Carrie Atzinger, MS, CGC
Ms. Atzinger was elected to a two year term as Director at Large for the Board of Directors of the National Society of Genetic Counselors.
Liming Bao, MD, PhD
Dr. Bao played an instrumental role in developing the joint international college of medicine between University of Cincinnati College of Medicine and Chongqing Medical University in China. This will be the first such international collaborative program between China and US. The success of the program will significantly elevate UC/Cincinnati Children’s standing in global medical education and facilitate clinical and research collaboration between two institutes.
Thomas Burrow, MD
Dr. Burrow has successfully initiated an industry funded trial evaluating the safety and efficacy of enzyme replacement therapy with recombinant human lysosomal acid lipase in individuals with cholesterol ester storage disease. This provides potential for a new specific therapy for these individuals.
Gregory A. Grabowski, MD, You-Hai Xu, MD, PhD, Ying Sun, PhD
Research efforts were concentrated in three areas: 1) The elucidation of the CNS pathogenesis of the α-synuclein and amyloid protein accumulation in Gaucher disease mouse brains. These studies indicate the disruption of the lysosome/autophagy/mitophagy system leading to complex abnormalities that predispose to Parkinson-like manifestations in Gaucher disease. 2) Comparative whole genome RNA-Seq analyses of the major organs in Gaucher disease before and following enzyme therapy. These analyses show that two highly similar biopharmaceuticals (differ only in oligosaccharide termination) have very different transcriptomic effects and lead to differential correction of the molecular pathology of this disease. 3) Development of neuroprogenitor and differentiated neurons as well as hepatocyte precursors from iPSCs derived from human and mouse fibroblasts. These cells are being used as potential therapeutics as well as for “disease in a dish” analyses for the glycosphingolipid storage diseases and lysosomal acid lipase deficiency, as prototypes.
Amber Hogart-Begtrup, PhD
Dr. Begtrup has spent her first year in the Molecular Genetics Laboratory engaging in the daily operations of the laboratory and laying the groundwork for future collaborations and research. Specifically, together with Dr. Kalfa of the Cancer and Blood Diseases Institute Dr. Hogart is developing comprehensive genetic testing for disorders of the red blood cell; the first in the country to offer functional characterization and comprehensive molecular genetic diagnostics to improve the care of children with RBC disorders. Also, Dr. Hogart together with Anne Lucky, MD and the Epidermolysis Bullosa (EB) Center are developing a rapid, comprehensive, genetic tests, for the diagnosis of this devastating skin disorder. In addition to improving clinical care by expediting a diagnosis, this program will expand our knowledge of the molecular basis of this disease, and ultimately lead to better therapeutic opportunities.
Taosheng Huang, MD, PhD
Dr. Huang has initiated the program of Mitochondrial Medicine at Cincinnati Children’s. The program integrates basic/translational research, genetic testing, and clinical service for mitochondrial diseases. He is an internationally recognize researcher, and he was appointed as a scientific advisor for Ministry and Health in China.
Mehdi Keddache, PhD
Dr. Keddache developed a nationally available webinar for the U01 “Pluripotent Cell Biology Consortium” funded by the NIH. This educational webinar focused on the genomic technologies at the Cincinnati Cell Characterization Core (C4). Through collaborative projects with the US-EPA, Dr. Keddache developed and implemented new technologies in the Genetic Variation and Gene Discovery facility of the DHG in the fields of metagenomics and bioinformatics.
Nancy Leslie, MD
Dr. Leslie completed a two year collaborative project sponsored by HRSA to create uniform case definitions for all inborn errors included in the Newborn Screening Uniform Panel. This resource will be provided to state newborn screening programs to aid in classification of identified cases, promote future outcomes research, and assure that incidence rates reflect standardized assignments of affected status. A major hurdle to appropriate classification in some states is lack of funding for molecular diagnostic testing. It is hope that this tool will help states advocate for coverage of essential diagnostic testing for these disorders.
