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
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). [http://www.ncbi.nlm.nih.gov/pubmed/23611563]
KC Russell, MR Lacey, JK Gilliam, HA Tucker, DG Phinney and KC O'Connor*. Clonal analysis of proliferation potential of human bone marrow mesenchymal stem cells as a function of potency. Biotechnol Bioeng, 108: 2716-26 (2011). [FEATURED ARTICLE; K O'Connor earned the 2013 Gaden Award from Biotechnology & Bioengineering for this article.] [http://www.ncbi.nlm.nih.gov/pubmed/21538337]
KC Russell, DG Phinney, MR Lacey, BL Barrilleaux, KE Meyertholen and KC O'Connor*. In vitro high-capacity assay to quantify the clonal heterogeneity in trilineage potential of mesenchymal stem cells reveals a complex hierarchy of lineage commitment. Stem Cells, 28: 788-98 (2010). [Among Top 50 Downloaded Articles in Stem Cells for March 2010, 100+ Citations] [http://www.ncbi.nlm.nih.gov/pubmed/20127798]
B.S., Rice University, Chemical Engineering Dept., 1982
Ph.D., California Institute of Technology, Chemical Engineering Dept., 1987
Postdoctoral, California Institute of Technology, Chemistry Dept., 1987-1988
Northwestern University, Chemical Engineering Dept. & Biochemistry, Molecular Biology & Cell Biology Dept., 1988-1990
Prof. O’Connor specializes in stem cell engineering. She earned a B.S. magna cum laude in chemical engineering from Rice University where she was a George R. Brown, Robert A. Welch and Max Roy Merit Scholar, and a recipient of the Texas Society of Professional Engineers Outstanding Engineering Student Award. As a Weyerhaeuser Fellow at Caltech, Kim O’Connor earned a doctorate under the tutelage of James E. Bailey, a leader in the field of biomolecular engineering. After completing postdoctoral training in molecular and cellular biology at Caltech and Northwestern University, Dr. O’Connor joined the faculty of Tulane University where she is currently a professor in the Department of Chemical and Biomolecular Engineering and holds courtesy appointments in the Center for Stem Cell Research and Regenerative Medicine, Department of Surgery, Cancer Center, Biomedical Sciences Graduate Program, DeBakey Scholars Program and Biological Chemistry Undergraduate Program. She has served as a visiting professor in the Center for Cell and Gene Therapy at the Baylor College of Medicine.
Human mesenchymal stem cells (MSCs) are the subject of Prof. O’Connor’s research. These adult stem cells differentiate into multiple mesenchymal cell lineages and secrete trophicfactors to regulate a variety of cellular processes, including fibrosis and the immune system. As such, MSCs have potential application to treat a range of disorders including arthritis, heart attack and cancer. Prof. O’Connor’s research focuses on the heterogeneity of MSCs and its implications for regenerative therapy and disease. Her research grouphas made several important contributions tothe field of MSC heterogeneity, including development of a high-capacity assay of heterogeneity, resolution of proliferation-potency relationship at the clonal level, and identification of cell-surface markers of MSC subsets. To date, she has obtained research funding as principal investigator from such agencies as NASA, NIH and NSF that resulted in the publication of more than 100 research articles, including approximately 60 peer-reviewed publications and patents cited over 900 times. Her research has been featured in leading professional journals and in poster competitions. Prof. O’Connor has been invited to deliver numerous presentations on this work in the US and abroad.More than 20 postdoctoral fellows and graduate students, as well as over 30 undergraduates and technicians have trained under her direction. They have obtained prestigious positions at NIH, Memorial Sloan-Kettering Cancer Center, Johns Hopkins and Merck, among others.
In the area of professional service, Prof. O’Connor has served on the Editorial Board of the Journal of Cellular and Molecular Medicine. She founded and directs a Combined Degree Program that awards a M.S. in Biomedical Sciences and Ph.D. in Chemical Engineering, and was past Co-Director and Interim Director of the Interdisciplinary Molecular and Cellular Biology Graduate Program (now, Biomedical Sciences Graduate Program) that encompasses over 100 faculty across three campuses of Tulane University. Additionally, Prof. O’Connor has served as Chair of the Promotion and Tenure Committee for the School of Science and Engineering at Tulane and founded the Newcomb lectureship series to recognize professional accomplishments of female chemical engineers.
For her research achievements, Prof. O’Connor is the 2013 recipient of Biotechnology & Bioengineering’s Gaden Award for an outstanding publication that reflects exceptional innovation and creativity, NASA Space Act Award, Tulane IDEA Award, and Tulane Health Sciences Award for Leadership & Excellence in Intercampus Collaborative Research. For her teaching, she has been honored by Who’s Who Among American Teachers and by Tulane University with the Interdisciplinary Teaching Award, Provost’s Award for Excellence in Undergraduate Teaching, and Society of Tulane Engineers and Lee H. Johnson Award for Teaching Excellence. Her academic achievements have been recognized by Sigma Xi, Tau Beta Pi and Phi Lambda Upsilon.
