Mammalian genomes are folded in a hierarchy of compartments, topologically associating domains (TADs), subTADs, and looping interactions. As genome-wide chromatin architecture maps become widely available, the field is shifting focus from mapping to understanding the dynamics of such structures in development, the cell cycle, and on short time scales in single cells. A critical emerging goal will be to unravel the cause and effect relationship between genome folding and functions such as transcription, replication, recombination, and stability/maintenance. There is also a great need to evaluate the organizing principles governing chromatin topology across many biological conditions and genetic perturbations. Moreover, the role for 3D genome misfolding in the onset and progression of a wide range of human disease states remains an area of high interest across multiple disciplines and organ systems. Overall, this Keystone eSymposia virtual event is meant to highlight new frontiers across disciplines in tackling the dynamics and functional roles of the 3D genome in cellular functions across time and space in development and disease.
#VKSChromatin22
The female genital tract environment represents an intricate interplay between commensal microbes, pathogens, small molecule metabolites and host immune cells resulting in health and disease consequences for women, their sexual partners, and neonates. Refined characterization of the genital tract using sophisticated methods has expanded our understanding of mucosal immunology, the microbiome, the metabolome, and the proteome. Mechanisms leading to adverse outcomes, particularly elevated risk of HIV acquisition, are being unraveled, and an increasing number of interventions are in clinical trials. In this meeting, we will examine cutting-edge knowledge needed to tackle some of the most challenging global problems in reproductive and sexual health, including current understanding of female genital tract microbiology and immunology, and advances in therapeutics and preventatives intended to modify or protect these environments. Potential mechanisms leading to adverse outcomes, and prospective prevention and/or treatment interventions will be presented and discussed. Pathways for development of novel interventions, including industry partnership and regulatory strategies will be considered. The progress made in recent years at the bench and in clinical trials should inform global health interventions aimed at sustaining sexual and reproductive health for women especially in resource-limited settings, where women suffer the most severe consequences of these challenges.
#VKSVaginalHealth22
Worldwide, deaths from adverse pregnancy outcomes of preterm birth (PTB) and stillbirth (SB) represent the longest, deadliest pandemic in human history. Neonatal infection (e.g. sepsis) is the main cause of death for children under 5 years; with premature babies being especially susceptible to infection. While the final common pathway for SB, PTB and neonatal sepsis is associated with aberrant inflammation in the maternal-fetal dyad, lack of insight into the underlying mechanisms has hampered identification of effective upstream preventative or downstream therapeutic interventions. A focus on immune regulation during pregnancy and in early life is thus urgently warranted. This interdisciplinary Keystone Conference on maternal-fetal-newborn immunity brings together the world’s experts across maternal, fetal and neonatal/infant immunity for the first time with the following goals:
#VKSMaternal22
This eSymposia is organized in collaboration with the Vitamin D Workshop, the premier meeting in the field of vitamin D biology since 1973. This virtual 23rd Vitamin D Workshop will accelerate scientific discoveries that optimize the health effects of the vitamin D endocrine system.
Ever since E.V. McCollum coined the term “vitamin D” in the 1920s, we’ve known that vitamin D plays an essential role in bone and calcium metabolism. However, decades of research show that vitamin D can also impact physiological and pathological processes beyond bone. As a molecular regulator of cell differentiation, lineage determination, apoptosis, autophagy, and metabolism, Vitamin D influences carcinogenesis, metabolic diseases, and various aspects of immunity. Meanwhile, the presence of the Vitamin D receptor and multiple metabolizing enzymes in most human tissues highlights the complexity of this system as a modulator of health and wellness throughout the body.
This virtual conference will be a venue for sharing insight into the molecular actions and translational potential of vitamin D in a variety of disease-relevant physiologic contexts, covering the following key scientific questions:
By answering these and other questions, participants will generate new scientific ideas and form collaborations that enable translation of this knowledge to improve human health.
