Clark Chen, M.D.Ph.D.

Chair, Department of Neurosurgery

E-MAIL: [email protected]

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, Alattar AA, Bartek J Jr, Ma J, Bydon M, Venteicher AS, Chen CC. Racial disparity in recommendation for surgical resection of skull base chondrosarcomas: A Surveillance, Epidemiology, and End Results (SEER) analysis. J Clin Neurosci. 2021 Dec;94:186-191.
  • Johnson RA, Do TH, Palzer EF, Cramer SW, Hanson JT, Huling JD, Hoody DG, Rice AL, Piazza AN, Howard MA, McGovern RA, Chen CC. Pattern of technology diffusion in the adoption of stereotactic laser interstitial thermal therapy (LITT) in neuro-oncology. J Neurooncol. 2021 Jul;153(3):417-424.
  • Hirshman BR, Compton J, Carroll KT, Ali MA, Wang SG, Chen CC. Cumulative intracranial tumor volume as a prognostic factor in patients with brain metastases undergoing stereotactic radiosurgery. Acta Neurochir Suppl. 2021;128:57-69.
  • Leschke J, Chen CC. Supplementing decompression with instrumented fusion for symptomatic lumbar spinal stenosis – a critical appraisal of available randomized controlled trials. Neurosurg Rev. 2021;44(2):643-648.
  • Ferreira C, Sterling D, Dusenbery K, Reynolds M, Chen CC, Parham Alaei. First clinical implementation of GammaTile permanent brain implants after FDA clearance. Brachytherapy 2021 May-Jun;20(3):673-685.
  • 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 Discov. 2021;10(11):1722-1741.
  • 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 Oncol. 2021 Mar 25;23(3):400-411.
  • 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. J Neuroonc. 2021;151:429-442.
  • Cramer SW, Chen CC.  Photodynamic therapy for the treatment of glioblastoma. Front Surg. 2020 Jan 21;6:81.
  • Dhawan S, Patil CG, Chen CC, Venteicher AS.  Early versus delayed postoperative radiotherapy for treatment of low-grade gliomas. Cochrane Database Syst Rev. 2020 Jan 20;1(1):CD009229.
  • 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. J Neurooncol. 2020;148(2):281-290.
  • 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. EBioMedicine. 2020 May;55:102736.
  • Koga T, Chen CC, Furanri FB. Genome engineering evolves brain tumor modeling. Neurol Med Chir (Tokyo). 2020 Jul 15;60(7):329-336.
  • Dhawan S, Bartek J, Chen CC. Cost-effectiveness of stereotactic laser ablation (SLA) for brain tumors. Int J Hyperthermia. 2020 Jul;37(2):61-67.
  • Chen CC, Freeman D, Warnke PC. Frame-based stereotactic-endoscopic third ventriculostomy – towards improved precision and minimizing morbidities. World Neurosurg. 2020 Aug;140:e240-e246.
  • 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 Neurosurg. 2020 Jul;139:583-587.
  • 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 electrokinetic platform. Front Neurol. 2020 Jul 14;11:685.
  • 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 Jul;39(27):5042-5055.
  • 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;148:455-462.
  • 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. Effect of cocimagene amiretrorepvec in combination with vlucytosine vs standard of care on survival following tumor resection in patients with recurrent high-grade glioma: A randomized clinical trial. JAMA Oncol. 2020;6(12):1939-1946.
  • Gessler D, Ferreira C, Dusenbery K, Chen CC. GammaTileTM (GT): a new brachytherapy platform for glioblastomas. Future Oncol. 2020;16:2445-2455.
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