Department of Molecular Medicine
 

Chun-Liang Chen, PhD Chun-Liang  ChenPh.D.

Assistant Professor/Research


Profile and Contact Information | Research


RESEARCH

 

Research Program

I am currently utilizing single-cell approaches to study on normal stem/progenitor, cancer-initiating cells (CIC) and circulating tumor cells (CTC) to discover biomarkers for cancer detection and diagnosis. Single cell analysis has recently emerged as an important field of research because technologies have improved in sensitivity and throughput sufficiently to begin measuring and understanding heterogeneity in complex biological systems and correlating it with genetic and epigenetic changes: 1) during normal stem/progenitor cell differentiation and 2) malignant progression of cancer-initiating cells. Earlier detection and improved treatments have reduced cancer (e.g. breast, prostate, colorectal) mortality rates; however, incidence and recurrence rates for the cancer remain high, and therapy is usually not personalized and can have many detrimental side effects. These problems exist largely because the precise biological mechanisms that underlie tumor heterogeneity remain poorly understood. Due to the limits of detection, the common approaches use pooled cells to improve sensitivity. The development of cancer starts with a single initiating cell. The cancer-initiating cell undergoes subtle malignant changes that are generally overwhelmed and diluted out and eventually hard to detect. Therefore, early tumorigenesis and metastasis detection makes single cell study extremely important and clinically and translationally relevant. Single stem/progenitor, CICs, and CTCs are isolated using cell markers, size-based ScreenCell filters, micromanipulators, DEPArray. Isolated single cells are subject to high throughput omics analysis including single-cell RNA-seq (SMART-seq2) and whole genome sequencing using Illumina HiSeq, Nanopore technology, DNA methylation detection and molecular profiling using qRT-PCR with BioMark HD system. This single cell approach will reveal driver tumorigenic mutations, transcriptional fluctuations and epigenetic modifications during the early development of tumorigenesis and metastasis. This will largely increase our ability to detect early status of cancer and dissect the underlying epigenetic mechanisms. It also facilitates and broadens the translational study on the clinical samples and lead to new and effective therapeutic strategies to cure diseases.

 

Selected Publications

  1. Mahalingam D, Osmulski P, Wang CM, Horning AM, Louie AE, Lin CL, Gaczynska ME and Chen CL (Corresponding author): (2016) Chapter 16: Single-cell molecular profiles and biophysical assessment of circulating tumor cells. Circulating Tumor Cells: Isolation and Analysis. John Wiley & Sons, Inc. pp. 329 - 350.

  2. Sunkel B, Wu D, Chen Z, Wang CM, Liu X, Ye Z, Horning A, Liu J, Mahalingam D, Lopez-Nicora H, Lin CL, Goodfellow, PJ, Clinton S, Jin V, Chen CL, Huang TH, Wang Q: (2016) Integrative analysis identifies targetable CREB1/FoxA1 transcriptional co-regulation as a predictor of prostate cancer recurrence. Nucleic Acids Res. In Press.

  3. Horning AM, Awe JA, Wang CM, Liu J, Lai, Wang VY, Jadhav RR, Louie AD, Lin CL, Kroczak T, Chen Y, Jin VX, Abboud-Werner SL, Leach RJ, Hernandez J, Thompson IM, Saranchuk J, Drachenberg D, Chen CL, Mai S, Huang THM: (2015) DNA methylation screening of primary prostate tumors identifies SRD5A2 and CYP11A1 as candidate markers for assessing risk of biochemical recurrence. Prostate. 75(15):1790-801.

  4. Osmulski P, Mahalingam P, Gaczynska ME, Liu J, Huang S, Horning MA, Wang CM, Thompson IM, Huang THM and Chen CL(senior correspondence author): (2014) Nanomechanical biomarkers of single circulating tumor cells for detection of castration resistant prostate cancer. Prostate, 74 (13), 1297-1307. Highlighted in Nature Urology Reviews. 11, 486. 2014.