#VKSVitaminD22
Vaccines have the power to prevent and potentially eradicate a wide range of infectious diseases, representing one of the most effective life-saving measures at our disposal against global health threats. The recent coronavirus pandemic has brought the importance and urgency of vaccine development efforts into sharp focus. Moreover, the vaccinology field is evolving very rapidly, thanks to advances in our understanding of microbiology, immunology and genomics, as well as advances in structural analysis of antigens and antigen-antibody complexes and impacts of variation. Over the years, this field has also experienced an elucidation of mechanisms of immunity and protection, and identification of correlates. However, many questions are still unsolved and innovative approaches are needed to address new vaccine challenges like antimicrobial resistance, emerging infectious diseases, cancer and diseases associated with our aging population. This conference will cover the latest advances and novel approaches towards vaccine development, including:
Together these topics will provide attendees with the new ideas and tools to continue to forge new frontiers in vaccine capabilities.
#VKSInnoVax21
The discovery of genomic and epigenetic alterations in individual cancers has led to a plethora of precision medicine innovations and therapeutic successes in oncology. Accordingly, cancer treatments have migrated away from the “one size fits all” approach. However, even as precision medicine is becoming more multi-disciplinary, progress is still hindered by insufficient collaboration between basic researchers, drug development programs, and physician scientists with broad expertise across cancer biology, genomics and other relevant fields. Therefore, this conference will bring together diverse experts from academic, pharma/biotech, medical and government sectors to discuss current challenges and future directions in precision oncology. In particular, the meeting will foster crosstalk between clinicians, cancer biologists and genomic scientists to identify and address key knowledge gaps that limit the advancement of new precision therapies. This conference program will cover topics such as novel genomic insights, therapeutically promising mechanisms and cancer drug targets, recent translational breakthroughs, and the incorporation of new diagnostic tools as companions to new precision treatments. The program will emphasize leading-edge advances in “reverse translation” technologies, such as liquid biopsies and single cell genomics, in addition to innovative, first-in-class approaches to novel therapeutics. Ultimately, the goal of the conference is to forge new collaborations across scientific and clinical boundaries, to advance the next generation of precision medicines against cancer.
#VKSPrecisionOnco21
Targeted protein degradation plays a critical role in regulating nearly all cellular functions, and as such, its dysfunction is associated with severe pathologies including diseases like cancer, neurodegeneration and age-associated diseases. Therefore, fundamental insights into protein clearance pathways might be harnessed for therapeutic applications against a wide range of diseases. While much progress has been made in revealing mechanisms of autophagy and the ubiquitin-proteasome system, the major protein degradation pathways defined thus far, these fields continue to remain isolated from each other despite the interconnection of these processes. This separation is now leading to an urgent need to discuss the interplay of these pathways at the molecular and cellular levels to integrate our understanding of these processes and how they contribute to disease pathology. This conference will bring together researchers from these different fields, who do not typically interact, to build a holistic and integrated vision of protein degradation. Such an integrative conference highlighting the connections between the different branches of protein degradation research does not yet exist, so this Keystone Symposia conference will be the first of its kind to reshape how these fields interact and collaborate to yield transformative insights into both basic science and disease processes.
Topics of discussion will include:
Attendees will be exposed to novel perspectives, as well as methods, techniques and approaches, that will advance research within their field, and across the many different components in the protein degradation landscape.
#VKSPDegradation21
Joint with: NeuroImmune Interactions in Health and Disease
Neurodegenerative diseases, such as Alzheimer’s disease (AD) and AD-related disorders (ADRD) are quickly becoming a global burden. The number of diagnosed cases of neurodegenerative diseases is staggering and rising at an alarming rate as the population ages. While it is well-recognized that neurodegenerative diseases are characterized by aberrant protein misfolding and aggregate formation, the mechanisms that initiate or promote proteinopathy in disease-specific neural circuits remain poorly understood. Recent advances in human genetics and genome-wide association study (GWAS) have uncovered several genetic loci that are critical for the pathogenesis of neurodegenerative diseases. Furthermore, technological advances in transcriptomics, proteomics, and metabolomics offer many critical new insights into the disease mechanism, as well as opportunities for the development of novel therapeutics that can reverse or mitigate neurodegeneration. Despite these exciting new developments, there are significant gaps in connecting genetic information with disease mechanism and in harnessing the critical role of glia-neuron interactions to develop therapeutic interventions.
