4249 Fifth Ave
- Gene expression
- cellular transcription
- mRNA synthesis
- RNA polymerase II
4401 Penn Ave.
- Lipid signaling and lipid imaging in cell death and inflammation; Mitochondrial injury and mitochondria - targeted therapies; Redox biomedicine
Hillman Cancer Center Research Pavilion 2.42
- DNA repair, DNA recombination, DNA replication, double-strand break repair, Shu complex, Rad51 paralogs, breast and ovarian cancers
My work is to determine what genetic factors make some people more likely to develop cancer, particularly breast and ovarian cancers. The genes that we study are important for fixing damage to DNA. If these genes are not operating properly and DNA damage is uncorrected, cancer may develop. DNA damage can be caused by our bodies themselves or from outside sources such as chemicals found in the environment. We are working to better predict who is likely to get cancer by understanding both people's genes and their environmental exposures. By doing so, we aim to create new tailored strategies for treating people's tumors and ultimately prevent patients from developing breast and ovarian cancers at all.
- biological microscopy
- light-harvesting structures
- single molecule biophysics
- protein translation
- protein folding
- protein trafficking
130 DeSoto Street
The purpose of my laboratory’s research is to investigate the effects of environmental exposure on the host. We are particularly interested in infection and immunity on the lung and its associated pathophysiological response during injury, repair, and regeneration. The primary focus of my current research is the cellular and molecular actions of exposures to toxic chemicals and microorganisms that underlie the pathogenesis of chronic human diseases. Areas of research: 1. Lung epithelial cell phenotype, differentiation, and function upon exposure; 2. Inflammation-associated tissue remodeling and lung tumorigenesis; 3. Development of novel antibiotics to overcome antimicrobial resistance (AMR).
My research is centered on pathophysiology of hematologic disease such as bone marrow failure and leukemia. I have a broadbackground in hematopoiesis, stem cell biology & aging, cellular metabolism and tumor microenvironment, with specific training andexpertise in DNA damage response/repair, mouse modeling, metabolite profiling, and in vivo disease modeling.
5117 Centre Avenue
- Multiple myeloma
- breast cancer
- cancer-induced bone disease
- signal transduction
- epigenetic regulation
- transcription factors
- bone biology
- Paget's disease
Dr. Deborah Galson's laboratory is focused on two main areas:
(1) Determining the mechanism by which multiple myeloma (MM) cells reduce bone formation via suppression of the differentiation capacity of osteoblast progenitor cells in a manner that persists even after removal of the myeloma cells. These MM-altered bone marrow stromal cells also enhance osteoclastogenesis and microenvironmental support of myeloma growth. We have shown that myeloma cells induce the upregulation of expression of the transcriptional repressor Gfi1 in osteoblast precursor cells and that Gfi1 has a role in repressing Runx2, the key osteoblast transcription factor. We are currently investigating the mechanisms by which Gfi1 represses Runx2; MM cells and TNF-alpha/IL-7 regulate Gfi1 expression and activity; and roles for Gfi1 in MM cells and osteoclasts. Our preliminary data suggests that Gfi1 may prove to be a useful 3-way therapeutic target in MM bone disease. We are also expanding these studies into other cancer-induced bone disease models and into inflammatory diseases that cause bone formation suppression.
(2) Determining the mechanism by which measles virus nucleocapsid protein (MVNP) activates cellular genes and alters osteoclast differentiation. MVNP has been shown to be able to induce a Pagetic phenotype when transduced into osteoclast precursors and there is increasing evidence that it can play a role in the development of Paget's disease. Understanding the mechanisms involved may aid in developing additional treatments for Paget's disease as well as increase our understanding of how viral proteins alter cells. We have made the important discovery that MVNP signals through the IKK family members TBK1 and IKKepsilon to increase IL-6, a key player in creating the pagetic microenvironment. We are also studying MVNP regulation of C/EBPbeta and FoxO proteins, as well as autophagy, in generating aberrant osteoclasts. We have found that MVNP alters both the level of C/EBPbeta expression as well as the translation regulation of the C/EBPbeta LAP/LIP isoforms ratio. MVNP also alters the regulation of FoxO1 cellular localization, preventing nuclear localization, which increases autophagy, Further, MVNP alters the stability of FoxO3a, leading to rapid degradation and loss of SIRT1 expression, which thereby increases NF-kappaB activity. We are expanding the investigation of TBK1 and IKKepsilon signal transduction into other disease models that elevate osteoclasts including cancer-induced bone disease and arthritis.
