collaboration protects our airways from damage and stabilizes breathing, but can become dysregulated in disease. Despite their vital importance to human health, fundamental questions about how sensory transduction is accomplished at these sites remain unsolved. We use the mammalian airways as a model system to investigate how physiological insults are detected, encoded, and addressed at essential barrier tissues — with the ultimate goal of providing new ways to treat autonomic dysfunction.
We investigate crosstalk between CD8+ T cells and their environment at a molecular level, by dissecting the biological and metabolic programs engaged under conditions of stress. Using an array of approaches to model and perturb the local microenvironment, our research aims to reveal both the adaptive molecular changes as well as intrinsic vulnerabilities in T cells that arise within the tumor niche. Our goal is to understand how disease states remodel the fundamental mechanisms that regulate immune cell function and contribute to pathogenesis.
The immune system mounts destructive responses to protect the host from threats, including pathogens and tumors. However, a trade-off emerges: if immune responses cause too much damage, they can compromise host tissue function. Conversely, if they fail to generate sufficient damage, the host may succumb to a given threat. How is the optimal balance achieved? The Wong lab investigates how cells communicate with one another and their surrounding tissue environment to accurately control the magnitude of immune responses, both in time and space. To this end, we combine the tools of immunology with interdisciplinary methods—including high-resolution fluorescence microscopy, computational approaches, and gene manipulations—to resolve, model, and perturb the control of immune responses in intact tissues. Ultimately, we aim to understand how subtle shifts in control can lead to widely divergent host outcomes, including the successful elimination of threats, tolerance, autoimmunity, chronic infection, and cancer.
We study chromatin — the complex of DNA and proteins that make up our chromosomes. We aim to understand how post-translational modifications to these building-blocks, as well as the factors that regulate these events, play essential roles in maintaining the integrity of cells, tissues, and ultimately entire organisms. We implement a combination of functional genomics, biochemical, genetic, and epigenomic approaches to study how chromatin and epigenetic factors decode the chemical language of chromatin, and how these are dysregulated in diseases such as cancer.
To survive extreme environments, many animals have evolved the ability to profoundly decrease metabolic rate and body temperature and enter states of dormancy, such as torpor and hibernation. Our laboratory studies the mysteries of how animals and their cells initiate, regulate, and survive these adaptations. Specifically, we focus on investigating: 1) how the brain regulates torpor and hibernation, 2) how cells adapt to these states, and 3) whether inducing these states can slow down tissue damage, disease progression, and even aging. Our long-term goal is to explore potential applications of inducing similar states of “suspended animation” in humans.
By utilizing an innovative and intersectional approach, our lab main goal is to reveal fundamental immune-related pathways that modulate organ and tissue physiology. Our work will help to develop new strategies to tune these molecular pathways in health and disease, leading to the development of much-needed therapeutic approaches for human diseases.