The Research Affinity Group structure at Children’s Hospital reflects the increasingly interdisciplinary and multidisciplinary nature of many key research questions. This approach aligns with the emerging national consensus that multidisciplinary centers are essential to advancing the nation's research agenda.
The Institute designed the Research Affinity Group structure to build on areas of existing strength, identify new and important research areas, and explore important, broad and interdisciplinary scientific questions that may have an impact on the health of children. Our investigators now collaborate across disciplines more easily to address issues of central importance to children's health. This collaboration has the potential to link multi-talented investigators with common research interests who are widely dispersed through the Institute.
Here are our current Research Affinity Groups:
Leader: Pam Weiss, MD, MSCE
The Clinical Trials Research Affinity Group was created to build a community of investigators conducting clinical trials at CHOP and the greater UPENN community. The goals of this group are to: 1) Establish a collaborative network of investigators with knowledge of or interest in clinical trials; 2) Serve as a liaison between investigators, the CHOP Research Institute and hospital administration to facilitate not only the conduct and enhancement of on-going trials but also the start-up of new trials within the CHOP network; 3) Provide a forum to keep investigators informed about the changing face of clinical trials (methodologies, regulations); 4) Facilitate identification of shared barriers to the conduct of trials and development of streamlined solutions.
Leaders: Judy Grinspan, PhD, and Stewart Anderson, MD
Understanding developmental biology is fundamental to the diagnosis, management and cure of childhood disorders. The mission of the Developmental Biology program at CHOP is to investigate the fundamental mechanisms of developmental and translate this work into improved, scientifically based, care for all children. In addition to being engaged in cutting edge basic and translational research, we seek to provide training for the next generation of Pediatric Physician/Scientists. The mission of education will be advanced through a seminar series that focuses on bringing the most recent and exciting advances in the field to CHOP.
Led by Judy Grinspan, PhD, and Stewart Anderson, MD, the affinity group alos provides a forum for students and fellows to present their work and receive feedback from faculty and other students and fellows. Finally, the developmental biology program has been conceived and is being implemented as an interdepartmental and interdivisional Program positioned to augment and elevate existing research efforts at CHOP. This program aspires to implement a "bench to bedside and back to the bench" paradigm inherent when developmental biology research is tightly linked to the care of children.
Fetal Biology and Therapy
Leader: Alan Flake, MD
The convergence of technologies in modern medicine suggests that essentially all anatomic and genetic diseases could one day be diagnosed early in gestation. Early diagnosis could enable physicians to not only treat fetal disease, but also to anticipate childhood and adult disease. Led by Alan Flake, MD, the Fetal Therapy Research Affinity Group investigates the possibilities for treating many disorders during fetal development, which may provide a therapeutic “window of opportunity” for treatment.
As part of its mission, the affinity group facilitates interaction between a diverse group of Children’s Hospital investigators interested in fetal biology and therapy. Investigators focus on fetal diagnosis and treatment, maternal aspects of fetal therapy, new methods of minimally invasive intervention, treatment of anatomic malformations, and fetal stem cell or gene therapy.
As part of its mission, the affinity group facilitates interaction between a diverse group of Children's Hospital investigators interested in fetal biology and therapy. Investigators focus on fetal diagnosis and treatment, maternal aspects of fetal therapy, new methods of minimally invasive surgical or fetoscopic intervention, treatment of anatomic malformations and fetal stem cell or gene therapy.
Some specific areas of research focus the affinity group centers on include congenital diaphragmatic hernia, a defect in the diaphragm that allows the abdominal organs to enter the chest cavity, as well as pharmacological and gene therapy approaches to pulmonary vascular hypertension. To this end, fetal therapy investigators are developing models of congenital lung malformation and abdominal wall defects.
In collaboration with the Hospital’s Center for Fetal Diagnosis and Treatment and the Fetal Heart Program, the Fetal Therapy Affinity Group is developing techniques for fetal cardiac intervention, and researchers are also investigating stem cell and gene therapy in utero, with the clinical goal of treating sickle cell disease and other hematologic disorders.
