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Rebecca A. Simmons, MD

Rebecca A. Simmons, MD Non-Penn Medicine Provider

Hallam Hurt Professor in Neonatology

Dr. Simmons is employed by the Children's Hospital of Philadelphia.

About Dr. Rebecca A. Simmons

Recognized by Best Doctors in America 2005-2006, 2007-2008, 2009-2010, 2011-2012

Recognized by Best Doctors in America - 2013-2014

Clinical Specialties

Specialty:

  • Pediatrics
    • Neonatology and Newborn Services

Programs & Centers:

Board Certification:

  • Neonatal-Perinatal Medicine, 1989

Practice Locations and Appointments

Insurance Accepted

  • Aetna US Healthcare
  • Cigna
  • Devon Health Services (Americare)
  • Gateway Health Plan
  • Geisinger Health Plan
  • HealthAmerica / HealthAssurance, a Coventry Plan
  • HealthPartners
  • HealthPartners Medicare
  • HealthSmart
  • Highmark Blue Shield
  • Horizon Blue Cross Blue Shield of New Jersey
  • Humana / Choicecare
  • Independence Blue Cross (Keystone East)
  • Intergroup
  • Keystone First
  • Multiplan
  • NJ Medicaid
  • NJ Qualcare
  • Oxford Health Plan
  • PA Medicaid
  • Preferred Care
  • Preferred Health Care/LGH
  • Tricare
  • United Healthcare
  • UnitedHealthcare Community Plan
  • US Family Health Plan

Education and Training

Medical School: University of Arizona College of Medicine
Residency: University of Arizona Medical Center
Fellowship: UCSF Medical Center and Hospital

Memberships

Ad Hoc Reviewer American Diabetes Association, National Ad Hoc Reviewer Health Research Council of New Zealand, International Ad Hoc Reviewer March of Dimes, National Ad Hoc Reviewer Medical Research Council, Canada, International Ad Hoc Reviewer Medical Research Council, Great Britain, International Ad Hoc Reviewer Wellcome Trust, UK, International American Academy of Pediatrics, National American Board of Pediatrics, National American Diabetes Association, National Association, Auckland Medical Research Foundation, International Danish Diabetes Academy, International Eastern Society for Pediatric Research, Local Endocrine Society, National Gravida Center for Growth and Development, University of Auckland, Auckland New Zealand, International OBELIX Project (Obesiogenic Endocrine Disruptors: Linking prenatal Exposures to the development of obesity later in life) Funded by the European Union, International Perinatal Research Society, National Society for Study of Fetal Physiology, National The Society for Pediatric Research, National Winthrop-University Hospital, National

Hospital Affiliation

Dr. Simmons is employed by the Children's Hospital of Philadelphia.

Hospital Privileges:

  • Hospital of the University of Pennsylvania: Has privileges to treat patients in the hospital.

Research

Description of Research Expertise:

