Stem Cell Technology: mesenchymal stem cells, clonal heterogeneity, cell signaling, aging and regenerative therapies
Prof. O'Connor's research is in the area of stem cell technology with the goal of improving human health through advances in regenerative medicine. Her research focuses on the cellular heterogeneity of mesenchymal stem cells (MSCs). These are highly robust cells with broad differentiation potential that regulate the immune response and migrate to injured tissue, among other therapeutic properties. As such, these adult stem cells have potential application to treat a wide range of disorders including arthritis, heart attack and cancer.
The goal of Prof. O'Connor's research is to understand how MSC heterogeneity can be manipulated at the molecular level to improve the efficacy of MSC therapies. MSCs are a heterogeneous mixture of cells with different regenerative properties. This cell-to-cell variation impacts their effectiveness to repair damaged tissues and is a major challenge to achieve the therapeutic potential of MSCs. Typically only the average properties of the overall MSC culture are investigated. Instead, Prof. O'Connor takes a more engineering approach - - treating MSCs as an ensemble of distinct cell subsets. This quantitative, systems approach provides unique insights into MSC properties, allowing the O'Connor lab to make unique contributions to the field. This research is relevant to other types of stem cells because all stem cells are intrinsically heterogeneous.
The scope of Prof. O'Connor's research projects ranges from fundamental discovery at the cellular and molecular levels to computational analysis that resolves complex interactions among cells and signaling pathways. With both approaches, the objective is to gain unique insight into the mechanisms by which stem cells interact with their surroundings and to employ this knowledge to develop novel strategies to regenerate tissue. This research is inherently interdisciplinary and provides opportunities to collaborate with stem cell biologists, computer scientists and clinicians.
Prof. O'Connor received the 2013 Elmer Gaden Award from Biotechnology and Bioengineering as determined by the editorial board. Past recipients include James Bailey, James Swartz, Jonathan Dordick, Mark Davis, and E. Terry Papoutsakis. Clonal analysis of the proliferation potential of human bone marrow mesenchymal stem cells as a function of potency." The paper is a seminal work that enables the resolution of MSC heterogeneity at the molecular level and serves as template to deconvolute the heterogeneity of other types of stem cells.
REPRESENTATIVE RESEARCH ARTICLES
SD Madsen, MK Giler, BA Bunnell, and KC O’Connor*. Illuminating the regenerative properties of stem cells in vivo with bioluminescence imaging. Biotechnol J. 16: e2000248 (2021). [https://pubmed.ncbi.nlm.nih.gov/33089922]
SD Madsen, SH Jones, HA Tucker, MK Giler, DC Muller, CT Discher, KC Russell, GL Dobek, MC Sammarco, BA Bunnell and KC O’Connor*. Survival of aging CD264+ and CD264- populations of human bone marrow mesenchymal stem cells is independent of colony-forming efficiency. Biotechnol & Bioeng. 117 (1): 223-237 (2020). [3 citations, Featured on back cover] [https://www.ncbi.nlm.nih.gov/pubmed/31612990]
KC O’Connor. A cautionary tale about the use of colony-forming efficiency as a proxy for the survival of mesenchymal stem cells. Stem Cell Res Ther. 11: 292 (2020). [490 accesses, 1 citation] [https://pubmed.ncbi.nlm.nih.gov/32678014]
KC O’Connor*. Molecular profiles of cell-to-cell variation in the regenerative potential of mesenchymal stem cells. Stem Cells Int, article ID 5924878 (2019). [1560 views, 11 citations] [https://www.ncbi.nlm.nih.gov/pubmed/31636675]
SD Madsen, KC Russell, HA Tucker, J Glowacki, BA Bunnell and KC O'Connor*. Decoy TRAIL receptor CD264: A cell surface marker of cellular aging for human bone marrow-derived mesenchymal stem cells. Stem Cell Res Ther. 8: 201 (2017) [2097 accesses, 11 citations] [http://www.ncbi.nlm.nih.gov/pubmed/28962588]
KC Russell, HA Tucker, BA Bunnell, M Andreeff, W Schober, AS Gaynor, KL Strickler, S Lin, MR Lacey and KC O'Connor*. Cell-surface expression of neuron-glial antigen 2 (NG2) and melanoma cell adhesion molecule (CD146) in heterogeneous cultures of marrow-derived mesenchymal stem cells. Tissue Eng Part A, 19: 2253-66 (2013). [26 citations] [http://www.ncbi.nlm.nih.gov/pubmed/23611563]