KC and the Sunshine Band

Kenneth R. Cooke, M.D.

Associate Professor in Pediatrics
Ohio Eminent Scholar in Stem Cell and
Regenerative Medicine
Rainbow and Hillary Vassil Endowed Professor in Stem Cell Research and Pediatric Oncology
Director, Pediatric Bone Marrow Transplant Program
Wolstein Research Building
2103 Cornell Rd
Cleveland, OH 44106
Phone: (216) 368-1481
e-mail: kenneth.cooke@uhhospitals.org

                                                                                          Ohio "Not-So" Eminent Scholar

Research

Allogeneic stem cell transplantation (SCT) is the only curative therapy for many patients with malignant and non-malignant diseases. Graft-versus-host disease (GVHD) and acute pulmonary toxicity (idiopathic pneumonia syndrome or IPS) are the two most frequent and life threatening complications of SCT and limit the broader application and efficacy of this powerful treatment strategy.

My scientific interests have been directed toward understanding the immunologic mechanisms that contribute to the development of IPS and acute GVHD following allogeneic SCT. Data generated in my laboratory using mouse models of human disease support the hypothesis that the lung is a target organ of acute GVHD and is susceptible to two distinct, but inter-related pathways of immune-mediated injury. The first is fundamentally dependent upon the interactions of donor T cells and host antigen presenting cells and the generation of allo-antigen specific cellular effectors which home to the lung and cause damage and dysfunction. The second involves aspects of the innate immune response including donor accessory cells (macrophages and neutrophils) and the effects of inflammatory mediators like TNF alpha and endogenous endotoxin as they interact via a “gut-liver-lung” axis of inflammation.  These findings are significant because they support a paradigm shift away from identifying lung injury after SCT solely as an idiopathic clinical syndrome and toward understanding IPS as a process in which the lung is a target of two distinct, but inter-related pathways of immune mediated injury. Although a significant body of data supports a role for both lymphoid and myeloid cellular effectors in the development of IPS, the mechanisms by which donor leukocytes traffic to the lung and other GVHD target organs are still poorly defined. Currently, my laboratory is currently focused on determining the role of chemokines and adhesion molecules in this context.

Importantly, laboratory insights are being actively translated back to the clinical setting in the form clinical protocols wherein agents used initially in mouse models are being used to treat our patients who have developed lung injury after SCT. Promising data from pilot studies have resulted in the development of national multi-center trials that are currently open to accrual. It is anticipated that the development of a clinical-laboratory data base from these trials will result new leads for laboratory investigation and foster the next generation of clinical trials.

Michelle M. Milano
Administrative Assistant

David Askew, PhD
Senior Research Associate

David earned his Ph.D in Microbiology at Virginia Tech examining the role of macrophage in tumor-induced immunosuppression. David completed a post-doc at St. Jude Children’s Research Hospital where he characterized phenotypic and functional differences in specific subsets of antigen-presenting cells in the spleen and in the brain. Prior to joining Ken Cooke’s laboratory in the department of Pediatrics, David studied the role of innate immunity in regulating immune response and in promoting the development of graft-versus host disease.

David is currently examining the role of innate immunity in determining the type of GVHD that is generated (cytotoxic vs. fibrotic), and how the innate immune system may be manipulated to reduce the severity of GVHD

Lixin “David” Zhou, MD, PhD
Senior Research Associate

David received his MD from Norman Bethune Medical University in the People’s Republic of China in 1985.  He then went on to complete his PhD at the Children’s Hospital of Florida in 1995. 

Selectins and their complementary ligands are known to orchestrate the movements of WBC migration during other forms of inflammation. I am using well-established mouse models of IPS to test the hypothesis that these molecules significantly contribute to WBC recruitment to the lung after BMT. The aims of this study will specifically characterize where and to what extent these selectin proteins and their binding partners are expressed, and determine how their interactions contribute to inflammation engendered during IPS. It is hoped that insights generated in the laboratory will pave the way for novel strategies to prevent or treat this serious complication and improve the outcomes for our BMT patients. Meantime, I also am working on Genotyping or gene chip analysis for experimental IPS.

     
Elizabeth Pierce, PhD
Research Associate

Elizabeth received her bachelor degree from James Madison University in Harrisonburg, VA in Aug. 2002.  During her time at James Madison, she worked in the laboratory of Chris Lantz, Ph.D.  working first on breeding a double-knockout mouse for interleukin (IL)-3 and IL-4 receptor alpha chain (IL-4Ra).  This model was meant to explore the perceived synergy between IL-3 and IL-4 in the development and function of mast cells.  She also started a chronic inflammation model looking to address the role of mast cells in the pathogenesis of the inflammation.  She was a member of Beta Beta Beta, the honors biology fraternity and participated in the research experience for Undergraduates (REU) program.  In July, 2002, Elizabeth began her doctoral work at University of Michigan.  She rotated first in the laboratory of Gary Glick, Ph.D.  Her work there included a microarray analysis of the effects of benzodiazepam in systemic lupus erythematosus (SLE).  Her second rotation was in the laboratory of Bruce A. Richardson, M.D., Ph.D.  She looked into the role of protein kinase C (PKC) in T lymphocytes in the context of SLE.  During her final rotation, in the laboratory of Cory M Hogaboam, Ph.D., she started her dissertation project exploring the role of CCR7 in idiopathic interstitial pneumonias.  Elizabeth defended her dissertation on December 1, 2006 and then taught genetics at Triton College in Chicago, IL.

Currently, Elizabeth is working on the effects of CCR1 in idiopathic pneumonia syndrome (IPS) as well as the role of CD8+ T lymphocytes their cytotoxic effects in the IPS.  Her interests include mouse models of human disease as well as understanding the signaling pathways involved in the pathogenesis of this disease. 

Saada Eid, MS
Lab Manager

Saada graduated from the University of California, Riverside with a B.S. in biochemistry.  She acquired employment in the pathology department of Case Western Reserve University in November 2000 where their research was concentrated on colon cancer.  Two years later she joined a different laboratory in the same department where the research was concentrated more on T cell immunology including tumor immunology and autoimmunity.
 
Saada joined Dr. Cooke’s lab in August 2007 as a research assistant and the lab manager.  Her functions in the lab include maintaining the mouse colony, maintenance of equipments, and providing assistance to all researchers in the lab.

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