Affinity Groups
Scientists and physicians in the NICHD Division of Intramural Research (DIR) are organized into 14 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
We use 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 use of zebrafish as a research tool for investigating biological processes in vivo. The five 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 Bldg 6 complex, create a critical mass of talent unsurpassed at NIH.
The affinity 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 members of the affinity group promote the exchange of reagents and technical information to ensure that researchers at NICHD remain at the cutting edge of zebrafish research worldwide.
Basic Mechanisms of Genome Regulation
The mission of the Basic Mechanisms of Genome Regulation 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 our understanding of both health and disease. The members of the BMGR group have a strong history of producing knowledge-changing advances in several fundamental processes 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 BMGR group is a unique collection 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 BMGR members, as well as others, has revealed that although these processes are ubiquitous, defects in them are often manifested as specific health disorders with distinctive deficiencies in development and with tissue-specificity, or in cancer. Inherent to the mission is to increase understanding of how natural genetic diversity in a population contributes to these fundamental processes in ways that affect disease and to apply such knowledge so that specific strategies for improving health can be developed.
The vision is to elucidate new knowledge about fundamental processes that will promote the 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, the BMGR group will continue to generate new knowledge relevant to the fundamental processes essential to growth, development, and health.
The BMGR 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, they extend beyond the tissue-specific gene expression aspects of animal development and provide unique perspectives into growth, development, and disease. Indeed, different defects in a single process can be manifested as different diseases. Given the NIH's penchant for high-risk endeavors, the BMGR group and the many collaborations among its member foster a greater depth and breadth of fundamental discovery than would exist in its absence.
Behavioral Determinants and Developmental Imaging
The mission and vision of the Behavioral Determinants and Developmental Imaging Group is to understand determinants of behavior and behavioral changes occurring during development using its unique nonhuman primate (NHP) and normative and clinical populations. Novel in vivo structural and functional imaging methods will be developed and applied to provide correlative information to assist in addressing these processes and potentially provide translational methods for assessing salient changes in the developing brain. In collaboration with the Perinatal and Obstetrical Group, we plan to develop new imaging tools to scan pregnant mothers and children from the fetal period to young adulthood and to coordinate resulting insights in brain development with parallel studies of the ontogeny of cognition, emotion, and behavior. With the Neurosciences Group, we plan to study possible neuroanatomical sequelae of plasticity and learning in these populations.
We seek greater understanding in the identification of quantitative in vivo imaging biomarkers for salient functional or structural changes in the brain associated with cognitive and emotional behavior or cognitive changes or abnormalities that could be used clinically or as enabling technologies in the neurosciences. We also seek to better integrate and correlate imaging (i.e., radiological) changes in the developing brain and gene expression changes in human and NHP populations.
Bone 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.
- Anirban Banerjee
- Juan Bonifacino
- Andres Buonanno
- Mary Lilly
- Jennifer Lippincott-Schwartz
- Matthias Machner
- 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 to enhance understanding of how dysregulation of these processes contributes to human disability and disease.
By combining expertise in the genetics of model organisms (including transgenic and null mouse models), cell biology, biochemistry, molecular biology, biophysics, and enzymology, 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 will facilitate future discoveries in the areas of molecular mechanisms of synaptic circuit assembly and function, the mechanisms and regulation of protein synthesis and transcriptional activation, the functions and regulation of GRTH/DDX25 in spermatogenesis, the role of signaling pathways in transcriptional control of LH and Prolactin receptors, the identification of molecular markers for diagnosing and treating prostate diseases, 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, and the mechanisms governing adult organ formation during postembryonic vertebrate development.
- Mary Dasso
- Tom Dever
- Maria Dufau
- Alan Hinnebusch
- Chi-Hon Lee
- Henry Levin
- Jon Lorsch
- Ida Owens
- Mihaela Serpe
- Yun-Bo Shi
Developmental Endocrine Oncology and Genetics
The mission and vision of the Developmental Endocrine Oncology and Genetics Group is to 1) establish new and improved methods, strategies, technologies, and algorithms for the diagnosis, localization, and management of various endocrine tumors, 2) explain the molecular basis for different clinical presentations and establish pathways of tumorigenesis for these tumors, 3) search for new molecular, genetic, proteomic, and metabolomic markers for the development of better diagnosis and localization and seek novel targets for the treatment of metastatic endocrine tumors and biomarkers for predicting responses to therapies, 4) facilitate the implementation of newly available diagnostic techniques and treatment options, including the initiation of new clinical trials, 5) facilitate new and improved intramural, national, and international collaborations, interdisciplinary studies, and team approaches, and 6) facilitate the establishment of national and international databases/networks and train physician-scientists in endocrine tumors.
- Peter Backlund (Mass Spectrometry Core)
- Maya Lodish (Pediatric Endocrinology Inter-Institute Training Program)
- Karel Pacak
- Constantine Stratakis
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.
Integrative Membrane, Cell, and Tissue Pathophysiology
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 Integrative Membrane, Cell, and Tissue Pathophysiology 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, cryoelectron 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.
Metals Biology and Molecular Medicine
The mission and vision of the Metals Biology and Molecular Medicine Affinity Group is to continue our current research in the areas of metal biology and implications for pathophysiology and treatment of human diseases, including gene therapy. There is much synergy to be gained by comparing mechanisms for maintenance of iron and copper homeostasis.
Neurosciences
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 the underlying basic biological processes in both health and disease.
- Tamás Balla
- R. Douglas Fields
- Dax Hoffman
- Y. Peng Loh
- Chris McBain
- Vincent Schram (Microscopy and Imaging Core)
- Mark Stopfer
Pediatric Endocrinology, Metabolism, and Molecular Genetics
The mission of the Pediatric Endocrinology, Metabolism, and Molecular Genetics Affinity Group is to advance our understanding of endocrine, genetic, and metabolic disorders 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 develop new diagnostic and therapeutic approaches.
Perinatal and Obstetrical Research
The mission and vision of the Perinatal and Obstetrical Research Affinity Group is to 1) To conduct clinical and translational research to elucidate mechanisms of disease responsible for pregnancy complications, and to develop diagnostic, prognostic, therapeutic and preventive strategies to reduce adverse pregnancy outcome; and 2) To train physicians and scientists in the areas of obstetrics and perinatal medicine.
Reproductive Endocrine and Gynecology
The reproductive endocrine and gynecology affinity group consists of the primary investigators in NICHD 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.
