Seminar series speakers 2022 - 2023

The Ostuni Lab investigates how microenvironmental factors shape the diverse functions of innate immune cells in homeostasis and disease (Nat Immunol 2019). We defined genomic interplays in macrophages exposed to antagonistic immune signals (Nat Immunol 2017), and recently discovered a new mechanism of action of the immune modulatory lipid PGE2 (Immunity 2021); these findings have broad relevance for the treatment of infectious diseases or cancer, as well as for tissue regeneration. My group leveraged on the power of advanced single-cell genomics to dissect myeloid cell heterogeneity. Together with other experts, we first proposed (Nat Rev Immunol 2019) and then contributed to demonstrate (Cell 2020) that transcriptional and chromatin dynamics underlie tissue-specific adaptations of mouse neutrophils. We are now investigating diversification mechanisms of human neutrophils in clinically relevant settings of hematopoietic stem cell transplantation and cancer.

The Carmona Lab focuses on understanding how the immune system responds to cancer. We aim to define cancer-associated immune cell states, to identify the genetic programs that drive their differentiation, to reveal how immune cells are impacted by cancer immunotherapies and what is their role in immunotherapies resistance. Our vision is that improved cancer immunotherapies will derive from innovative systems biology approaches that can exploit the vast amounts of single-cell omics data that are being generated. We develop novel computational methods, conduct meta-analyses of public data and generate hypotheses that are tested by our experimental collaborators.

The Rao Lab's verarching goal is to determine how the cells of the ENS detect and integrate information to modulate autonomic behaviors, including gastrointestinal motility, intestinal epithelial functions, innate immune responses, and nutrient handling. We strive to learn fundamental principles about how the nervous, immune and endocrine systems interact with each to regulate organ function. We are also driven by the idea that learning how enteric circuits regulate autonomic behaviors will ultimately elucidate how ENS dysfunction contributes to human disease. In order to investigate the molecular mechanisms by which enteric neurons, glia and specialized epithelial cells in the gut transduce information and communicate with each other to modulate behaviors, we use mouse genetic models, imaging of live and fixed tissues, as well as a variety of in vivo and in vitro assays.

The Morrissey Lab uses synthetic biology, biochemical reconstitution and high resolution imaging to understand how macrophages measure and add different signals. We uncover the biochemical and biophysical principles that build robust, quantitative signaling networks in the macrophage. We think this information can be used to improve the design of immunotherapies. So far, we have focused on phagocytic signaling - designing a chimeric antigen receptor that triggers phagocytosis of cancer cells, and elucidating the mechanism of CD47 ‘Don’t Eat Me’ signaling. Most recently, we have used DNA origami to determine how nanoscale patterns of IgG affect phagocytosis. Long term, we are interested in applying our synthetic biology and imaging toolkit to other macrophage signaling pathways that are targeted in cancer immunotherapy.

The Neuro-Immune Regulome Unit (NIRU) aims to understand the mechanisms that precisely regulate gene expression in lymphoid cells through multidisciplinary genomic approaches. Lymphoid cells communicate the perturbation of homeostasis by production of cytokines, dysregulation of which results in neural and ocular inflammation in many disorders, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, uveitis, and age-related macular degeneration. Understanding the basic pathophysiology of cytokine production in these contexts – for example, their source and regulation – represents a promising path for the development of more specific and efficacious therapies. We now are focusing on two key biological questions 1) How do distinct stimuli regulate cytokines in a context-specific manner? 2) How cytokines contribute to the progression of neurodegeneration, such as Alzheimer’s disease and age-related macular degeneration? By analyzing lymphocyte regulomes with distinct genetic background in human and engineered mice, we aim to further our understanding of molecular mechanisms that contribute to aging and neurodegenerative diseases.

The Orzalli Lab aims to understand how non-hematopoietic cells contribute to antiviral immunity in human skin and how viruses modulate signaling pathways in these cell types to subvert the host immune response. We study a variety of viral pathogens, including herpes simplex virus 1 and vesicular stomatitis virus, to gain insight into common and unique strategies employed by the host to defend against distinct viruses.