Genes, Genomics, and Pediatric Disease
Leaders: Nancy Spinner, PhD and John Maris, MD
Genetics is a discipline with unique implications for pediatric medicine and the field impacts all aspects of childhood healthcare. As new technologies have allowed for increasingly precise probing of the genome, the field has undergone tremendous growth in recent years. The completion of the Human Genome Project provided the essential roadmap for these studies, and the creation of robust methods for defining the entire genetic and epigenetic architecture of an organism or even an individual cell has catalyzed discoveries that are shaping modern pediatric clinical care.
Genetics and genomic research at Children’s Hospital is multifaceted and spans many divisions. These research efforts are conducted in the Genes, Genomes, and Pediatric Disease Research Affinity Group, which is led by Nancy B. Spinner, PhD and John M. Maris, MD The affinity group houses an outstanding program focused on the molecular genetic basis of human disease. Major recent advances include discovering the genetic basis of many human conditions, application of molecular diagnostics in the everyday clinical setting, discovery of the mechanisms by which genetic alterations lead to disease, and a translational genomics program that has led to new therapies in pediatric cancers and other conditions.
Because genomic medicine is by definition multidisciplinary, the GGPD research affinity group further enables ongoing collaborative research efforts at Children’s Hospital. The affinity group has a successful monthly chalk talk series for CHOP investigators, and a monthly seminar series that draws international experts from around the country. These activities provide a forum for establishing or extending collaborations with colleagues at CHOP, the University of Pennsylvania and at leading institutions worldwide.
Leader: Liz Lowenthal, MD, MSCE
The Global Health Research Affinity Group will provide a formal structure to bring together local CHOP-based researchers interested in and/or conducting Global Health research and other stakeholders (e.g., IS, research finance, development, bioinformatics). This collaboration will link multi-talented investigators with common research interests and implementation challenges who are widely dispersed throughout CHOP’s Research Institute.
- Provide a forum for educational and networking opportunities to enhance knowledge of existing resources within CHOP and on the Penn campus at large to support international pediatric research.
- Foster collaborative efforts to expand CHOP’s infrastructure to support pediatric research collaborations between CHOP and Penn researchers and partners in resource-limited settings.
- Serve as a liaison between CHOP Global Health and the CHOP Research Institute on needs and prioritization of resources to enhance and facilitate the work of CHOP researchers working in resource-limited settings.
Health and Behavior
Leaders: Stephen Leff, PhD and Joel Fein, MD, MPH
The Health and Behavior Research Affinity Group (RAG) is a multidisciplinary network of researchers from CHOP, PENN, and other research institutions throughout Philadelphia (such as Drexel and Temple) devoted to further understanding the direct and indirect effects of behavior on children’s health.
The goals of the Health and Behavior RAG are to strengthen the community of researchers in health and behavior research by enhancing multidisciplinary and translational activities and initiatives, and provide leadership and support to the Children’s Hospital community for research questions and activities related to behavior and child health.
The goals of the Health and Behavior RAG are to strengthen the community of researchers in health and behavior research, enhance multidisciplinary and translational activities and initiatives, and provide leadership and support to the Children's Hospital community for research questions and activities related to behavior and child health.
Through workshops, seminars, working lunch events and retreats, the Health and Behavior RAG brings together nationally prominent investigators from highly specialized disciplines to provide opportunities for mentoring and development, facilitate research accomplishments, and ultimately enhance the effectiveness of pediatric care for children and their families.
Metabolism, Nutrition, and Physical Development
Leaders: Babette Zemel, PhD and Rebecca Simmons, MD
Disorders of nutrition and metabolism affect the majority of patient populations cared for at Children's Hospital. Failure-to-thrive, obesity and bone deficits are common complications in a wide variety of chronic conditions. Malabsorption, inflammation, reduced physical activity, altered dietary intake and medical treatments often have a profound effect on nutrient metabolism, growth, body composition, and health and disease outcomes. In addition, many of the major chronic diseases of adulthood, such as diabetes, hypertension, osteoporosis, cardiovascular disease and some cancers are nutrition-related and have antecedents in childhood.
