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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Al Dhaheri N, Wu N, Zhao S, Wu Z, Blank RD, Zhang J, Raggio C, Halanski M, Shen J, Noonan K, Qiu G, Nemeth B, Sund S, Dunwoodie SL, Chapman G, Glurich I, Steiner RD, Wohler …June 24, 2020
The Pediatrics Research Week 2020 Abstract Book is now available. University of Wisconsin Department of Pediatrics faculty, staff, fellows and residents submitted over 50 research abstracts for the virtual conference, which is taking place May 26-29, 2020. …May 21, 2020
1. Ascierto PA, Fox B, Urba W, Anderson AC, Atkins MB, Borden EC, Brahmer J, Butterfield LH, Cesano A, Chen D, de Gruijl T, Dillman RO, Drake CG, Emens LA, Gajewski TF, Gulley JL, Stephen …May 4, 2020
In response to COVID-19, the Department of Pediatrics’ annual Research Week will offer alternative programming to spotlight the scholarly work from its residents, fellows, faculty and staff. Through a mix of livestreamed lectures and interactive …April 28, 2020
Coller RJ, Berry JG, Kuo DZ, Kuhlthau K, Chung PJ, Perrin JM, Hoover CG,Warner G, Shelton C, Thompson LR, Garrity B, Stille CJ. Health System Research Priorities for Children and Youth With Special Health Care …April 16, 2020
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