Zu Lab
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About Our Lab
Our Research
Dr. Zu's research interests include diagnosis of hematopoietic and lymphoid disorders. His research centers on the development of novel diagnostics and treatments for these disorders. His laboratory was the first to use aptamer probes to enhance the diagnostic abilities of multi-color flow cytometry and immunohistochemical staining, and for rapid detection of circulating tumor cells in whole blood samples. By combining nanotechnology with aptamer technology, Dr. Zu's laboratory is also developing new multi-functional nanomedicine for specific tumor imaging and targeted therapy of several cancer types, including lymphomas, multiple myeloma, pancreatic cancer, breast cancer, prostate cancer, and hepatocellular (liver) carcinoma. Other projects in his laboratory include studies on the role of cancer stem cells in the development of multiple myeloma and elucidating the molecular mechanisms underlying the myelodysplastic syndrome.
Our Research
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.
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 (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 (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.
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.
Nanomedicine Study
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.
Our Program Faculty
Youli Zu, MD, PhD
Professor of Pathology and Genomic Medicine, Academic Institute
Full Member, Research Institute
Department of Pathology & Genomic Medicine
Houston Methodist Hospital
Houston Methodist
Weill Cornell Medical College
Full Member, Research Institute
Department of Pathology & Genomic Medicine
Houston Methodist Hospital
Houston Methodist
Weill Cornell Medical College
Jianjun Qi, PhD, Research Associate
Dr. Qi received his PhD in Medicinal Chemistry from Peking Union Medical College (Beijing, China) and completed his postdoctoral training at the University of Tennessee Health Science Center. He is an expert on organic synthesis and related technologies, including HPLC, mass spectrometry, UV-visible spectrophotometers, and fluorometers. Dr. Qi’s research focuses on drug design and synthesis, antitumor drug delivery, biomolecular sensors, including pH-sensitive fluorescent dyes, and advanced technologies in general organic synthesis. He is working with Youli Zu, MD, PhD to develop molecular probes for early cancer detection and a DNA aptamer-based cancer drug delivery system.
Zihua Zeng, MD, Research Associate
After earning his MD and MSci in Cancer Pathology, Dr. Zeng worked in the Department of Pathology at the Medical College of Jinan University in Guangzhou, China, where he was involved with teaching, cancer research, and diagnosis of clinical pathologies. His research interests included carcinogenesis, cancer metastasis, and in vitro and in vivo cancer treatment. Dr. Zeng then worked as a visiting scholar in the Institute of Pathology from October 1997 to August 2000 at the Free University in Berlin, Germany, where he used cDNA array to characterize gene expression profiles of CD30-positive lymphomas, including Hodgkin’s lymphoma and Anaplastic Large Cell Lymphoma (ALCL) treated with a single-chain anti-CD30 antibody. From May 2006 to November 2007, Dr. Zeng worked in the Center for Cell and Gene Therapy at Baylor College of Medicine and participated in a project entitled “Strategies to Enhance Virotherapy for Solid Cancers” using in vitro and in vivo strategies. He joined Dr. Youli Zu’s laboratory at the Houston Methodist Research Institute in November 2007 and has worked on projects involving gene therapy for human ALCL in vitro and in mouse models.
Zhenghu Chen, MD, PhD, Post-doctoral Fellow
Dr. Chen received his MD and PhD from Tongji University (Shanghai, China) in 2017. Dr. Chen was trained at the Baylor College of Medicine Department of Hematology and Oncology as a visiting scholar in the joint-training program from 2013-2016. During his time at Baylor, Dr. Chen conducted in-depth translational research in neuroblastoma, one of the most common and deadly pediatric cancers, by screening small-molecule compounds for targeted cancer therapy. After graduation, Dr. Chen spent two years in postdoctoral training at Baylor College of Medicine before he joined the Houston Methodist Research Institute in 2019. Dr. Chen’s current research interests focus on the mechanisms underlying cancer heterogeneity and aggressiveness and on developing novel therapies for cancer patients through a clinic-based, hypothesis-driven translational approach. Dr. Chen’s central objective is to end cancer and save lives through his close work with leading physicians and scientists in the field.
Xiaohui Liu, PhD, Post-doctoral Fellow
Dr. Liu received his PhD in Analytical Chemistry at The State Key Laboratory of Analytical Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University (Nanjing, China) in September 2018. He has been trained in the field of aptamer SELEX (Systematic Evolution of Ligands by Exponential Enrichment). Dr. Liu’s research focuses on screening cell/protein/small molecule nucleic acid aptamers, fabricating microfluidic devices for nucleic acid aptamer SELEX and biochemical analysis, and creating aptamer-conjugated nanomaterial-based assays to detect multiplexed proteins. Dr. Liu has successfully established a protein microarray microfluidic aptamer screening method (PMM-SELEX) that is suitable for high-throughput, rapid screening of protein aptamers. Dr. Liu is a recipient of the Outstanding PhD Candidate Award from Nanjing University. He is now working with Dr. Youli Zu on developing ssDNA aptamers for early cancer cell detection and targeted drug delivery systems for cancer therapy.
QUanyuan Wan, PhD, Post-doctoral Fellow
Dr. Wan earned his PhD in Aquatic Animal Medicine at the Huazhong Agricultural University in China. Using molecular and cellular techniques, he discovered functional differences in how RIG-I and MDA5 genes control the induction of interferon, and the relationship between iron metabolism and antiviral immune responses. Subsequently, Dr. Wan was trained in cancer immunotherapy as a post-doctoral fellow at the Houston Methodist Research Institute (HMRI). In an animal model of melanoma, he studied the therapeutic efficacy of Type I interferon (IFN-I) and nano-vaccine combination therapy. Dr. Wan also investigated ways in which to optimize the therapeutic efficacy of CAR-T in lymphoma. Currently, he is a post-doctoral fellow in the lab of Youli Zu, MD, PhD, developing novel clinical applications for oligonucleotide aptamer technology in disease diagnosis and precision therapy. Dr. Wan is also interested in developing aptamer-guided cancer vaccines for tumor-specific immunotherapy.
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