The goal of the Metabolism, Nutrition and Development Affinity Group is to identify the causes and consequences of metabolic and nutritional disorders of childhood and to identify effective strategies for disease prevention and treatment. An additional goal is the prevention of obesity and nutrition related diseases in adulthood that have their origins in infancy and childhood.
The group boasts many multidisciplinary research projects across a wide range including gastroenterology, hepatology and nutrition, endocrinology, psychiatry, cardiology, hematology, nephrology, rheumatology, pulmonology, neurology, nursing, child development and neonatology. Obesity is a common theme across many of the specific areas of research. The obesity epidemic is a growing concern, and is increasingly becoming a problem in the pediatric patient population. Major research efforts include evaluation of behavioral and medical treatments for obese adolescents, practice-based obesity prevention and treatment, effect of obesity on bone strength, early life determinants of obesity and diabetes, prevention and treatment of diabetes, and the effect of obesity on sleep apnea, asthma and other pulmonary complications.
The State Tobacco Resettlement Act funded the project titled Risk Factors for the Pediatric Metabolic Syndrome to evaluate the contribution of obesity, obstructive sleep apnea, fasting insulin levels and family history of diabetes to overall glucose tolerance, insulin sensitivity, and lipid and blood pressure abnormalities. This study has shown relationships between disordered sleep, insulin resistance and other abnormalities associated with the metabolic syndrome such as lower adiponectin and HDL, and higher HbA1C and waist circumference. The State Tobacco Resettlement Act funds also support a new multi-center study of obesity led by Robert Berkowitz, MD, that provides office based obesity treatment in both urban and rural settings.
The research program led by Rebecca Simmons, PhD, is focused on elucidating the underlying molecular mechanisms that link the abnormal milieu of diabetic or obese pregnancies to the development of obesity and type 2 diabetes in offspring. Having developed a number of models of diabetes and/or obesity in pregnancy, Dr. Simmons' research has determined that this abnormal metabolic environment induces epigenetic modifications in key genes that regulate β-cell and adipocyte development. One study of newborns whose mothers had diabetes during pregnancy was conducted to determine whether diabetes in pregnancy alters genomic DNA methylation in genes important for regulating glucose homeostasis, and whether these epigenetic changes permanently alter gene expression, resulting in an adverse phenotype. To test this hypothesis investigators are using a novel technology to compare genome-wide cytosine methylation in amniocytes and in a single population of CD34+ cells derived from the cord blood of newborns of mothers who have diabetes.
Abnormalities of growth and body composition in children with chronic diseases are another major research theme in the Metabolism, Nutrition and Development Affinity Group. Various research projects are underway to describe the timing, magnitude, causes and consequences of growth failure and altered body composition in children with sickle cell disease, cystic fibrosis, Crohn disease, renal insufficiency, juvenile rheumatoid arthritis, Down syndrome, intractable epilepsy, liver disease, lupus erythymatosis and cardiac malformations. As part of a current ongoing collaboration, Barbara Medoff-Cooper, PhD, RN; Virginia Stallings, MD; and Babette Zemel, PhD, have identified patterns of growth failure in infants after cardiac surgery, demonstrating the need to develop nutritional care intervention strategies for these at-risk infants. Another set of collaborative studies, directed by Dr. Stallings and conducted over the past 15 years, have identified numerous nutritional deficiencies and potential treatment strategies for children with sickle cell disease. This series of studies has identified increased energy requirements, poor growth and delayed maturation, and deficiencies of zinc, vitamin D and vitamin A. A study on zinc supplementation demonstrated the benefits of this important nutrient for improved growth. Investigators are now studying vitamin A supplementation to determine the effect of improved vitamin A status on frequency of hospitalizations and sickle cell-related illness episodes.
Another major research focus is skeletal development and the effects of nutrition, inflammation and obesity on bone density, the attainment of peak bone mass and fractures. Mary Leonard, MD, MSCE; Sandy Burnham, MD; and Meena Thayu, MD, are conducting studies of children with renal, rheumatologic and gastrointestinal disorders to examine the effects of medication use, disease effects and physical activity on bone density and strength. Nicolas Stettler, MD, MSCE, has recently initiated a study of the effects of weight loss treatment on bone accrual in obese adolescents. Dr. Zemel has several studies of bone development in healthy children to improve our understanding of the normal patterns of development of the skeleton.
