- Director of the Drukier Institute for Children's Health
- Ronay Menschel Professor of Pediatrics
I am a pediatric rheumatologist with long standing experience in Translational Research. My laboratory is focused on understanding the pathogenesis, finding biomarkers to guide therapeutic interventions and identifying therapeutic targets for human inflammatory and autoimmune diseases, including Systemic Lupus Erythematosus (SLE), various forms of Arthritis, Dermatomyositis, as well as immune responses to a broad variety of infections and vaccinations. I am Program Director of a NIAID-funded Autoimmunity Center of Excellence and a NIAMS-funded Center for Lupus Research. I have also directed the NIAID-funded Baylor Human Immunology Program Consortium Center focused on vaccine responses in health and disease. Pioneering genomic studies from my laboratory identified the role of dendritic cells and Interferon in SLE, and of cytokines such as IL1 in Systemic-onset Juvenile Arthritis, which has led to successful therapeutic interventions in this disease. More recently, we developed a personalized approach to identify molecular drivers of disease activity in pediatric SLE patients. This approach enabled us to stratify patients into seven major molecular subgroups, which might lead to improved design of clinical trials for this disease.
- Stavros S. Niarchos Professor in Pediatric Cardiology
- Professor of Pediatrics
Early work in the Lyden Lab resulted in several fundamental discoveries that involve the role of bone marrow-derived stem and progenitor cells in tumor vasculogenesis and in metastasis. Using pediatric and adult cancer models, Dr. Lyden and his colleagues made a pivotal discovery in the metastatic cascade revealing that tumor-secreted factors induce the formation of microenvironments in distant organs conducive to tumor cell survival and outgrowth. Remarkably, these microenvironments are generated prior to tumor cell arrival at these sites, an observation that led Dr. Lyden and his team to develop the concept of the "pre-metastatic niche". Work in the pre-metastatic niche has been translated to clinical care leading to advances in prediction, imaging and targeting of early metastatic disease progression. Dr. Lyden also found that tumor-secreted microvesicles, known as exosomes, initiate pre-metastatic niche via induction of vascular leakiness, stromal cell education and immunoregulation through key proteins (i.e., oncoproteins, integrins) and nucleic acids in exosomes. Tumor exosomes not only initiate pre-metastatic niche formation, but also determine organotropic metastasis, a hypothesis proposed by Stephen Paget more than 120 years ago. Dr. Lyden’s work has engendered a new appreciation for how primary tumor cells dictate future sites of metastasis by decoding how cancer-derived exosomes mediate intercellular communication. In addition, the Lyden team demonstrated the presence of double-stranded DNA in tumor exosomes. Thus, exosomal molecules may serve as valuable biomarkers for tumor detection and to follow metastatic progression.
Most recently, Dr. Lyden has identified specific exosome subpopulations (Exo-Large vesicles and Exo-Small vesicles) and discovered a new subset of particles known as exomeres, which have distinct functional roles in the systemic effects of cancer. Dr. Lyden’s group has a long-standing interest and collaborations to study the role of exosomes in pediatric cancers, such as medulloblastoma, osteosarcoma, neuroblastoma and leukemia. Last but not least, Dr. Lyden is collaborating with faculty in the Department of Pediatrics to elucidate the functional roles of exosomes and exomeres in other pediatric disorders, such as autism and systemic lupus erythematosus.
- Professor of Genetic Medicine and Pediatrics
- Distinguished Professor of Pediatric Pulmonology
Work in the Pediatric Pulmonary Research Laboratory is focused on how lungs of children with common chronic diseases respond to viral and bacterial infections. A main focus of the research efforts is on Pseudomonas aeruginosa in cystic fibrosis lung disease and common respiratory viral infections in asthma. Part of this work involves the development and assessment of novel genetic vaccines. A recent focus is on the role of sphingolipids in the development of childhood asthma and its responses to viral infections that most often trigger asthma flares in children. In addition, the laboratory is engaged in collaborative studies on mast cells and their products for lung disease of premature infants and the interaction of lung microbiota with infections in asthma and cystic fibrosis.
- Assistant Professor of Neuroscience in Pediatrics
Our mission is to understand the molecular mechanisms of neurodevelopmental and neurocognitive diseases such as autism and schizophrenia. Our projects focus on RNA molecules and how they control neuronal development. We also would like to understand the contribution of glial cells and interneurons to defects seen in neurocognitive diseases.
LABORATORY OF DIABETES AND OBESITY SIGNALING: Terminal cell differentiation is crucial for developing, maintaining, and regenerating tissues in all multi-cellular organisms. The overarching focus of the Teruel Lab is to understand how to control terminal differentiation in order to maintain a dynamic balance between progenitor and differentiated cells that ensures healthy tissue development and prevents disease. To tackle this problem, my lab developed a platform to understand adipogenesis (fat cell differentiation) and other differentiation processes based on live and fixed-cell microscopy and analysis tools to simultaneously monitor and perturb signaling, cell cycle, and differentiation processes in thousands of single cells. To validate the relevance of our discoveries, we combine in vitro cell culture, organoid, and in vivo mouse models.