This conference aims to provide an integrated discussion of the latest advances in research and therapeutic development for neurodegenerative diseases. This conference program will focus on the roles of genetic risk factors and their contributions to glial and neuronal health in the aging brain, the biophysical properties of protein misfolding and the propagation of disease-specific proteinopathy, the role of intracellular vesicular trafficking in disease pathogenesis, new insights into the diverse role of glia, innate immunity and microbiomes in neurodegeneration, and novel therapeutic approaches that specifically target each of the novel biological areas. It is anticipated that this conference will stimulate more discussions and promote new collaborations among scientists in the academia and industry that ultimately lead to new therapeutic targets to combat neurodegenerative diseases.
#VKSNeuroDegen21
Joint with: Neurodegenerative Diseases: Genes, Mechanisms and Therapeutics
The emerging field of neuroimmunology is one of the most exciting and fastest moving areas in biomedical research. Communication between the brain and the immune system play critical roles in neural development, homeostasis and disease. Emerging human genetics implicate innate and adaptive immune pathways in many neurological diseases; however, the disease mechanisms remain elusive. Intersections between the nervous and immune systems are complex and can have both beneficial and detrimental impact on brain function depending on the context. It is thus crucial that we understand the mechanisms that give rise to these divergent outcomes. The extraordinary depth and breadth of science is emphasized by the program and includes topics such as peripheral immunity, inflammation, and interactions between the brain and the periphery, microglia function and dysfunction, microbiome and gut-brain axis, immune mechanisms of synapse loss in development and disease, mechanisms of neuroimmune communication at brain borders, and glymphatic-lymphatic connections. The program will also include several workshops on new discoveries, tools and approaches to analyze and integrate big-data (omics) aspects of neuroimmunology research, and to model neural-immune signaling in different contexts, including human disease.
This conference will bring together an interdisciplinary group of scientists to discuss these and other emerging topics in neuroimmunology, with emphasis on the mechanisms underlying neural-immune crosstalk in health and disease. A major goal is to cultivate cross-disciplinary research by bringing together cutting-edge researchers that represent the entire spectrum of the field, from pure neuroscience to pure immunology, with the emerging field of neuroimmunology in between them. The conference will also provide opportunities for outstanding senior leaders to inspire young scientists in the field to move in innovative directions.
#VKSNeuroImmune21
Joint meeting with HIV Pathogenesis and Cure
Development of effective prophylactic human immunodeficiency virus (HIV) vaccines are still urgently needed to halt the spread of the HIV/AIDS pandemic. However, development of these vaccines has proven to be a challenge that, despite intensive research efforts over the last 30 years, science has failed to surmount. Nevertheless, the prospects for an effective HIV vaccine have recently been transformed by a series of advances in science. These advances suggest that induction of broadly-reactive antibodies that confer protection via neutralization and/or neutralization-independent mechanisms and elicitation of cytotoxic (CD8) T cell responses can potentially eradicate the virus early after transmission and may ultimately prove to be achievable goals for drug development.
This conference will bring together interdisciplinary investigators whose complementary expertise will synergize to inform HIV vaccine design and evaluation to discuss progress and outstanding challenges in areas such as: 1) The design of immunogens and strategies for optimization of germinal center responses to elicit HIV-1 broadly neutralizing antibodies; 2) Identifying prospects for harnessing other antibody effector functions to confer protection; 3) Developing approaches for eliciting rapidly-acting, efficacious HIV-specific CD8 T cell responses; and 4) How to use novel technologies, animal model systems and small-scale clinical trials to inform vaccine development efforts. This conference is being held jointly with HIV Pathogenesis and Cure. This pairing will provide an opportunity for interaction between investigators working in these related areas, and for joint discussion of therapeutic vaccination strategies.
