Udall Center - Johns Hopkins School of Medicine

Udall Center - Johns Hopkins School of Medicine

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Director: Ted M. Dawson, M.D., Ph.D.

Title: The Udall Center of Excellence for Parkinson's Disease Research at Johns Hopkins University School of Medicine

Website: http://www.hopkinsmedicine.org/neurology_neurosurgery/research/labs/udall_center/


Central Theme

Mutations in the alpha-synuclein, LRRK2 and parkin genes have been linked to familial Parkinson's Disease (PD).  The Johns Hopkins University School of Medicine Udall Center seeks to elucidate the pathogenic processes underlying PD by identifying the molecular mechanisms through which associated gene mutations act, as well as their relationship to the common sporadic form of PD. Along these lines, Center studies focus on in vitro and in vivo models of the biology of alpha synuclein and LRRK2, as well as identification and development of PD biomarkers that emerge from these investigations.  

Center Structure 

The Johns Hopkins University School of Medicine Udall Center is focused on the most common autosomal recessive (parkin) and autosomal dominant PD (LRRK2) linked genes and alpha-synuclein due to potential roles in both sporadic and familial PD. One of the major goals of this Center is to understand the interrelationship between parkin, the most common cause of autosomal recessive PD (Project 1), a-synuclein, which is causal in sporadic PD (Project 2) and LRRK2, the most common cause of autosomal dominant PD (Project 4) and to use related discoveries to develop disease and progression biomarkers (Project 3) and ultimately new therapies.  The insights into how these three genes interact in the pathogenesis of PD and the discovery of biomarkers would not be possible without the Udall Center structure as it enables the evaluation of these major causes of PD and the ability to evaluate findings in each arm of PD to elucidate common pathways if they exist as these may provide the best opportunities for comprehensive new therapies and biomarkers. This multi-disciplinary approach has the capacity to produce unique information concerning the mechanisms of neuronal injury in animal models of PD that will lead to a better understanding of the function and the role of a-synuclein, parkin, and LRRK2 in normal and pathophysiologic processes related to PD.

The Center is comprised of four Research Projects and four supportive Cores. Research Projects include: Project 1: Biology of parkin and its role in Parkinson’s disease (Ted M. Dawson); Project 2: Understanding mechanisms of α-synuclein pathology (Han Seok Ko); Project 3: Establishing clinical utility of CSF biomarkers for PD (Akhilesh Pandey); Project 4: LRRK2 Biology in Parkinson’s Disease (Valina L. Dawson). Cores include: Administrative (Ted M. Dawson); Clinical (Liana Rosenthal); Neuropathology (Juan C. Troncoso); and Proteomics (Chan-Hyun Na). The program represents a multi-disciplinary, mechanistic approach involving investigators with complementary areas of expertise who have long been committed to studies of neurodegenerative diseases, including PD.

Recent Advances

  • Identification of novel targets to slow the progression of PD by targeting the molecular mechanisms by which genetic mutations cause PD
  • Identification of LRRK2 phospho substrates
  • Discovery that microglia activate A1 astrocytes, which contributes to neurodegeneration in PD
  • Discovery that immune response in PD is driven by HLA display of a-synuclein peptides 

Public Health Statement

Tremendous advances in understanding the pathogenesis of a variety of neurodegenerative disorders have been made by the study of genes implicated in familial degenerative disorders such as Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), familial prion disorders and triple repeat (CAG) disorders such as Huntington’s disease. Most importantly for this Center, mutations in alpha-synuclein, parkin and LRRK2 have been linked to familial PD.  The Johns Hopkins University School of Medicine Udall Center studies the most common autosomal recessive (parkin) and autosomal dominant PD (LRRK2) linked genes and alpha-synuclein due to its potential role in both sporadic and familial PD. It is our tenet that understanding the molecular mechanisms by which mutations in these three genes and their relationship to the more common sporadic form of PD has the greatest potential to enhance our understanding of pathogenic mechanisms in PD.  

Budget End Date: 2019/07/31

NIH Grant Number: P50 NS038377