Clark Chen, M.D.Ph.D.

Chair, Department of Neurosurgery


Research Interests:

Our research program is focused on understanding the reciprocal interactions between brain cancer cells and the unique microenvironment of the central nervous system (CNS). Elements of the CNS microenvironment fundamentally differ from those of other anatomic compartments, characterized by microglia immune surveillance, high density of synaptic transmission, and an unique extracellular matrix. Dynamic interplays between these constituents and the cancer cell modulate all aspects of tumor biology, including DNA damage response, immune invasion, metabolic energetics, and cancer stem cell states. Moreover, cancer cells interface with neural elements to influence intrinsic physiology and neuro-network. From a basic science perspective, studies of this dynamic interplay offer a glimpse into the biologic processes that govern the inner workings of the CNS.  Clinically, these interplays dictate clinical survival and quality of life for patients afflicted with brain cancer; insights into these reciprocal communications afford opportunities for diagnostic and therapeutic development.

We utilize an integrated approach in our studies, including synthesis of functional/clinical genomics, clinical tumor specimen interrogation, meso-scale/clinical imaging, transgenic murine/induced pluripotent cell models, and 3D-printing methods. Our work demonstrating essential contribution of dopamine neuro-transmission to brain tumor mitogenesis has led to an ongoing clinical trial at the University of Minnesota investigating the anti-neoplastic effects of dopamine receptor 2 (DRD2) inhibition in glioblastomas, the most common form of brain cancer in adult. Our finding that microglia, though exerting anti-tumoral effects in its native state, is reprogrammed by cancer cells to facilitate glioblastoma growth, has led to the development of a new class of clinical therapeutics. In collaboration with Timothy Ebner, another faculty in the Graduate Program in Neuroscience, meso-scale imaging unveiled the impacts of tumor growth on the neural connectome, availing opportunities for early detection diagnostics. These and other ongoing work in our group aim to improve our understanding of CNS physiology as well as clinical outcomes for patients afflicted with brain cancer.

Selected Publications:

  •  Dhawan S, Patil CG, Chen CC, Venteicher AS.  Early versus delayed postoperative radiotherapy for treatment of low-grade gliomas, Cochrane Library 2020, in press.
  •  Cramer SW, Chen CC.  Photodynamic therapy for the treatment of glioblastoma. Frontiers in Surgery 2020, 6(81): 1-1.
  • Leschke J, Chen CC. Supplementing decompression with instrumented fusion for symptomatic lumbar spinal stenosis – a critical appraisal of available randomized controlled trials. Neurosurgery Review 2020, in press.
  • Ramakrishnan V, Xu B, Akers J, Nguyen T, Ma J, Dhawan S, Ning J, Mao Y, Hua W, Kokkoli E, Furnari F, Carter BS, Chen CC. Radiation-induced extracellular vesicle (EV) release of miR-603 promotes an insulin-like growth factor (IGF1) signaling induced stem cell state in glioblastomas. EBioMed 2020, in press.
  •  Koga T, Chen CC, Furanri FB. Genome engineering evolves brain tumor modeling. Neurologia Medico Chilurgica 2020, in press.
  • Dhawan S, Bartek J, Chen CC. Cost-Effectiveness of Stereotactic Laser Ablation (SLA) for Brain Tumors. International Journal of Hyperthermia 2020, in press.
  •  Bartek J, Dhawan S, Thurin E, Alattar A, Gulati S, Rydenhag B, Henriksson R, Chen CC, Jakola AS. Short-term outcome following surgery for rare brain tumor entities in adults: a Swedish nation-wide registry-based study and comparison with SEER database. Journal of Neuro-Oncology 2020, in press.
  • Dhawan S, Bartek J, Chen CC. Cost-Effectiveness of Stereotactic Laser Ablation (SLA) for Brain Tumors. Hyperthermia 2020, in press.
  • Freeman D, Guillaume D, Bell WR, Chen CC. De-vascularization of a hemorrhagic pineocytoma by laser thermal ablation followed by endoscopic resection: a proof-of-principle case report. World Neurosurgery 2020, in press.
  •  Chen CC, Freeman D, Warnke PC. Frame-based stereotactic-endoscopic third ventriculostomy – towards improved precision and minimizing morbidities. World Neurosurg 2020, in press
  • Cloughesy TF, Petrecca K, Walbert T, Butowski N, Salacz M, Perry J, Damek D, Bota D, Bettegowda C, Zhu JJ, Iwamoto F, Placantonakis D, Kim L, Elder B, Kaptain G, Cachia D, Moshel Y, Brem S, Piccioni D, Landolfi J, Chen CC, Gruber H, Rao A, Hogan D, Accomando W, Ostertag D, Montellano TT, Kheoh T, Kabbinavar F, Vogelbaum MA. Vocimagene amiretrorepvec in combination with Toca FC in patients with recurrent high grade glioma. JAMA Oncology 2020, in press.
  • Yu S, Yu X, Sun L, Zheng Y, Chen L, Zu H, Jin J, Lan Q, Chen CC, M Li. GBP2 enhances glioblastoma invasion through Stat3/Fibronectin pathway. Oncogene 2020, in press.
  • Steed TC, Treiber JM, Taha B, Engin HB, Carter H, Patel KS, Dale AM, Carter BS, Chen CC. Glioblastomas located in proximity to the subventricular zone (SVZ) exhibited enrichment of gene expression profiles associated with the cancer stem cell state. J Neurooncol 2020, in press.
  • Lewis JM, Dhawan S, Obierze AC, Sarno B, Akers J, Heller MJ, Chen CC. Plasma Biomarker for Post-concussive Syndrome: A Pilot Study using an Alternating Current Electro-kinetic Platform. Front. Neurol. 2020, in press.
  • Gessler D, Ferreira C, Dusenbery K, Chen CC. GammaTileTM (GT): a new brachytherapy platform for glioblastomas. Future Oncol. 2020, in press.
  • Ferreira C, Sterling D, Dusenbery K, Reynolds M, Chen CC, Parham Alaei. Commissioning and Clinical Aspects of the first clinical use outside of a clinical trial of GammaTile permanent brain implants. Brachytherapy 2020, in press.
  • Prager, BC, Vasudevan HN, Dixit D, Bernatchez JA, Wu Q, Spangler LC, Bhargava S, Lee D, King BH, Morton A, Gimple RC, Pekmezci M, Zhu Z, Siqueira-Neto JL, Wang X, Xie Q, Chen CC, Barnett GH, Vogelbaum MA, Mack SC, Chavez L, Perry A, Raleigh DR. Rich JN.  The Meningioma Enhancer Landscape Delineates Prognostic Subgroups and Drives Druggable Dependencies. Cancer Discovery 2020, in press.
  • He Y, Li J, Koga T, Ma J, Dhawan S, Suzuki Y, Furnari F, Prabhu VV, Allen JE, Chen CC. Epidermal Growth Factor Receptor (EGFR) as a molecular determinant of glioblastoma response to dopamine receptor 2 (DRD2) inhibitors. Neuro-Oncology 2020, in press.
  • Elder T, Lee I, Tatsui C, Chen CC, Sloan A. Laser Interstitial Thermotherapy (LITT) for the treatment of Tumors of the Brain and Spine: A Brief Review. Journal of Neuro-Oncology 2020, in press.
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