#VKSHIVVax21
Joint meeting with HIV Vaccines
Human Immunodeficiency Virus type 1 (HIV) is the cause of a global pandemic that has a very high mortality rate, with an estimated 35 million deaths to date. In addition, another 37 million people are currently living with HIV infection and will likely succumb from acquired immune deficiency syndrome (AIDS) without lifelong antiretroviral therapy (ART). Optimal ART can halt viral replication, thereby preventing disease progression and allowing immune reconstitution. However, ART is not curative due the persistence of a latent form of the virus. This latent form is the major barrier to cure and the subject of an intense international research effort. Along with efforts to develop an HIV vaccine, targeting the HIV latent reservoir is a major priority for AIDS research. Achieving a better understanding of the basic biology of HIV infection is likely to be essential to HIV cure efforts.
This conference will bring together scientists studying basic aspects of HIV virology as well as investigators working directly on the cure problem. Immune-based strategies to eliminate infected cells are an important component of many cure strategies, providing a logical connection to hold the joint conference on HIV Vaccines. This pairing will provide a unique opportunity to bring together basic and translational immunologists and virologists to consider the challenging goal of curing HIV infection. In addition to joint sessions focusing on exciting new developments in the study of antibody and T cell responses to HIV and novel technologies that will aid future studies of HIV biology, sessions also include basic mechanisms of HIV integration and transcriptional control, strategies for reversing latency and eliminating infected cells, and trials of novel cure strategies in animal models and in patients on ART. The goal of this conference is to bring together an amalgamation of basic and applied scientists working on functional cures and eradication of HIV in an effort to not only better understand HIV treatment strategies but also the emerging technologies and approaches that will lead to the eventual eradication of HIV from infected individuals.
#VKSHIVPath21
The mechanisms underlying nucleosome- and chromatin-based functional control of genomes are studied very broadly across biological systems and at an increasing rate. Moreover, the three-dimensional (3D) organization is an important component in the regulation of gene expression, with more recent implications emerging for DNA replication and repair. Additionally, the research being conducted in this field is important as it ultimately impacts and informs basic biology, as well as also contributing to a translational importance in human disease.The conference will showcase the interdisciplinary nature of the field, with talks combining state-of-the-art super resolution imaging, sophisticated genetics and single cell regulatory genomics focusing on chromatin mechanisms, including genome topology, DNA and RNA modifications, histone modifications, ATP-dependent nucleosome remodeling complexes, histone variants, chaperones and others.
#VKSEpigenetics21
Injury-induced Damage Associated Molecular Patterns (DAMPs) are beginning to shape modern medicine in the field of both diagnostics and therapeutics. For example, DAMPS are already recognized to be major contributors to rejection in the field of transplantation, and efforts are underway to target them. Research is showing that they can also contribute to rejection of tumors, for example with immunogenic cell death, and efforts are underway to stimulate them for cancer eradication. With their use, new vaccination modalities will be developed against viral infections, including HIV and ZIKA virus. Further, DAMPs-based innovative diagnostic methods and new therapeutic strategies will soon improve survival rates of critically ill patients, such as those who have undergone major trauma. Due to its involvement in autoimmune diseases, chronic inflammatory diseases, and allergic diseases, as well as plant resistance to predators, initiation of innate immune responses by DAMPs is currently a thriving research area. It covers both medical and agricultural fields. The goal of this conference is to convene internationally renowned experts from academia, biotech and pharma, in fields reflecting the diversity listed above, to present and discuss their latest findings in DAMPs research and applications.
#VKSDAMPs21
Preponderant experimental and clinical evidence has demonstrated that pervasive cancer cell heterogeneity in both phenotypic presentations and functional properties exists, such that a population of cancer cells with cardinal stem cell properties (i.e., cancer stem cells) pre-exists in untreated tumors and spatiotemporally evolves during tumor progression and therapeutic interventions. Recent studies have also revealed significant phenotypic and functional plasticity in cancer cells, regulated by both genetic networks and epigenetic mechanisms. Both cancer cell heterogeneity and plasticity constitute major barriers to effective and durable clinical treatments.