Another major focus of the RAG is to foster career development of junior investigators. We established the Pilot and Feasibility program, which is intended to provide support for both junior and established investigators to collect preliminary data sufficient to support a federal RO1 grant application for independent research support. We solicited submission of applications for support to perform pilot and feasibility studies in nutritional sciences, obesity and related disorders. To date, we have funded three projects. The first is a collaboration led by Myles Faith, PhD, Dr. Medoff-Cooper and other members of the affinity group to examine the genetics of feeding style and body composition in twin infants. Two new investigators, Andrea Kelly, MD, and Jon Burnham, MD, were recently awarded pilot grants.
These projects focused on determining whether vitamin D supplementation improves bone health in children with lupus and the effects of vitamin D supplementation on body composition and markers of inflammation in children with cystic fibrosis. The RAG has also provided funds for a study of vitamin D status in children with perinatally acquired HIV infection.
In addition, researchers in the affinity group investigate biliary atresia and bile duct development through the Fred and Suzanne Biesecker Center for Pediatric Liver Disease. Bringing together experts across hospital disciplines, such as gastroenterology, human genetics and pathology, the affinity group also partners with the adult liver program at the University of Pennsylvania.
Affinity group members participate in several seminar series to promote interdisciplinary interactions and generation of innovative lines of research. At Children's Hospital these include the Nutrition Center Seminar Series and the Seminars of the Division of Pediatric Endocrinology. At the University of Pennsylvania RAG members attend the seminar series held by the Institute for Diabetes, Obesity and Metabolism, the Penn Center for Musculoskeletal Disorders, and the Center for Clinical Epidemiology and Biostatistics.
Leader: Helen Loeb, PhD
METACHOP (Math, Engineering, Technology At CHOP) is a community of over 60 mathematicians, physicists, and engineers working in various research groups at CHOP. Our members meet every other month to discuss diverse research topics conducted at CHOP, such as:
- Pediatric biomechanics and child injury prevention
- Health informatics
- Bedside monitoring tools, imaging
- Clinical Decision Support Tools, machine learning
- Computer vision
- Protein structure modeling/design, proteomics
- Simulated driving, robotics, automation, teen driving
- Virtual and Augmented Reality
The goals of METACHOP include:
- Develop communication channels to facilitate collaboration with other quantitative scientists and/or clinicians, allowing engineers to present physicians with innovative solutions to clinical needs, and clinicians to present engineers with relevant medical information
- Organize workshops for emerging technologies (medical imaging, machine learning, virtual reality...) in order to stay informed of emerging technology and engineering research
- Develop a resource catalog to efficiently share equipment, technologies, and students
Leaders: Nadia Dowshen, MD, MSHP, Lisa Schwartz, PhD and Linda Fleisher, PhD, MPH Coordinator: Dare Henry-Moss, BA
mHealth (mobile Health) technology can be used for assessment/monitoring (eg, physical activity tracking), intervention dissemination (eg, just-in-time interventions), and communication with participants (eg, telemedicine). Such devices and platforms range from the basic (text messages, apps, and social media) to the complex (wearable devices linked to apps and electronic health records; highly tailored text messaging) to the futuristic (implantable and ingestible devices). The mHealth Research Affinity Group will provide a formal structure to coalesce local CHOP-based researchers interested in and/or conducting mHealth research and other stakeholders (e.g., IS, bioinformatics), as well as researchers from other local institutions.
- Foster collaborative efforts to expand the capability to develop, test and integrate mHealth tools and approaches for children, adolescents, and their families.
- Provide a forum for educational and networking opportunities to enhance knowledge of mHealth and develop potential collaborations both within and outside the RAG.
- Serve as a liaison to CHOP Research Institute and hospital administration on needs and prioritization of resources to enhance and facilitate mHealth research and its implementation in clinical practice.
