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
Dr. O'Connor earned a B.S. in Chemical Engineering from Rice University in 1982 and a Ph.D. in Chemical Engineering with a Minor in Biology under James Bailey at the California Institute of Technology in 1987. Her postdoctoral training was in molecular biology at Caltech and in cell biology at Northwestern University. Dr. O'Connor joined the faculty of the Department of Chemical Engineering at Tulane University in 1990 as an Assistant Professor, and currently is an Associate Professor. In addition to her primary appointments at Tulane, she has served as Co-Director (1996-1999) and Interim Director (1997) of the Interdisciplinary Molecular & Cellular Biology Graduate Program at Tulane University and School of Medicine, adjunct associate professor in the Department of Surgery at Tulane Medical School (1999-present), and a member of the Tulane Cancer Center since its founding in 1994. Dr. O'Connor's recent awfards include the NASA Space Act Award, Tulane Award for Excellence in Undergraduate Teaching, Tulane Interdisciplinary Teaching Award, and Society of Tulane Engineers and Lee H. Johnson Award for Excellence in Undergraduate Teaching. She has authored a total of 50 publications including 2 patents and over 20 peer-reviewed articles. Dr. O'Connor's research in the field of oncology is interdisciplinary, applying engineering theory and techniques to cancer biology to develop new cancer tissue models. The focus of her work has been multicellular spheroids of neoplastic cells, which mimic micrometastases and avascular regions of tumors from the perspectives of differentiated function and spatial organization. Using DU 145 human prostate carcinoma cells as a model system, Dr. O'Connor's laboratory has demonstrated that there are profound changes in protein expression and signal transduction when DU 145 cells form spheroids from monolayer culture. The resulting phenotype is more consistent with that of an intact tumor. In a second line of investigation using both well and poorly differentiated human prostate carcinoma cell lines, her laboratory applied computational and image analysis to characterize the kinetics of spheroid self-assembly. The kinetic properties are sensitive to changes in adhesive properties among different cell lines and within a given cell line in response to an up-regulation of cell adhesion molecules upon spheroid formation. The applications of Dr. O'Connor's research include in vitro drug testing and assessing the metastatic potential of tumor cells.
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, Center for Aging, Center for Computational Science, 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 trophic factors 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 group has 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 over 60 peer-reviewed publications and patents cited approximately 1,200 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.
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. The award-winning paper is entitled "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.
Stem Cell Migration and Homing
Adult stem cells exist as a reservoir for tissue repair during homeostasis. They have a remarkable capacity for self-renewal in an undifferentiated state and can differentiate to replace damaged cells in tissue. It may be possible to harness the unique properties of stem cells to cure disease, regenerate tissue, repair traumatized tissue and reverse the degenerative effects of aging.
The efficacy of systemically delivered stem cell therapies is contingent on their homing to injured tissue. Our research group is interested in elucidating the molecular mechanisms underlying stem cell homing. In particular, we were the first to report that a potent pro-inflammatory cytokine, macrophage migration inhibitory factor, inhibits the migration of adult stem cells derived from bone marrow stroma. A small-molecule antagonist to this cytokine restores migration in stem cell preparations from all donors examined. Macrophage migration inhibitory factor is broadly implicated in trauma and disease and is likely to be upregulated in injured tissue targeted by stem cell therapy. This cytokine and its antagonist may have utility to regulate stem cell motility and improve the homing of stem cell therapies to injured tissue.
One of the challenges to realizing the therapeutic potential of stem cells is their scarcity in adult tissue. To collect the quantity of cells required for clinical procedures, stem cells are subject to ex vivo amplification. Although adult stem cells can repair tissue in vivo throughout an entire lifetime, they do not proliferate and differentiate as effectively ex vivo. Preserving the regenerative capacity of stem cells during amplification is essential to the development of effective stem cell therapies and is the subject of research in our laboratory.
Clinical applications of human bone marrow stromal cells are limited by rapid depletion of progenitors from culture during ex vivo amplification. As a consequence, improved amplification methods that enrich progenitor content are required for marrow stromal cells to be a feasible cell source for stem cell therapies. Our research group utilizes an integrative experimental and computational approach to achieve a mechanistic understanding of progenitor enrichment that will facilitate the rational design of amplification strategies.
A new era in tissue engineering is emerging, one which interfaces with computer science. This trend parallels the integration of computational analysis into the biological sciences as a whole. Computation has dramatically changed the degree of complexity in research and yielded significant insight into living systems. To date milestones in tissue engineering have been achieved largely through empirical investigation. Mathematical models have the potential to significantly influence future developments in this field given the intrinsic complexity of its products. Our research group has developed a computational model that predicts the kinetics of tissue self-assembly. The representative system for this work is spheroids of human prostate cancer cells that have application to high-throughput and patient-specific drug testing.
Clejan S, O'Connor KC, Cowger NL, Cheles MK, Haque S, Primavera AC. (1996) Effects of simulated microgravity on DU 145 human prostate carcinoma cells. Biotechnol Bioeng 50: 587-597.
O'Connor KC, Enmon RM, Dotson RS, Primavera AC, Clejan S. (1997) Characterization of autocrine growth factors, their receptors and extracellular matrix present in three-dimensional cultures of DU 145 human prostate carcinoma cells grown in simulated microgravity. Tissue Eng 3: 161-171.
O'Connor KC. (1999) Three-dimensional cultures of prostatic cells: tissue models for the development of novel anti-cancer therapies. Pharm Res 16: 486-493.
Clejan S, O'Connor KC, Rosensweig N. (2001) Tri-dimensional prostate cell cultures in simulated microgravity and induced changes in lipid second messengers and signal transduction. J Cell Mol Med 5: 60-73.
Enmon RM, O'Connor KC, Lacks DJ, Schwartz DK, Dotson RS. (2001) Dynamics of spheroid self-assembly in liquid-overlay cultures of DU 145 human prostate cancer cells. Biotechnol Bioeng 72: 579-591.
View Pubmed listing of Dr. O'Connor's research publications