Ever since the revival of the cancer stem cell research field in the last two decades, we have made great strides in identifying and elucidating the biology of cancer stem cells in virtually all tumor systems. Significant progress has also been made in understanding how cancer stem cells interact with the cellular constituents and soluble factors in the proinflammatory and immune-suppressive tumor microenvironment. Facilitated by an explosion of technical advances in recent years, especially single-cell RNA-seq, we are achieving an unprecedented appreciation of the complexity of the cellular heterogeneity of human tumors. Significantly, novel therapeutic strategies that target cancer stem cells and cancer cell heterogeneity and plasticity are rapidly progressing to the clinical arena.
This conference is organized to recapitulate these recent advances in our understanding of cancer stem cell biology and, importantly, the clinical translation of targeting cancer stem cells.
#VKSStemCell21
A large number of long non-coding RNAs (lncRNAs) with a surprisingly wide-range of cell-type specific expression profiles are present in human transcriptomes. Emerging evidence points to their critical roles in human physiology and pathology and some are recognized as potential therapeutic targets. However, many seminal questions regarding their mechanism of action remain largely unexplored. There is a need to understand how different regulatory RNAs are processed and regulated, how they act in different physiological and disease contexts, how their essential structural modules are built, organized, and interact with proteins and other RNAs in the cell to carry out their functions. Additionally, there is a need to elucidate how the fundamental biology of regulatory RNA can be translated to therapeutic approaches.
Therefore, this conference will bring together scientists who study the basic biology of diverse types of ncRNA molecules from generation and processing, structure, mechanisms of action to functional significance in different model organisms, as well as those who develop cutting-edge RNA technologies, biomarkers and medicines for translational purposes. It is anticipated that this conference will provide an integrated platform for scientists to communicate the latest innovative technologies and methodologies that will speed up the exploration of both fundamental regulatory RNA biology and translational applications.
#VKSNonCodingRNA21
Synthetic Biology tools and principles have matured tremendously over the last decade and have reached extraordinary levels of sophistication, both in eukaryotic and prokaryotic systems. Synthetic biology as a therapeutic modality is starting to enter multiple clinical studies and has the potential to have a significant impact on medicine across a wide range of diseases (e.g., metabolic, immune-mediated, cancer, and neurologic diseases). This Keystone Symposia conference will delve into the field of synthetic biology with a special emphasis on its applications to medicine. While there are conferences that capture synthetic biology in only a few talks mixed in among other various topics, there is a paucity of conferences focused on synthetic biology as drugs to treat disease.
However, due to the rapid pace of fundamental scientific advances along with an expanding number of biotechnology companies and emerging clinical studies with synthetic biology at their core, this conference will be highly relevant for a wide audience of scientists both from academia and industry. In addition, other meetings in this field have a highly technology-driven focus on synthetic biology techniques with relatively little attention given to biological and medical context. Ultimately, this Keystone Symposia conference should inspire researchers from diverse backgrounds to discuss synthetic biology via many new angles.
#VKSSynthBio21
Hematopoiesis is a highly regulated and dynamic developmental process by which hematopoietic stem cells self-renew and differentiate to form all blood lineages. Disruption of hematopoiesis resulting from genetic, epigenetic, transcriptional, and/or post-translational defects or due to environmental stressors can result in benign or malignant hematologic disorders. Advances in model systems, genome-editing tools, single-cell analyses, and imaging technologies have provided insight into the molecular, cellular, and developmental basis of normal and malignant hematopoiesis. This Keystone Symposia conference brings together basic and translational researchers to discuss and debate emerging topics and recent advances on developmental hematopoiesis, adult stem cell self-renewal and stem cell niches, novel hematopoietic regulators, and the pathogenesis of bone marrow failure syndromes and leukemia. Taken together, participants at this conference will gain new insight into the biology of normal and malignant hematopoiesis and cutting-edge technologies, as well as have opportunities to cultivate new ideas and establish collaborations with researchers from disparate disciplines.
