Dr. Zu's research centers on the development of novel diagnostics and treatments for hematolymphoid disorders. With this focus in mind, major research projects are taking place in Dr. Zu’s laboratory, some of which are described below.
Study of Oligonucleotide Aptamers
As a class of small-molecule probes, aptamers are composed of short, synthetic, single-stranded DNA or RNA oligonucleotides. As "chemical antibodies," aptamers can specifically bind with high affinity to virtually any type of targets, including biomarkers on tumor cells. To develop clinical applications, Dr. Zu's laboratory has demonstrated the use of synthetic aptamer probes for flow cytometry-based detection of cancer cells, immunostaining of cancer cells in paraffin-embedded tumor tissues and a one-step method for the detection of circulating tumor cells (CTCs) in a drop of patient-derived whole blood.
In addition, his group’s preclinical studies indicate that synthetic aptamers can be used as imaging probes for specific detection of tumors in vivo, as well as for targeted cancer therapy. The findings demonstrate the exceptional clinical value of oligonucleotide aptamers as a new class of molecular theranostics.
Dr. Zu's laboratory has investigated the applicability of various nanoparticles and nanomedicines for clinical use. These nanomedicines are composed of biomaterials (protamine, biotin-avidin), chemical polymers (PEI, PBAE) and gold nanospheres, armed with tumor cell-specific aptamers and loaded with therapeutic agents and/or equipped with siRNAs for oncogene silencing. The Zu laboratory’s studies demonstrated that nanomedicines, guided by aptamers, could specifically target and inhibit tumor cells of interest with no off-target effects. In addition, by introducing an imaging reporter, the nanomedicines could also be used for real-time imaging and disease staging. Multi-functional theranostic nanomedicines specific for different types of tumors are currently under investigation in the Zu laboratory.
Multiple Myeloma Cancer Stem Cell Study
Although significant progress has been made in the treatment of multiple myeloma (MM), which is the second most prevalent type of blood cancer, the disease still remains incurable. Cancer stem cells (CSCs) are resistant to chemotherapy and are key drivers of disease progression and recurrence in MM. However, little is known about the regulation of MM stem cells. Dr. Zu’s recent study showed that the MM tumor cells are heterogeneous and contain a subtle population of tumor stem cells, and the size of this CSC population is regulated by the environmental conditions, such as hypoxic stress and stimulation of the cellular TGF-β1 pathway. These findings support the hypothesis that tumor stem cells can be regenerated through de-differentiation of mature tumor cells, opening new avenues to cure MM by developing novel therapeutics aimed at eliminating tumor stem cells. In addition, Dr. Zu’s team is also focusing on understanding the molecular mechanisms underlying the interaction of the MM tumor stem cells and the marrow stromal mesenchymal cells, which provide a supportive microenvironment that fosters CSCs. Elucidating the ways to interrupt the interaction between cancer stem cells and the stromal microenvironment, hence blocking the stromal-mediated tumor stem cell survival, may lead to effective approaches of controlling this disease.
Myelodysplastic Syndrome (MDS) Study
MDS is a group of clonal hematopoietic stem cell diseases characterized by chronic anemia caused by decreased maturation of myeloid cells and ineffective hematopoiesis in the bone marrow. Together, the intrinsic genetic abnormalities and the extrinsic microenvironmental alterations drive MDS pathogenesis. Dr. Zu’s group is aiming to establish the genetic signatures of MDS through the next-generation sequencing of genomes and transcriptomes, and the microRNA-based assays. In addition, in order to elucidate key signaling pathways involved in MDS, the team will evaluate proteomic and phospho-proteomic profiles of MDS-associated cellular proteins by reverse-phase proteomic assays.