New tricks for red blood cells -genetically engineering stem cells for cell therapeutics
Alex Hongsheng Chang, M.D., Ph.D.
Senior Research Fellow
Center for Cell Engineering
Memorial Sloan-Kettering Cancer Center
New York, NY
In my current lab at Memorial Sloan-Kettering Cancer Center, I have made an important discovery that erythroid cells derived from genetically engineered stem cells can be used for high levels of therapeutic protein production in vitro and in vivo (Chang A.H. et. al. 2006.. Nature Biotechnology. 24(8):1017-21.). I am interested in further studying this interesting finding and translating this knowledge into hematopoietic stem cell –based gene therapy, immune tolerance induction and cell-based vaccine development.
Dr. Alex Chang received his medical degree in China, at Capital Medical University, and obtained his PhD from the University of British Columbia, Canada. In late 2001, he was recruited to a PEGT Scholarship program (Program of Excellence in Gene Therapy, NHLBI) hosted by Weill Medical College/Cornell University and Memorial Sloan-Kettering Cancer Center. He is currently a Senior Research Fellow at the prestigious Memorial Sloan-Kettering Cancer Center, New York, NY.
Two-chain Kininogen Inhibition of Endothelial Progenitor Cell Biology: a Connection between Kallikrein-Kinin Coagulation System and Vascular Dysfunction
Yi Wu MD/PhD
Department of Medicine Section of Hematology
The plasma kallikrein-kinin system (KKS) consists of three proteins factor XII, prekallikrein, and high molecular weight kininogen (HK). Activation of this system is tightly involved in thrombosis, angiogenesis, and inflammation. HK is responsible for the assembly and activation of this system on membrane surface of platelets, leukocytes and endothelial cells. Our recent studies have demonstrated that cleaved form of HK (two-chain HKa), a kallikrein cleavage product of HK, associates with caveolae via uPAR and inhibits bidirectional signaling of ?v?3 integrin in endothelial cells. Endothelial progenitor cells (EPCs) express high level of uPAR and ?v?3 integrin. Two-chain HKa inhibits their colony-forming capacity and differentiation into vessels. It also induces EPC apoptosis by triggering ROS production. Because kininogen deficiency delays vascular injury-induced thrombosis, KKS activation may dampen vascular repair through reduction and dysfunction of EPCs.
Dr. Wu received his MD in
ADAMTS13 and TTP
Zhou Wenhua, M.D., Ph.D.
Division of Hematology
Albert Einstein College of Medicine
New York, USA
Thrombotic thrombocytopenic purpura (TTP) is a serious disease that affects primarily adolescents and adults and almost invariably and rapidly leads to death if not treated. This disease is characterized by the development of microangiopathic hemolysis in the peripheral blood and widespread VWF-rich hyaline thrombi in the brain, heart, and other organs. Recent studies have shown that a metalloprotease in the circulation, ADAMTS13, is critical in preventing platelet thrombosis in the microcirculation and that a severe deficiency of this enzyme, due to autoantibodies or genetic mutations, causes the thrombosis as observed in patients with TTP.
Plasma exchange has been the standard treatment of TTP, with approximately 70% - 90% of remission rates. However little can be done for patients who poorly response to the plasma exchange. This presentation will discuss: 1. the importance of ADAMTA13 activity assay for the management of TTP patients; 2. some novel ADAMTS13 mutants that may therapeutically advantage for the patients who do not response to plasma exchange. 3. Study about ADAMTS13 in mouse. Finally, a future direction about this topic will be briefly discussed.
Dr. Zhou received his Ph.D degrees in Pharmacy of Microbiology and Biochemistry from the China Pharmaceutical University in 2002. He also obtained his master degree in animal physiology and biochemistry and a bachelor degree from College of Animal Medicine, at Nanjing Agricultural University. From 2002, Dr. Zhou work as a Reseach Associate in the Division of Hematology, at Albert Einstein College of Medicine. His research is focus on an intricate clotting disease, TTP, and achieved an outstanding accomplishment as proved by the publications in journal of Blood, J.B.C., Thromb Haemost and others.
Molecular Mechanisms define the Fate of the Hematopoietic Stem Cells
Jizhou Yan, M.D., Ph.D.
Abramson Family Cancer Research Institute
Department of Cancer Biology
Epigenetic reprogramming of somatic cells into a pluripotent embryonic stem cell-like state has been achieved through retroviral transduction of murine fibroblast with four transcription factors. A large amount of studies aimed at identifying the molecular pathways that regulate stem cell plasticity is examining the potential epigenetic role of the microenvironment on the emergence of cell phenotype. Recent publications, and my own studies have provided intriguing information regarding the role of transcription factors Foxi1 and Cdx4 and well as menin in epigenetic regulations of Hox-dependent stem cell differentiation and malignant transformation. My goal is to further explore the detailed mechanism whereby Cdx4-Hox pathway is regulated to control hematopoiesis and leukemogenesis.
From 1980 to 1988, Dr. Jizhou Yan received his M.D. and M.S. degrees in Wuhan University School of Medicine (