Dr. Zu's research focuses on developing novel diagnostics and treatments for hematolymphoid disorders. Exciting research projects taking place in Dr. Zu’s laboratory are described below.
Oligonucleotide Aptamers Study
Aptamers are a class of small-molecule probes comprised of short, synthetic, single-stranded DNA or RNA oligonucleotides. As "chemical antibodies," aptamers can target virtually any type of molecule with high affinity, including tumor cell biomarkers. Dr. Zu's laboratory is interested in developing aptamers for clinical applications. His lab has used synthetic aptamer probes for flow cytometry-based detection of cancer cells, immunostaining of cancer cells in paraffin-embedded tumor tissues, and as a one-step detection method for circulating tumor cells (CTCs) in a drop of patient-derived whole blood.
His group’s preclinical studies indicate that synthetic aptamers can be used as imaging probes to detect tumors in vivo and for targeted cancer therapy. These findings support the exceptional clinical value of oligonucleotide aptamers as a new class of molecular theranostics.
Dr. Zu's laboratory has investigated the clinical applicability of various nanoparticles and nanomedicines. The 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 demonstrate that aptamer-guided nanomedicines can target and inhibit tumor cells of interest with no off-target effects. By introducing an imaging reporter, the nanomedicines may be useful for real-time imaging and disease staging. Multi-functional theranostic nanomedicines targeting different types of tumors are currently being developed in the Zu laboratory.
Multiple Myeloma Cancer Stem Cell Study
Multiple myeloma (MM) is the second most prevalent type of blood cancer. Although significant treatment progress has been made, the disease 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 lab showed that MM tumors are heterogeneous and contain a subtle population of CSCs. The size of this population was regulated by environmental conditions, such as hypoxic stress and stimulation of the cellular TGF-β1 pathway. These findings support the hypothesis that CSCs can be regenerated through de-differentiation of mature tumor cells, opening new avenues to cure MM via development of novel therapeutics targeting CSCs. Dr. Zu’s team is also interested in understanding the molecular mechanisms underlying the interaction of MM CSCs with marrow stromal mesenchymal cells, which provide a supportive microenvironment to foster CSCs. Interrupting the interaction between CSCs and the stromal microenvironment may inhibit stromal-mediated tumor stem cell survival and offer an effective approach for disease control.
Myelodysplastic Syndrome Study
Myelodysplastic syndrome (MDS) comprises 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, intrinsic genetic abnormalities and extrinsic microenvironmental alterations drive MDS pathogenesis. Dr. Zu’s group aims to characterize the genetic signatures of MDS using next-generation sequencing of genomes and transcriptomes, and microRNA-based assays. To elucidate key signaling pathways involved in MDS, the team will evaluate proteomic and phospho-proteomic profiles of MDS-associated cellular proteins using reverse-phase proteomic assays.