Dr. Brufsky’s research interests include novel clinical therapeutics for breast cancer, bone-breast cancer interactions and therapeutics, molecular biology of metastatic breast cancer, and novel management strategies for metastatic breast cancer.
Dr. Buckanovich’s research interests are ovarian cancer stem cells, mesenchymal stem cells, tumor vascular niche, ovarian cancer therapeutics, and ovarian cancer clinical trials.
Dr. Galson investigates signal transduction pathways and gene regulation in osteoclasts (OCL) and osteoblasts (OB) both during normal differentiation and in pathological states. The goal is to better understand pathological changes in the bone microenvironment, particularly OCL and OB, in Paget’s disease of bone and Multiple Myeloma (MM) bone disease. Her current studies focus on four main areas: (1) Determine the mechanism by which Measles virus nucleocapsid protein (MVNP) alters expression of cellular genes and increases osteoclast differentiation in Paget’s disease of bone. Dr. Galson has shown that MVNP signals through interaction with the IKK family members TBK1 and optineurin to generate pagetic OCL. Additional studies aim to determine the mechanism of cooperation between MVNP and p62 (SQSTM1) with pagetic mutations to generate Paget’s lesions. (2) Determine the mechanism by which MM cells suppress the differentiation capacity of osteoblast progenitor cells, which persists even after removal of the MM cells. These MM-altered bone marrow stromal cells also enhance osteoclastogenesis and microenvironmental support of myeloma growth. The focus is on understanding signaling mechanisms and the epigenetic changes induced in BMSC by MM cells. (3) Determine the roles of Gfi1 and EZH2 in osteoclasts. These studies derive from finding a key role for these proteins in MM-induced epigenetic changes in BMSC. (4) Determine if inhibition of TBK1/IKKe signaling is a useful therapeutic strategy to inhibit MM bone disease. Inhibition of TBK1/IKKe signaling blocks OCL formation and slows MM growth in vitro. These studies are being extended to in vivo MM models. Dr. Galson is also involved in additional studies involving other cancers that invade the bone, such as breast cancer.
Dr. Herman’s research explores changes in DNA methylation in cancer, and his lab is the first to demonstrate that tumor suppressor genes are silenced by promoter region methylation. The Herman Lab has characterized changes in methylation associated with the development and progression of cancer, including the demonstration of changes in DNA methylation in premalignant lesions. Current research is aimed at utilizing these findings to improve the management of patients through the development of prognostic, predictive, and early detection epigenetic biomarkers, and in studies of epigenetic therapy. They have developed new methods for study of DNA methylation (methylation specific PCR, in Situ MSP, ERMA, and, more recently, nanotechnology-based detection methods, included MS-QFRET and MOB, DREAMing). These sensitive methods have been used for the early detection of cancer and for developing predictive biomarkers.
Dr. Horn’s primary research is the neurobiology of vagus nerve signaling. This research uses neuromodulation devices to control nerve-organ communication for the treatment of cancer, inflammation, gastrointestinal motility, and side effects of cancer therapies.
Dr. Kirkwood’s research focuses on melanoma immunobiology, therapy, and prevention. His translational laboratory studies have shown the immunological basis of IFN adjuvant benefits in the first neoadjuvant immunotherapy trial for melanoma. His research is now expanding these studies at Hillman and through ECOG-ACRIN, probing the role of molecularly targeted agents (BRAF, MEK, and PI3Kδ/γ inhibitors) that may improve upon the efficacy of anti-PD1 immunotherapy for adjuvant therapy of operable high-risk melanoma and treatment of advanced melanoma. His studies of monoclonal antibodies to the gangliosides of melanoma—and peptide differentiation antigens of melanoma alone and in combination with cytokine and growth factor immunomodulators—paved the way for the recent progress with immunotherapies in multiple other cancers. He has advanced the multimodal therapy of melanoma with surgery, stereotactic radiotherapy, and molecular antitumor agents.
The Novelli Lab focuses on elucidating the fundamental mechanisms underlying vascular dysfunction in sickle cell disease (SCD). Dr. Novelli’s initial research sought to clarify the mechanisms underlying pulmonary hypertension in sickle cell disease. Most recently, his research has focused on the risk factors and mechanisms of cognitive impairment in sickle cell disease.
