Hematology/Oncology Research Opportunities

Laboratory Research Opportunities in Oncology

Laboratory Research Opportunities in Oncology

Brenda Weigel, MD
Associate Professor

Dr. Weigel's research focuses on new immunotherapy strategies for pediatric cancers. Her laboratory utilizes 2 models of common childhood cancers, namely rhabdomyosarcoma and AML.  The model of rhabdomyosarcoma was established in Dr. Weigel's lab and has been used to develop pre-clinical data to support clinical trials of new agents for this disease.  Dr. Weigel is focusing her research efforts on identifying promising new agents that may improve the treatment of childhood cancers.  Using her laboratory models, these agents can be identified and screened, then translated into clinical trials for patients.

Timothy C. Hallstrom, PhD
Assistant Professor

Dr. Hallstrom’s research is focused on the cellular control of Retinoblastoma(Rb)/E2F-induced apoptosis in cancer.  Dr. Hallstrom is studying the cellular mechanisms controlling Rb/E2F induced apoptosis during normal proliferation and in cancer development.   He recently identified the domain in E2F1 responsible for its unique pro-apoptotic function and used this to identify Jab1/CSN5 as an E2F1 specific binding partner responsible for the transcription factors pro-apoptotic but not pro-proliferatory activity.  Dr. Hallstrom is currently studying the mechanisms that control Jab1 binding to E2F1, how this complex promotes expression of apoptotic but not proliferation target genes and whether formation of this complex is inhibited during tumorigenesis. 

Emily Greengard, MD
Assistant Professor

Dr. Greengard’s research focuses on the childhood cancer, Neuroblastoma, with an emphasis on children with stage IV disease. She is currently involved in analyzing data from the most recently completed Children’s Oncology Group (COG) high-risk Neuroblastoma study to better understand those patients with refractory or progressive disease upfront. In addition, Dr. Greengard has an interest in drug development and identifying new agents to move forward for the treatment of childhood cancers, particularly Neuroblastoma and other solid tumors. Based on exciting research done at the University of Minnesota, Dr. Greengard is actively developing a clinical trial using a Salmonella-IL-2 conjugate for children with relapsed and refractory solid tumors.

Laboratory Research Opportunities in Blood and Marrow Transplantation

Laboratory Research Opportunities in Blood and Marrow Transplantation

Bruce Blazar, MD
Section Chief

Dr. Blazar has an extremely active and productive laboratory where his research spans a multitude of areas.  The following are a sampling of research areas that Dr. Blazar is currently investigating:

  1. Prevention of graft-versus-host disease (GVHD).  Dr. Blazar has developed new approaches to propagate and expand CD4+25+ T regulatory cells that can suppress allo-responses after in vivo adoptive transfer and has isolated novel populations that have more potent regulatory/suppressor cell activity.  In other studies, he has developed an ex vivo induction of tolerance as a means of preventing GVHD.  Dr. Blazar has analyzed the biochemical events associated with tolerance induction and has applied these findings to the development of new approaches to induce tolerance via the use of inhibitors of signal transduction or cell cycle progression.  Such methodologies are being applied to the analysis of CD4+25+ T regulatory cells.  Ongoing studies are testing regulatory T cells in patients undergoing hematopoietic cell
  2. Development of new strategies to enhance immune recovery after transplantation. Because GVHD and the conditioning regimens used for bone marrow transplantation induce severe thymic injury, Dr. Blazar is exploring novel approaches to protect the thymic epithelial cells (TEC) against injury including the use of cytokines that stimulate TEC proliferation/repair (keratinocyte growth factor), agents that protect against genotoxic stress (p53 inhibitors), and those that prevent endogenous hormone induced suppression of thymopoiesis (sex steroid hormone blockade).
  3. Prevention of tumor/leukemia relapse.   Projects are ongoing to utilize dendritic cell hybrid fusion vaccines as a means of inducing anti-leukemia immune responses in vivo.  Adoptive T cell immunotherapy is being utilized alone, in conjunction with dendritic cell fusion vaccines, or via the use of tumor antigens associated with gp96 heat shock proteins.  For adoptive immunotherapy, Dr. Blazar has developed new approaches to simultaneously track green fluorescent cytotoxic lymphocytes that are generated in vitro against leukemia cells and tumor cells.
  4. Gene therapy and tissue repair.  As an alternative to allo-transplantation, Dr. Blazar will use molecular strategies to correct immune and enzymatic disorders. Transposans or DNA oligonucleotides are being tested for this purpose along with reporter gene constructs and disease correction constructs in murine models and in murine models in which human cord blood cells are given.  In addition, Dr. Blazar is infusing murine multi-potent adult progenitor cells as a means of repairing tissue injuries caused by genetic and acquired disorders.

