Scientists and physicians in the NICHD Division of Intramural Research (DIR) are organized into 12 affinity groups (AGs). Each AG is an intellectual hub for a group of investigators, creating a forum to share ideas and collaborate around common themes in support of the DIR mission.
The AGs serve as catalysts for new initiatives. Each investigator has a primary affiliation with an AG most closely aligned with his or her scientific interests. Secondary affiliations allow for communication across specialties in support of translational research and new collaborations.
Each AG has its own mission statement, shared research goals and objectives, and resources. Collectively, the AGs contribute to recruitment, mentoring, and the annual DIR scientific retreat.
Aquatic Models of Human Development
The Aquatic Models of Human Development Group uses zebrafish as a model vertebrate organism to study human development. We exploit the advantages of the zebrafish model for genetic screens, genomic manipulation, microscopic imaging, and cell and behavioral biology to gain insights into mechanisms controlling human development and defects therein that can result in disease. By maintaining a high level of expertise and resources, the group lowers the barrier to entry for other researchers in the intramural program for useof zebrafish as a research tool for investigating biological processes in vivo. The four PIs and the Zebrafish Core Facility, along with approximately 30 postdocs, doctoral trainees and technical staff, all focusing on zebrafish as a model system and all working in the Building 6 complex, create a critical mass of talent unsurpassed at NIH.
The group specializes in the generation of induced and engineered mutations and transgenic zebrafish lines that are used to study in vivo the function and integration of regulatory factors and pathways that are critical to the development, health, and survival of vertebrates, including humans. Extensive formal collaborations and informal interactions between group members promote the exchange of reagents and technical information to ensure that NICHD researchers remain at the cutting edge of zebrafish research worldwide.
Bone and Matrix Biology in Development and Disease
Matrix biology is central to the NICHD mission because it is intrinsic to the formation and reshaping of tissues before and after birth. This group aims to elucidate the mechanisms by which primary gene defects cause skeletal fragility and other matrix disorders and to apply this knowledge to the treatment of affected children. This goal is pursued with a close relationship between basic, translational, and clinical science.
The current primary focus of the group is on translational studies of skeletal dysplasias and related bone disorders. We have identified and characterized molecular mechanisms of several novel skeletal development disorders in this spectrum. In addition to building on these successes and expanding our knowledge of mechanisms and pathology of skeletal development, we are developing novel approaches to therapeutic intervention, which will be translated to clinical trials. We are expanding our research to extracellular matrix (ECM) development and pathology in other tissues and organs. We also anticipate expanding our research program toward studies of ECM disorders in placenta, cartilage, growth plate, and other tissues and organs that are involved in fetal health, prematurity, and early child growth and development.
Cell and Structural Biology
The Cell and Structural Biology Group (CSBG) conducts basic research on the molecular mechanisms that underlie fundamental cellular processes, such as organelle biogenesis and function, regulation of cell metabolism by small RNAs, small proteins, post-translational modifications and developmental programs, host-pathogen interactions, and the structure, traffic, and function of signaling proteins in the central nervous system. Knowledge gained from these studies is applied to the elucidation of the pathogenesis of various diseases, including neurodevelopmental, behavioral, and neurodegenerative disorders, metabolic disorders, and infectious diseases.
The CSBG has outstanding facilities for microscopic imaging of cell structure and function and for recombinant protein production in multiple prokaryotic and eukaryotic expression systems for X-ray crystallographic and biochemical analyses. In addition, the group has expertise in generating targeted mutations in rodents and in the anatomical, neurochemical, electrophysiological, and behavioral analyses of the mutant animals.
- Matthias Machner, Head
- Philip Adams
- Anirban Banerjee
- Juan Bonifacino
- Andres Buonanno
- Mary Lilly
- Gisela Storz
Cell Regulation and Development
The mission and vision of the Cell Regulation and Development Group is to increase fundamental knowledge of basic molecular mechanisms of cell biology and animal development and enhance understanding of how dysregulation of these processes contributes to human disability and disease.
