Clark Chin-Chung Chen
Prof. Clark Chin-Chung Chen, PhD, MD
Chief, Stereotactic and Radiosurgery
Director, Medical Education
Associate Professor, Division of Neurosurgery
Vice Chairman, Research and Academic Development
Department of Surgery, University of California, San Diego, USA
Clinical Innovations Brain tumors are commonly treated with biological agents that alter MRI findings. These alterations make difficult the interpretation of radiographic abnormalities; surgical biopsies/resections of these abnormalities are often required to exclude tumor progression and treatment failure. Dr. Chen has conducted clinical studies to develop predictive algorithms for combining multiple advanced imaging modalities including PET, SPECT, MR perfusion, RSI, ASL, tractography, and CBF imaging to determine tumor progression. These algorithms should minimize the need for surgical intervention and improve the quality of life for patients afflicted with brain cancer. Additionally, Dr. Chen has a dedicated interest in minimally invasive cranial surgery, including the application of laser thermal ablation, endoscopy, oncolytic virus delivery, tractography guided surgery, and awake craniotomy.
Laboratory Interest Integrated genomic analyses of glioblastoma specimens are beginning to unveil insights into the native tumor physiology of as it exists within the human brain. The laboratory of Dr. Chen has focused on developing comprehensive to tools synthesize these insights with mechanistic understanding of the fundamental biologic processes, such as DNA replication, repair, and mitosis, to identify novel therapeutic and diagnostic platforms. By coupling integrate genomic analysis with patient survival data, they have identified the first predictive biomarker for glioblastoma response to chemotherapy Functional analysis of this biomarker, a microRNA, suggest that it serves as a master regulator of multiple DNA repair processes. Using this approach they have identify other master regulating miRNA of glioblastoma resistance. Paralleling these efforts, Dr. Chen’s laboratory has carried out genome scale RNAi screens to systematically evaluate genes required for glioblastoma proliferation. Hybridizing these results with genomic mutational landscape and statistically rigorous interrogation of glioblastoma trancriptiome profiles have led to the identification of a number of novel therapeutic targets including the G-Protein Coupled Receptor (GPCR) Dopamine Receptor 2 (DRD2), the mitosis regulating kinase, Polo-Like Kinase 1 (PLK1), and the metabolic enzyme, Lactate Dehydrogenase (LDHA) uncovered systems level cross talk between molecular network mediating , metabolism, and chromatin structure.
Taken together, studies of Dr. Chen suggest that combining molecular genetic/cell biologic approaches with integrative cancer genome analysis constitutes a powerful platform toward diagnostic and therapeutic development. However, this approach fundamentally neglects the interactions between the tumor and its microenvironment. To overcome this limitation, Dr. Chen performed studies to examine how glioblastoma biology is altered by the presence of micro-glia and bone marrow cell, both present in the glioblastoma micro-environment. The emerging picture is a reciprocal dynamic synergism whereby the glioblastoma cells express specific cell surface molecules to suppress the immunologic function of microglia and the microglia/bone marrow cells secrete select cytokines to stimulate glioblastma growth. Significant portions of this dynamic interaction are mediated through secreted microvesicles, suggesting these platforms as a viable platform for diagnostic and therapeutic development.
Bibliography of Dr. Chen includes 91 original articles, 27 reviews, chapters, monographs, and editorials on stereotactic radiosurgery and radiotherapy in neuro-oncology.
Title of presentation: “Microvesicles as a Platform for Glioma DIagnostic and Therapeutic Development”.