Laura F. Gibson
Deputy Director - Mary Babb Randolph Cancer Center
Deputy Director - Mary Babb Randolph Cancer Center
Alexander B. Osborn Distinguished Professor Hematological Malignancies
Co-Leader Osborn Hematological Malignancies Program
Program 3: Alexander B. Osborn Hematopoietic Malignancy and Transplantation
West Virginia University,
Ten Most Recent:
Breaking and entering into the CNS: clues from solid tumor and nonmalignant models with relevance to hematopoietic malignancies.
Basu SK, Remick SC, Monga M, Gibson LF.
Clin Exp Metastasis. 2014;31(2):257-267.
RepSox slows decay of CD34+ AML cells and decreasesTim-3 expression.
Jajosky AN, Coad JE, Vos JA, Martin KH, Senft JR, Wenger SL, Gibson LF.
Stem Cells Transl Med. 2014;3(7):836-848.
PMCJournal - In Process.
Bone marrow osteoblast vulnerability to chemotherapy.
Gencheva M, Hare I, Kurian S, Fortney JE, Piktel D, Wysolmerski RB, Gibson LF.
Eur J Haematol. 2013;90(6):469-478.
Sibling donor and recipient immune modulation with atorvastatin for the prophylaxis of acute graft-versus-host disease.
Hamadani M, Gibson LF, Remick SC, Wen S, Petros WP, Tse WW, Brundage KM, Vos JA, Cumpston AD, Bunner P, Craig M.
J Clin Oncol. 2013;31(35):4416-4423.
Three-dimensional hierarchical plasmonic nano-architecture enhanced surface-enhanced Raman scattering immunosensor for cancer biomarker detection in blood plasma.
Li M, Cushing SK, Zhang J, Suri S, Evans R, Petros WP, Gibson LF, Ma D, Liu Y, Wu NQ.
ACS Nano. 2013;7(6):4967-4976.
Adipocytes as a critical component of the tumor microenvironment.
Vona-Davis LC, Gibson LF.
Leuk Res. 2013;37(5):483-484.
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. 2012;47(1):146-148.
Bone marrow osteoblast damage by chemotherapeutic agents.
Rellick SL, O'Leary HA, Piktel D, Walton C, Fortney JE, Akers SM, Martin KH, Denvir J, Boskovic G, Primerano DA, Vos JA, Bailey NG, Gencheva M, Gibson LF.
PLoS One. 2012;7(2):e30758
Melphalan exposure induces an interleukin-6 deficit in bone marrow stromal cells and osteoblasts.
Rellick SL, Piktel D, Walton C, Hall B, Petros WP, Fortney JE, Gencheva M, Denvir J, Hobbs GR, Craig M, Gibson LF.
A smoking-associated 7-gene signature for lung cancer diagnosis and prognosis.
Wan YW, Raese RA, Fortney JE, Xiao C, Luo D, Cavendish J, Gibson LF, Castranova V, Qian Y, Guo NL.
Int J Oncol. 2012;41(4):1387-1396.
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
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.