Seminar Series Speakers 2023 - 2024

Dr. Covarrubias is a macrophage biologist with expertise in immuno-metabolism, and how inflammation and metabolism are integrated to regulate metabolic health and disease states including aging. Dr. Covarrubias identified the nutrient-sensing Akt-mTORC1 pathway as a critical regulator of macrophage polarization. He also showed that activation of the Akt-mTORC1 target ACLY catalyzes the increase in macrophage cytosolic/nuclear pools of acetyl-CoA. These findings suggest how nutrient and metabolic status can fine-tune macrophage function via nutrient sensing pathways. Dr. Covarrubias’ recent work is focused on how diet and aging-related inflammation impacts the aging process. In a recent manuscript he showed that the decline of NAD+ during aging is driven by the activation of tissue resident macrophages via senescent cells. As senescent cells progressively accumulate in aging tissues, these results highlight a new causal link between visceral tissue senescence, NAD+, and immuno-metabolic dysregulation during aging, an active area of investigation in the Covarrubias Lab at UCLA.

​The mucosae represent the border between our body and the environment, and they act as the first barrier against infections. Therefore, inflammatory responses must be tightly regulated to combat infection without causing excessive self-damage or interfering with the repair process. An imbalance in these processes could result in the loss of barrier function and tissue functionality. Achille Broggi and his team study the interplay between the immune system and the mucosal layer, with a particular interest in understanding how immune mediators production and functions are regulated in the intestinal mucosa and how they regulate the pathogenesis of inflammatory bowel disease (IBD).

The immune system mounts destructive responses to protect the host from threats, including pathogens and tumours. 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. The Wong lab investigates how coordinated communication between cells gives rise to dynamic circuits that steer ongoing immune responses toward desired target values, both in time and space. To this end, we employ various interdisciplinary methods—including advanced fluorescence microscopy, computational modelling, and inducible gene perturbations—to resolve, model, and manipulate immune cell behaviours directly in situ. Ultimately, we aim to understand how imbalanced circuit functions lead to immune-related disorders, including autoimmunity, chronic infection, and cancer.

Our group investigates the tumor microenvironment with a focus on the crosstalk between macrophages and tumor cells in distinct tissue zones. Using spatial transcriptome techniques, imaging, and ex-vivo functional assays, our aim is to establish a spatio-temporal landscape of tissue-resident macrophages revealing their molecular profiling at the very early onset of solid tumors. These projects rely on close collaboration with oncologists and pathologists and a multidisciplinary group of researchers involved in uncovering new therapeutic targets for the treatment of cancer.

Dr. Wei-Le Wang received his Master’s degree in Immunology from the National Taiwan University in 2009. He continued his training in immunology under the guidance of Dr. Mark Boldin at City of Hope and obtained his Ph.D. in 2019. Dr. Wang then conducted his postdoctoral training in the laboratory of Dr. Marco Colonna at Washington University in St. Louis from 2019 to 2022. In October 2022, he established his lab at the Institute of Molecular Biology Academia Sinica, Taiwan.
Dr. Wang’s research focuses on immune regulations. Through analysis of immune cells in the tissue barriers, he identified novel niches at CNS borders for B cell lymphopoiesis and a novel eosinophil subset unique to the small intestine and modulates the type 2 immune responses. His current research interests include: 1) B cell tolerance in the meninges. 2) Meningeal B cells in neurodegeneration diseases. 3) Eosinophils and Group 3 innate lymphoid cells in host defense and mucosal immunity.

The Chen laboratory studies the molecular and biological processes governing the development of brain malignancies, including primary (e.g., glioblastoma) and metastatic (tumors originating from other locations in the body, such as breast cancer) brain cancers. Specifically, the laboratory focuses on characterizing the molecular mechanisms governing the symbiotic interactions between cancer cells and immune cells (including macrophages, microglia, myeloid-derived suppressor cells and T cells) in brain malignancies, and how such heterotypic signaling enables a tumor-promoting ecosystem and informs therapeutic strategies intercepting these co-dependencies.

We are a systems immunology lab affiliated with the University of Pittsburgh's Department of Immunology. Our lab specializes in the use of a high-throughput approach which has demonstrated the ability to identify the target antigen of a given T cell. Our research aims to examine the shifting antigenic landscape of anti-tumor T cell responses, determine the fundamental rules of TCR-pMHC interactions, and to investigate novel immunotherapies to autoimmune diseases.