The principal goal of our research program is to elucidate the underlying molecular mechanisms that link fetal growth retardation to the later development of obesity and type 2 diabetes in adulthood. We currently have 3 major projects and several smaller projects. The first project focuses on the relationship between oxidative stress and ß-cell dysfunction and insulin resistance. We have developed a model of fetal growth retardation in the rodent (mice and rats) which leads to the later development of diabetes and obesity in adult animals. We have established that fetal growth retardation induces progressive mitochondrial dysfunction, oxidative stress, mtDNA mutations, and electron transport defects. These defects cause abnormal ß-cell function and development, and hepatic and muscle insulin resistance. Oxidative stress decreases transcription of key genes related to ß-cell development, induces modifications of proteins of the Krebs cycle in the liver, and muscle. Pdx-1 is a critical transcription factor that regulates ß-cell function and development. Transcription of this gene is permanently down-regulated in ß-cells of IUGR rats leading to a gradual reduction in ß-cell function and ß-cell replication. We have determined that oxidative stress induced by uteroplacental insufficiency in IUGR fetal pancreas induces aberrant methylation and chromatin remodeling at the Pdx-1 promoter, which in turn induces transcription silencing. The focus of the second project is to determine whether the effects of an aberrant intrauterine milieu can be reversed after birth, we have designed a number of therapeutic modalities including diet modifications and antioxidant treatment. In collaboration with Dr. Doris Stoffers, we have successfully prevented the development of diabetes in IUGR rats with several of these treatments. Administration of a pancreatic ß-cell trophic factor, Exendin-4, during the neonatal period dramatically prevents the development of diabetes in our model. Neonatal Exendin-4 treatment prevents the progressive reduction in ß-cell mass that is observed in IUGR rats over time. Expression of Pdx-1 is restored to normal levels, and islet ß-cell proliferation rates are normalized by the neonatal Exendin-4 treatment. Of major clinical significance is our finding that Exendin-4 treatment in the newborn period prevents the onset of obesity in IUGR rats. This surprising finding has stimulated a new direction for this project and we are currently determining the mechanisms by which Exendin-4 treatment reverses epigenetic modifications such as DNA methylation and histone modifications of key genes related to ß-cell development. The third project is focused on the effects of obesity during pregnancy and the long-term outcome in the offspring. The specific aims of this project are to determine the window of susceptibility of the developing organism to the effects of obesity during gestation, determining whether regulation of the adipogenic pathway is altered in offspring, and defining the molecular mechanisms responsible for enhanced adipogenesis observed in offspring of obese mothers.

Methods/Model Systems:

1. Cell culture and animal models to study fetal programming (the effect of an abnormal in-utero environment- IUGR, obesity, diabetes-upon fetal growth and development and the later development of obesity and diabetes).
2. Epigenetic regulation of gene expression (DNA methylation and histone acetylation and methylation) using bisulfite sequencing and ChIP assays
3. Measures of Mitochondrial function-oxidative phosphorylation and electron transport chain activity.

Selected Publications:

Stoffers DA, Desai BM, DeLeon DD, Simmons RA: Neonatal exendin-4 prevents the development of diabetes in the intrauterine growth retarded rat Diabetes 52 (3): 734-740,2003.

Selak MA, Storey BT, Peterside IE, Simmons RA: Impaired oxidative phosphorylation in skeletal muscle of intrauterine growth-retarded rats Am J Physiol Endocrinol Metab 285 (1): E130-E137,2003.

Chennathukuzhi V, Stein JM, Abel T, Donlon S, Yang S, Miller JP, Allman DM, Simmons RA, Hecht NB: Mice deficient for testis-brain RNA-binding protein exhibit a coordinate loss of TRAX, reduced fertility, altered gene expression in the brain, and behavioral changes Mol Cell Biol 23 (18): 6419-6434,2003.

Peterside IE, Selak MA, Simmons RA: Impaired oxidative phosphorylation in hepatic mitochondria in growth-retarded rats Am J Physiol 285 (6): E1258-1264,2003.

Pallotto EK, Macones GA, Simmons R: Small for gestational age infants at risk for prolonged hypoglycemia Epidemiology : 2003.

Pallotto EK, Woelnerhanssen B, Macones G, Simmons RA: Hypoglycemia in small for gestational age infants: How extensive is the problem and what are the risks? Pediatr Res 53 : 499A,2003.

Simmons RA, Selak MA: Intrauterine growth retardation increases oxidative stress and induces mitochondrial DNA deletions in rat ß-cells Pediatr Res 53 : 804A,2003.

Vuguin P, Raab B, Xiaohui-Ma, Liu B, Barzilai N, Stoffers DA, Simmons RA: Exendin-4 decreases body weight and improves insulin action in intrauterine growth retarded rats. Pediatr Res 53 : 877A,2003.

Simmons RA, Crutchlow M, Desai BM, Stoffers DA: Reduced islet vascularity in intrauterine growth retarded rats Endocrinology : PI-295,2003.

Simmons, RA: Cell glucose transport handling during fetal and neonatal development Fetal and Neonatal Physiol : 2003.

Academic Contact Info

BRB II/III, 13th floor, Rm 1308, 421 Curie Blvd
Philadelphia, PA 19104
Phone: (215) 662-3269
Patient appointments: 800-789-PENN (7366)

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