The major focus of the Wilhelm Research Group is the molecular mechanisms underlying learning and memory and how they are perturbed in inherited or congenital brain diseases. We use a variety of in vitro and in vivo tools to study synaptic and dendritic biology to elucidate these mechanisms. The ultimate goal of this research is to improve the neurodevelopmental outcomes of children with both congenital and acquired forms of central nervous system injury. These efforts are imperative because neurodevelopmental disabilities remain the primary negative consequence of critical illness in infants and children despite ever-improving mortality rates for our sickest patients.
Regulation of Dendritic Proteins by Synaptic Activity
Long-term potentiation (LTP) and long-term depression (LTD), the electrophysiological correlates of memory, require rapidly induced, long lasting changes in synaptic proteins in response to neuronal activity. Our lab is currently investigating how the c-Jun N-terminal kinase (JNK) pathway is involved in regulating protein turnover within dendritic spines in response to metabotropic glutamate receptor activation and how this regulates synaptic function. Current translational research efforts are focusing on how this pathway is altered in Fragile X Syndrome. Fragile X Syndrome is the most common inherited cause of mental retardation and provides a “clean” (single gene deletion) model in which to study these molecular signals.
We use synaptoneurosomes (SNs) to study the turnover of dendritic proteins in the absence of nuclear gene regulation. We also use confocal immunomicroscopy to determine local signaling events in dendritic spines in intact, cultured neurons. Electrophysiologic studies and behavioral testing are used to determine the consequences of the molecular events identified in these studies. We are also interested in how acquired CNS injuries (hypoxia-ischemia, HI) in the developing brain affect these pathways. Our lab is housed within the Waisman Center, one of nine national facilities that includes a Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Center and a University Center for Excellence in Developmental Disabilities. This allows collaboration with other basic and clinical scientists studying FXS and neonatal HI.
Molecular Mechanisms of Hypertrophic Cardiomyopathy (HCM) and Heart Failure
Our lab collaborates with Dr. Carter Ralphe in Pediatric Cardiology investigating the cellular signaling events that occur in cardiomyocytes subjected to genetic and environmental stressors. Cardiomyopathy from a variety of insults may ultimately lead to heart failure and this may be due in part to apoptotic death of cardiomyocytes. Several hypertrophic signaling events may promote pro-apoptotic signaling, and one such pathway is the c-Jun N-terminal kinase (JNK) pathway. Our lab is investigating the regulation of the JNK pathway in normal cardiomyocytes and those genetically pre-disposed to hypertrophic cardiomyopathy. Understanding how stress signaling contributes to the ultimate pathobiology of HCM and heart failure will have important implications for the treatment of patients and their family members who carry these mutations.
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Three Department of Pediatrics faculty were among those honored at this years UW Health Physician Excellence Awards ceremony, held June 14, 2018, at the Health Sciences Learning Center. The peer-nominated awards recognize those who demonstrate …June 1, 2018
Congratulations to the 28 Department of Pediatrics faculty who were named in Madison Magazine’s biennial guide of top doctors in the area. Critical Care Medicine: Michael Wilhelm, MD Medical Genetics: David Wargowski, MD Neonatology: Jamie …April 1, 2018
Eighteen Department of Pediatrics faculty are playing key roles in the UW School of Medicine and Public Health’s (SMPH) MD curriculum transformation, a multi-year initiative that, starting in August 2017, will provide medical students with …July 26, 2016
The Department of Pediatrics Research and Development Committee recently awarded grants to thirteen faculty members for the following projects: Awni Al-Subu, MD – Pediatric Acute Respiratory Distress Incidence and Epidemiology (PARDIE) Study Pelin Cengiz, MD …May 1, 2016
Congratulations to the 2012 recipients of the Departments various teaching and patient care excellence awards. Award winners were announced at the recent resident graduation ceremony: Charles C. Lobeck Medical Education Award: Margaret Bartholomew, MD Varness …June 1, 2012
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