Dr. Giulia Adriani is a biomedical engineer with expertise in cancer immunology. Dr. Adriani is a Principal Scientist at the Singapore Immunology Network (SIgN), established by the Agency for Science, Technology and Research (A*STAR), and an Adjunct Assistant Professor at the Department of Bioengineering of the National University of Singapore (NUS). Dr. Adriani is leading her research group in SIgN, working on 3-dimensional vascularized immuno-competent tumor models to study the interactions of cancer cells with their microenvironment and develop better anti-tumor therapies. Recently, to replicate the complexity of the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME), Dr. Adriani Lab developed 3D multicellular PDAC models that incorporate multiple cell types, including immune, endothelial, and stromal cells, alongside cancer cells to advance the understanding of cellular interactions and treatment response. As recently published, these multicellular PDAC microtumors displayed increased expression of collagen-I, HIF-1α, tumor-associated macrophage markers, and cytokine patterns that resemble the ones observed in patients. Further, single-cell RNA sequencing data collected from PDAC multicellular microtumors revealed the modulation of genes that correlate with unfavorable prognosis in patients, suggesting that these microtumors could accurately represent response to chemo and immunotherapy.

Previous research has shown that some cancer cells can reprogram themselves in a way that closely mimics the stem cells in a developing fetus. Recently, my laboratory discovered that the environment in which these tumour cells grow undergoes a similar transformation. Because cells in this environment also share core characteristics with fetal cells, we coined the term 'oncofetal ecosystem' – the fertile 'soil' where cancer cell 'seeds' thrive and evade the immune response. I will present data on the presence of this 'oncofetal reprogramming' in cancer and it's implication in understanding therapy response in the clinic.

Tumors originate and evolve surrounded by a heterogeneous cellular context, which composes the tumor microenvironment (TME). The dynamic interaction between cancer and the surrounding cells generates a complex system that can sustain tumor growth, metastasis formation and resistance to therapies.  Diletta Di Mitri’s research has been driven by the interest to elucidate the role of immune cells within the cancer microenvironment. Primary objective of her research is to reveal the mechanisms underlying the interaction between cancer cells and immune cells, with the ultimate goal of identifying novel therapeutic targets against cancer that can harness the TME to render it anti-tumoral. The team applies multi-parametric flow cytometry and advanced RNA sequencing approaches to dissect at the single cell level the mechanisms underlying the evasion of cancer from the immune recognition, mechanism of cancer invasion and causes of resistance to therapies.

Justin Erquem received his PhD from the University of Paris-Diderot in collaboration with the biotech company Cellectis. During his PhD, he participated to the development of gene editing tools such as Meganuclease or TALEN in primary human cells and notably identified genomic location for safe integration of therapeutic genes. In 2014, he joined Michel Sadelain’s lab at the MSKCC and used CRISPR/Cas9 to engineer CAR T cells. He showed how targeting CAR transgene into specific loci enhance T cell efficacy, advance CAR immuno-biology and facilitate T cell manufacturing. Early 2019, He received the Parker Fellow Award and opened his lab in the department of Microbiology and Immunology at UCSF where he is developing a gene editing platform to enhance CAR T and NK cell functions in hematological and solid tumors.

Homeostasis is the system to maintain regulated variables (body temperature, blood glucose, tissue size, and so on) within acceptable ranges. Immune system can be considered as a type of homeostatic mechanism in order to keep our body harmless. Our goal is to understand the mechanisms of tissue homeostasis and immune homeostasis as well as the mechanisms of diseases caused by the abnormality/exaggeration of homeostatic regulation.

Carla is the Principal Investigator of the Mucosal B Cell lab at NYU Langone Grossman School of Medicine, department of Pathology. Carla has long been obsessed with B cells and how they respond to their environment. She loves to build new tools to visualize B cells communicating, responding and evolving.

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Carla is a Polish/Italian Brit, who got her PhD in London before moving to the US for her postdoctoral studies. Carla has a deep love for New York City, slowly eating, strolling and dancing her way around town. Carla loves creative and driven people, and strives to build a team of diverse thinkers to help grow the future of science.

Our focus is on understanding the intricate workings of the immune system and its role in maintaining a balanced state of health and protection. We delve into the essential elements that regulate and execute immune responses to safeguard against both internal and external threats, particularly infections. In addition to immunity, we investigate a fascinating phenomenon known as 'Tolerance.' This mechanism actively induces a state of non-responsiveness within the immune system toward various substances that could otherwise trigger immune reactions. Maintaining a delicate balance between these immune compartments, known as 'Immunological homeostasis,' is crucial for overall well-being. Disruptions in this equilibrium can lead to inflammation, driving a wide range of human diseases and conditions, including autoimmune diseases, cancer, and potentially, neurodevelopmental disorders.