- Assistant Professor of Immunology in Pediatrics
My laboratory is focused on studying how dysregulated interactions between immune cells of the gut and gut microbiome at the maternal-fetal/neonatal interface contribute to the development of neonatal or pediatric inflammatory diseases. Specifically, ongoing studies in my laboratory involve in vitro cell biology assays, disease models in gnotobiotic mice and examination of clinical samples from newborns and children. We recently reported the presence of antigen-specific IgG antibodies that were induced by gut commensal bacteria under homeostatic conditions and a protective role for these pre-existing antibodies in conferring rapid protection against systemic pathogenic infections in mice, due to cross-reactivity to conserved IgG antigens expressed on pathogens. As a result, current efforts in the lab are centered on understanding the role of maternal gut microbiome-induced immune components in neonatal inflammatory complications, such as premature birth and necrotizing enterocolitis. An overarching goal for these studies is to develop strategies to use gut bacteria or bacterial components as candidates for maternal immunization to help facilitate appropriate immune responses in the fetus during pregnancy or in the newborn after birth. Another research effort is to identify gut bacteria in the newborn that induce aberrant gut inflammation, which is associated with development of food allergies, asthma or obesity in later life. Our diet or gut microbiome contributes significantly to the development of these kinds of inflammatory disorders commonly found in children from most developed countries. Understanding the underlying mechanisms will advance the development of therapeutics for these diseases.
- Director of the Englander Institute for Precision Medicine
- Professor of Physiology and Biophysics
- Professor of Computational Genomics in Computational Biomedicine
The focus of my research group is on the systems biology of cancer; we focus on prostate cancer and hematological malignancies. In these cancers, we are elucidating the patterns of aberrant pathway activities, rewiring of regulatory networks and cancer mutations that have occurred in cancer cells. We are also trying to understand how tumors evolve at the genomic and epigenomic level. We use high-throughput sequencing (ChIP-seq, RNA-seq, bisulfite conversion followed by sequencing – specifically RRBS-, ATAC-seq, exome capture and sequencing, single cell RNAseq using DropSeq) to decipher epigenetic mechanisms and regulatory networks at play in malignant cells and study how they affect gene expression. My lab has developed several computational approaches for analysis of deep sequencing data, e.g. ChIPseeqer (for integrative analysis of ChIP-seq data) and SNVseeqer/INDELseeqer (full pipeline for mutation detection and characterization from deep sequencing data). My lab has developed several additional computational approaches that include a pathway analysis tool (iPAGE) several tools for regulatory element detection (FIRE and FastCompare) and RRBseeqer for ERRBS analysis (including detection of differentially methylated regions). We use drug repositioning to identify small molecules that can target mutated signaling pathways and classically undruggable proteins such as transcription factors. We model complex signaling pathways to identify drug combinations that can most efficiently shutdown aberrantly active pathways in cancer.
- Brine Family Professor of Cell & Developmental Biology
- Professor and Vice Chair for Research
- Associate Dean for Faculty Development
Dr. Katherine Hajjar is physician-scientist, Professor of Pediatrics, Professor of Medicine, and the Brine Family Professor of Cell and Developmental Biology at the Weill Cornell Medical College. She received her undergraduate degree from Smith College, and her MD degree from the Johns Hopkins University School of Medicine. She completed clinical training in Pediatrics at Children’s Hospital of Pittsburgh, where she also served as Chief Pediatric Resident, and completed a fellowship in Pediatric Hematology-Oncology at Johns Hopkins University School of Medicine. She has been a member of the faculty at Weill Cornell since 1984.
Dr. Hajjar’s lab studies the biologic roles of the annexins, a family of calcium-sensing, membrane-binding proteins. Her lab identified the major endothelial cell fibrinolytic receptor as the annexin A2 complex, and defined its binding interactions with plasminogen and its activator tissue plasminogen activator. She created the annexin A2 deficient mouse and related knockouts, and demonstrated that A2 is critical for normal hemostasis in mice and humans. Dr. Hajjar also defined the role of annexin A2 in pathologic angiogenesis, and, based on these findings, her group is now developing a first-in-class therapeutic agent for retinopathy of prematurity and diabetic retinopathy. Other projects in her lab explore the role of the annexin A2 system in the regulation of vascular permeability and innate immunity.
Dr. Hajjar is a member of the American Society for Clinical Investigation, the Association of American Physicians, and the American Clinical and Climatological Association. She is also a fellow of the American Association for the Advancement of Science, and Member-at-Large of its Section on Medical Sciences. She is the recipient of an Established Investigator Award from the American Heart Association (AHA), a Syntex Scholar Award, the AHA’s Irvine Page Award, and the Key to Life Award from the Children’s Blood Foundation. She has served as president of the New York Society for the Study of Blood, the Interurban Clinical Club, and the Harvey Society. She has organized numerous international meetings and workshops, and served on multiple review panels and editorial boards.