Additional information is available on Prof. O’Connor’s website:
Peer-Reviewed Publications (2 in preparation) and Patents (* Corresponding Author)
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).
KC O'Connor and KC Russell. Method for identification and culture of multipotent mesenchymal stem cells with high proliferation potential. Utility patent application 13992953, USA; 11851821.6, Europe; 2818699, Canada; 2011349168, Australia; 2013-546358, Japan (2013); 201180061596.0, China (2013).
K O'Connor*, BL Barrilleaux, DG Phinney, BW Fischer-Valuck, KC Russell and DJ Prockop. Regulating in vitro motility of human mesenchymal stem cells with macrophage migration inhibitory factor (MIF) and a small-molecule MIF antagonist. Cellular Solutions for Clinical Challenges, N Jenkins, N Barron and PM Alves, Eds. (Springer Publishers, Netherlands, 2012), 149-160.
KC Russell, MR Lacey, JK Gilliam, HA Tucker, DG Phinney and KC O'Connor*. Clonal analysis of proliferation potential of human bone marrow mesenchymal stem cells as a function of potency. Biotechnol Bioeng, 108: 2716-26 (2011). [FEATURED ARTICLE; K O'Connor earned the 2013 Gaden Award from Biotechnology & Bioengineering for this article.]
KC Russell, DG Phinney, MR Lacey, BL Barrilleaux, KE Meyertholen and KC O'Connor*. In vitro high-capacity assay to quantify the clonal heterogeneity in trilineage potential of mesenchymal stem cells reveals a complex hierarchy of lineage commitment. Stem Cells, 28: 788-98 (2010). [Among Top 50 Downloaded Articles in Stem Cells for March 2010]
BL Barrilleaux, BW Fischer-Valuck, JK Gilliam, DG Phinney and KC O'Connor*. Activation of CD74 inhibits migration of human mesenchymal stem cells.In Vitro Cell Dev Biol - Anim, 46: 566-72 (2010).
BW Fischer-Valuck, BL Barrilleaux, DG Phinney, KC Russell, DJ Prockop and KC O'Connor*. Migratory response of mesenchymal stem cells to macrophage migration inhibitory factor and its antagonist as a function of colony-forming efficiency. Biotechnol Lett, 32: 19-27 (2010).
BL Barrilleaux, DG Phinney, BW Fischer-Valuck, KC Russell, G Wang, DJ Prockop and KC O'Connor*. Small-molecule antagonist of macrophage migration inhibitory factor enhances migratory response of mesenchymal stem cells to bronchial epithelial cells. Tissue Eng Part A, 15: 2335-46 (2009).
KC O'Connor*. An introductory course in bioengineering and biotechnology for chemical engineering sophomores. Chem Eng Edu, 41: 247-52(2007).
K O'Connor*, C Vidulescu, S Clejan, H Song and M Venczel. Predicting tissue assembly of prostate cancer spheroids. Cell Technology Processes for Cell Products, R Smith, Ed. (Springer Publishers, Netherlands, 2007), 297-302.
KC O'Connor*,JW Muhitch, DJ Lacks and M Al-Rubeai. Modeling suppression of cell death by Bcl-2 over-expression in myeloma NS0 6A1 cells. Biotechnol Lett, 28: 1919-24 (2006).
BL Barrilleaux, DG Phinney, DJ Prockop and KC O'Connor*. Ex vivo engineering of living tissue with adult stem cells. Tissue Eng, 12: 3007-19 (2006). [FEATURED ARTICLE]
KC O'Connor* and M Venczel. Predicting aggregation kinetics of DU145 human prostate cancer cells in liquid-overlay culture. Biotechnol Lett, 27:1663-8 (2005).
KC O'Connor*. Incorporating molecular and cellular biology into a chemical engineering degree program. Chem Eng Edu, 39: 124-127 & 133 (2005).
H Song,S Jain, RM Enmon and KC O'Connor*. Restructuring dynamics of DU 145 and LNCaP prostate cancer spheroids. In Vitro Cell Dev Biol - Anim, 40: 262-7 (2004). [FEATURED ARTICLE]
C Vidulescu, S Clejan and KC O'Connor*. Vesicle traffic through intercellular bridges in DU 145 human prostate cancer cells. J Cell Mol Med, 8: 388-96 (2004).
H Song,O David, S Clejan, CL Giordano, H Pappas-LeBeau, L Xu and KC O'Connor*. Spatial composition of prostate cancer spheroids in mixed and static cultures. Tissue Eng, 10: 1266-76 (2004).
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