Amy Sanghavi Shah, MD, MS

Dr. Shah’s research continues to study how types of cholesterol (lipids) become dysfunctional as a result of obesity and type 2 diabetes in adolescents. Work in 2016 from the Shah Laboratory, in collaboration with several investigators at Cincinnati Children’s and the University of Cincinnati (Lawrence Dolan, MD; Thomas Inge, MD, PhD; and W. Sean Davidson, PhD) has shown that the dysfunctional profile seen in obesity and diabetes is reversible after weight loss surgery. Furthermore, they have shown this reversibility persists for up to eight years post-surgery, despite weight regain and residual obesity. These findings suggest that weight loss surgery influences lipids in a positive way by additional pathways other than weight loss. Future work will focus on determining these pathways.

Deborah Elder, MD

Since April 2014, 19 children and adolescents have undergone total pancreatectomy with islet cell transplantation (TPIAT) for significant, recurrent abdominal pain and impaired quality of life associated with acute or chronic pancreatitis. Dr. Deborah Elder, MD, the endocrine director of the program, in collaboration with other faculty members on the team (Division of Gastroenterology, Hepatology and Nutrition; Division of Pediatric General and Thoracic Surgery; and Pain Management Service) have used Academic and Research Committee (ARC) funding to establish a database, create several education tools for families (PCC website, educational videos, and patient handbook), and marketing tools to increase referral base. These efforts have resulted in 1-2 TPIAT procedures per month with a vast majority of the individuals coming from outside of Ohio. In March 2017, the team published a manuscript in Pediatric Transplantation, “Post-Operative Continuous Glucose Monitoring Following Pancreatectomy with Islet Auto Transplantation”. A second manuscript, “Severe Fasting Hypoglycemia in a Child after Total Pancreatectomy with Islet Autotransplantation” is under review at Pediatric Transplantation, and submitted abstract, “Thrombocytosis Following Pancreatectomy with Islet Auto Transplantation in Children: Cincinnati Children’s Hospital Experience” sent to the American Pancreatic Association meeting. In the near future, the team will focus on identifying predictors of glucose intolerance and insulin independence post TPIAT and assessing quality of life after TPIAT.

New International Guidelines for Children and Adults with Turner Syndrome

A published comprehensive, international guideline that incorporates the most up-to-date knowledge on diagnosis, treatment and patient impact of Turner Syndrome (TS), is in the European Journal of Endocrinology, with Dr. Philippe Backeljauw, MD, as the senior author. Dr. Backeljauw, and his colleague, Dr. Claus Gravholt, MD, PhD (Aarhus University, Denmark), initiated the guideline project in collaboration with several professional societies, to incorporate the latest evidence-based advice for diagnosis and treatment of girls, and women, with TS throughout the entire lifespan. Drs. Gravholt and Backeljauw, co-chairs of the guideline consensus working group, agree that in particular, "the new cardiovascular-related advice should lead to lower morbidity and mortality, while the recommendations on growth hormone/estrogen replacement therapy and monitoring for co-morbidities, as well as guidance for pregnancy consideration, should lead to improved quality of life for all TS individuals."

Sarah D. Corathers, MD

Dr. Corathers’ research focuses on psychosocial outcomes of adolescents and young adults with diabetes and health system based interventions to improve care. An example of these intersecting interests is the reliable implementation of depression screening of adolescents with diabetes at Cincinnati Children's Hospital Medical Center, which has resulted in referral and evaluation for treatment needs of approximately 20% of individuals screened who endorse moderate or high symptoms and immediate evaluation for 7% of individuals who endorse suicidal ideation. At a national level, Dr. Corathers is working with colleagues in the Type 1 Diabetes Exchange Learning Network, supported by funding from the Helmsley Charitable Trust, to build a quality improvement community for type 1 diabetes patients, families, clinicians, researchers, and advocates. Currently, as part of her role as faculty leader with the Type 1 Diabetes Exchange, Dr. Corathers is applying the model of integrating patient reported outcomes in clinical diabetes care to spread depression screening to six pilot pediatric and adult diabetes centers across the network.

Andrew Dauber, MD, MMSc

Dr. Dauber’s research continues to focus on defining the genetic etiologies of severe growth disorders. In a follow up of earlier work, Dr. Dauber published a report in the Journal of Clinical Endocrinology and Metabolism describing a large international cohort of patients with mutations in the Aggrecan gene. This cohort included 103 individuals from 20 families spread across seven countries. He found that patients with Aggrecan deficiency have a range of short stature with a median height of -2.8 standard deviations and the majority of children had a significantly advanced bone age at diagnosis. Early onset osteoarthritis was present in 12 of the families. Nineteen individuals had received growth hormone with some evidence of an increased growth velocity in those patients. Dr. Dauber and his colleagues in the Cincinnati Center for Growth Disorders are now planning on a prospective clinical trial of growth hormone for these patients.

In other work, Dr. Dauber and his collaborators from the University of Sao Paolo in Brazil, identified a second gene that, when mutated, causes precocious puberty. This gene, DLK1, is an imprinted gene and is only expressed when inherited from the father. This is similar to their prior findings of mutations in the imprinted gene MKRN3 as a major cause of familial precocious puberty. The current study used a combination of genetic techniques including linkage analysis followed by whole genome sequencing to find the mutation in DLK1 in a large Brazilian family.

Vivian Hwa, PhD

Dr. Hwa’s group continues involvement in a number of projects stemming from genes/variants identified by WES (whole exome sequencing) analysis in patients with monogenic growth disorders. Highlights include: (a) recent functionally proven dominant-negative mutations in the GHR (GH receptor) gene (published in J. Endocrine Society) and the STAT5B gene (submitted) expands the spectrum of GHI and IGF-I deficiency, and provided valuable insights into functional properties of the affected proteins; (b) CRISPR/Cas knock-in mouse model of pathological human missense PAPPA2 mutation recapitulates patient growth phenotype. Characterization of these mice is on-going; (c) CRISPR/Cas knock-in mouse model of a rare, in-frame. IGF1R homozygous mutation, together with studies involving reconstitution system and primary cells, are currently in progress to understand the mechanism(s) for the microcephalic primordial dwarfism and insulin resistance phenotype observed in affected children; (d) iPSC lines are being generated from patient cells for future organoid model studies of the human GH-IGF-I axis.