UPMC Cancer Pavilion, POB2, Rm. 533 5150 Centre Avenue
- Radiation mitigator
- radiation protection
- lung cancer
Dr. Greenberger is examining the use of manganese superoxide dismutase (MnSOD) plasmid liposome gene therapy and GS-nitroxides, as agents to protect the normal tissues in the esophagus and lung from damage during radiation therapy. Damage to normal tissues during radiation therapy has been a major limitation to the effective treatment of lung cancer. The goal of his research is to improve the quality of life for cancer patients by potentially allowing the use of higher doses of radiation or chemotherapy to effectively treat lung cancer without the damaging side effects.
100 Technology Drive
- Free radical biochemistry
- phospholipid signaling in cell death pathways
- nitric oxide (NO) interactions with cellular components
- antioxidant activity of pulmonary epithelial and endothelial proteins
3550 Terrace Street
- Gene expression
- prostate cancer
- signal transduction
- molecular diagnostics
Clinical Lab Building, 8th Floor Room 8031
- Thyroid cancer genetics
- chromosomal rearrangements
- radiation-induced carcinogenesis
- novel mutations in thyroid cancer
- next-generation sequencing
- thyroid fine-needle aspiration (FNA)
5117 Centre Avenue Suite 2.26h
- Apoptosis regulation and the role of the Bcl-2 protein family in cancer biology and therapy
5117 Centre Avenue Lab 2.42a
- Colorectal cancer
- targeted therapy
- tumor suppressor
The immediate goal of our research is to understand how anticancer drugs kill cancer cells, and more importantly, why they fail so often. In the long term, we will attempt to use this knowledge to identify novel molecular targets and treatment strategies to improve cancer chemotherapy and chemoprevention. Cell Death in Anticancer Therapies Our research program has centered on several molecules that control discrete steps of programmed cell death. The first one, PUMA, is a downstream target of the tumor suppressor p53 and a BH3-only Bcl-2 family protein. PUMA is required for DNA damage-induced and p53-dependent apoptosis, and also plays a key role in apoptosis induced by several targeted anticancer drugs. The second one, SMAC, is a mitochondrial apoptogenic protein and a caspase activator. SMAC helps to execute apoptosis induced by anticancer drugs via a mitochondrial feedback loop. Regulators of non-apoptotic cell death, such as the autophagy inducer Beclin 1 and the necrosis regulator RIPK3, have also been studied. Through analyses of these molecules and their associated protein networks, we try to gain deep understanding on how cell death is initiated and executed in human cancer cells, why some cancer cells are not sensitive to anticancer drugs, and what can be done to restore their sensitivity. Oncogenic Stem Cells as the Target of Cancer Chemoprevention Prevention of human cancer through the use of chemical agents such as non-steroidal anti-inflammatory drugs (NSAIDs) has emerged as a promising strategy to reduce morbidity and mortality of cancer. Our recent studies showed that intestinal stem cells that have acquired oncogenic alterations are targeted by NSAIDs in chemoprevention of colon cancer. We are investigating how NSAIDs trigger apoptosis in such oncogenic stem cells, and if induction of apoptosis is critical for the chemopreventive effects of NSAIDs. We will also determine if apoptosis regulators can be used as markers to predict outcomes of chemoprevention of cancer patients, and if manipulation of apoptosis regulators can be used to improve the chemopreventive effects of NSAIDs. Manipulation of Cell Death Regulators To target PUMA, we have developed a high-throughput screening system for identifying small molecules that can activate PUMA in p53-deficient cancer cells. In collaboration with the UPCI Chemical Biology Facility, we will screen compound libraries to identify novel PUMA inducers. We have also identified and characterized small molecules that mimic the functional domains of PUMA and SMAC. Efforts are undertaken to apply these small molecules to chemotherapy and chemoprevention.