Who We Are
The molecular biology core supports the brain imaging group investigators by providing services, such as cell culturing, animal handling and treatment, drug screening, and histopathologic analysis of tissue specimens collected from experimental animal models as well as patient samples. It also provides hands-on training undergraduate/graduate/medical school students. Dr. Liang is an expert in immunohistochemical analysis, real-time RT-PCR, drug screening, preclinical animal models, and microRNA/siRNA research.
Director: Zhongxing Liang, MD, PhD
We developed the ability to automate quantitation of infiltrative neoplastic cells among normal cells (neuronal and glial) on the brain tissue sections. While glioblastoma (GBM) tumor cells can be visualized after regular H&E staining, there is insufficient differentiation between neoplastic and non-neoplastic cells by this methodology for (unbiased) precise quantitation. We developed an automated tumor cell recognition tool together with immunohistochemical staining for SOX2 to evaluate the presence and degree of neoplastic cells within biopsied specimens from regions of differential MRSI signal. SOX2 is a transcription factor that is best known for its role in maintaining the pluripotency of stem cells; however, in diffuse gliomas, including GBM, immunohistochemical for SOX2 shows remarkable specificity for infiltrating glioma cells, while non-neoplastic cells remain largely negative. Examples of IHC staining for SOX2 are shown below, with only neoplastic cells demonstrating significant nuclear staining. For quantitation, hematoxylin counterstain was applied to SOX2-stained specimens in order to highlight all cell nuclei, both neoplastic and normal. Images were digitized using our Hamamatsu Nanozoomer slide scanner, and the SOX2 and hematoxylin signals separated by digital unmixing. An image segmentation algorithm can be used on the hematoxylin channel to delineate the nuclei of all cells, and the unmixed DAB channel is used to quantify SOX2 expression with each delineated nucleus. A machine classifier can then be applied to classify each nucleus as either neoplastic or non-neoplastic, enabling calculation of the %-total and neoplastic cell density measures in whole slides, not just selected regions-of-interest. These tissue-based measures of tumor infiltration can then be correlated with metabolite levels individually by regression analysis to determine whether our MRSI results correlates with histological results, as shown in our preliminary results.
MicroRNAs (miRNAs) are a recently identified class of cellular RNAs that regulate protein expression at the translational level. MiRNAs are expressed in the nucleus as parts of long primary miRNA (Pri-miRNA) transcripts. The pri-miRNA acts as a signal for digestion by a double-stranded ribonuclease (Drosha) to produce the precursor miRNA (Pre-miRNA) and then Exportin-5 mediates nuclear export of pre-miRNAs to cytoplasm. Finally, a cytoplasmic dsRNA nuclease (Dicer) cleaves the pre-miRNA into mature miRNA. The active, mature miRNAs are 17–24 bases, known to affect the translation or stability of target messenger RNAs. MicroRNA is believed to regulate multiple genes, with predictions that greater than one third of all human genes may be regulated by miRNA molecules.
The role of miRNAs in cancer is further supported by the fact that more than 50% of the human miRNA genes are located in cancer-associated genomic regions or at fragile sites. There is great interest currently in the use of miRNAs as biomarkers and therapeutic targets for cancer and other diseases, given their involvement in cancer initiation, progression, migration, invasion and metastasis. Many properties of miRNAs make them attractive candidates as sensitizers for radioresistance and chemoresitance for a number of different cancers.
The core focuses are to research and develop miRNA biomarkers for evaluating the response of brain tumors to radio- and chemo-therapy. Additionally, the core is investigating miRNAs as sensitizers for resistant brain tumors to radiotherapy and chemotherapy.
Training Program Alumni
High School Students
Donna Guo, high school student from Northview High School 2012
Sentosh Reddy, high school student 2006
Charity Omeoga, Undergraduate student at University of Rhode Island 2014
Marie Bangura, Emory student 2012
Jeffrey Ahn, Emory Student 2011
Samuel Hong, Emory Student 2011
Chunsu Jiang, Emory Student 2010
Donguk Lee, Emory Student 2010
Maylene Xie, Yale Student 2009
Dean Blevins, Emory Student 2006
Ghazala Datoo, Emory Student 2005
Heidi Choi, Emory Student 2005
Ke Liang, Emory Student 2004
Sijia Wang, Emory Student 2004
Eric Sagaldo, Emory MSP Graduate Student 2014
James S. Cordova, Emory MD/PhD Student 2014
Nusaiba Baker, Emory MD/PhD Student 2014
Andrew Brown, Emory MSP Graduate Student 2007
Xuehai Bian, M.D., China Jilin University Visiting Scholar 2013
Doohyoung Lee, M.D., Ajou University Hospital Visiting Scholar 2008
Yawei Zhang, M.D., China Fudan University Visiting Scholar 2007
Joann Brooks Powell, Ph.D., Emory Post-doctoral Fellow 2005
Young Yoon, Ph.D., Emory Post-doctoral Fellow 2004
Seunghee Kang, M.D., Ajou University Hospital Visiting Scholar 2004
Hui Wu, Emory School of Medicine Technician 2006