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The British Society for Developmental Biology (BSDB) has awarded the Waddington Medal to Christopher Wylie, PhD, director of the Division of Developmental Biology.
The medal is the society’s most prestigious award, given to an individual still active in the field who has made major contributions to developmental biology – outstanding research as well as service to the scientific community.
Wylie has served as director of the Division of Developmental Biology and professor of Pediatrics at Cincinnati Children’s for 11 years. He has been president of the American Society for Developmental Biology and was founding editor of the journal Development.
His research focuses on the migration of embryonic stem cells, the control of actin assembly in morphogenic movements and the formation of the primary germ cell layers in vertebrate embryos. He also studies the development of spinal disorders and cellular processes that form tendons.
Wylie and his wife, Janet Heasman, PhD, share a laboratory at Cincinnati Children’s. They were the first to use sophisticated methods of knocking down expression of maternal and zygotic messages for a given gene. This allowed them to conduct loss-of- function experiments in the Xenopus frog, an approach to experimentation adopted by laboratories around the world.
Among Wylie’s achievements is his mentoring of students and post-docs. His methods include working marathon lunchtime table tennis tournaments and coin-rolling contests into the research day. Current and past colleagues note Wylie’s “amazing manual dexterity and deep scholarship, and his truly inspirational leadership.”
After spending his early years in Kenya, Wylie attended University College Medical School in London and earned a BSc in anatomy and a PhD in developmental biology. Prior to Cincinnati Children’s, he held faculty positions at University College London and St. George’s Hospital Medical School and was Frederick James Quick Chair.
A genetically-engineered line of mice developed 10 years ago in Cincinnati to study intestinal disorders is helping scientists in China shed new light on ADHD and other neuropsychiatric disorders.
A study published in August in Science reports that the intestinal membrane receptor protein, Guanylyl cyclase-C (GC-C), is also expressed in critical areas of the brain. This is the first time the GC-C receptor has been linked to ADHD, according to the researchers.
The senior author on the study is Minmin Luo, a researcher at the National Institute of Biological Sciences and Tsinghua University in Beijing. Mitchell Cohen, MD, director of Gastroenterology, Hepatology and Nutrition at Cincinnati Children’s, is a co-author.
The study establishes that the “GC-C knockout” mice, originally developed at the University of Cincinnati and maintained at Cincinnati Children’s for ongoing studies of intestinal and diarrheal disorders, can function as a model for ADHD. The mice exhibit symptoms of the disorder and they respond to known medications.
“This could make the GC-C knockout mouse a good research model for ADHD and other behavioral disorders,” Cohen says. “Efforts to develop activators or inhibitors of this signaling pathway may lead to novel treatments for other disorders such as schizophrenia, Parkinson’s disease and addiction.”
Finding new approaches to treat congenital heart disease got a boost this summer when the Heart Institute added Alistair Phillips, MD, to its roster of specialists.
Phillips has been named surgical director of our Adolescent and Adult Congenital Heart Disease (AACHD) Program and Heart Transplant Program. He was formerly with Children’s Hospital in Columbus, Ohio.
In addition to heart transplantation and mechanical circulatory support for patients of all ages, Phillips has a special interest in developing novel surgical approaches for congenital heart disease. One such approach is a hybrid treatment in which heart surgeons and cardiologists collaborate to fix complex structural heart problems with catheters.
Cincinnati Children’s was one of the first children’s hospitals in the United States to develop an adult congenital heart disease program, which is now overseen by Gary Webb, MD. Phillips will expand the program’s treatment capabilities.
“The recruitment of Dr. Phillips, an experienced expert in the surgical care of these patients, allows the Cincinnati Children’s Heart Institute to care for all aspects of congenital heart disease at all ages,” says Jeffrey Towbin, MD, co-director of the Cincinnati Children’s Heart Institute.
One major factor in why rare “orphan” diseases can be so deadly is that many involve mutations in genes essential to survival, according to a study in The American Journal of Human Genetics.