- Activities include:
- Facilitate and track collaborations among RAG members
- Showcase innovative ideas and boost dissemination of RAG member publications
- Track new mHealth proposals and awarded grants
- Develop guidelines and a list of recommended vendors for mHealth development
- Identify key priorities in the integration of mHealth research into the research strategic plan
Leader: Marni Falk, MD
Led by Marni Falk, MD, the Mitochondrial Research Affinity Group addresses the needs of the diverse community of researchers engaged in mitochondria-focused research. Due to the importance of mitochondrial biology in many forms of disease, the clinical backgrounds of these investigators are wide-ranging and include clinical genetics, metabolism, endocrinology, anesthesiology, hematology, oncology, gastroenterology, neonatology, immunology, neurology, pathology, and ophthalmology. The basic science affiliations of these investigators are equally wide-ranging and include pathology, biochemistry and biophysics, biology, genetics, metabolism, animal biology, and anthropology.
Mitochondria are experiencing a scientific and medical renaissance. When mitochondrial DNA mutations’ role in human disease were recognized in 1988, it was thought that the function of these cellular organelles was generally understood. However, mitochondria are increasingly being recognized as having a complex and widespread role in contributing to many common disorders.
Mitochondria are experiencing a scientific and medical renaissance. It was recognized in 1988 that mitochondrial DNA mutations can contribute to human disease. At that time it was thought that the function of these cellular organelles was generally understood. However, mitochondria are increasingly being recognized as having a complex and widespread role in contributing to many common disorders.
Mitochondrial function has been found to play a role in disorders such as non-insulin dependent diabetes mellitus, Parkinson’s disease, Alzheimer’s disease, Huntington disease, hearing loss, stroke, liver disease, renal disease, and cancer. In addition, a mitochondrial basis is increasingly becoming clear for rare pathologies that cross all ages and many medical specialties.
Dozens of faculty members at Children’s Hospital are currently pursuing mitochondria-focused research. The goals of the Mitochondrial Research Affinity Group include improved collaborations in mitochondrial research, enhanced interaction between graduate students and faculty, and increased familiarity with research programs involving mitochondria at the University of Pennsylvania and beyond.
Leader: Michael Robinson, PhD
A startling number of children are afflicted with diseases of the nervous system. These disorders include epilepsy, stroke, head trauma, autism, and attention-deficit hyperactivity disorder. In addition, many genetic disorders, such as inborn errors of metabolism, manifest with primary brain dysfunction. Concern for pediatric health related to these disorders has heightened because of evidence that some have had an increased incidence over the past three decades.
Although some of these disorders, like stroke, have been traditionally associated with the elderly, recent studies suggest that children are also at risk. Additionally, the incidence of autism and seizures are troubling. These disorders collectively place a significant strain not only on children and their families but also on society.
Children’s Hospital follows the largest and most diverse population of children with neurologic, psychiatric, and developmental disabilities in the country. Outstanding clinical and basic researchers complement the clinical care programs throughout the Hospital. Led by Michael Robinson, PhD, the Neuroscience Research Affinity Group facilitates the development of targeted investigation and fosters the interactions necessary to rapidly translate research into best clinical practices. The affinity group targets four areas of research priorities: neuroprotection, epilepsy, stress biology, and autism/complex neurobehavioral disorders. The group also organizes seminar series and meetings to attract esteemed scientists from around the world.
Normal and Malignant Hematopoiesis
Leader: Carolyn Felix, MD
Gene and protein networks that signal blood cell maturation from blood stem cells and primitive bone marrow progenitor cells, as well as networks that regulate the balance of cell growth, survival and cell death, are especially relevant to hematopoiesis. Research at Children’s Hospital into this field focuses on networks that regulate the development of specific blood cell elements in normal and diseased states. The Normal and Malignant Hematopoeisis Research Affinity Group, which is led by Carolyn Felix, MD, aims to address problems in these networks to develop more effective treatments and targeted prevention for disordered hematopoiesis, leukemia, and lymphoproliferative diseases in children.
