Department of Pediatrics

Hematology/Oncology Research

The division of Pediatric Hematology/Oncology is actively involved in clinical research primarily through our participation in the Pediatric Oncology Group. This large, multi-institutional cooperative group has been a leader in developing effective therapy for children with a wide variety of malignant disorders. In fact, participation in open research protocols represent the state of the art in pediatric cancer care. We have a long and productive history as a member of POG, which continues to this day. In addition to our participation in POG, the Division has been active in smaller local and regional research activities. Recent examples include pediatric evaluation of anti-emetic agents, new factor products for treatment of hemophilia, and better utilization of permanent indwelling central venous access devices.

Laura F. Gibson, Ph.D.

Background
Approximately 4,200 new cases of acute lymphoblastic leukemia (ALL) are diagnosed annually in the United States, accounting for 80% of leukemias in pediatric patients. While treatment strategies have improved in recent years, it is estimated that 20% of children relapse with leukemic disease following standard therapy. The group of children that have resistant disease typically have a very poor prognosis, and tend not to respond well to additional therapy. The poor outcome associated with leukemic relapse makes it essential to better understand the factors that contribute to survival of leukemic cells during chemotherapy.

Basic Research
One focus of our laboratory is to investigate methods to disrupt survival signals provided by the bone marrow, with the long-term goal being the development of strategies that make leukemic cells more susceptible to chemotherapy.

A second area of investigation is aimed at better understanding how to minimize the detrimental effects of dose escalated chemotherapy. Often, aggressive chemotherapy is turned to as an approach in the treatment of diverse malignancies. In addition to affecting the tumor cells, it has become increasingly clear that normal components of the bone marrow are also damaged. Members of our research team shown below focus on various aspects of these projects as described.

James Fortney

Jim Fortney joined the Department of Pediatrics in 1986. He is a Research Associate in Dr. Gibson’s lab where he works on projects investigating bone marrow microenvironment and leukemic cell regulation. He has a biology degree from West Virginia University and over 20 years of research experience.

Jim is the senior research assistant in the laboratory, and currently is focused on optimizing the use of siRNA technology to interrupt gene expression in bone marrow stromal cells to develop models that identify signaling that is crucial to normal hematopoiesis.

In addition, several undergraduate research fellows, additional graduate students, and Department of Pediatrics residents have trained in the Gibson lab. Current projects being undertaken by students rotating through the lab include investigation of the factors that influence tumor egress from the bone marrow, the role of VEGF in regulating tumor cell response to chemotherapy, and alterations of Smad signaling in chemotherapy altered bone marrow stromal cells.

Contact Dr. Gibson: lgibson@hsc.wvu.edu

	Heather O’Leary: Heather O’Leary is a doctoral student in Department of Pediatrics. She joined Dr. Gibson’s lab in 2003 and is in the Cancer Cell biology program. Her project focuses on how cues from the stromal cell microenvironment regulate the survival and signaling of Philadelphia Chromosome positive leukemia.
Matt Akers: Matt Akers is an M.D./Ph.D. student in the Department of Pediatrics. He joined Dr. Gibson’s lab in 2006 and is in the Cancer cell biology program. His project focuses on  leukemic cell regulation by the central nervous system.
	Sreekumar Othumpangat : Dr Sreekumar othumpangat joined the Department of Pediatrics in February 2007. His projects span the laboratories of Drs. Giovanni  Piedimonte and Laura Gibson and are focused on microenvironment niche in chemotherapy; role of respiratory syncytical virus (RSV) in rat airway epithelial cells and embryonic stem cell differentiation. He holds PhD degrees in Toxicology from Japan and Microbiology from India.
Fariba Rezaee: Dr. Rezaee joined the Department of Pediatrics in the West Virginia University Health Sciences Center in July 2006 following residency at the Newark Beth Israel Medical Center.  Her project focuses primarily on Respiratory Syncitial Virus-mediated alteration of bone marrow microenvironment function.
	Debbie Piktel: Debbie Piktel  joined the Department of Pediatrics research group in 2007.  She works jointly between Drs Gibson and Piedimonte laboratory.  She has a chemistry degree from West Virginia University and has been a Research Assistant at the University for 20 years.
Ayman Saad, a clinical fellow of Hematology and Oncology, department of Medicine has been working in Dr Gibson’ laboratory since March 2006. He has participated in experiments evaluating the protective effect of the bone marrow microenvironment on multiple myeloma. Our team has shown that AMD3100 could be a novel drug in combating this protective effect thus enhancing tumor cell killing. Further experiments are being performed to validate this idea

Recent Publications

Lin Wang, Heather O’Leary, James Fortney and Laura F. Gibson. 2007. Ph+/VE-cadherin+ identifies a stem-cell like population of acute lymphoblastic leukemia sustained by bone marrow niche cells (Blood; in press).

S Clutter, J. Fortney, and L.F. Gibson. 2006. Chemotherpy Disrupts Activity of Translational Regulatory Proteins in Bone Marrow Stromal Cells. Experimental Hematology, Nov;34(11):1522-31.

SD Clutter, JE Fortney, and LF Gibson. 2005. MMP-2 Is Required for Bone Marrow Stromal Cell Support of Pro-B Cell Chemotaxis. Exp. Hematology Oct;33(10):1192-200.

L Wang, JE Coad, JE Fortney, and LF Gibson. 2005. VEGF-induced survival of chronic lymphocytic leukemia is independent of Bcl-2 phosphorylation. Leukemia 2005 Aug;19(8):1486-7.

L Wang, SE Clutter, J Benincosa, JE Fortney, and LF Gibson. 2005. Etoposide-activated TGF-b1/p38/Smad3 signaling requires MMP-2 activity in bone marrow stromal cells. Stem Cells Sep;23(8):1122-34. *Recognized as one of the top three papers, based on impact on the field, published in Stem Cells in 2005 with Dr. Wang (post-doctoral fellow) awarded honorable mention in the young investigator award competition.

L Wang, L Chen, J Benincosa, JE Fortney and LF Gibson. 2005. VEGF induced phosphorylation of Bcl-2 influences B lineage leukemic cell response to apoptotic stimuli. Leukemia 19(3):344-53. ”Spotlight article”