Youli Zu, M.D., Ph.D.
Medical Director, Hematopathology
Postdoctoral Research Fellowship, Tsukuba Life Science Research Center, RIKEN, Tsukuba, Japan
Dr. Zu joined the department of pathology and genomic medicine at The Methodist Hospital in 2004, and is currently the medical director of the hematopathology section. In addition to his clinical responsibilities, Dr. Zu is also the director of the cancer pathology laboratory at The Methodist Hospital Research Institute. As a physician scientist, Dr. Zu's research directly addresses clinical questions and has the potential to immediately improve the standard of care and patient outcomes. Dr. Zu's research has been funded by the National Institutes of Health/National Cancer Institute since 2007. He has also received grants from the American Cancer Society, the American Heart Association, and numerous other research foundations.
Dr. Zu's research centers on the development of novel diagnostics and treatments for hematolymphoid disorders.
Current research projects in the Cancer Pathology Laboratory:
Aptamer study: As a class of small-molecule probes, aptamers are composed of short, single-stranded DNA or RNA oligonucleotides and can bind with high affinity to virtually any type of target, including biomarkers on tumor cells. Recently, Dr. Zu's laboratory revealed that synthetic aptamer probes can be used, in combination with antibodies, for multi-color flow cytometry analysis of patient specimens. In addition, they also showed the first demonstration of specific immunohistochemical staining of paraffin-embedded tumor tissues by aptamer probes. Their unpublished studies indicate that aptamer probes can be used for specific in vivo imaging of tumors in a preclinical model. Other ongoing projects include a validation study of a unique hybrid SELEX system for aptamer development, and investigation of new clinical applications of synthetic aptamers for disease diagnosis and treatment.
Nanomedicine study: This study is focused on developing nanomedicines that are both tumor cell type-selective and cancer oncogene-specific. Various nanomedicines composed of biomaterials (protamine, synthetic peptides), chemical polymers (PEI, PBAE), and gold particles were generated, loaded with therapeutic agents and/or siRNA and armed with tumor cell-specific aptamers. The studies demonstrated that the nanomedicines, under aptamer guidance, could specifically target and inhibit tumor cells of interest with no off-target effects. In addition, by introducing an imaging reporter, the nanomedicines can also highlight tumors for real-time monitoring and disease staging. Multi-functional nanomedicines specific for different types of tumors are currently under investigation in the Zu laboratory.
Multiple myeloma cancer stem cell study: Although there has been significant progress in the treatment of multiple myeloma (the most common cancer of blood cells), the disease still remains incurable. The lack of a cure is largely due to the persistence of cancer stem cells, which are resistant to chemo-drug therapy and are responsible for residual disease and recurrence. To overcome this obstacle, Dr. Zu's laboratory is investigating the potential therapeutic effects of natural killer (NK) cells, a primary defense system of the body, on cancer stem cells. Such NK cell-mediated immunotherapy may lead to a cure for multiple myeloma by eliminating the cancer stem cells. In addition, a sub-project is focused on understanding the molecular mechanisms involved in the interaction of the cancer stem cells with marrow stromal mesenchymal cells, which provide a micro-environment to support cancer stem cells in multiple myeloma. Interrupting interaction between cancer stem cells and the stromal micro-environment, and blocking stromal signaling to cancer stem cells, may be an effective approach in curing this disease.
Myelodysplastic syndrome (MDS) study: MDS is a group of clonal hematopoietic stem cell diseases characterized by chronic anemia due to decreased maturation of myeloid cells and ineffective hematopoiesis of marrow. The intrinsic genetic abnormalities and the extrinsic micro-environmental alterations are collaborative pathogenic factors for MDS development. The genetic signatures of MDS will be determined by systemic analysis of data from the next-generation sequencing of genomes and transcriptomes, and microRNA assays. In addition, to identify key signaling pathways involved in MDS, the profiles of cellular proteins and their phosphorylated forms will be investigated by reverse-phase proteomic assays. To study the potential role of the p38 MAP kinase pathway in MDS, we are generating a transgenic preclinical model which expresses an active form of p38 exclusively in hematopoietic cells.
Aptamers, lymphoma, nanomedicine, multiple myeloma stem cells, myelodysplastic syndrome (MDS).
Zhao N, You J, Zeng Z, Li C, Zu Y. An Ultra pH-Sensitive and Aptamer-Equipped Nanoscale Drug-Delivery System for Selective Killing of Tumor Cells. Small. 2013 Apr 23. PMID: 23609964
Song Y, Zhang Y, Bernard PE, Reuben JM, Ueno NT, Arlinghaus RB, Zu Y, Qin L. Multiplexed volumetric bar-chart chip for point-of-care diagnostics. Nat Commun. 2012;3:1283.
