Zheng Named Experimental Hematology and Cancer Biology Director
Awards and Appointments
The National Center for School Crisis and Bereavement, within the Division of Developmental and Behavioral Pediatrics, under the direction of David Schonfeld, MD, has been providing consultation,
technical assistance and training to Half the Sky Foundation in China since the earthquakes in Sichuan Province.
Kimberly Risma, MD, PhD, has been selected to receive a Schmidlapp Scholar Award from the Fifth Third Bank/Charlotte R.
Schmidlapp Women Scholars Program. The $100,000 honor is given annually to a female faculty member at Cincinnati Children’s. A physician in the Division of Allergy and Immunology, Risma focuses her research on understanding how lymphocytes kill target cells by secreting toxic proteins.
James Wells, PhD, of the Division of Developmental Biology, has been awarded a Career Development Award from the Juvenile Diabetes Research Foundation. The award, titled “The Role of Sox17 in Beta Cell Homeostasis and Regeneration,” includes funding of $100,000 per year.
Stavra Xanthakos, MD, of the Division of Gastroenterology, Hepatology and Nutrition, has been awarded a grant from The National Institute of Diabetes and Digestive and Kidney Diseases. The grant, titled “Biological Determinants of Steatohepatitis after Adolescent Bariatric Surgery,” includes funding of $886,248 over five years. Xanthakos, also the medical director of the Surgical Weight Loss Program for Teens, is the grant’s principal investigator.
Yi Zheng, PhD , has been named director of Experimental Hematology and Cancer Biology at Cincinnati Children’s Hospital Medical Center. A faculty member and scientist at Cincinnati Children’s since 2002, Zheng has served as acting director of the division since 2007.
Zheng, who has also been director of the Cell Signaling Program of the division since 2002, was also named associate director of Basic Science at the Cincinnati Cancer Consortium, a joint program of Cincinnati Children’s and the University of Cincinnati College of Medicine.
The research focus of Zheng’s lab involves Rho proteins — molecular switches that playa vital role in the division, growth and programmed death of cells. Zheng’s research has led to the design and screening of small molecules that specifically target selected signaling pathways involved in the progression of leukemia and lung cancer and the maintenance of blood stem cells. He has licensed one potential drug (NSC23766) to a pharmaceutical company for further development. Research shows it works against leukemia, lymphoma, prostate cancer and lung cancer, killing a significant percentage of cancer cells and delaying cancer onset, although it still needs to be tested in humans.
“Yi is a talented scientist, with a wonderful record of funding and a highly successful program to understand the mechanisms underlying cancer and leukemia as well as normal brain development,” says Arnold Strauss, MD, director of the Cincinnati Children’s Research Foundation and chair of pediatrics. “His leadership has been and will continue to be crucial in understanding and developing drug targets to treat cancer.”
Researcher Discovers What’s Behind the Dust Mite-Asthma Connection
In what the American Asthma Foundation calls a “breakthrough discovery,” a research team led by Christopher Karp, MD, has found out how the tiny household pests called dust mites are a major source of airborne allergens for patients with allergic asthma.
Dust mites apparently trick the body’s immune system into believing it is facing a bacterial infection, the researchers wrote in a study published online at Nature.com. This kicks the immune system into action as it mounts a strong allergic response to the mites. This response is what triggers asthma attacks.
Dust mites are known to cause asthma attacks, but until this study it wasn’t known what prompted the response to mites to be so strong.
Karp, director of Molecular Immunology at Cincinnati Children’s, received a three-year senior investigator award in 2006 from the asthma foundation’s strategic program in causes of asthma, with the goal of improving treatment and curing and preventing the disease.
According to the American Asthma Foundation, nearly one in every 13 people in the United States has asthma, making it more common than coronary heart disease, cancer or Parkinson's disease. Asthma is the most serious chronic disease of childhood and disproportionately strikes the poor.
New Scientific Director Appointed to Imaging Research Center
Charles Dumoulin, PhD, has been named Scientific Director of the Imaging Research Center (IRC) at Cincinnati Children’s. Dr. Dumoulin comes to Cincinnati Children’s from General Electric’s Global Research Center in Niskayuna, New York, where he was a senior scientist for more than 24 years.
Dumoulin was part of the team that developed GE’s first prototype magnetic resonance imaging systems, and has made ground-breaking contributions in the fields of magnetic resonance angiography (MRA), dynamic MRI and interventional MRI. In addition to more than 100 publications in the scientific literature, Dumoulin holds 101 patents.
Dr. Dumoulin’s research interests complement the existing IRC strengths in neuroimaging, spectroscopy, cardiac imaging and animal imaging. At Cincinnati Children’s he will be working on neonatal MRI and new approaches to accelerate MR scanning. He will also continue research efforts in interventional MRI, including the use of MR-guided focused ultrasound for the ablation of tissue.
Imaging Research Center Gets New Scanner
In November, the Cincinnati Children’s Imaging Research Center (IRC) installed a new 3 Tesla Magnetic Resonance Imaging (MRI) scanner dedicated for use in pediatric imaging research.