The progenitor cells in the hematopoietic system give rise to heterogeneous blood cell populations — red and white blood cells, as well as platelets — that execute specific functions. Technologies like next generation sequencing, gene expression profiling and proteomics have revealed global pictures of the networks that distinguish specific blood cell elements in normal and malignant states. Current research in the affinity group involves deciphering which elements in these networks can be targeted for new treatments and, ultimately, for preventing diseases of the hematopoietic system.
The Normal and Malignant Hematopoeisis Research Affinity Group brings together investigators engaged in a variety of clinical, translational and basic research. Activities of the group, including a rich seminar series and annual retreat, facilitate the progress of an ever-expanding web of researchers with a common interest in broad areas of hematopoiesis within the CHOP Research Institute, the Children’s Hospital campus, and beyond. This avenue to combining expertise in specific areas from new interchanges beyond the clinic and the individual laboratory will speed the Hospital’s advances in promoting bench-to-bedside research.
Leader: Yair Argon, PhD
Most diseases are caused by malfunctions of a protein. A defective receptor may preclude proper function of pancreatic cells; an altered protein may lead to malignant transformation, or the inability of a hormone to be secreted may lead to abnormal organ development. Understanding the changes in the expression or function of proteins is therefore key to developing therapies.
However gaining such understanding is no small feat, because each of the 30,000 genes in human DNA can encode more than one form of a protein, increasing the complexity of the information contained in DNA. In addition, not every pathologic change is due to a single gene mutation. In many diseases, the alteration is in an atypical realignment of interacting proteins.
Research conducted in the Proteins and Disease Research Affinity Group, led by Yair Argon, PhD, focuses on this problem by investigating how proteins function, how they interact, and how they differ between normal and diseased tissues. The Proteins and Disease Affinity Group provides a forum for investigators from a variety of divisions to work together, improving the effectiveness of their research. Shared instruments in the Protein Core Facility, a seminar series featuring outside speakers, a monthly in-house lab meeting and a multi-investigator seed project all allow group members to interact and gain feedback on ongoing research.
Protective Immunity and Immunopathology
Leaders: Ed Behrens, MD, and Paula Oliver, PhD
Infectious diseases remain the leading cause of death for children around the world. Researchers at The Children’s Hospital of Philadelphia are using different approaches to understand how protective immunity develops and the causes and consequences of immunopathology. These approaches include defining how the immune system functions to eliminate infectious agents, how pathogens have evolved to evade the immune system, how to boost the immune response with vaccines, and how failures in immune function drive disease.
In response to infection, the immune system employs multiple defense systems to limit tissue damage and eliminate the invading pathogen. Sometimes it continues its attack long after clearing the invading pathogen. Other times the immune system may initiate an attack even when no pathogen is evident -- . during sterile inflammation, as an example. Such immune system dysfunction is involved in autoimmune disorders as varied as asthma, inflammatory bowel disease, and rheumatoid arthritis. While autoimmune disorders often develop during childhood, they are debilitating chronic illnesses that last a lifetime. As discoveries in the laboratory shed light on how the immune system regulates its own function, novel and exciting approaches to treating these diseases are being developed.
Rapid strides have also been made in understanding how the immune system can detect and destroy cancer. Unfortunately, unlike infectious diseases against which the immune system is prepared to defend, cancer often evades detection. Furthermore, traditional treatments designed to kill cancer also destroy healthy cells, leaving the immune system weak and the body defenseless.
Many diseases involve a component of immune system dysfunction. The Protective Immunity and Immunopathology Affinity Group, including investigators from such different fields as cancer research, gene therapy, immunology, infectious disease, allergy, rheumatology and vaccine development, is applying shared knowledge toward a better understanding of the immune system and its powers to protect and heal.
Leader: Cynthia Mollen, MD, MSCE
The Qualitative Methods Research Affinity Group (RAG) aims to build and support a growing community using qualitative and mixed methods approaches at CHOP. While quantitative data can tell us what happened, qualitative methods play a key role in exploring and contextualizing the hows and whys of research. To date, many investigators at CHOP have been conducting qualitative research among small research teams, without the benefit of collaboration and with varying degrees of experience in qualitative methods. The primary focus of this affinity group is to provide a formal framework that brings these groups together to share expertise, develop ideas, and build skills. Additional effort will be put into facilitating mentorship opportunities - junior faculty, fellows, and other trainees at CHOP will have greater access to mentorship and training resources to support the integration of qualitative methods into research studies. Networking, mentoring, and learning opportunities will be facilitated with works in progress meetings, invited speaker events, mentorship mixers, and poster presentations. With these activities, we hope to achieve the following aims:
- Foster collaborative efforts to expand the capability for CHOP investigators to conduct high-quality, efficient research utilizing qualitative methods.