#VKSHemato21
The innate immune system is the first line of response to pathogens and tissue injury. Specialized cells have evolved mechanisms to detect microbial and distress signals and translate these into effector mechanisms that fight infections, amplify inflammation, initiate acquired immunity and eventually resolve. Although the innate immune response is usually associated with infectious disease, it has been implicated in a broad range of diseases, including cancer, autoimmunity, degenerative and vascular diseases. This conference provides multidisciplinary perspectives on innate immunity, from fundamental science to clinical aspects of disease, as well as therapeutic approaches to immune modulation. The conference program will focus on recent advances in this rapidly developing field. Presentations will provide new insights into mechanisms of microbial and distress sensing and the effector mechanisms of innate immune cells including macrophages, neutrophils, dendritic cells and innate lymphoid cells. The program will also highlight new approaches to understanding protective and pathogenic innate immune function, and emerging therapeutic opportunities for targeting these mechanisms in disease.
#VKSInnateImmunity21
Lipid metabolism provides the building blocks for cell growth and replication, signaling molecules that initiate and propagate signals inside and outside of cells, and fuel for cell function and division. The role of these molecular species in human disease has become more apparent with advancements in ability to detect and accurately quantify them. This meeting will integrate information generated through lipidomics studies. Specific areas of focus will include using genetic and proteomic data to identify changes in particular molecular species, the importance of changes in lipid metabolism and signaling and the regulatory enzymes for neurodegeneration, metabolic disorders, cancer and inflammation and immune responses. Featured talks will extend beyond methodologies to integrate the current biological and clinical importance of lipids with lipidomics approaches. This will allow us to focus upon the mechanistic importance of lipids in neurodegeneration and other neurological disorders, cancer, inflammation and metabolic disorders. By identifying enzymes that regulate changes in lipidomics, new targets for therapeutics can also be identified. This approach is inspired by PI3kinase, where the basic biochemistry has led to the development of effective inhibitors. We hope to discover other targets for lipid enzyme therapeutics. By moving towards lipid analysis and the biological and medical importance of lipid regulatory pathways, the goal is to use lipidomic profiling to get to better understand and treat different diseases. The majority of lipid related meetings focus on methodologies. We believe that PI3kinase should be reintegrated into meetings about lipid-related disease because it represents successful implementation of this approach. The PI3Kinase specific meeting is no longer attracting sufficient attendees but it remains an important scientific area for discussion. This meeting will also address the importance of particular lipid molecular as opposed to lipid classes. Modern lipidomic methodologies enabled us to identify more than 20,000 potential lipid species in a cell. There are particular species that regulate enzyme activities and membrane properties and thus functions like signaling and cellular migration. This meeting will include a workshop, led by members of LIPID MAPS, on lipidomics methodologies, data handling and storage to further emphasize the biological and medical importance of lipid diversity.
#VKSLipidomics21
Metabolism was once regarded as a homeostatic, housekeeping process that supported but did not instruct cell signaling, gene expression and other networks. In recent years, it has become apparent that metabolism is intimately intertwined with many other networks that determine cellular fate and tissue function, and that metabolites can transmit signals within and between cells. The impact of metabolic signaling is illustrated by the consequences of its dysregulation; we now understand that many diseases involve pathologically altered metabolism. Mutations in metabolic enzymes underlie numerous developmental disorders, and metabolic alterations in malignant cells impair cellular differentiation and fuel tumor growth. These observations have rekindled interest in disease-oriented metabolism research, which now benefits from increasingly sophisticated analytical and computational tools to understand metabolism and to localize important activities in space and time. With this new symposium, we aim to capitalize on both the technological and conceptual momentum of this budding field.
The unifying theme of this symposium is that proper development requires exquisite metabolic control, and that perturbed metabolism can result in developmental diseases. The symposium will bring together scientists exploring how metabolites impact cellular and developmental decisions in a diverse range of model systems, and mechanisms underlying developmental disorders caused by aberrant metabolism. Topics will include – but need not be confined to – the epigenetic roles of metabolites and their oncogenic potential, signalling roles of metabolites across organs, metabolic control of development, and the impact of microbiota-mediated signaling in ageing and metabolic disease. Collectively, we hope to foster collaborations across a range of disciplines, provide biological questions for emerging technologies, and ultimately develop a new conceptual framework for the study of the instructive roles of metabolites in biology and disease.
#VKSMetaDisease21