Ronghua Li, PhD
Dr. Li began his independent research career to study human mitochondrial diseases using cell-specific models by developing specific transmitochondrial cybrids to study pathogenesis of maternally transmitted hypertension. His general research is focused on using iPSCs to study tissue specific effects of mitochondrial diseases.
Derek Neilson, MD
Dr. Neilson assumed leadership in developing the greatly expanding Ehlers-Danlos clinic and research program at Cincinnati Children’s. This nationally recognized center is among the few in the nation to provide comprehensive approaches to Ehlers-Danlos syndrome.
Sunghee Oh, PhD
Dr. Oh developed a statistical approach to the analyses of differential expression using RNA-seq profile data. These approaches are being applied to the identification of differential expression of alternative splicing variability, cell cyclic regulation and stimuli-response data, and time course analyses. These methodological accomplishments will significantly contribute to analyzing various types of time-dependent data including, disease progression, age-related gene expression, and integrative analysis with chip-seq and methylation epigenetic factors omics data.
Manoj Pandey, PhD
Dr. Pandey recognized C5a mediated signaling as a positive regulator for immunological inflammation in Gaucher disease mice. This finding may provide an approach to control the inflammatory propagation of Gaucher brain diseases.
Cindy Prows, MSN, CNS
Ms. Prows’ research is aimed at measuring responses (parents and clinicians) to integration of genomic research results into the health care system. Toward this aim, she provides leadership as co-PI on three different studies: DHG Performance of Exome Sequencing with Greg Grabowski, MD; Return of eMERGE Research Results with John Harley, MD (Rheumatology); and Pre-emptive Genotyping of Children and Adolescents with Senthil Sadhasivam, MD (Anesthesia). These data collection phases for the first two projects are ongoing and updates are initiated for Genetic Pharmacology Service test offerings and associated EPIC alerts.
Ms. Prows was an Editorial Advisory Board member and invited author for a Special Genomic Nursing Clinical Issue published the first quarter of 2013 by the Journal of Nursing Scholarship. In conjunction with the special issue, a webinar series was produced in which authors presented additional content and answered questions from a national online audience. Links to the published articles and webinar series can be found on genome.gov. This effort is part of an ongoing national initiative to integrate genetics / genomics into nursing education and practice.
Daniel Prows, PhD
Dr. Prows has successfully propagated a newly discovered mutant mouse that develops severe cardiac fibrosis and right ventricular dilated cardiomyopathy (DCM), with affected mice dying prematurely of heart failure and/or sudden cardiac arrest. Results from exome sequencing of mutants with heart failure combined with ratios of affected-to-unaffected offspring suggest that 2-3 genetic variants interact to produce the DCM and heart failure. Because most cardiomyopathies have only been associated with single gene variants, this mutant may represent a unique multigenic model of DCM with potential to identify and investigate an important gene-gene interaction causal for early-onset right-sided heart failure and premature death.
Howard Saal, MD
Dr. Saal served as President of American Cleft Palate Association (term ended 12/31/12) and served as a member of the AAP Neuromotor Screening panel. In addition, he was named to the top 1% of Clinical Geneticists by US News and World Report and listed in Best Doctors in America.
Elizabeth Schorry, MD
Dr. Schorry was re-funded by the Department of Defense for the NF Clinical Trials Consortium. She is the lead for the internationally recognized NF Clinic and is the PI for Cincinnati Children’s for the NF Consortium, which now includes 13 sites internationally and is funded through 2017 to perform clinical trials for NF1 and NF2. Two trials have been completed, an additional three trials are ongoing and enrolling, and two additional trials will open in the near future. Of particular interest are the trials of agents for treatment of plexiform neurofibromas, which will likely bring in the near future the first reports of drugs (MEK inhibitors) capable of shrinking these tumors. These trials have the potential to significantly impact health outcomes for children and adults with neurofibromatosis.
Teresa Smolarek, PhD
A collaborative effort between Drs. Sund, Zimmerman, Thomas, Mitchell, Prada, Bao, Martin, Smolarek and Grote, showed that SNP microarray will identify copy neutral regions of homozygosity (ROH) and demonstrated the clinical utility of ROH. Genetic information obtained from the array rapidly aided in the diagnosis of autosomal recessive disorders in some cases.