By combining expertise in the genetics of model organisms (including yeast, fruit fly, frog, zebrafish, and mouse), cell biology, biochemistry, molecular biology, electrophysiology, biophysics, genomics, and structural biology, members of the Group advance individual research objectives by regularly providing insights and advice to one another and through collaborations enabling synergy in research methods and experimental approaches. These interactions have engendered the development of novel technologies and strategies that underlie past accomplishments and will facilitate future discoveries by the Group in areas including the mechanisms and regulation of protein synthesis and transcriptional activation of gene expression, the functions and regulation of hormone receptors, signaling events and their responsive genes, mechanisms governing accurate segregation of the genetic information during cell division, mechanisms of nucleocytoplasmic trafficking, RNA processing and RNA export, technologies based on transposable elements and deep sequencing for genome-wide profiles of gene function, the role of transposable elements in reorganizing the host genome in response to stress, technologies for analyzing gene expression at the single cell level during development, transcriptional control of the specification and differentiation of cells during vertebrate embryogenesis, the mechanisms governing adult organ formation during postembryonic vertebrate development, and molecular mechanisms of synaptic circuit assembly and function.
- Alan Hinnebusch, Head
- Mary Dasso
- Tom Dever
- Maria Dufau
- Jeffrey Farrell
- Henry Levin
- Jon Lorsch (NIGMS)
- Mihaela Serpe
- Yun-Bo Shi
Developmental Endocrinology, Metabolism, Genetics, and Endocrine Oncology
The mission of the Developmental Endocrinology, Metabolism, Genetics and Endocrine Oncology (DEMGEO) Affinity Group Affinity Group is to advance our understanding of endocrine, genetic, and metabolic disorders and endocrine tumors that impair human development, causing disease and disability. The research in this group encompasses basic, translational, and clinical science to elucidate the etiology of these diseases and to develop new diagnostic and therapeutic approaches.
- Karel Pacak, Head
- Jeffrey Baron
- Janice Chou
- Deborah Merke (CC)
- Anil Mukherjee
- Forbes Porter
- Kristina Rother (Training Program)
- Stanko Stojilkovic
- Constantine Stratakis
- Jack Yanovski
- NIH Inter-Institute Endocrinology Training Program)
Genetics and Epigenetics of Development
The mission of the Genetics and Epigenetics of Development Group is to research the genetic and epigenetic mechanisms that control reproduction, embryogenesis, and organ system development. Our vision is to apply the knowledge gained to enhance human health.
Genomics and Basic Mechanisms of Growth and Development
The mission of the Genomics and Basic Mechanisms of Growth and Development (GBMGD) group is to do basic research into the molecular mechanisms of fundamental processes ubiquitous to all cells. Such research inevitably results in new knowledge that impacts understanding of both health and disease. The members of the GBMGD group have a strong history of producing knowledge-changing advances in a number of fundamental processes that are essential to life; DNA replication, DNA repair, nucleotide metabolism, RNA biogenesis and metabolism, chromatin-mediated control of gene expression, and genome integrity. Simply put, the GBMGD is a unique group of world experts in processes involving DNA and RNA metabolism and the consequences of alterations of these processes to cells and organisms. Recent advances from work by GBMGD members, as well as others, has revealed that although these processes are fundamental and ubiquitous, defects in them are often manifested as specific health disorders with distinctive phenotypes affecting human development and with surprising tissue-specificity, or in cancer. Indeed, a substantial number of the most common clinically relevant genetic disorders affecting children are due to polymorphisms/mutations in factors required for the maintenance of basal cellular functions. Inherent to the GBMGD mission is to increase understanding of how natural genetic diversity in the human population contributes to these fundamental processes in ways that affect health and disease, and to apply such knowledge so that specific strategies toward improving health can be developed.
The vision of the GBMGD group is to elucidate new knowledge about fundamental processes that will promote discovery of novel strategies for treatment and prevention alternatives across a multitude of diseases that share involvement of altered nucleic acid metabolism, gene expression and genome integrity. Through basic research that incorporates modern advances in biochemistry, genetics and genomics, GBMGD group members will continue to generate new knowledge relevant to the fundamental processes essential to growth, development and health.