John Wagner, MD
Division Director

Dr. Wagner’s research is focused on the development of novel strategies for preventing the immunologic complications of allogeneic hematopoietic stem cell transplantation, namely through bone marrow graft engineering and the use of neonatal umbilical cord blood. In collaboration with Catherine Verfaillie, M.D., his investigations also include ex vivo expansion of umbilical cord blood stem cells and multipotent adult progenitor cells (MAPC) as well as gene transfer studies in patients with Fanconi anemi.

Keli Hippen, PhD
Assistant Professor

Dr. Hippen’s research is focused on inhibiting Graft Versus Host Disease (GVHD), which is a frequent and severe complicating factor in bone marrow transplants.  GVHD is a T cell mediated disease that arises in autoimmune fashion due to graft-derived immune cells recognizing recipient cells as non-self.   Activation of auto-reactive T cells (and those that induce GVHD) is normally prevented by a subset of T cells termed regulatory T cells (Treg).   Transplant of donor Treg has been shown to ameliorate disease in mouse models of both GVHD and autoimmunity.   Dr. Hippen’s specific interest is defining the mechanisms that control human regulatory T cell proliferation and function with the goal of generating large numbers of very active cells that can be co-transferred at the time of bone marrow transplantation and reduce or completely abolish GVHD.   In collaboration with Dr. Jakub Tolar, he is also exploring gene transfer studies to create more effective Treg cells based on antigen specificity and/or longevity.

Jakub Tolar, MD, PhD
Associate Professor

Dr Tolar’s research is focused on the use of hematopoietic transplantation for bone marrow failure (e.g., aplastic anemia and dyskeratosis congenita) and metabolic disorders (e.g., mucopolysaccharidosis type I and adrenoleukodystrophy).  He is using bone marrow derived stem cells and transposon gene therapy for correction of genetic diseases and improving outcome of blood and marrow transplantation.  Transposons are gene elements that can move from one location in a genome to another and it is Dr. Tolar’s goal to establish whether gene transfer mediated by transposons is safe and efficient for the metabolic diseases.  Dr. Tolar is also investigating Multi-potent Adult Progenitor Cells (MAPC) and Mesenchymal Stem Cells (MSC) as cellular therapy.  MAPC and MSC are cells derived from adult bone marrow and in contrast to blood forming cells in bone marrow, MAPC and MSC can significantly contribute to multiple organs, such as liver, lung, heart, intestine, and brain.  Dr. Tolar aims to determine if MAPC and MSC facilitate tissue repair and improve overall survival of patients after chemo-radiotherapy regimens in the setting of bone marrow transplantation. 

Angela Panoskaltsis-Mortari, PhD

Dr. Panoskaltsis-Mortari’s research focuses upon the study of bone-marrow transplant-related lung injury (idiopathic pneumonia syndrome) and the biology of graft-versus-host disease, both of which are major complications causing morbidity and mortality post-BMT.  She is also exploring novel methods of enhancing lung repair after transplant using growth factors and multi-potential adult stem cells.