- Assistant Professor of Pathology and Laboratory Medicine
(1) Functional Histone Genetic Experiments in a Mouse Model:
There exists a gap in our understanding of fundamental epigenetics in complex organisms. This is because most of what we know of histone function comes from elegant genetic experiments performed in model organisms that share a common ancestor with humans and mice more than 500 million years ago. In this work, we are developing tools to perform functional histone genetic experiments in mouse. The goal is to provide the capability to perform functional studies of histone genes and residues in vivo in a mammalian model system. Given our focus on the hematopoietic and immune systems, and their function, there is an exciting potential for this project to synergize with other work in the lab and for expanding these tools to study the role of histone residues in epigenetic features of immunity such as immunologic memory, immune cell exhaustion, “trained immunity” (see below), and more.
(2) Mechanisms and Function of Epigenetic Memory of Inflammation in Hematopoietic Stem Cells:
The term "trained immunity" indicates an organism's durable memory of inflammation that is independent of immunologic memory as mediated by adaptive immune cells. It has become clear that such memory can reside in the hematopoietic stem cell (HSC) compartment. The implications of such memory are remarkable and likely to feature in immunity, autoimmunity, and vaccine responses, but the mechanisms of transcriptional and epigenetic regulation of this "training" in HSCs are unknown. We explore these mechanisms and functional implications of “HSC training”, leveraging a specialized toolkit for working with HSC, functional histone genetic experiments, epigenomic assays (including HiC, small cell number ChIP). We are especially interested in investigating epigenetic “memory” of childhood inflammatory events and if these may contribute to pediatric inflammatory disease.
(3) “Signaling to Chromatin” Pathways in Immune Cell Development and Function:
We study how immune signaling events are transmitted to chromatin to selectively induce inflammatory genes in macrophages responding to inflammatory cues. These studies establish the cooperative role of epigenetic mechanisms (histone modifications) and transcription factor activity— both regulated by signaling kinases— highlighting the coordinated function of these factors. Our ongoing studies are revealing epigenetic mechanisms that have dedicated function in rapid stimulation-induced transcription, critical for immunity and coopted in cancer. Targeting such dedicated mechanisms that enable inflammatory gene (and oncogene) induction may provide more selective therapeutic strategies for diverse inflammatory diseases and cancer. A long term career goal is to apply mechanistic knowledge of epigenetic regulation of inflammation to better understand inflammatory disease, trained immunity, immune cell exhaustion, and other epigenetic immune phenomena.
- Assistant Professor of Clinical Pediatrics
Dr. Perdita Permaul is a clinical investigator, pediatric allergist/immunologist and an assistant professor of pediatrics at Weill Cornell Medicine. She completed her undergraduate degree at the University of Pennsylvania, her medical degree at the Icahn School of Medicine at Mount Sinai, and completed her pediatric residency at New York-Presbyterian/Weill Cornell Medical Center. She then moved to Boston and continued her training at Boston Children’s Hospital, where she completed a fellowship in Allergy and Immunology. During her three-year fellowship, she served as a research fellow in the Division of Pulmonary and Critical Care Medicine at Brigham and Women’s Hospital where she participated in the development and execution of asthma clinical trials of the Asthma Clinical Research Network (ACRN)/NHBLI. Upon completing fellowship, Dr. Permaul continued on as a pediatric allergist and immunologist at Massachusetts General Hospital and assistant professor of pediatrics at Harvard Medical School until her return to Weill Cornell.
Dr. Permaul has authored a number of scientific papers, reviews and book chapters on original research showing how indoor allergen exposures affect asthma outcomes in urban children with asthma, both in the school and home environments. Her current clinical/translational asthma research is supported by grant funding from the National Institutes of Health (NIH) to study the interactions between childhood obesity, the environment, and asthma morbidity in an established cohort of inner-city children with asthma. Obesity and asthma are two chronic childhood diseases that have shown a striking surge in prevalence over the past two decades. Obese children with asthma experience significantly greater symptoms, poor response to inhaled corticosteroid therapy, loss of asthma control, and higher asthma-associated health care utilization. The underlying pathophysiologic mechanisms for explaining why obesity leads to poorly controlled asthma is largely unknown. Ongoing work has focused on studying how obesity related systemic inflammation contributes to the development of severe asthma in children through profiling of cytokines and other inflammatory and immune mediators. Dr. Permaul is also a co-investigator of NIH funded multi-center pediatric asthma clinical trials focused on early interventions to prevent the development of asthma.
- Friedman Family Foundation Clinical Scholar in Newborn Medicine
- Assistant Professor of Pediatrics
Matthew Smith-Raska is a neonatologist who is studying the role of epigenetics in fetal and neonatal growth and development. Dr. Smith-Raska obtained his MD and PhD degrees from Columbia University, where he studied the stem cell-like properties of T lymphocytes. He then completed Pediatric Residency at UCLA, and Fellowship in Newborn Medicine at Boston Children’s Hospital, where he served as Chief Fellow. He came to Weill Cornell in 2018, where his research is focused on the role of epigenetic processes in fetal growth and neurodevelopment. Dr. Smith-Raska also cares for patients in the Neonatal Intensive Care Unit in the Weill Cornell Department of Pediatrics.