- Provide a forum for educational and networking opportunities to enhance knowledge of qualitative methodologies and develop potential collaborations both within and outside the RAG.
- Serve as a liaison to CHOP Research Institute on needs and prioritization of resources to enhance and facilitate qualitative research and its potential application to different lines of investigation.
In order to measure our success in these areas, we will use surveys to 1) identify the needs of the community related to qualitative methods and shape programming, 2) track collaborations and mentorship relationships established among RAG members, and 3) track proposals, awarded grants, and publications that employ qualitative approaches.
Given the wide range of faculty, fellows, and research staff that are involved in qualitative methods, events will be open to interested parties at all levels. Our primary goals relate to enriching the Research Institute community, but in time, we hope to expand to other local academic and research institutions.
Spatial and Functional Genomics
Leaders: Struan F.A. Grant, PhD, Andrew D. Wells, PhD, and Gerd A. Blobel, MD, PhD
Drs. Struan Grant, Andrew Wells and Gerd Blobel started the Spatial and Functional Genomics Initiative (SFGI) at the Children’s Hospital of Philadelphia (CHOP) in June 2015. It was established with funding received from the hospital in order to facilitate the many needs across the CHOP and University of Pennsylvania (UPenn) campus for chromatin conformation capture methods and related techniques. These three faculty members have complimentary expertise in genome-wide association studies (GWAS) and functional studies related to epigenetic/transcriptional regulation of disease and have already demonstrated a track record of productivity with respect to collaborative publications(1-4). SFGI already has all the key equipment in place and is staffed by seven personnel, including Dr. Matthew Johnson who serves as the Technical Director. Indeed, there are already a myriad of activities in various disease settings, both at the laboratory level but also at the bioinformatics stage, where three dedicated staff made up of accomplished computational analysts have transformed our initiative in to full pipeline for 3D Genomics efforts.
- Johnson ME, Deliard S, Zhu F, Xia Q, Wells AD, Hankenson KD, Grant SF. A ChIP-seq-defined genome-wide map of MEF2C binding reveals inflammatory pathways associated with its role in bone density determination. Calcified tissue international. 2014;94(4):396-402. Epub 2013/12/18. doi: 10.1007/s00223-013-9824-5. PubMed PMID: 24337390.
- Johnson ME, Schug J, Wells AD, Kaestner KH, Grant SF. Genome-wide analyses of ChIP-Seq derived FOXA2 DNA occupancy in liver points to genetic networks underpinning multiple complex traits. The Journal of clinical endocrinology and metabolism. 2014;99(8):E1580-5. Epub 2014/06/01. doi: 10.1210/jc.2013-4503. PubMed PMID: 24878043.
- Johnson ME, Zhao J, Schug J, Deliard S, Xia Q, Guy VC, Sainz J, Kaestner KH, Wells AD, Grant SF. Two novel type 2 diabetes loci revealed through integration of TCF7L2 DNA occupancy and SNP association data. BMJ Open Diabetes Res Care. 2014;2(1):e000052. Epub 2014/12/04. doi: 10.1136/bmjdrc-2014-000052 [pii]. PubMed PMID: 25469308.
- Chen Y, Chen C, Zhang Z, Liu CC, Johnson ME, Espinoza CA, Edsall LE, Ren B, Zhou XJ, Grant SF, Wells AD, Chen L. DNA binding by FOXP3 domain-swapped dimer suggests mechanisms of long-range chromosomal interactions. Nucleic Acids Res. 2015;43(2):1268-82. doi: 10.1093/nar/gku1373. PubMed PMID: 25567984; PMCID: PMC4333414.