Orphan diseases are defined as those that affect fewer than 200,000 Americans. However, there are 8,000 orphan diseases altogether, including cystic fibrosis and several types of childhood cancer. They afflict more than 25 million people in the United States.
“Only about 300 of these 8,000 diseases have effective drug therapy, so collectively orphan diseases pose a formidable challenge,” says Anil Jegga, PhD, a researcher in the Division of Biomedical Informatics and the study’s senior investigator. “Previous studies on disease networks have not separated out these rare diseases, many of which are fatal.”
The study, conducted at Cincinnati Children’s, used bioinformatic technology to link diseases with causative genes, interacting proteins and shared molecular pathways. The result: a global network map involving 1,772 orphan diseases linked to 2,124 mutant genes. Sixty-nine percent of the diseases have one implicated gene; the rest involve two or more. In some cases, the same gene can be implicated in multiple orphan diseases.
The “systems-level” gene map gives scientists a precise starting point to develop new therapies or reposition existing drugs to treat orphan diseases, Jegga says.
Infants who live in “moldy” homes are three times more likely to develop asthma by age 7, according to a study led by researchers at the University of Cincinnati and Cincinnati Children’s.
Results were published in the August 2011 Annals of Allergy, Asthma & Immunology, the journal of the American College of Allergy, Asthma and Immunology (ACAAI).
Researchers analyzed seven years of data on 176 children to evaluate the effects of early mold exposure.
“Early life exposure to mold seems to play a critical role in childhood asthma development,” says Tiina Reponen, PhD, the study’s lead author and UC professor of environmental health. “Genetic factors are also important, since infants whose parents have allergies or asthma are at the greatest risk of developing asthma.”
Infants in the study were identified at high risk for allergies based on family medical history. Researchers measured mold exposure levels using the environmental relative moldiness index (ERMI), a DNA-based analysis tool. Eighteen percent of the children in the study were found to be asthmatic by age 7. That compares with about 9 percent of school-age children nationwide who develop asthma.
The findings could help raise parents’ awareness about the risks of mold in their homes. Researchers and physicians might find ERMI to be a useful measure of mold exposure in children, says Gurjit “Neeru” Khurana Hershey, MD, PhD, an allergy and immunology expert at Cincinnati Children’s and study co-author.
“We have needed better ways to quantify mold exposure, specifically mold exposure that promotes disease,” Hershey says.
Marc Levitt, MD, has been named director of the Colorectal Center at Cincinnati Children’s.
The center was established in 2005 by Levitt and renowned surgeon Alberto Peña, MD, who will continue as founding director.
The only multidisciplinary pediatric colorectal center in the world, the center performs more than 800 procedures a year for children with anorectal malformations, Hirschsprung's disease and other issues related to the bowel. The center also partners with surgeons who treat ulcerative colitis and Crohn’s disease as well as with colleagues in pediatric gynecology and urology. Patients have come to the center from 80 countries and all 50 states.
The center’s surgeons pioneered reconstructive posterior sagittal anorectoplasty (PSARP), also known as the pull-through procedure, to treat complex anorectal malformations and related disorders. They have performed thousands of these procedures in Cincinnati and around the world.
Watch Online: Hear Drs. Levitt and Pena talk about their work in our Tell Me a Story section.
Outbreaks of food-borne illness continue to make headlines and the American government wants it to stop. Now, researchers at Cincinnati Children’s will participate in a USDA-sponsored $25 million grant to help eradicate food-borne sickness caused by noroviruses.
The five-year project, coordinated by North Carolina State University, involves scientists from more than 30 institutions nationwide. It is the largest food safety grant ever awarded by the USDA.
“We will receive $400,000 in the initial three years of the project focusing on methodology and research model development,” says Xi Jason Jiang, PhD, who leads research at Cincinnati Children’s to develop a next-generation norovirus vaccine. “We may receive additional funding from the project in later years to use a new viral infection model to assess food safety following disinfection.”
