Department of Systems Biology
The Department of Systems Biology aims to understand the complex biological systems involved in signal transduction and in the transcriptional, epigenetic and metabolic regulation of hematological malignancies, leukemia and lymphoma. By integrating data on signal transduction, transcriptional and metabolic activity at the single-cell level with clinical information and drug-resistance profiles from clinical trials, our computational analyses can extract features of drug resistance and relapse in leukemia and lymphoma based on machine learning tools that are commonly used in face recognition systems.
The Department of Systems Biology was established in 2017 under the leadership of Markus Müschen, M.D., Ph.D., who joined Beckman Research Institute of City of Hope as founding Chair of the department and the Norman and Sadie Lee Foundation Professor in Pediatrics. Müschen’s group is mainly interested in oncogenic signaling in B cell leukemia and B cell lymphoma, relative to normal mechanisms of B lymphocyte development. Reflecting the translational focus of his research on diagnosis and treatment of B cell lineage acute lymphoblastic leukemia, the most frequent type of cancer in children, Müschen also serves as the Associate Director of pediatric oncology of City of Hope's National Cancer Institute (NCI)-designated Comprehensive Cancer Center. Markus Müschen is a Faculty Scholar of the Howard Hughes Medical Institute and his research is supported by an NCI Outstanding Investigator Award.
The Department of Systems Biology includes 11 research faculty and 65 postdoctoral fellows and staff scientists and is supported by an annual budget of $4.5 million in research grants from the National Institutes of Health (NIH), The Leukemia & Lymphoma Society and the Howard Hughes Medical Institute. The nine research groups are housed in a 16,000-square-foot lab in City of Hope’s new Biomedical Research Center in Monrovia, California. The facility features state-of-the-art flow cytometry, imaging, metabolomics and proteomic capabilities, and is home to the Division of Epigenetic and Transcriptional Engineering in the Department of Systems Biology.
With a focus on hematological malignancies, primary research interests of the department include oncogenic B cell receptor signaling in B-lineage leukemia and lymphoma, molecular genetics of B cell chronic lymphocytic leukemia, genetic engineering of epigenetic writers and erasers in MLL-rearranged leukemias, noncoding RNAs and RNA-modifications in malignant transformation of leukemia and lymphoma, feedback control of oncogenic signaling in B cell malignancies, and metabolic control of clonal selection and evolutionary fitness in heterogeneous leukemia and lymphoma populations.
Lai N. Chan, Ph.D., is an Assistant Research Professor in the Department of Systems Biology. Dr. Chan is mainly interested in metabolic regulation of oncogenic signaling in B cell malignancies and mitochondrial dynamics, including mitochondrial fusion and fission in B cell development and malignant transformation.
David Chen, Ph.D., is an Assistant Professor and the Director of the Division of Epigenetic and Transcriptional Engineering in the Department of Systems Biology. Combining patient-derived leukemia and lymphoma xenografts, dCas9-technology for genetic engineering, and computational modeling, Dr. Chen and his team will interrogate the genome-wide effects of modifiers that write and erase epigenetic marks and their contribution to malignant leukemia and lymphoma. Dr. Chen trained in the group of Scott Armstrong, M.D., Ph.D., at Memorial Sloan Kettering Cancer Center and the Dana-Farber Cancer Institute and is currently a National Institute of Health Pathway to Independence Award (K99/R00) scholar, with a main research emphasis on MLL-rearranged leukemias.
Jianjun Chen, Ph.D., is a Professor and Vice Chair of the Department of Systems Biology and a scholar of The Leukemia & Lymphoma Society. He is also a permanent member of the Developmental Therapeutics Study Section for the National Cancer Institute (NCI). Supported by four NCI R01 grants, Chen’s research program is mainly focused on integrated analyses of noncoding RNAs regarding both genetic and epigenetic changes in the development of leukemia and lymphoma. Most recently, his group discovered the role of the fat mass- and obesity-associated protein as N6-methyladenosine RNA demethylase and as a driver of leukemogenesis.
Zhengshan Chen, M.D., Ph.D., is an Assistant Research Professor and mainly interested in feedback control mechanisms of tyrosine kinase and STAT5 signaling in normal B cell development and B cell leukemia and lymphoma. In addition to his research program, Dr. Chen pursues his clinical training in pathology at the University of Southern California in Los Angeles.
Nora Heisterkamp, Ph.D., is a Professor in the Department of Systems Biology. Dr. Heisterkamp is a pioneer in cancer genetics and uncovered the structure of the so-called “Philadelphia chromosome” (Ph), the first known genetic lesion that was discovered as a cause of cancer in humans. After graduate training at the University of Groningen and the Erasmus University in Rotterdam, the Netherlands, Dr. Heisterkamp joined the lab of John Stephenson, first at the Laboratory of Viral Carcinogenesis, a division of the National Cancer Institute (NCI).
Jaewoong Lee, Ph.D., is an Assistant Research Professor with a main interest in basic cell biology and protein-protein interactions between components of the B cell and T cell receptor and oncogenes in B cell and T cell leukemia and lymphoma. His studies focus on the dynamic interplay of amplifiers and negative feedback mechanisms of oncogenic signaling.
Markus Müschen, M.D., Ph.D., Chair of the Department of Systems Biology and Norman and Sadie Lee Foundation Professor in Pediatrics, explores oncogenic signaling in B cell-derived leukemia and lymphomas. Unlike other types of cancer, B cell tumors are subject to an autoimmunity checkpoint. As with normal B cells, B cell tumor cells are weeded out if they are self-reactive. Müschen uses pharmacological agents to engage autoimmunity checkpoints in B cell tumors, with the ultimate goal of overcoming resistance to conventional drug treatment.
Vu Nguyen Ngo, Ph.D., is an Associate Research Professor in the Department of Systems Biology and completed his B.A. degree from the University of California, Berkeley and earned a Ph.D. in biomedical sciences from the University of California, San Francisco. His postdoctoral training was with Dr. Louis M. Staudt at the National Cancer Institute, National Institutes of Health, Bethesda. Prior to joining the Department of Systems Biology, he was an assistant professor in the Division of Stem Cell and Leukemia Research at City of Hope. He has received the American Society of Hematology Scholar Award, Gabrielle’s Angel Foundation for Cancer Research Award and Department of Defense’s Career Development Award.
Lili Wang, M.D., Ph.D., is an Associate Professor in the Department of Systems Biology. Dr. Wang trained with Sonoko Habu (Tokai University, Japan) and Amy L. Kenter (University of Illinois at Chicago) and as an instructor with Catherine J. Wu at the Dana-Farber Cancer Institute. With extensive experience in B cell and T cell development, Dr. Wang discovered recurrent genetic lesions in B cell chronic lymphocytic leukemia (CLL), in particular lesions of the splicing factor SF3B1, elucidated their role in the clonal evolution of CLL, and developed genetic mouse models for mechanistic studies.
Gang Xiao, Ph.D., is an Assistant Research Professor in the Department of Systems Biology and a member of the Division of Epigenetic and Transcriptional Engineering. With a background in immunology and T cell signaling, Dr. Xiao is mainly interested in lineage-specific drivers of leukemia and lymphoma and mechanisms by which these molecules affect the course of disease in leukemia patients and their clinical associations as favorable or unfavorable outcome predictors. His research program includes dCas9-mediated forward genetic analyses in patient-derived leukemia and lymphoma xenografts and computational modeling of interactions between oncogenes and tumor suppressors.