Publications

Ten Most Recent:
Cellular elements of the subarachnoid space promote ALL survival during chemotherapy.
Akers SM, Rellick SL, Fortney JE, Gibson LF.
Leuk.Res. 2011;35(6):705-711.
PMC3099259.

Impact of response to thalidomide-, lenalidomide- or bortezomib- containing induction therapy on the outcomes of multiple myeloma patients undergoing autologous transplantation.
Awan FT, Osman S, Kochuparambil ST, Gibson LF, Remick SC, Abraham J, Craig M, Jillella A, Hamadani M.
Bone Marrow Transplant. 2011;47(1):146-148.

The evolving role of statins in hematopoietic stem and progenitor cell transplantation.
Hamadani M, Craig M, Gibson LF, Remick SC.
Am J Blood Res. 2011;1(1):57-64.

Higher busulfan dose intensity does not improve outcomes of patients undergoing allogeneic haematopoietic cell transplantation following fludarabine, busulfan-based reduced toxicity conditioning.
Hamadani M, Craig M, Phillips GS, Abraham J, Tse WW, Cumpston AD, Gibson LF, Remick SC, Bunner P, Leadmon S, Elder P, Hofmeister C, Penza S, Efebera Y, Andritsos L, Garzon R, Benson DM, Jr., Blum W, Devine SM.
Hematol.Oncol. 2011;29(4):202-210.

Higher infused CD34+ cell dose and overall survival in patients undergoing in vivo T-cell depleted, but not t-cell repleted, allogeneic peripheral blood hematopoietic cell transplantation.
Kanate AS, Craig M, Cumpston AD, Saad A, Hobbs GR, Leadmon S, Bunner P, Watkins K, Bulian D, Gibson LF, Abraham J, Remick SC, Hamadani M.
Hematol.Oncol Stem Cell Ther. 2011;4(4):149-156.

Respiratory syncytial virus infection in human bone marrow stromal cells.
Rezaee F, Gibson LF, Piktel D, Othumpangat S, Piedimonte G.
Am.J Respir.Cell Mol.Biol. 2011;45(2):277-286.
PMC3175557.

VE-cadherin and PECAM-1 enhance ALL migration across brain microvascular endothelial cell monolayers.
Akers SM, O'Leary HA, Minnear FL, Craig M, Vos JA, Coad JE, Gibson LF.
Exp.Hematol. 2010;38(9):733-743.
PMC2929642.

VE-cadherin Regulates Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Sensitivity to Apoptosis.
O'Leary HA, Akers SM, Piktel D, Walton C, Fortney JE, Martin KH, Craig M, Coad JE, Gibson LF.
Cancer Microenviron. 2010;3(1):67-81.
PMC2990486.

Neurotrophins regulate bone marrow stromal cell IL-6 expression through the MAPK pathway.
Rezaee F, Rellick SL, Piedimonte G, Akers SM, O'Leary HA, Martin KH, Craig M, Gibson LF.
PLoS One. 2010;5(3):e9690
PMC2837737.

NGF is an essential survival factor for bronchial epithelial cells during respiratory syncytial virus infection.
Othumpangat S, Gibson LF, Samsell L, Piedimonte G.
PLoS.One. 2009;4(7):e6444
PMC2715860.

Awards

1993-1994 - Department of Pediatrics Outstanding Research Award
1996-1997 - Department of Pediatrics Outstanding Research Award
2004 - Dean’s Award for Excellence in Research
2004 - Nominated for Outstanding Teacher of the Year
2007-2011 - Robert C. Byrd Professorship

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Current CV

Program

Alexander B. Osborn Hematopoietic Malignancy and Transplantation Program

Statement

Apoptotic pathways in tumor cells regulated by survival cues in the marrow microenvironment, beta-catenin, VE-cadherin in non-endothelial cell tumors, IL-6 expression in chemotherapy damaged stromal cells, tumor stem cell gene expression, leukemia, stem cell niche stroma and osteoblast function.
 
A primary interest in our laboratory is to understand the factors that regulate leukemic cell response to therapy.  The National Cancer Institute reports that acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children and represents 23% of cancer diagnoses among children younger than 15 years.  Approximately 2,400 children and adolescents younger than 20 years diagnosed with ALL each year in the US, with a gradual increase in the incidence of ALL observed in the past 25 years.  While significant progress has been made in the treatment of ALL, there remain children that do not respond to standard chemotherapy.  Leukemic cells that are not successfully killed by treatment often survive in the bone marrow, and later begin to grow and contribute to relapse of disease after treatment has stopped.  Using a model system of bone marrow and leukemic cell co-culture, we investigate the protective effects of the marrow on leukemic cells, and investigate strategies to attempt to make the cancer cells more vulnerable to treatment.  We have identified expression of VE-cadherin on a tumor stem cell like population which subsequently stabilizes the survival factor beta-catenin in this leukemic cell model.  Bone marrow microenvironment derived cues, including VCAM-1 and TGF-beta, increase, and sustain both survival signals as well as tumor stem cell gene expression patterns.   Our current efforts include development of strategies to interrupt the survival pathways we have identified, and to expand our model to include malignancies in addition to leukemia in our microenvironment model.
 
A second primary focus of our work is to better understand the effects of aggressive chemotherapy on capacity of the bone marrow to support immune system recovery following stem or progenitor cell transplantation.  Often, treatments for cancer can seem as devastating as the disease itself because it is difficult to spare the healthy cells of a patient from the harsh side effects of certain drugs.  The bone marrow provides a unique setting for development of blood cell formation, with the regulatory components of the marrow that direct production referred to as the “microenvironment”.  While the microenvironment is not the intended target of chemotherapy, it is exposed to various drugs during treatment, and can suffer damage from them.  We are investigating changes in the microenvironment that result from chemotherapeutic insult, and how these changes may negatively impact patient recovery.  We are specifically interested in factors that may reduce the efficiency with which transplanted stem cells migrate to the bone marrow, where they will ultimately develop into functional cells of the immune system that protect the patient from infection.  The goal of our work is to help physicians have available treatments for cancer, and for preparation for bone marrow transplantation, that are less harsh for the patient, but still maintain optimal effectiveness.  We have identified a variety of mechanisms that underlie treatment induced damage, and have recently expanded our efforts to evaluate the stromal and osteoblast components of the stem cell niche to understand how treatment may influence the ability of this niche to direct stem cell survival and development of cells required for sustained patient recovery.
 

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