Noroviruses are the most common cause of food-borne disease, spreading through contaminated food and water – particularly shellfish and fresh produce. The virus causes more than 5 million illnesses a year in the United States.
In developing nations, it kills 200,000 children a year. There is currently no vaccine to prevent norovirus infection and no specific drug to treat it.
Among the project’s objectives are gaining a better understanding of the role of norovirus in food-borne illness, developing rapid methods to detect noroviruses, providing training for food safety and health professionals and food service workers and educating produce and shellfish producers and processors on the risks, management.
Greg Tiao, MD, is principal investigator for a five-year, $1.9 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to explore the connections between a common virus and biliary atresia. Biliary atresia is the condition that necessitates most liver transplants in children.
Scientists have long suspected that rotavirus infections trigger an inflammatory immune response in some children that damages the biliary epithelium, ultimately destroying liver function. The new study seeks to understand that process at the molecular level.
Tiao and fellow researchers developed a series of gene-knockout mice that reflect all 11 rotavirus gene segments. They will use the mice to search for an autoimmune process or a protein mimicry process at work in biliary atresia.
If a specific peptide sequence within the rotavirus gene can be identified as the trigger for liver damage, it could become a target for treatments to stop the damage before patients need transplants.
Nationwide, surgeons perform 300 to 400 biliary atresia-related liver transplants a year. At Cincinnati Children’s, nearly half the 25 to 30 liver transplants performed each year are triggered by biliary atresia.
“We’re trying to slow the disease process so that patients don’t have to undergo liver transplant,” says Tiao, surgical director of liver transplantation at Cincinnati Children’s. “Our goal is to make liver transplant unnecessary for this disease.”
The study will involve two researchers in Tiao’s lab – Sujit Mohanty, PhD, and Bryan Donnelly, BS. Collaborators from other divisions within Cincinnati Children’s include Claire Chougnet, PhD, Molecular Immunology; and Jarek Meller, PhD, Biomedical Informatics.
The Center for Simulation and Research at Cincinnati Children’s is the first pediatric institution nationwide, and one of only nine centers overall, to receive accreditation from the Society for Simulation in Healthcare.
“Accreditation is recognition that we teach to the highest national standards. That’s important to any organization considering sending students here,” says Tom LeMaster, MSN, MEd, program director.
As technology improves, simulation-based training is playing a growing role in healthcare. Far beyond the CPR practice mannequin, today’s patient simulators are highly sophisticated devices that can cost as much as $230,000. The latest models can exchange medical gases, produce palpable pulses and generate audible respiratory sounds. They can talk, cry and bleed (a lot), LeMaster says.
The Simulation Center trains more than 5,300 medical professionals a year. Its expansive training space includes 11 simulators placed in fully equipped operating rooms, trauma bays, intensive care units and other settings.
The center’s training stands out because it not only teaches staff to manage difficult patient situations, but also focuses on how teams communicate. Here, physicians, nurses, technicians and others practice working more effectively as a unit.
“It’s all about the communication,” LeMaster says. “As the teams interact with the simulator, we monitor the team, then lead them in debriefing to help them understand the communication problems that can occur.”
To learn more about training available through the Simulation Center, call: 513-636-6992 or email: firstname.lastname@example.org
A molecular pathway that triggers blood vessel branching could play a role in controlling cancer tumor growth and certain diseases of the retina, according to research at Cincinnati Children’s.
A study, published in Nature, reports that myeloid cells use the Wnt protein signaling network to guide blood vessel patterning in the retina. Opening the pathway can accelerate blood vessel growth, which helps heal damaged tissues. Suppressing the pathway restricts blood vessel branching, which could be useful as an anti-tumor weapon.
“We show in the setting of the retina that myeloid cells use this pathway to direct vascular traffic,” explains Richard Lang, PhD, study senior investigator and director of the Visual Systems Group in the Division of Ophthalmology. “Modulating this pathway might become a promising therapeutic option.”
The Wnt pathway is known for its role in early development as well as in cancer. Although myeloid cells are important to the immune system, they also promote tumor progression.