Our team is passionately engaged in unraveling novel mechanisms that control the function and development of immune cells. We explore how the breakdown of these mechanisms contributes to the onset and progression of inflammatory disorders. Additionally, we are dedicated to identifying the factors that impact immunological homeostasis in both normal and disease conditions, with a particular focus on host factors (especially immune and neuronal) and bacteria-factors. Ultimately, our goal is to translate this knowledge into potential treatments for human inflammatory disorders such as autoimmunity, cancer, and neurodevelopmental disorders.

The advent of immunotherapy has revolutionized cancer therapy. The durable clinical success of PD-1/ PD-L1 blockade illustrates the key concept of targeting immune-evasion mechanisms within the tumor microenvironment to restore tumor-specific immunity. However, given that a substantial subset of patients does not respond to or develop resistance to anti-PD-1/PD-L1 therapy, our major research interest is to discover novel mechanisms that enable immune escape and to utilize these pathways to modulate anti-tumor immunity within the tumor-site for cancer immunotherapy.

The Koch lab studies how maternal-derived signals shape infant development, immunity and metabolism. In addition to nutrients, breastmilk transfers immune-modulatory factors, such as antibodies, to infants. These antibodies protect offspring from infection and can also influence gut health by shaping the assembly of the gut microbiota and regulating immunity to beneficial gut bacteria. The microbiota is key to health, and perturbations in early-life host-microbiota interactions can have long-term effects on infant immunity and physiology, including risk of immune and metabolic dysfunction. A major goal of our work is to define the mechanisms by which maternal antibodies regulate interactions between the infant and resident gut microbes, and reveal how perturbations in this process translate to long-term health outcomes. The Koch lab is also interested in understanding how other breastmilk components, such as maternal T cells, impact infant immune development and susceptibility to infection.  

The Zhou lab investigates the intricate immune circuits that exist between tumors and the related immune organs. Our primary focus lies in understanding the generation and perturbation of the adaptive anti-tumor response during tumor initiation and progression. At the age of immunotherapy era, we also delve into comprehending the immunological mechanisms underlying immune regimen treatments, such as cytokines and cellular therapies. Furthermore, our lab pursues pharmacological designing novel molecules that align with these immunological insights. Our ultimate goal is to tackle cancer "from bench to bed" and foster new hope in patients.

Dr. Heping Xu is currently serving as an Assistant Professor in the School of Life Sciences at Westlake University.  He obtained his Ph.D. from the Institute for Immunology at Tsinghua University in 2014. Following the completion of his doctoral studies, he pursued postdoctoral research training at Cincinnati Children's Hospital Medical Center and the Broad Institute of MIT and Harvard from 2014 to 2019. In 2019, he joined Westlake University.

Dr. Xu's research interests primarily lie in the field of immunophysiology and systems immunology. The long-term research goal of his laboratory is to gain a comprehensive understanding of the intricate communication networks between immune cells and tissue-specific microenvironments in both homeostatic and inflammatory conditions. The ultimate objective of this research is to develop precision immunotherapies that can effectively treat chronic inflammatory disorders, including allergy, inflammatory bowel disease (IBD), and autoimmune diseases. 

The current focus of the laboratory includes investigating 1) meningeal B cell development and function, 2) the regulation of antibody maturation and humoral immunity, and 3) the neuronal and metabolic control of immune cell activities in the mucosal tissues, such as the intestine and lung.

One of the main focuses of our group is to understand how mucosal homeostasis develops in infants and young children, particularly as it relates to development and maintenance of adaptive immunity. Using a combination of single cell techniques, we are studying intestinal immunity of fetal, premature and term infants and pediatric subjects. Furthermore, we are interested in determining how mucosal homeostasis becomes dysregulated in intestinal diseases such as necrotizing enterocolitis and inflammatory bowel disease.

Ana Luisa Correia is an enthusiastic Cancer Biologist with a main interest in understanding what makes a tissue favorable or not to metastasis, and leverage this biology into therapeutic interventions that reliably prevent the emergence of metastases in patients with cancer. Anahas developed a tool to follow dormant disseminated tumor cells live, offering opportunities to investigate the anatomical distribution, composition and dynamics of dormant reservoirs within and across distant sites. This approach has steered the discovery of a pivotal role for a part of the innate branch of the immune system, the natural killer cells, in luling disseminated tumor cells into dormancy, and how disruption in liver physiology breaches the NK cell barrier to metastasis. This provides a foundational framework for studying the dynamics of antimetastatic innate immunity within and across sites, which the Correia Lab has been pursuing at the Champalimaud Foundation in Lisbon.