The GBMGD group vision includes the promotion of collaborations and communication that support its mission. This group has the ability to discover fundamental aspects of growth and development from multifaceted perspectives and disciplines, and to investigate how disturbances in one process can affect another. Because our interests are not principally focused on any particular disorder or discipline, they extend beyond classical developmental biology and the gene pattern-specific expression aspects of animal development. By focusing on basal cellular functions, the GBMGD approach provides unique and complimentary perspectives on developmental biology and growth in health and disease states. Given the NIH’s tolerance to high-risk endeavors not usually fostered elsewhere, the GBMGD group, and the many collaborations among its members, fosters a greater depth and breadth of fundamental discovery than would exist in its absence.
Maternal-Fetal Medicine and Translational Imaging
The mission of the Maternal-Fetal Medicine and Translational Imaging Affinity Group is to understand the biology of normal pregnancy and its complications, as well as normal/abnormal neurodevelopment during childhood by the application of innovative, state-of-the art cellular, molecular, and imaging methods to improve the diagnosis, treatment, and prevention of conditions responsible for maternal, perinatal, and infant morbidity and mortality.
Quantitative Imaging and Tissue Sciences (Basser) invents, develops, and translates novel in vivo microstructural and functional MRI methods designed to measure salient properties of the developing brain and assess and characterize their changes in diseases and disorders. These novel quantitative imaging biomarkers are also used in neuroscience application to characterize brain network connectivity and dynamics, as well as brain tissue architectural organization.
Nervous System Development and Plasticity (Fields): Our research is concerned with understanding the molecular and cellular mechanisms by which neural activity and experience regulates development and plasticity of the nervous system, with three main areas of emphasis: (1) myelination and neuron-glia interactions, (2) cellular mechanisms of learning, and (3) gene regulation by neuronal firing.
Translational Biophotonics (Gandjbakhche) uses multi-disciplinary approaches to devise functional imaging technologies and methodologies for translating benchtop studies to the bedside. For example, near infrared spectroscopy and electroencephalogram are used to assess biomarkers for a wide range of brain development abnormalities and injuries, specifically, but not limited to, cognitive and behavioral disorders in children and traumatic brain injury. The laboratory explores endogenous (scattering and absorption) and exogenous (using fluorescence probes) optical contrast mechanisms for characterizing abnormal development and function in tissues such as the placenta. They also are involved in clinical and preclinical studies aimed at characterizing growth and development of various abnormal tissues and monitoring the efficacy of their treatment using photonics methods, such as fluorescence life time and multi spectral imaging.
Intercellular Interactions (Margolis) studies viral and non-viral pathogenesis in the context of human tissues. The laboratory developed a system of ex vivo human tissues that preserves their cytoarchitecture and important in vivo functions, and it studies lymphoid, cervico-vaginal, and placenta tissues to investigate mechanisms of cell-cell, cell-pathogen, and cell-extracellular vesicles interaction under normal as well as disease conditions.
Perinatology Research (Romero) investigates normal pregnancy and its most frequent complications such as preterm labor, preterm prelabor rupture of membranes, preeclampsia, fetal growth disorders, and fetal death—conditions which account for the excessive rate of infant mortality in the United States. The Laboratory conducts clinical and translational research and develops diagnostic, predictive, therapeutic, and preventative methods to reduce adverse pregnancy outcomes.
Biomedical Optics (Tromberg) develops models, methods, and devices for understanding and controlling light interactions with biological tissues. These methods are used to perform real-time quantitative measurements of clinically-relevant information, including: tissue blood flow, oxygen extraction, metabolic rate of oxygen consumption, and body/tissue composition (lean mass, hydration, and fat mass). Advanced capabilities include continuous dynamic monitoring of intrinsic physiological signals that can be used in feedback optimization for guiding therapies and clinical decision making. Our technology development effort includes portable, bedside, non-contact and wearable sensor platforms, as well as the design and integration of probes into instruments for minimally invasive surgical feedback and guidance.