Researchers performed experiments in cell cultures and mouse models to determine that myeloid cells use the Wnt pathway to regulate expression of the Flt1 gene, which encodes a protein called vascular endothelial growth factor receptor-1 (VEGFR1). This protein suppresses vascular growth by binding vascular endothelial growth factor (VEGF).
The study’s first author, James “Tony” Stefater, is an MD-PhD graduate student in the University of Cincinnati College of Medicine. Lang, Stefater and their colleagues already have begun followup studies with Jeff Pollard, PhD, a cancer cell biologist at the Albert Einstein College of Medicine and co-author on the Nature study.
Brian Coley, MD, has been named radiologist-in-chief and director of the Department of Radiology.
Coley came here from Children’s Hospital in Columbus, Ohio. He will continue to pursue research projects, with a focus on ultrasound research for diagnostic and interventional radiology.
Coley received his medical degree from the University of California – San Diego School of Medicine, where he also completed a radiology residency and a fellowship in imaging research. He completed an additional fellowship in pediatric radiology at Cincinnati Children’s.
Raouf Amin, PhD, Division of Pulmonary Medicine, received a five-year, $753,000 award from the National Institutes of Health to set up a pediatric sleep research program.
David Bernstein, MD, Division of Infectious Diseases, received a $1.8 million grant from LigoCyte Pharmaceuticals for “Dose Range Evaluation of Norovirus Challenge Pool.”
John Bissler, PhD, Division of Nephrology, received a $1 million Tuberous Sclerosis Alliance Courage Award to pursue research in tuberous sclerosis over three years.
Steve Danzer, PhD, Division of Anesthesia, won $1.8 million over five years from the National Institute of Neurological Disorders and Stroke to study “Selective disruption of hippocampal dentate granule cells.”
Brian Gebelein, PhD, Division of Developmental Biology, received $1.4 million over five years from the National Institute of General Medical Science to study “Hox Regulation of Sensory Organ Development in Drosophila.”
Harry Leighton Grimes, PhD, Division of Immunobiology, will use a five-year, $1.8 million award from the National Cancer Institute to study “MicroRNA in Acute Myeloid Leukemia.”
William Hardie, MD, Division of Pulmonary Medicine, received a grant of $932,248 over two years from the National Heart, Lung and Blood Institute to study “Molecular Interventions for Pulmonary Fibrosis.”
Rulang Jiang, PhD, Division of Developmental Biology, was awarded $2.2 million over 4 years from the National Institute of Dental and Craniofacial Research to study “Molecular Genetic Analysis of Craniofacial Development.”
Vladimir Kalinichenko, MD, PhD, Section of Neonatology, Perinatal and Pulmonary Biology, received $1.5 million over four years from the National Heart, Lung and Blood Institute to research “Fox 1 Transcription Factor in Development of Pulmonary Capillaries.”
Christopher Karp, PhD, received $1.5 million over four years from the Cystic Fibrosis Foundation to establish the Cincinnati Children’s cystic fibrosis research development program.
Zaza Khuchua, PhD, Division of Molecular Cardiovascular Biology, will use a $1 million grant from the National Heart, Lung and Blood Institute to study “A Mouse Model of Barth Syndrome, a Mitochondrial Cardiolipin Disorder.”
Melinda Butsch Kovacic, PhD, Division of Asthma Research, received $1.9 million from the National Heart, Lung and Blood Institute for five years to study “Fanconi Anemia as a Model for Susceptibility to Human Papillomavirus Infection.”
Richard Lang, PhD, Division of Ophthalmology, received $1.5 million over four years from the National Eye Institute to study “Wnt Pathway Regulation of Lens Polarity.”
Carole Lannon, MD, James Anderson Center for Healthcare Excellence, received a one-year, $934,476 grant from the Hamilton County Public Health Department to expand the Ohio Immunization registry to include body mass index.
Xinhua Lin, PhD, Division of Developmental Biology, received a four-year grant of $951,596 from the National Institute of General Medical Science to study “Roles of Retromer Complex in Development.”
