Civin Lab

Civin Lab Overview

My breakthrough discovery of the CD34 lympho-hematopoietic stem cell antigen and monoclonal antibody accelerated basic research in stem cell and leukemia biology and improved stem cell transplantation for thousands of patients. This led to multiple honors, including the 1999 National Inventor of the Year Award and the 2009 Landsteiner Award (Civin et al., Transfusion 2010, PMID: 20561292). In parallel with my own research, I built a leading Pediatric Oncology division including initiation of a longstanding large Pediatric Oncology-Hematology clinical fellowship program and T32 training grant at Johns Hopkins that trained many physicians and scientists who are now field leaders. I co-launched and continue as co-PI of the large T32 Cancer Biology training grant at UMSOM (2011-Present), where I continue scholarly productivity, collaboration, and mentoring, the latter as evidenced by my receipt of the 2015 American Society of Hematology Mentor Award and my mission at UMSOM to perform and inspire research and train leaders of the next generation of physicians and scientists.

My early discoveries continue to guide stem cell research and provide a lasting direct impact in patient care of cancer, transplant, and gene therapy patients. I discovered CD34⁺ lympho-hematopoietic stem-progenitor cells (Civin et al., J. Immunology 1984, PMID: 6586833), opening entirely new directions in stem cell, leukemia, and transplantation research. My work led to the first successful stem cell therapies emanating from basic research, as I proved in my own patients (Civin et al., J. Clinical Oncology 1996, PMID: 8708711). CD34 was the first and is still the best marker for hematopoietic stem-progenitor cells, as well as endothelial cells (Beschorner et al., Am. J. Pathology 1985, PMID: 3885751). CD34 monoclonal antibodies have provided an efficient, robust technology to immunoaffinity-purify these key cells. Tens of thousands of scientific articles involve CD34 (Loken et al., Blood 1987, PMID: 2947644), and thousands of patients have received CD34⁺ cell transplants and/or have had their mobilized peripheral blood stem cell harvests assessed for numbers of CD34⁺ cells. My colleagues and I discovered several key human stem-progenitor cell molecules, such as the human FLT3 receptor (Small et al., PNAS 1994, PMID: 8562934). We were among the first to find that certain microRNAs were key normal hematopoietic regulators (Georgantas et al., PNAS 2007, PMID: 17293455), and we continue to use microRNAs to identify novel target molecules and pathways involved in regulation of normal and leukemic human hematopoiesis, including miR-144, miR-451, RAB14 (Kim et al., British J. Haematology 2015, PMID: 25312678), miR-509, RAB5C (Tan et al., PLoS One 2014, PMID: 25368993), EYA and SIX (Creed et al., Development 2020, PMID: 31806659). My own current research focuses on targeting leukemias (Moses et al., Blood Advances 2021, PMID: 33560385); on the roles of key molecules including microRNAs, and their targets in normal and leukemic stem-progenitor cells; and directly relevant to this grant application, on applying new bioengineering technologies to problems in hematology and oncology, such as CAR-T lymphocyte manufacturing (Campos-González et al., SLAS Technology 2018, PMID: 29361868).

Research Team

Curt Civin, MD, ScD (hon)
Phillip A. Zaffere Distinguished Professor in Regenerative Medicine
Professor of Pediatrics and Physiology
Director, Center for Stem Cell Biology & Regenerative Medicine 
Scientist, UM Greenebaum Comprehensive Cancer Center
HSF2 Rm S103D
Phone: 410-706-1181
Email: ccivin@som.umaryland.edu

Current Research Projects

Maryland’s Cancer Moonshot Initiative in Pediatric Cancer Research

Major Goals: Expand pediatric cancer research at the University of Maryland School of Medicine. Civin contributes to the Administrative Core and the following projects: Proj 1- Develop PROTAC-based inhibitors of pediatric cancer drivers. Proj 3- Determine whether UPR pathway molecules and NUPR1 contribute to ARTs’ antileukemic MOA. Proj 5- Validation of nanogels and situ gelling systems for leukemia and brain cancer treatment.

Roles of the Induced Stress Response and NUPR1 Signaling in the Antileukemic Activity of Artemisinins

Major Goals: Determine if the Curate® microchip captures functional hematopoietic stem and progenitor cells in high yield.

Roles of the Induced Stress Response and NUPR1 Signaling in the Antileukemic Activity of Artemisinins

Major Goals: Determine whether UPR pathway molecules contribute to the antileukemic MOA of ARTs.

DACH as a Novel Human Megakaryopoietic Regulator

Major Goals: Investigate the cellular effects and molecular mechanisms of DACH as a novel megakaryopoietic regulator and investigate the use of DACH to enhance expansion of megakaryocytic cells.

Inferring the Mechanistic Regulation of Human Hematopoietic Stem-Progenitor Cells During Standard and ROS-induced States

Major Goals: (1) Identify the dynamic transcriptional regulation of in vitro cultures of human HSPCs. (2) Transform understanding of how hematopoietic stem-progenitor cells integrate intrinsic and extrinsic (i.e. reactive oxygen species) signals to balance quiescence with differentiation. Civin is co-PI and mentor.

Training Grant in Cancer Biology

Major Goals: Lead post- and pre-doctoral Cancer Biology research training on our NCI T32 training grant.

Enhancing Mesenchymal Stem Cell’s Intrinsic Expression of IL-10 and MMP-9 to Augment their Anti-inflammatory and Anti-fibrotic Capacities for the Treatment of Liver Diseases

Major Goals: Evaluate the ability of microencapsulated IL10/MMP9-overexpressing mesenchymal stem cells to reduce hepatic inflammation and fibrosis. Civin is a co-investigator and mentor.

Synthetic Strategies to Restore the Efficacy of Venetoclax in Acute Myeloid Leukemia

Major Goals: Evaluate novel venetoclax-based chimeric compounds that inhibit additional AML targets beyond BCL-2 or induce BCL-2 degradation.

Validation of the GPB Curate® Cell Processing System for Manufacture of Therapeutic Hematopoietic Stem Cells

Major Goals: Determine if the Curate® microchip captures functional hematopoietic stem and progenitor cells in high yield.