In addition, our laboratory uses human skin equivalents (HSEs) to study cell-to-cell communication in human skin following viral infection and in response to inflammatory stimuli. HSEs are in vitro tissues that consist of a stratified squamous epithelium grown at an air-liquid interface on a collagen matrix populated with dermal fibroblasts. These tissues provide an in vivo-like system to study biologically meaningful crosstalk between the epidermis and dermis of human skin.

The Nabekura Lab focuses on the cellular and molecular mechanisms that potentiate memory formation in the innate immune system. This research involves studying the response of Natural Killer cells to viral infection through fate-mapping and functional genomics. Uncovering these fundamental mechanisms will inform new strategies for harnessing NK cell responses against viruses and cancer.

The Posey Lab focuses on the development of novel cancer therapies for humans and dogs that genetically alter cancer patients’ own T cells to improve the ability of the immune system to fight cancer. This research involves antigen discovery to identify tumor-specific targets, engineering strategies to surmount the tumor microenvironment, and altering the signaling influences of T cells to develop robust anti-tumor efficacy.

The Ballesteros Lab ("Imaging  and  Immune Response lab") at CNIC aims to understand the diversity of the innate immune system. This  heterogeneity is critical both for daily homeostatic function and may underlie many forms of disease however, the mechanisms underlying functional reprograming of myeloid cells in tissues remain poorly understood. Our goal is to develp new tools, approaches and concepts  to address unmet questions on the mechanisms of specification of  innate immune cells, neutrophils and microglia, in tissues. We aim to determine whether regional differences of microglia across the CNS regulate specific brain functions and contribute to the onset, development and treatment response of brain disease. In addition we aim to understand how the neutrophil lineage is organized both in health and inflammation and its consequence for disease outcome.”

The Acton Lab is focused on understanding the communication between different cell types of the immune system, specifically the mechanisms controlling cellular trafficking, multicellular organization and lymphoid organ architecture. The lymph node is a highly organized and tightly controlled environment. The dynamic nature of lymph node swelling and contraction is critical to all immune responses and is not well understood.  We want to understand the processes involved in lymph node swelling/expansion, and how the interplay between immune cells and non-haematopeotic stromal cells is key to this process. By studying lymph node-dynamics we can learn about the control of immune responses. In addition, the lymph node as an experimental model is hugely relevant to the interplay between immune cells and stroma in settings such as tumours. There are many parallels in the function of fibroblastic reticular cells (FRCs) of lymphoid tissues and tumour-associated fibroblasts. Taking lessons from the cell-cell interactions in the lymph node may provide novel avenues for tumour immunotherapy.

The Akkaya Lab is focused on defining the molecular mechanisms through which regulatory T cells mediated their suppressive functions. Autoimmune disorders and cancer are among leading causes of chronic disease and death in the US and worldwide. While Regulatory T cells (Tregs) are central to protecting body from autoimmunity, they can also promote tumor progression via restricting anti-tumor immune responses. These make Tregs an attractive, yet risky, target for treating both ends of the spectrum, therefore we need a thorough understanding of how they mediate their inhibitory functions. It is still largely unclear how Tregs function in the body, constituting a critical roadblock for designing new therapies that utilize or eliminate Tregs. I have recently uncovered the first antigen-specific mechanism of suppression, that is operated by the T cell antigen receptor (TCR) of Tregs. I demonstrated that Treg TCR removes peptide-bound major histocompatibility complex class II (pMHCII) from APC surface. Moving forward, I will uncover the molecular basis of antigen-specific suppression by deciphering the unique molecular events triggered by antigen recognition of Tregs but not helper T cells to discover new precision therapies against autoimmunity and cancer. 

The Lim Lab is focused on developmental aspects of the immune system. Optimal development of immune system requires defined environmental input in a spatiotemporally regulated manner. This fundamental process begins in utero in parallel to organogenesis. Numerous epidemiological data
suggested that maternal environmental exposure during pregnancy, particularly infection, can shape the offspring immunity in the long term. During this critical window, the mother also undergoes dramatic immunological changes to nurture and adapt to the semi-allograph fetus. Despite the vast clinical and societal implications, the mechanisms underlying maternal-offspring immune crosstalk and how specific encounters during pregnancy alter offspring immune trajectory remains largely elusive. My research aims to establish a mechanistic understanding of how maternal infection impacts offspring long-term tissue immunity, and reciprocally, how maternal immunity adapt to physiological changes during pregnancy and lactation. My unique training in human and murine immunology allow me to develop a program combining in-depth mechanistic studies using murine models in concert with biological observations from human populations.