Dan Lovell, MD, Division of Rheumatology, will use a four year, $1.4 million grant from Centocor, Inc. to study “Subcutaneous Golimumab in Pediatric Subjects with Active Polyarticular Course JIA Despite Methotrexate Therapy.”
Masato Nakafuku, MD, PhD, Division of Developmental Biology, will use a five-year, $2.6 million grant from the National Institute of Neurological Disorders and Stroke to study “Molecular Control of Neurogenesis in the Adult Subventricular Zone.”
Jennie Noll, PhD, Division of Behavioral Medicine and Clinical Psychology, will use a $2.4 million grant over five years from the National Institute of Child Health and Human Development for the project, “Preventing Teen Pregnancy.”
Mary Patterson, MD, Division of Emergency Medicine, received $1 million over three years from the Agency for Healthcare Research and Quality to study “Simulation as a Tool to Improve Patient Safety.”
Saima Riazuddin, PhD, Division of Otolaryngology, received a five-year, $1.9 million grant from the National Institute of Deafness and Other Communication Disorders to study “Functional Analyses of Tricellular Tight Junctions in Hearing and Deafness.”
Kurt Schibler, MD, Section of Neonatology, Perinatal and Pulmonary Biology, received $1.5 million for five years from the National Institute for Child Health and Human Development to conduct studies as principal investigator for the NICHD Cooperative Multicenter Neonatal Research Network.
Gregory Tiao, MD, Division of General and Thoracic Surgery, received a $1.8 million grant over five years from the NIDDK to study “The Molecular Determinants of Virus Induced Biliary Atresia.”
Bruce Trapnell, MD, Section of Neonatology, Perinatal and Pulmonary Biology, won a $1.8 million grant for five years from the National Heart, Lung and Blood Institute to study “The Role of Anti-GM-CSF Antibodies in Myeloid Cell Function.”
Alexander Vinks, PhD, Division of Clinical Pharmacology, received a five-year, $939,533 award from the National Institute of Child Health and Human Development for a “Clinical Training Program in Pediatric Clinical and Developmental Pharmacology.”
Jeffrey Whitsett, MD, Section of Neonatology, Perinatal and Pulmonary Biology, will use a four-year, $1.6 million grant from the National Heart, Lung and Blood Institute to study “Transcriptional Control of Submucosal Gland Formation and Function.”
Hector Wong, MD, Division of Critical Care Medicine, received a four-year, $1.2 million grant from the National Institute of General Medicine Sciences to study “MMP-8 as a Novel Therapeutic Target in Sepsis.”
Yutaka Yoshida, PhD, Division of Developmental Biology, will use a $1.6 million, five-year grant from the National Institute of Neurological Disorders and Stroke to study ”Regulation of Sensory-Motor Connectivity by Semaphorin-Plexin Signaling.”
Edward H. Giannini, MSc, DrPH, will receive the Distinguished Clinical Investigator Award from the American College of Rheumatology at its annual scientific meeting in November 2011.
Tracy Glauser, MD, has been named associate director of Clinical Translational, Outcomes and Health Services Research in the Cincinnati Children’s Research Foundation (CCRF). Glauser is director of the Comprehensive Epilepsy Center and professor in the Department of Pediatrics, University of Cincinnati College of Medicine.
James Greenberg, MD, has been named co-director of the Perinatal Institute, joining Jeffrey Whitsett, MD. Greenberg has been associate director of the Institute since its formation in 2009. He will continue as director, Division of Neonatology, and as professor of Pediatrics, University of Cincinnati College of Medicine.
Scott Holland, PhD, was appointed for a 2-year term to the Biobehavioral and Behavioral Sciences Study Section at the National Institute for Child Health and Human Development. The subcommittee reviews grant applications to the Child Development and Behavior Branch at NICHD.
Sally Shott, MD, received the Christian Pueschel Memorial Research Award from the National Down Syndrome Congress for her research into the impact of ear, nose and throat problems on children with Down syndrome.
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