Qing Richard Lu, PhD

Dr. Qing Richard Lu’s research continues to focus on glial cell fate specification and how glial progenitors transform into brain tumors including glioma and medulloblastoma under pathological conditions. Dr. Lu’s lab has established a series of animal models for brain tumors. His recent work has demonstrated that transcription factor Olig2+ proliferative cells are the critical source of glioma growth and that Olig2 functions as a tumor-promoting factor for gliomas. Targeting Olig2 sensitizes brain tumor cells to chemotherapy. Hence, Olig2 is the molecular arbiter of genetic adaptability that makes high-grade gliomas aggressive and resistant to treatment. This work is recently published in Cancer Cell. Dr. Lu is also investigating the regulation of microenvironment and immunologic responses for enhancing brain cancer therapy.

Dr. Lu continues to study the underlying mechanisms of neurological diseases associated with white matter defects. The recent work of his team finds that a CHARGE syndrome-related chromatin-remodeling enzyme CHD7, which was previously thought as a ubiquitously expressed factor, is highly enriched in myelinating cells, oligodendrocytes, in the brain. His work further shows that Chd7 regulates the onset of myelination in the developing brain and myelin regeneration after injury, suggesting that Chd7 mutations contribute to white matter pathogenesis in CHARGE syndrome. This work is recently published in Nature Neuroscience. In addition, the study from his lab shows that a Mowat-Wilson syndrome requires related factor Zeb2 for the onset of peripheral myelination and remyelination. Zeb2 functions through recruiting histone deacetylases HDAC1/2 complexes to antagonize myelination block in the peripheral nervous system. This work is recently published in Nature Neuroscience. Furthermore, Dr. Lu’s recent study shows that a myelinating cell-enriched microRNA, miR-219, can overcome myelination block in demyelinating disease conditions, and that treatment with this microRNA partially restores myelination and limb function. This work is recently published in Developmental Cell. Dr. Lu is also developing new strategies to identify potential drugs and targets for brain repair.

Daniel T. Starczynowski, PhD

Dr. Daniel Starczynowski, PhD, has a long-standing interest in a family of poorly understood malignant blood diseases known as Myelodysplastic Syndrome (MDS). Ineffective treatment approaches, insufficient understanding of the underlying biology and pathogenesis, and lack of mouse models have all contributed to dismal outcomes for MDS patients. A major focus of Dr. Starczynowski’s laboratory has been the intersection of inflammation and MDS, and how patients with MDS can develop acute myeloid leukemia. Namely, they have found aberrant activation of the Toll-like receptor (TLR) pathway in MDS hematopoietic stem cells (HSC), which are the disease-propagating cells, and now have evidence that TLR signaling is a major unifying driver of MDS pathogenesis. His research team recently found that overexpression of TRAF6, a protein that normally functions as an immune sensor of pathogens, impairs blood cell formation and drives the onset of MDS, through an unexpected mechanism involving ubiquitin modification of RNA binding proteins. While dissecting the role of TLR signaling in MDS HSC, Dr. Starczynowski’s team has identified an essential function of TLR signaling in normal HSC, a finding that has implications in chronic inflammatory disorders, autoimmunity, and acute infections. As such, Dr. Starczynowski’s research program has been developing transformative and innovative approaches to investigate the molecular, cellular, and genetic basis of MDS. Dr. Starczynowski’s research program has three main long-term objectives: (1) To evaluate the developmental requirement of TLR signaling components in normal HSC function; (2) To dissect the genetic, molecular, and cellular underpinnings of MDS; and (3) To use the knowledge gained by our basic research to develop novel therapeutic modalities for the treatment of MDS.