Mark Osborn, PhD
Assistant Professor

Dr. Osborn’s research focus is in the development of new strategies for the treatment of inherited genetic disorders. One approach he is actively pursuing in his laboratory is direct gene replacement utilizing non-integrating, plasmid-based gene delivery vehicles. In addition, ex vivo therapies where the genetic defect is first corrected in adult stem cells (hematopoietic, mesenchymal, and inducible pluripotent) by genome editing prior to infusing into the affected host are also being pursued.

Troy Lund, MD, PhD
Assistant Professor

Dr. Lund is studying hematopoiesis using a zebrafish model in which hematopoietic stem cells are fluorescent and can be visualized in their migration process to the hematopoietic stem cell niche. Transgenic zebrafish are being generated to permit visualization of the stem cell niche. The goal of the project is to identify novel regulators of stem cell homing and hematopoietic cell engraftment using an adoptive transfer model in which zebrafish are irradiated and then reconstituted with fluorescent hematopoietic progenitor cells to permit visualization and trafficking of stem and progenitor cells, facilitating identification of stem cell niche factors that regulate this process. Additionally, recent projects have shown that tissue/limb regeneration utilize some of the same homing mechanisms as the hematopoietic cell niche and we have several projects to investigate regeneration at a cellular level.

Laboratory Research Opportunities in Hematology

Laboratory Research Opportunities in Hematology

Robert P. Hebbel, MD
Dr. Hebbel's research interests include: the vascular pathobiology of sickle cell disease; endothelial cell signal transduction and cell cycle in angiogenesis; genetic determination of endothelial cell biology; and novel, endothelial-based gene therapy approaches to hemophilia and cancer.  Dr. Hebbel's lab is currently emphasizing [a] the molecular physiology of tissue factor in the sickle cell transgenic mouse, and [b] the genetically determined variation in endothelial biology as an explanation for clinical phenotypic heterogeneity; the latter is relevant to multiple vascular diseases, including angiogenesis.

Mark Reding, MD
Dr. Reding’s clinical interest is the treatment of nonmalignant hematologic disorders, with particular emphasis on disorders of thrombosis and hemostasis, including hemophilia.  His current research efforts focus on the immune response to factor VIII, the cellular mechanisms involved in the synthesis of factor VIII inhibitors, and the immunologic consequences of gene therapy.

Gregory Vercellotti, MD
Dr. Vercellotti’s research focuses on sickle cell anemia in regards to iron overload, inflammation and endothelial cell biology.  His particular interests involve the role of inflammation in vaso-occlusion in sickle cell anemia, the role of infection and oxidative stress in vascular disease. 

Gerhard Johnson, MD
Dr. Johnson focuses on platelet biology and related coagulation problems. Current studies include: [a] elucidation of thromboxane receptor biology, using the characteristic canine signaling defect as a model to provide evidence that control involves thromboxane receptor phosphorylation; [b] evaluation of the role of platelet serotonin uptake and release in pathogenesis of dexfenfluramine cardiopulmonary toxicity; [c] clinical studies of prophylactic therapy for deep vein thrombosis in high risk orthopedic surgery patients.

Arne Slungaard, MD
Dr. Slungaard's research interests are 1) the biology and pathology of eosinophil peroxidase-mediated oxidant tissue damage; and 2) interactions of cationic proteins such as platelet factor 4 with the thrombomodulin/ protein C natural anticoagulant system.

Clinical Research Opportunities in Oncology

Clinical Research Opportunities in Oncology

Christopher L. Moertel, MD
Clinical Director, Pediatric Brain Tumor Program

As Clinical Director of the Pediatric Neuro-Oncology program, Dr. Moertel’s research focuses on development of new strategies for the treatment of brain tumors and the neoplastic complications of Neurofibromatosis and other neurocutaneous syndromes. This is achieved through clinical trial participation and cooperative work with basic science and translational laboratories, specifically those of David Largaespada, PhD and John Ohlfest, PhD. In addition, Dr. Moertel has specific interests in the complications of brain tumors and supportive care. Dr. Moertel is also the Director of the University of Minnesota / Neurocutaneous Syndromes Clinic Without Walls Neurofibromatosis Clinic and he serves on the advisory panel for the Children’s Tumor Foundation’s Preclinical Consortium.