Dr. Ofori-Acquah has a research interest in molecular hematology, endothelial barrier function, sickle cell disease (SCD), and global health. His basic science research is on the mechanisms of neutralizing erythroid danger associated molecular pattern (eDAMP) molecules. This work encompasses studies of developmental, genetic, and epigenetic regulation of hemopexin and heme oxygenase-1—the key neutralizing molecules of extracellular heme the prototypical eDAMP. His basic research is translated to understanding the role and mechanism of extracellular heme in the pathobiology of vascular complications in SCD. A major translational focus is acute chest syndrome, the leading cause of premature death in SCD. The Ofori-Acquah lab developed the first mouse model of acute chest syndrome. This preclinical model is currently being used to find targeted therapies for this syndrome. His global health research centers on a longitudinal observational study of a large newborn cohort in Ghana to define markers of end-organ damage in SCD. Additional global health work focused also on SCD is performed under the auspices of the H3Africa consortium with a multi-disciplinary team of collaborators in Cameroon, Tanzania, and South Africa.
Dr. Ragni’s research studies were among the first multi-center NIH-funded investigator-initiated studies in hemophilia malignancy, hemophilia inhibitor formation, hemophilia HIV/HCV infection, hemophilia AIDS therapy, and hemophilia adult prophylaxis . She has also collaborated on multi-center organ transplant HIV trials, hemophilia gene therapy trials, VWD genotype-phenotype studies, novel therapeutics for hemophilia, and rhIL-11 and recombinant VWF for VWD.
Dr. Shlomchik’s research program is dedicated to understanding the complex immunology of allogeneic hematopoietic stem cell transplantation. His research has primarily taken genetic approaches with mouse models to test fundamental hypotheses regarding alloSCT immunology, in particular mechanisms of graft-vs-host disease (GVHD), graft-vs-leukemia (GVL) and GVL-resistance. A goal of these studies is to make discoveries that can be translated in the clinic. One such discovery resulted in co-developing a reagent to deplete naïve T cells (TN) from stem cell products, thereby allowing the transfer of only memory phenotype T cells. The results of the first-in-human trial of this approach in patients with acute leukemia suggest that the depletion of naïve T cells results in a remarkably low rate of chronic GVHD without an increase in relapse or infections. This approach is now being examined in a 4-arm clinical trial that includes high or lower intensity conditioning and grafts that are from HLA-matched related HLA-matched unrelated donors.
Dr. Wozniak’s research focuses on lung cancer, including small cell, non-small cell, and mesothelioma, as well as thymus gland cancer.
Dr. Zarour’s research interests include the identification of novel MHC class II epitopes derived from tumor antigens expressed by melanoma. His laboratory has successfully developed the approach to identify T-helper epitopes derived from a number of human tumor antigens and capable of stimulation antigen-specific CD4+ T cells in patients with advanced cancer. A second interest is the development of novel melanoma vaccines trial with T-helper epitopes and adjuvants. His lab has performed clinical trials with MHC class I and MHC class II epitopes derived from the cancer/testis antigen NY-ESO-1 in combination with CPG in patients with advanced melanoma. The lab has also demonstrated the capability of CPG to stimulate potent and ex vivo detectable CD8+ T cell responses to NY-ESO-1. A third research focus is the study of the mechanisms of melanoma-induced T cell dysfunction, including the role of the PD-1, Tim-3, BTLA and TIGIT pathways. These studies serve as rationale for ongoing clinical trials with dual PD1/Tim-3 and PD-1/TIGIT blockade in cancer patients, including melanoma. Finally, Dr. Zarour studies the role of the gut microbiome in modulating clinical and immune responses to immune checkpoint blockade in the context of a novel clinical trial with fecal microbiota transplant and anti-PD-1 antibodies in patients with PD1 refractory melanoma.
HEAD AND NECK CANCER
Division of Hematology/Oncology
UPMC Cancer Pavilion
5150 Centre Avenue, 5th floor
Pittsburgh, PA 15232
412-648-6575 | Email Us
UPMC Hillman Cancer Center
5115 Centre Avenue
Pittsburgh, PA 15232