  5. Choi DS, Blanco E, Kim YS, Rodriguez AA, Zhao H, Huang THM, Chen CL, Jin G, Landis MD, Burey LA, Wei Q, Granados SM, Dave B, Wong HH, Ferrari M, Wong STC, Chang JC: (2014) Chloroquine eliminates cancer stem cells through deregulation of Jak2 and DNMT1. Stem Cells. 32(9):2309-23.
  6. Chen CL, Yang J, James IOA, Zhang H, Besner GE. 2014. Heparin-binding EGF-like Growth Factor Restores Wnt/beta-catenin Signaling in Intestinal Stem Cells Exposed to Ischemia/Reperfusion Injury. Surgery. 155(6):1069-80.

  7. Hsu YT, Gu F, Huang YW, Liu J, Ruan J, Huang RL, Wang CM, Chen CL, Jadhav R. Lai HC, Mutch DG, Goodfellow PJ, Thompson IM, Kirma NB, Huang THM: (2013) Promoter hypomethylation of EpCAM-regulated bone morphogenetic protein gene family in recurrent endometrial cancer. Clinical Cancer Research, 19(22):6272-85.

  8. Mishra S, Deng JJ, Gowda PS, Rao MK, Lin CL, Chen CL, Huang T, Sun LZ: (2013) Androgen receptor and microRNA-21 axis down-regulates transforming growth factor beta receptor II (TGFBR2) expression in Prostate Cancer. Oncogene. 2013 Sep 16.

  9. Huang RL, Gu F, Kirma NB, Ruan J, Chen CL, Wang HC, Liao YP, Chang CC, Yu MH, Pilrose JM, Thompson IM, Huang HC, Huang TH, Lai HC, Nephew KP: (2013) Comprehensive methylome analysis of ovarian tumors reveals hedgehog signaling pathway regulators as prognostic DNA methylation biomarkers. Epigenetics. 2013 Jun;8(6):624-34.

  10. Chen CL, Mahalingam D, Osmulski P, Jadhav RR, Wang CM, Leach RJ, Chang TC, Weitman SD, Kumar AP, Sun L, Gaczynska ME, Thompson IM, and Huang TH: (2013) Single-cell analysis of circulating tumor cells identifies cumulative expression patterns of EMT-related genes in metastatic prostate cancer. Prostate 73(8): 813-26.

  11. Yang J, Radulescu A, Chen CL, Zhang HY, James IO, and Besner GE: (2013) Heparin-binding epidermal growth factor-like growth factor improves intestinal barrier function and reduces mortality in a murine model of peritonitis. Surgery. 153(1): 52-62.

  12. Yang J, Watkins D, Chen CL, Zhang HY, Zhou Y, Velten M, and Besner GE: (2012) A technique for systemic mesenchymal stem cell transplantation in newborn rat pups. J Invest Surg. 25(6): 405-14.

  13. Yang J, Watkins D, Chen CL, Bhushan B, Zhou Y, and Besner GE: (2012) Heparin-binding epidermal growth factor-like growth factor and mesenchymal stem cells act synergistically to prevent experimental necrotizing enterocolitis. J Am Coll Surg. 215(4): 534-45.

  14. Watkins DJ, Zhou Y, Chen CL, Darbyshire A, and Besner GE: (2012) Heparin-binding epidermal growth factor-like growth factor protects mesenchymal stem cells. J Surg Res. 177(2): 359-64.

  15. Zhang HY, James I, Chen CL, and Besner GE: (2012) Heparin-binding epidermal growth factor-like growth factor (HB-EGF) preserves gut barrier function by blocking neutrophil-endothelial cell adhesion after hemorrhagic shock and resuscitation in mice. Surgery. 151(4): 594-605.

  16. Chen CL, Yu X, James IO, Zhang HY, Yang J, Radulescu A, Zhou Y, and Besner GE: (2012) Heparin-binding EGF-like growth factor protects intestinal stem cells from injury in a rat model of necrotizing enterocolitis. Lab Invest. 92(3): 331-44.