The Oyler-Yaniv Lab is obsessed with understanding how the immune system tailors responses such that they are appropriate for the different types of challenges it faces. The air we breathe is teeming with bacteria and fungi, our skin and mucosal surfaces are home to trillions of bacteria, and our genome is littered with the remnants of countless viral infections. Our immune system must sift through this onslaught to respond to true threats in a manner that is tailored to the specific pathogen type and magnitude. Failure to clear a pathogen means the spread of infection, but overreaction leads to immune-driven tissue destruction, inflammatory disease, and fibrosis. Shockingly, the immune system only rarely fails. 

The Abdel Hakeem lab focuses on providing deep insights into the mechanisms of development of T cell exhaustion during chronic viral infection and cancer, the mechanisms underlying recovery from different aspects of the exhaustion program, and the subset dynamics implicated. We use an integrated systems approach to dissect the networks downstream the individual factors involved in exhaustion, as well as explore the modulation of the epigenetic exhaustion program upon exposure to various cytokines. This knowledge is essential for optimal design of novel immunotherapeutic strategies with enhanced efficacy and safety

The mission of the Tokuyama Lab is to understand how chronic interaction between viruses and the immune system impacts immunity at steady state and during inflammation. We study endogenous retroviruses (ERVs), which are viral sequences in our genome that originated from exogenous viruses and have undergone an evolutionary arms race with the host for millions of years. Despite outnumbering coding sequences by 4-fold across different organisms, ERVs have been largely ignored as “junk DNA” and the physiological functions of ERVs in immunity remains poorly understood.

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Ultimately, our goal is to identify novel endogenous viral factors that underlie immunity and contribute towards development of immune modulators to treat infections and chronic inflammatory diseases.

The Byrne Lab aims to understand the underlying immunobiology regulating therapeutic sensitivity in pancreatic cancer. Our research focuses on interrogating mechanisms of bridging innate and adaptive immunity that drive tumor rejection in preclinical models of cancer, and revealing correlates of response for patients receiving immunotherapy.

The Florsheim Lab is interested in how immunological defenses promote fitness and organismal survival. To address this problem, the lab studies allergies, mast cell biology, and neuro-immune interactions at the gastrointestinal tract to determine the impact of the immune system in physiology. The long-term goals of the lab are to a) transform the immunology field through a multidisciplinary approach, b) motivate the next generation of scientists interested in discovering the yet unsolved immunological mysteries, c) create an equal world in STEM.

The Xu laboratory integrates immunobiology and systems biology in an effort to systematically decipher fundamental mechanisms orchestrating immune reactions at both physiological and pathological states, with the ultimate goal of contributing to our understanding of how disorders of immune system result in chronic inflammation and autoimmune diseases. Currently the lab is interested in leveraging emerging systems and computational biology approaches in immunology for decoding tissue-specific microenvironments and molecular circuits that orchestrate (1) B cell development and immune response and (2) interactions between nervous and immune system in the brain and gut.

The Bryson Lab is focused on understanding the pathogenicity of Mycobacterium tuberculosis, which remains one of the world’s most deadly bacteria resulting in infection in nearly a third of the global population and millions of deaths per year. Recent advances in our understanding of tuberculosis infection demonstrate that infection within a given individual is highly heterogeneous; however, the determinants that drive lesions towards complete bacterial sterilization remain poorly understood. We are interested in developing new tools to dissect the complex dynamics of bacterial infection at a variety of scales ranging from single cells to infected animals sitting in both “reference frames” by taking both an immunologist’s and a microbiologist's perspective. Combining new technologies with classical approaches, we are focused on answering a critical question: “how can we manipulate the immune system to improve bacterial control?”