Together with Dr. Christine Phillips, MD of the CBDI, a collaborative study examined the use of low dose decitabine in children and young adults with refractory acute myeloid leukemia and demonstrated that this is an effective therapy for selected patients, thereby establishing a new therapeutic for these patients.
Rolf Stottmann, PhD
Dr. Stottmann, along with investigators from the Divisions of Human Genetics, Developmental Biology, and Hematology/Oncology, is undertaking studies to understand the genetic basis of congenital defects in patients with craniofacial and forebrain malformations. They have recently discovered the cause of two separate syndromes and have begun to uncover the molecular bases for these phenotypes.
Dr. Stottmann characterized a novel mouse mutation in the tubulin, beta 2B gene (Tubb2b) and showed that heterozygous mice for mutations in Tubb2b have behavioral abnormalities and subtle cortical defects. Homozygous mutants, however, die at birth and have major defects in growth and patterning of the forebrain. This is the first mouse model of a recessive mutation in tubulin genes and adds significantly to recent studies identifying the consequences of tubulin mutations (tubulinopathies) for brain development in mouse and human.
Dr. Stottmann was awarded a March of Dimes Basil O'Connor Research Scholar Award.
Ying Sun, PhD
Dr. Sun focuses her research on the glycosphingolipid storage diseases of the CNS in two major areas: 1) A detailed study of the glycosphingolipids in various regions of the brain and in visceral tissues showed that the accumulations of specific types of these lipids are region/organ and mutation dependent, and thereby, demonstrating substrate preference for specific mutations of acid β-glucosidase, the Gaucher disease enzyme. 2) Analysis of double deficiencies of the sphingolipids activator proteins (saposins) A and B showed differential in vivo effects on the sulfatide pathway and regionally specific effects in the CNS. These studies have implications for understanding the roles of glycosphingolipids and sulfated glycosphingolipids in regional brain development and disease as well as their treatment.
C. Alexander Valencia, PhD
Dr. Valencia has led the development of the bioinformatic analysis pipeline and the technical validation of the clinical exome program at Cincinnati Children’s. He has worked with the Division of Human Genetics, Rheumatology, and BMI to coordinate the launch of the two parallel analysis pipelines that meet CLIA/CAP regulatory requirements. The clinical exome will improve the diagnoses and potentially alter patient management, and provide identification of genes related to specific phenotypes which will be essential for addressing functional questions. In addition, his articles have shown that next-generation sequencing panels for congenital muscular dystrophies increases the diagnostic yield when compared to single gene Sanger sequencing testing. In the realm of protein-targeted delivery of cancer biomarkers, he demonstrated that his novel heptamer molecules successfully targeted EGFR and HER2 with high stability and avidity. He presented, “MetaboSeq: A clinical fatty acid oxidation disorders next generation sequencing panel” at the 130th OMICS Group Conference and International Conference on OMICS studies in Orlando, Florida.
Ge Zhang, MD, PhD
Dr. Zhang has conducted multiple genome-wide association (GWA) studies and quantitative genetic analyses of human complex traits and diseases, including 1) metabolic syndrome and related traits; 2) preterm birth and 3) isocyanate-induced occupational asthma. In addition, he has developed computer packages for efficient storage and rapid analysis of massive genomic data and he has conducted multiple genome-wide association (GWA) studies and quantitative genetic analyses of human complex traits. The significant results generated from these studies provided deeper insights into the molecular etiology and genetic architecture of human complex traits.
Kejian Zhang, MD, MBA
Dr. Zhang leads the design, validation and implementation of the next-generation sequencing based testing program including OtoSeq, MetaboSeq, ImmunoSeq, and Clinical Exome Sequencing at Cincinnati Children’s. The successful introduction of these clinical testing programs positions Cincinnati Children’s as a leading pediatric academic institution in genetic diagnoses for rare childhood diseases. It has and will have significance positive impact on clinical and basic research as well as improving children’s health.