  17. Yu X, Radulescu A, Chen CL, James IO, and Besner GE: (2012) Heparin-binding EGF-like growth factor protects pericytes from injury. J Surg Res. 172(1): 165-76.

  18. Radulescu A, Zhang HY, Chen CL, Chen Y, Zhou Y, Yu X, Otabor I, Olson JK, and Besner GE: (2011) Heparin-binding EGF-like growth factor promotes intestinal anastomotic healing. J Surg Res. 171(2): 540-50.

  19. Zhang HY, Radulescu A, Chen CL, Olson JK, Darbyshire AK, and Besner GE: (2011) Mice overexpressing the gene for heparin-binding epidermal growth factor-like growth factor (HB-EGF) have increased resistance to hemorrhagic shock and resuscitation. Surgery. 149(2): 276-83.

  20. James IA, Chen CL, Huang G, Zhang HY, Velten M, and Besner GE: (2010) HB-EGF protects the lungs after intestinal ischemia / reperfusion injury. J Surg Res. 163(1) 86-95.

  21. Chen CL, Mehta VB, Zhang HY, Wu D, Otabor I, Radulescu A, El-Assal ON, Feng J, Chen Y, and Besner GE: (2010) Intestinal phenotype in mice overexpressing a heparin-binding EGF-like growth factor transgene in enterocytes. Growth Factors. 28(2): 82-97.

  22. Cen L, Hutzen B, Ball S, DeAngelis S, Chen CL, Fuchs JR, Li C, Li PK, and Lin J: (2009) New structural analogues of curcumin exhibit potent growth suppressive activity in human colorectal carcinoma cells. BMC Cancer. 9:99.

  23. Chen CL, Cen L, Kohout J, Hutzen B, Chan C, Hsieh FC, Loy A, Huang V, Cheng G, and Lin J: (2008) Signal transducer and activator of transcription 3 activation is associated with bladder cancer cell growth and survival. Mol Cancer. 7:78.

  24. Chen CL, Loy A, Cen L, Chan C, Hsieh FC, Cheng G, Wu B, Qualman SJ, Kunisada K, Yamauchi-Takihara K, and Lin J: (2007) Signal transducer and activator of transcription 3 is involved in cell growth and survival of human rhabdomyosarcoma and osteosarcoma cells. BMC Cancer. 7: 111.

  25. Chen CL, Hsieh FC, Lieblein JC, Brown J, Chan C, Wallace JA, Cheng G, Hall BM, and Lin J: (2007) Stat3 activation in human endometrial and cervical cancers. Br J Cancer. 96(4): 591-9.

  26. Chen CL, Hsieh FC, and Lin J: (2006) Systemic evaluation of total Stat3 and Stat3 tyrosine phosphorylation in normal human tissues. Exp Mol Pathol. 80(3): 295-305.

  27. Chen CL, Jensen RL, Schnepp BC, Connell MJ, Shell R, Sferra TJ, Bartlett JS, Clark KR, and Johnson PR: (2005) Molecular characterization of adeno-associated viruses infecting children. J Virol. 79(23): 14781-92.

  28. Schnepp BC, Jensen RL, Chen CL, Johnson PR, and Clark KR: (2005) Characterization of adeno-associated virus genomes isolated from human tissues. J Virol. 79(23): 14793-803.

  29. Wang CM, Chen CL, Robertson HM, and Fahrbach SE: (2003) A new member of the GM130 golgin subfamily is expressed in the optic lobe anlagen of the metamorphosing brain of Manduca sexta. J Insect Sci. 3: 35.
  30. Chen C: (2001) Two methods to improve permeability of wing discs for neuronal and glial immunostaining. Plant Prot Bull. 43: 199-204.

  31. Chen CL, Lampe DJ, Robertson HM, and Nardi JB: (1997) Neuroglian is expressed on cells destined to form the prothoracic glands of Manduca embryos as they segregate from surrounding cells and rearrange during morphogenesis. Dev Biol. 181(1): 1-13.