The IRC will use the new instrument as well as their expertise in pediatric imaging to continue to lead translational imaging research in child development and disease. Key areas in pediatric health research at the IRC include the study of language development, environmental neurotoxicity, hearing loss, juvenile arthritis, muscular dystrophy, cardiac abnormalities, brain disorders and epilepsy.
The new MR system is open to researchers at Cincinnati Children’s and in the Cincinnati community for use in research projects involving children and adults. In addition, the IRC has MRI, CT and bioluminescence imaging capabilities for imaging large and small animal models.
The new scanner and laboratory renovations represent an investment of more than $2 million; the scanner replaces an older, head-only scanner that was installed in 1994 when the IRC was first established. Funding for the system came from an NIH S10 shared instrument grant, the Department of Radiology and the Cincinnati Children’s Research Foundation.
Endowed Chair Fosters Emergency Medicine Research
Jacqueline Grupp-Phelan, MD, MPH, has been appointed to the newly-established Richard Ruddy and Barbara Wriston-Ruddy Chair of Pediatric Emergency Medicine Research . Ruddy is director of the Division of Emergency Medicine and professor in the Department of Pediatrics at the University of Cincinnati College of Medicine.
Cincinnati Children’s is the only pediatric hospital in the country to have an emergency medicine chair devoted to taking research from the bench to the bedside.
“We’re already recognized as a leader in pediatric emergency medicine research,” Grupp-Phelan says. “It’s a young field, so we feel we can really make an impact in getting what we learn in research into actual practice.”
Grupp-Phelan, who serves as director of Emergency Medicine and associate professor in the Department of Pediatrics at the University of Cincinnati College of Medicine, says the chair will allow the division to continue making improvements and innovations in the quality of clinical care, the experience of patients and families, advocacy and education. Ruddy says the chair will enable Grupp-Phelan to continue as a mentor within the division while contributing to institutional research efforts. She will also continue her research focus on mental health services for children and adolescents.
Type 2 Diabetes Reversed After Weight Loss Surgery in Adolescents
Teens who underwent gastric bypass surgery showed dramatic, often immediate, remission of type 2 diabetes, according to a new study by researchers at Cincinnati Children’s.
The study, published in the January issue of Pediatrics, found that bariatric surgery, specifically Roux-en-Y gastric bypass, helped teens lose, on average, a third of their body weight and induced remission of the diabetes in all but one teen. The study also notes other health improvements, such as lower blood pressure and cholesterol levels.
Previous studies have shown remission of type 2 diabetes in adults following bariatric surgery, but until now, little information was available for families considering surgical weight loss for adolescents.
The study found that in most cases, patients can come off diabetes medications by the time they leave the hospital following surgery, says Thomas Inge, MD, PhD, surgical director of Cincinnati Children’s Surgical Weight Loss Program for Teens and lead author of the study. “The results have been quite dramatic and, to our knowledge, there are no other anti-diabetic therapies that result in more effective and long-term control than that seen with bariatric surgery,” says Inge.
Cancer Treatment Chair Seeds Research in Childhood Cancer
John Perentesis, MD, director of the Oncology Program in the Division of Hematology / Oncology at Cincinnati Children’s, has been appointed the first Deb Kleisinger Chair of Novel Cancer Treatment.
According to Perentesis, the new chair is targeted to developing new cancer therapies by exploiting the disease’s genetic signature. “Cincinnati Children’s has a large established program in cancer molecular genetics, and a new Drug Discovery Center run in partnership with the University of Cincinnati,” he says. “Having this chair will allow us to support research focused on developing new anticancer therapies for children.”
Perentesis will use the chair to spark new translational cancer research projects that can be developed to a point where they can be funded at the federal level. “Childhood cancer is relatively uncommon, so a large part of research in cancer genetic signatures and new therapy development is focused on adult malignancies,” he says. “This will help generate data for new treatments in pediatric cancers. An endowed chair can help us make the leap from promising concept to fullfledged project for national funding sources like the NIH.”
“John is one of the world leaders in developing new cancer treatments and testing them in children,” says Frank Smith, MD, director of Hematology / Oncology. “The program he’s built here is one of the biggest internationally, and it attracts children from all over the world.”
Cincinnati Children’s Named One of Top Five Pediatric Hospitals
Cincinnati Children’s Hospital Medical Center is one of the top five children’s hospitals in the United States, according to the latest survey in Parents magazine. The survey ranks Cincinnati Children’s fourth among more than 100 pediatric hospitals.
The rankings are based primarily on overall quality. In addition, Parents judged hospitals on pediatric specialty areas. Cincinnati Children’s ranked in the top 10 in newborn intensive care, cancer care, heart care, pulmonary care and emergency care.
The Parents 10 Best Children’s Hospitals survey provides a data-driven comparison of children’s hospitals. All surveyed hospitals are members of the National Association of Children’s Hospitals and Related Institutions, more than 100 pediatric hospitals.