- Roberto Romero, Head
- Peter Basser
- R. Douglas Fields
- Amir Gandjbakhche
- Leonid Margolis
- Bruce Tromberg (NIBIB)
The Molecular Medicine Group brings together basic research programs that share the ultimate goal of developing treatments for human diseases through a better understanding of their pathophysiology. Main areas of research focus include the maintenance of iron homeostasis and mechanisms underlying neurodegeneration. At the intersection of our work, we hope to shed light on a group of rare diseases called neurodegeneration with brain iron accumulation or NBIA, which may also have broader implications for other types of related diseases.
Understanding the structure and function of the nervous system is a prerequisite for predicting and treating neuropathologies. Our group uses a variety of preparations, including animal models and human tissue, and a variety of techniques to study the biology of development and function of the nervous system and underlying basic biological processes in both health and disease.
Physical Biology and Medicine
Human development, on which the future child's health depends, is a complex phenomenon within the female starting with egg-spermatozoa fusion. In each individual, a plethora of molecular recognition events mediate the development of an immune system to defend against pathogens, a musculoskeletal system to maintain the body, and flexible networks of molecular expression to manage environmental stress. Traditionally, studies of these processes are divided into biochemistry, cell biology, virology, toxicology, etc. However, nature does not know these artificial divisions, and new understandings emerge from the crucible that interfaces mathematically minded physical scientists with biomedical researchers. The Physical Biology and Medicine Group is a unique scientific body that approaches human development in normal life and pathology as an integral process and encompasses first-class cell biologists, physical chemists, biophysicists, virologists, and immunologists who not only successfully train postdocs and students within their own fields, but widely collaborate, building and uniquely promulgating multidisciplinary approaches to the most important biomedical problems in the framework of the NICHD mission.
By choosing carefully which biophysical projects really answer the fundamental problems that limit advancement in medicine, we as a group will suffuse these identified problems with our basic wisdom of biophysics. This wisdom includes a deep knowledge of polymer physics, membrane biology and virology, inter- and intracellular communication, the theory of transporters and diffusion of domains, the physics of channel permeation and protein conformational change, the physical chemistry of membrane hydration forces and recognition, the physiology of cell signaling and receptor activation, lipid/protein interactions, and the physiology of secretion, viral infection, parasite invasion, fertilization, adipose transporter trafficking and insulin signaling, and developmental cell fusion. Our strategy is to sharpen our techniques and power of observation to prove our discoveries, including proteomic architecture of signaling complexes and cellular structures, TIRF microscopy, long-term live-cell time-lapse imaging of tissue and cultured cells, confocal and two-photon scanning microscopy, electrophysiology, physical theories to devise experimental tests of hypotheses, cryo-electron microscopy, and lipidomic analyses.
We are now in a position to tackle the developmental changes seen in obesity and genetic disorders, the pathophysiology of influenza, dengue, and HIV viral infection and assembly, a 3D immunohistochemical microscopy of normal and compromised placenta at super-resolution levels, the use of human brain culture in dissociated and slice culture to study traumatic brain injury and glioblastomal neoplasia, membrane domain organization, regulation of mitochondrial metabolism by cytosolic proteins, and muscle molecular ultrastructure. We currently anticipate testing if hydrogen bond theory can explain hydration repulsion of DNA and membranes, developing a deeper understanding of mechanical, electrical, and chemical interactions in complex, multicomponent cell communities, achieving the conceptual integration of cutting-edge immunological information and assays for cell-cell communication in the onset of tissue pathology and discovering the role and mechanisms of microRNA vehicles in serum.
Reproductive Endocrinology and Infertility and Pediatric and Adolescent Gynecology
The Reproductive Endocrinology & Infertility and Pediatric & Adolescent Gynecology Group consists of the primary NICHD investigators who carry out research and clinical care in women's health. Our mission is to conduct innovative translational research and provide direct patient care in reproductive endocrinology and gynecology. Consultative services are provided to all NIH institutes.