Faculty Research Interests, Division of Pediatrics Hematology and Oncology in the Department of Pediatrics at the University of Minnesota

Laboratory Research Opportunities in Oncology

Brenda Weigel, M.D.
Assistant Professor
weige007@umn.edu

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.

Ashish Kumar, M.D., Ph.D.
Assistant Professor
kumar036@umn.edu

Dr. Kumar’s research focuses on understanding the biology of infant leukemia which is most often a fatal disease, as opposed to leukemia in older children which boasts cure rates now over 90%.  A vast majority of infant leukemias are associated with rearrangements of the MLL gene, which are also found in secondary leukemias that may occur in children and adults as a complication of therapy for another cancer.  In the laboratory Dr. Kumar is studying mouse models of MLL-rearranged leukemia to identify the biologic pathways that are required for the pathogenesis of leukemia.  The ultimate goal is to develop therapies that would target such pathways.

John Ohlfest, Ph.D.
Assistant Professor
ohlfe001@umn.edu

Dr. Ohlfest’s research focuses on understanding the mechanisms of brain tumorgenesis and immune evasion, and translating these basic discoveries into improved gene therapy and immunotherapy.  There are currently four projects being aggressively pursued: 1) Toll-like receptor agonists as vaccine adjuvants 2) Characterizing the phenotype of glioma stem cells using in vitro and in vivo models 3) Nonviral and lentiviral vector targeting to tumor cells, employing immuno-gene therapy and 4) Transgenic and somatic cell gene transfer-based glioma models.

Wei Chen, M.D., Ph.D.
Associate Professor
chenw@umn.edu

Dr. Chen's research is focused on developing immune-based therapies of cancer, with particular research interest in treating leukemia, lymphoma and hematological malignancies.  His research group is developing new strategies to activate cancer patient's own immune cells, which have the ability to specifically recognize and kill tumor cells. The goal of his research is to apply cancer vaccines, cellular therapies, and novel immune enhancing drugs to prevent and treat tumor recurrences following chemotherapy or bone marrow transplantation.

Timothy C. Hallstrom, Ph.D.
Assistant Professor
halls026@umn.edu

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.

John Kersey, M.D.
CCRF Land Grant Professor, Director

Dr. Kersey’s research is focused on childhood leukemia, particularly leukemia caused by a chromosomal translocation resulting in the t(4;11) MLL-AF4 fusion oncogene. His laboratory has developed a transgenic mouse model of MLL-AF4 leukemia that permits studies of pathogenesis of the leukemia. Studies are underway to evaluate novel therapeutic strategies for these high risk leukemias including inhibitors of heat shock proteins that serve as molecular chaperones.

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Laboratory Research Opportunities in Blood and Marrow Transplantation

Bruce Blazar, M.D.
Professor
Section Chief
blaza001@umn.ed

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
Professor
wagne002@umn.edu

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, Ph.D.
Assistant Professor
hippe002@umn.edu

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, M.D., Ph.D.
Assistant Professor
tolar003@umn.edu

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 Mortari, Ph.D.
Associate Professor
panos001@umn.edu

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.

Michael Verneris, M.D.
Assistant Professor
verneris@umn.edu

Dr. Verneris's research interests include immunology, transplantation biology and therapy, and translational research.  Areas of specific interest include NK cell development and activating and inhibitory NK receptors.  Current laboratory efforts are focused on understanding the signaling pathways of a number of these receptors and how such pathways are influenced by allogeneic bone marrow transplantation and immunosuppressive medications.  His studies are aimed at enhancing NK cell responses to malignant diseases and adoptive transfer of NK cells to kill residual leukemia/cancer cells.

Xianzheng Zhou, M.D., Ph.D.
Assistant Professor
zhoux058@umn.edu

Dr. Zhou’s research focuses on how bone marrow transplant cures leukemia and causes graft-versus-host disease.  He is investigating what target molecules induce graft-versus-tumor and graft-versus-host disease post bone marrow transplantation and is studying the T cell response to tumor antigens and cancer vaccines.

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Clinical Research Opportunities in Oncology

Michael Burke, M.D.
Assistant Professor
burke@umn.edu  

Dr. Burke’s research focus is in childhood leukemias with a particular emphasis in high-risk patients.  He has been recently involved in analyzing bone marrow transplant outcomes in the Ph+ leukemias (Ph+ ALL and CML) including the role for and cardiac toxicity potential of the tyrosine kinase inhibitors (e.g. imatinib) in these patients.  Dr. Burke is a member of the Children’s Oncology Group (COG) high-risk ALL study committee and is involved with national protocol development for these patients.  Dr. Burke also has a current study investigating fetal cells collected from maternal peripheral blood of male children diagnosed with leukemia to study the leukemic pathogenesis through gene expression profiling.

Susan Kearney, M.D.
Assistant Professor
kearn054@umn.edu

Dr. Kearney’s clinical and research interests focus on hemoglobinopathies, iron metabolism and the monitoring and treatment of iron overload disorders.  Current emphasis is on determining the prevalence of transfusional iron overload in the long term follow-up patient population using non-invasive liver R2 MRI technology. Future research direction will investigate the optimal method of chelation in this population with emphasis on the use of oral iron chelators.

Christopher L. Moertel, M.D.
Professor
Clinical Director, Pediatric Brain Tumor Program
moert001@umn.edu

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.

Dan Mulrooney, M.D., M.S.
Assistant Professor
mulro006@umn.edu

Dr. Mulrooney’s research focuses on the late effects experienced by survivors of childhood malignancies.  He has been involved with the Childhood Cancer Survivor Study investigating fatigue and sleep disorders in these cancer survivors.  Dr. Mulrooney is also the co-chair of the Endocrine/Metabolic Task Force for the Long-Term Follow-up Guidelines of the Children's Oncology Group Late Effects Committee.  Other areas of research include adolescent/ young adult oncology and the transition of care from pediatric to adult medicine.

Joe Neglia, M.D., MPH
Professor              
jneglia@umn.edu

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, M.D.
Assistant Professor     
stein083@umn.edu

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.

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Clinical Research Opportunities in Blood and Marrow Transplantation

Scott Baker, M.D., M.S.
Associate Professor
baker084@umn.edu

Dr. Baker's research is focused on the use of epidemiologic methods to study treatment related acute and long-term complications in survivors after hematopoietic stem cell transplant.  This research forms the basis for his current grant support in which the incidence, risk factors, and characteristics of cardiopulmonary, renal, endocrine, reproductive late effects and quality of life outcomes in long-term survivors after transplantation are being studied.  Dr. Baker is also the principal investigator for several hematopoietic stem cell transplant clinical trials, particularly for treatment of children with Hemophagocytic Lymphohistiocytosis, primary immune deficiencies, and hemoglobinopathy disorders such as sickle cell anemia and Thalassemia.  For these patients, a novel type of transplantation that is designed to make transplantation safer by utilizing a reduced intensity transplant preparative regimen is being investigated.   Dr. Baker is a member of the Children's Oncology Group where he serves on the Late Effects Committee, the Soft Tissue Sarcoma Committee, and the Stem Cell Transplant Committee.  He also serves on the Metabolic and Immune Deficiency subcommittees of the Pediatric Blood and Marrow Transplant Consortium and the Center for International Blood and Marrow Transplant Research.

Margaret MacMillan, M.D.
Assistant Professor
Clinical Director
macmi002@umn.edu

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, M.D.
Associate Professor
orcha001@umn.edu

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.

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Last modified on Thursday Mar 22, 2007

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