Hospitals are ranked on their responses to detailed questions in the following areas: survival rates for childhood cancer, pediatric heart disease, and other critical conditions; their experience in performing certain complex procedures; the depth of the research program; safeguards to prevent medical errors; staffing ratios and quality; waiting times in the emergency department; community outreach; and services that address the emotional needs of sick children and their families.
Heart Institute Names Co-Director
Jeffrey Towbin, MD, has been named director of the Division of Cardiology and executive co-director of the Heart Institute . Towbin, who expects to begin his tenure with Cincinnati Children’s in March, comes from Texas Children’s Hospital, where he held positions including chief of Cardiology; co-director of the Cardiovascular Genetics Clinic and director of the Phoebe Willingham Muzzy Pediatric Molecular Cardiology Laboratory.
Towbin’s awards include the 2007 Distinguished Scientist Award (Basic) from the American College of Cardiology as well as numerous grants from the National Institutes of Health. His focus has been on heart failure, cardiomyopathy, congenital heart disease, arrhythmias and sudden cardiac death. He has developed several diagnostic tests and therapies for children and adults with congenital heart diseases.
He was drawn to Cincinnati Children’s for a variety of reasons, including the opportunity to help develop the Heart Institute.
“The structure of the institute has the potential to build on what we already know on a basic level, to link the basic science to the clinical side,” Towbin says. Among his plans are to build programs that set the standard for cardiac research and patient care, particularly heart failure and cardiomyopathies; transplant; cardiovascular genetics; and an adult congenital heart disease program that transitions patients from childhood to adult care.
“Individuals with congenital heart disease are now living well into adulthood and need treatment or surgery that many adult cardiologists do not have extensive experience with,” he says. “Cincinnati Children’s can address this unmet need.”
$6.4 Million Grant Helps Study of Neurofibromatosis
A center devoted to finding better treatments for neurofibromatosis 1 (NF1) has been made possible in part by a $6.4 million grant from the National Institute of Neurological Disorders and Stroke.
The grant, awarded to cancer biologist Nancy Ratner, PhD, and her research team, helped establish the Center for Neurofibromatosis Research at Cincinnati Children’s, aimed at translating research findings into patient treatments.
“Cincinnati Children’s has an outstanding pediatric NF1 clinic and has participated in ongoing NF1 clinical trials,” Ratner says. “We bring together world-class investigators who can conduct translational research for NF1 treatment.”
Ratner’s team has perfected a mouse model to study NF1, a disease that can cause disfigurement and learning disorders, and can sometimes lead to fatal tumors or leukemia. Ratner’s team sparked new interest in the study of NF1 with their development of the ideal mouse model and their discoveries into the timing of NF1 gene mutation and the formation of neurofibroma tumors.
Engineered Herpes Virus Kills Neuroblastoma Stem Cells
A study led by researchers at Cincinnati Children’s has successfully used a reprogrammed herpes virus to block tumor formation in mice. The study has also added to evidence that early stage cancer cells with stem-cell-like properties may explain how some cancers form, as well as why they are treatment resistant and prone to relapse.
Published online in January by PLoS (Public Library of Science) One, the study underscored how targeted biological therapies might help people with stubborn cancers like neuroblastoma. Timothy Cripe, MD, PhD of the Division of Hematology / Oncology at Cincinnati Children’s, was senior investigator on the study.
“Our main finding is that pediatric neuroblastomas seem to have within them a population of cells with stem cell characteristics that we can target for therapy,” Cripe says. “One promising approach seems to be treatment with an engineered oncolytic virus that seeks out and kills progenitor cells that could be the seeds of cancers.”
The engineered virus that Cripe and his colleagues tested was a herpes simplex virus called rQNestin34.5. Developed by cancer researchers at Ohio State University, rQNestin34.5 is genetically programmed to be toxic to cancer cells, while leaving healthy tissues alone.
To test the virus, the research team grew human neuroblastoma cells in lab cultures. The cultures generated cell colonies that acted like stem cells in the way they grew and were capable of differentiation. They formed tumor-like cell spheres that mimicked treatmentresistant neuroblastomas. Researchers also noted that cells from the tumorspheres carried a gene (MYCN) found at amplified levels in aggressive forms of neuroblastoma.
The tumorigenic cells were infected with rQNestin34.5, then injected into mice to see if neuroblastoma tumors would form. Tumors did not form in any of the mice over a 60-day observation period, leading the researchers to report that rQNestin34.5 “abolished tumor growth” by attacking apparent tumor-initiating cells.
A control that infected tumorigenic cells with another oncolytic herpes virus was much less successful, with the treated mice forming tumors within 40 days.
The findings could offer a breakthrough in treating neuroblastoma, which is known for its resistance to treatment and high rate of relapse and death. In patients with high-risk forms of the disease, long-term survival rates are under 50 percent.
Cripe cautions that though a promising step forward, more research is needed before determining whether rQNestin34.5 would be effective in treating neuroblastoma in a clinical setting.
Support for the study came from the division of Hematology/Oncology at Cincinnati Children’s, TeeOffAgainstCancer.org and the National Institutes of Health.