Visco C, Li Y, Xu-Monette ZY, Miranda RN, Green TM, Li Y, Tzankov A, Wen W, Liu WM, Kahl BS, d'Amore ES, Montes-Moreno S, Dybkær K, Chiu A, Tam W, Orazi A, Zu Y, Bhagat G, Winter JN, Wang HY, O'Neill S, Dunphy CH, Hsi ED, Zhao XF, Go RS, Choi WW, Zhou F, Czader M, Tong J, Zhao X, van Krieken JH, Huang Q, Ai W, Etzell J, Ponzoni M, Ferreri AJ, Piris MA, Møller MB, Bueso-Ramos CE, Medeiros LJ, Wu L, Young KH. Comprehensive gene expression profiling and immunohistochemical studies support application of immunophenotypic algorithm for molecular subtype classification in diffuse large B-cell lymphoma: A report from the International DLBCL Rituximab-CHOP consortium program study. Leukemia. 2012 Sep;26(9):2103-13.
McGowan P, Nelles N, Wimmer J, Williams D, Wen J, Li M, Ewton A, Curry C, Zu Y, Sheehan A, Chang CC. Differentiating Between Burkitt Lymphoma and CD10+ Diffuse Large B-Cell Lymphoma: The Role of Commonly Used Flow Cytometry Cell Markers and the Application of a Multiparameter Scoring System. Am J Clin Pathol. 2012 Apr;137(4):665-70.
Peng H, Wen J, Zhang L, Li H, Chang CC, Zu Y, Zhou X. A systematic modeling study on the pathogenic role of p38 MAPK activation in myelodysplastic syndromes. Mol Biosyst. 2012 Apr 1;8(4):1366-74.
Zhao N, Qi J, Zeng Z, Parekh P, Chang CC, Tung CH, Zu Y. Transfecting the hard-to-transfect lymphoma/leukemia cells using a simple cationic polymer nanocomplex. J Control Release. 2012 Apr 10;159(1):104-10.
McDonnell SR, Hwang SR, Basrur V, Conlon KP, Fermin D, Wey E, Murga-Zamalloa C, Zeng Z, Zu Y, Elenitoba-Johnson KS, Lim MS. NPM-ALK signals through glycogen synthase kinase 3ß to promote oncogenesis. Oncogene. 2012 Aug 9;31(32):3733-40.
Ito M, Zhao N, Zeng Z, Chang CC, Zu Y. Interleukin-2 functions in anaplastic large cell lymphoma cells through augmentation of extracellular signal-regulated kinases 1/2 activation. Int J Biomed Sci. 2011;7:181-90.
Zhao N, Fogg JM, Zechiedrich L, Zu Y. Transfection of shRNA-encoding Minivector DNA of a few hundred base pairs to regulate gene expression in lymphoma cells. Gene Ther. 2011 Mar;18(3):220-4.
Zhao N, Bagaria HG, Wong MS, Zu Y. A nanocomplex that is both tumor cell-selective and cancer gene-specific for anaplastic large cell lymphoma. J Nanobiotechnology. 2011 Jan 31;9(1):2.
Wen J, Feng Y, Bjorklund CC, Wang M, Orlowski RZ, Shi ZZ, Liao B, O'Hare J, Zu Y, Schally AV, Chang CC. Luteinizing Hormone-Releasing Hormone (LHRH)-I antagonist cetrorelix inhibits myeloma cell growth in vitro and in vivo. Mol Cancer Ther. 2011 Jan;10(1):148-58.
Zhang P, Zhao N, Zeng Z, Chang CC, Zu Y. Combination of an aptamer probe to CD4 and antibodies for multicolored cell phenotyping. Am J Clin Pathol. 2010 Oct;134(4):586-93.
Zeng Z., Zhang P., Zhao N., Sheehan AM., Tung CH., Chang CC., and Zu Y. Using oligonucleotide aptamer probes for immunostaining of formalin-fixed and paraffin-embedded tissues. Modern Pathology. 2010 Dec;23(12):1553-8.
Ito M, Zhao N, Zeng Z, Chang CC, Zu Y. Synergistic growth inhibition of anaplastic large cell lymphoma cells by combining cellular ALK gene silencing and a low dose of the kinase inhibitor U0126. Cancer Gene Ther. 2010 Sep;17(9):633-44.
Feng Y, Wen J, Mike P, Choi DS, Eshoa C, Shi ZZ, Zu Y, Chang CC. Bone marrow stromal cells from myeloma patients support the growth of myeloma stem cells. Stem Cells Dev. 2010 Sep;19(9):1289-96.
Feng Y, Ofek G, Choi DS, Wen J, Hu J, Zhao H, Zu Y, Athanasiou KA, Chang CC. Unique biomechanical interactions between myeloma cells and bone marrow stroma cells. Prog Biophys Mol Biol. 2010 Sep;103(1):148-156.
Wen J, Feng Y, Huang W, Chen H, Liao B, Rice L, Preti HA, Kamble RT, Zu Y, Ballon DJ, Chang CC. Enhanced antimyeloma cytotoxicity by the combination of arsenic trioxide and bortezomib is further potentiated by p38 MAPK inhibition. Leuk Res. 2010 Jan;34(1):85-92.
Zhang P, Zhao N, Zeng Z, Feng Y, Tung CH, Chang CC, Zu Y. Using an RNA aptamer probe for flow cytometry detection of CD30-expressing lymphoma cells. Lab Invest. 2009 Dec;89(12):1423-32.