Joseph Neglia, MD, MPH

Dr. Neglia's area of research involves the long-term effects of cancer therapy in cancer survivors and the occurrence of second malignancies following childhood cancer.  He is nationally and internationally recognized for his contributions to the field of childhood cancer long-term effects and currently is Principal Investigator at the University of Minnesota Cancer Center for the Children's Oncology Group (COG) and the vice-chair of the Voting Body of the COG.  Dr. Neglia is also the principal investigator of an American Cancer Society Grant investigation neuro-behavioral outcomes of children recently treated for leukemia. 

Marie Steiner, MD
Assistant Professor     

Dr. Steiner's research is focused on "coagulo-inflammatory pathophysiology." In collaboration with Dr. Nigel Key, formerly in the Department of Medicine, now Harold Roberts Chair of Hematology, University of North Carolina, several studies are in development to investigate aberrations of coagulation leading to bleeding and/or thrombosis in cancer patients and bone marrow transplant patients.  Through the Transfusion Medicine and Hemostasis Clinical Trials Network, she and Dr. Key are also developing a protocol to study use of recombinant Factor VIIa in the control of intractable bleeding after cardiopulmonary bypass.  Dr. Steiner has participated in the publication of over 30 articles, teaching manuals and book chapters.  She is a member of several professional societies, including American Society of Hematology, American Society of Pediatric Hematology/Oncology, International Society of Thrombosis and Hemostasis, International Academy of Clinical and Applied Thrombosis and Hemostasis and Society of Critical Care Medicine.

Clinical Research Opportunities in Blood and Marrow Transplantation

Clinical Research Opportunities in Blood and Marrow Transplantation

Margaret MacMillan, MD
Assistant Professor
Clinical Director

Dr. MacMillan's research is focused on the development and implementation of novel strategies for preventing the immunologic complications of allogeneic hematopoietic stem cell transplantation.  She is the Principal Investigator of 10 phase I/II clinical trials at the University of Minnesota and in collaboration with Bruce Blazar, M.D., she is studying the safety and efficacy of T regulatory cells to prevent graft-versus-host disease. Dr. MacMillan is co-director with John Wagner, M.D. of the University of Minnesota Fanconi Anemia Comprehensive Care Clinic, which follows the largest number of Fanconi anemia patients in the world.

Paul Orchard, MD
Associate Professor

Dr. Orchard’s research focus is in the use of hematopoietic cell transplantation for genetic metabolic and storage diseases.  A particular interest has been osteopetrosis, an inherited disorder leading to increased density of bone, which is also amenable to treatment with transplantation.  He is considered an International expert in this disorder and its treatment.  Another area of research interest has been gene therapy and cellular therapies in association with transplantation.  Dr. Orchard has developed methods of introducing genes into donor T cells to allow their administration to assist the recovery of the immune system, while providing the opportunity for elimination of the genetically engineered cells if complications occur.  This strategy will be used to increase the safety of cellular therapies.

Angela Smith, MD, MS
Assistant Professor

Dr. Smith’s research is focused on the etiology and prevention of acute transplant related complications. Her current emphasis is on endothelial biology and its relationship to the development of these complications. Dr. Smith is also the principal investigator (PI) on the hematopoietic stem cell transplant clinical trials for hemoglobinopathies. She is also the local PI coordinating the current international study looking at the use of Defibrotide for the treatment of hepatic veno-occlusive disease. Dr. Smith is a member of the Children’s Oncology Group Stem Cell Transplantation group.