Un Jung Kang, M.D.
Professor of Neurology
MC 2030, J219
Phone (773) 702-6389
My academic interests are the scientific and clinical aspects of neurodegenerative diseases associated with abnormal involuntary movement disorders such as Parkinson’s disease (PD). My primary research focus is on the cellular and molecular mechanisms that underlie these disorders and devising rational therapeutic approaches through laboratory investigation. My clinical activities include clinical investigations of new therapeutic agents, biomarker development, and specialty patient care. Teaching is an integral part of these activities.
Mechanisms of Dopaminergic Therapy and Its Complications in PD
Dopamine replacement remains the mainstay of PD therapy. We are interested in optimizing and understanding the limits of most optimal dopamine therapy. My initial research focus was to devise gene therapy methods to deliver dopamine locally into the denervated area of brain and continuously in an attempt to improve current symptomatic pharmacological treatment approaches for PD. Through the systematic neurobiological investigation of the biochemical steps, we have established the roles of each step in dopamine biosynthesis for gene therapy and found the optimal set of genes for effective dopamine replacement gene therapy. These studies have established guidelines for optimal combinations of genes to be used for dopamine replacement, and formed the basis of primate studies and current clinical trials by other investigators. More recently, in collaboration with Professor Xiaoxi Zhuang’s laboratory, we discovered the role of motor learning as the underlying mechanism for long-duration response, which is more beneficial response than short-duration response to dopamine therapy. A lay version of the story is on a science blog. We are studying molecular mechanisms mediating such learning and exploring clinical translation of this finding for optimal treatment of PD patient by combining motor training and dopamine therapy. A preliminary evidence for such synergistic interaction in PD patients has been obtained by analyzing data from clinical trials of levodopa, as described in another science blog.
We also study the molecular mechanisms underlying dyskinesia, a major limiting factor in current dopaminergic therapy regardless of the delivery methods. We have established toxic and genetic models of PD phenotype. Combining our in-depth understanding of the molecular and biochemical requirements for dopamine replacement, and the behavioral paradigms that allow the distinction between the akinesia improvement and dyskinesia development, we are examining the molecular and cellular mechanisms for motor response complications. Electrophysiological studies are also performed in collaboration with Professor Dan McGehee. Our recent study illustrates the role of cholinergic interneurons as critical mediator of dyskinesia. A lay version of this story is on a science blog.
We also try to understand the cognitive side effect of dopaminergic therapy, in particular, excessive behaviors that results in gambling, shopping spree, or other impulse control disorders.
Mechanisms of Neurodegeneration in PD
Currently, our major research focus is on understanding the mechanism of neurodegeneration in PD. We have investigated clues derived from environmental factors using toxic models. We are trying to understand the role of mitochondria and oxidative stress and the intrinsic properties of dopaminergic neurons that make them more susceptible to degeneration. More recently, we are studying rodent models of genetic PD (DJ-1 and PINK1 mutations) as complementary approaches to understand the disease mechanisms.
We are interested in applying these findings to develop biomarkers to track the disease progression and disease subtypes as well as to develop therapeutic approaches.
Please also see my websites for the Committee on Neurobiology for further information on research activities, Department of Neurology, the Center for Parkinson’s Disease and Movement Disorders, and University of Chicago Medical Center for clinical activities.
1978 The University of Chicago,
1982 The Johns Hopkins University,
1992-present Assistant/Associate/Full Professor, Department of Neurology, The University of Chicago
1993-present Committees on Neurobiology and Molecular Medicine (since 2002)
Directions and maps:
Office and lab: J219 in the Surgery – Brain Research Building.
Clinic: 4G of the Center for Advanced Medicine.
Driving directions & parking: valet parking at the Center for Advanced Medicine or self park in parking