Laura F. Gibson, PhD

Professor Emeritus

Organization:

West Virginia University School of Medicine

Department:

Microbiology, Immunology & Cell Biology

Classification:

Faculty

• PhD, West Virginia University, 1991

Ten Most Recent:

Loss of the redox mitochondrial protein mitoNEET leads to mitochondrial dysfunction in B-cell acute lymphoblastic leukemia.

Geldenhuys WJ, Piktel D, Moore JC, Rellick SL, Meadows E, Pinti MV, Hollander JM, Ammer AG, Martin KH, Gibson LF. G   Free Radic Biol Med. 2021 Nov 1;175:226-235.

Co-culture model of B-cell acute lymphoblastic leukemia recapitulates a transcription signature of chemotherapy-refractory minimal residual disease.

Rellick SL, Hu G, Piktel D, Martin KH, Geldenhuys WJ, Nair RR, Gibson LF. Sci Rep. 2021 Aug 4;11(1):15840.

Nair R.R, Piktel D, Hathaway QA, Rellick SL, Thomas P, Saralkar P, Martin KH., Geldenhuys WJ, Hollander JM, Gibson LF. Pyrvinium Pamoate Use in a B cell Acute Lymphoblastic Leukemia Model of the Bone Tumor Microenvironment. J Pharm Res 2020 Jan 27; 37(3): 43. doi.org/10.1007/s11095-020-2767-4.  PMID: 31989336.

Geldenhuys WJ, Nair RR, Piktel D, Martin KH, Gibson LF. The MitoNEET Ligand NL-1 Mediates Antileukemic Activity in Drug-Resistant B-Cell Acute Lymphoblastic Leukemia. J Pharmacol Exp Ther. 2019 Jul;370(1):25-34. doi: 10.1124/jpet.118.255984. Epub 2019 Apr 22. PMID: 31010844.

Nair RR, Piktel D, Geldenhuys WJ, Gibson LF. Combination of Cabazitaxel and Plicamycin Induces Cell Death in Drug Resistant B-cell Lymphoblastic Leukemia. Leukemia Research 2018 Sep; 72:59-66. Doi: 10.1016/j.leukres.2018.08.002. PMCID: PMC6414069.

Nair RR, Geldenhuys WJ, Piktel D, Sadana P, Gibson LF. Novel Compounds that Target Lipoprotein Lipase and Mediate Growth Arrest in Acute Lymphoblastic Leukemia. Bioorg Med Chem Lett. 2018 Jun 1;28(10):1937-1942.

Hare I, Evans R, Fortney J, Moses B, Piktel D, Slone W, Gibson LF. Chemotherapy-induced Dkk-1 Expression by Primary Human Mesenchymal stem cells is p53 dependent. Med Oncol. 2016 Oct; 33(10):113. doi: 10.1007/s12032-016-0826-9.

Moses BS, Evans R, Slone WL, Piktel D, Martinez I, Craig MD, Gibson LF.  Bone Marrow Microenvironment Niche Regulates miR-221/222 in Acute Lymphoblastic Leukemia. Mol Cancer Res. 2016 Oct;14(10):909-919. Epub 2016 Jun 29.

Moses BS, Slone WL, Thomas P, Evans R, Piktel D, Angel PM, Walsh CM, Cantrell PS, Rellick SL, Martin KH, Simpkins JW, Gibson LF. Bone Marrow Microenvironment Modulation of Acute Lymphoblastic Leukemia Phenotype. Exp Hematol. 2016 Jan;44(1):50-9.e1-2. doi:10.1016/ j.exphem.2015.09.003.

Rubenstein JN, Beatty C, Kinkade Z, Bryan C, Hogg JP, Gibson LF, Vos JA. Extranodal Marginal Zone Lymphoma of the Lung: Evolution from an Underlying Reactive Lymphoproliferative Disorder.  J Clin Exp Pathol. 2015 Feb;5(1). pii: 208.

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

Alexander B. Osborn Hematopoietic Malignancy and Transplantation Program

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.