Janice Blum, Ph.D.

Modulation of T cell immunity by viral infections, autophagy
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Dr. Blum’s research examines the role of hematopoietic cells in immunity. Her laboratory has define the importance of autophagy in regulating immunity.  Her team has also examines the role of hematopoietic cells in autoimmune diabetes and metabolic disorders. She also studies functional defects in hematopoietic cells in immune-deficient patients.

Hal E. Broxmeyer, Ph.D.

Regulation of self-renewal, differentiation, apoptosis & homing/migration of HSC
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The laboratory focuses on mechanisms regulating the growth, self-renewal, survival, differentiation, and homing/mobilization of hematopoietic stem and progenitor cells, embryonic stem cells and induced pluripotent stem cells at cellular, intracellular, and animal levels, and cytokine/chemokine actions, and immune cell regulation for translation for clinical utility.

Randy Brutkiewicz, Ph.D.

Immune evasion, antigen presentation, signal transduction in innate & adaptive immunity
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The Brutkiewicz laboratory studies immune evasion by tumors, in the context of the regulation of antigen presentation by various signal transduction pathways, in both innate and adaptive immune responses, including MHC class I and MHC class II molecules, as well as the CD1d/NKT cell axis.

D. Wade Clapp, M.D.

Molecular pathogenesis of Fanconi anemia & neurofibromatosis
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My laboratory focus on understanding the molecular pathogenesis of NF1 and particularly the role of immune cells in tumor initiation and progression.  We utilize a combined approach of using GEMMs and bone marrow transplantation to identify molecular and pharmacologic targets to treat the benign tumors in mice and in humans.

Utpal Davé, M.D.

Structure and function of the LIM domain Only-2 protein and its partners
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Our work revolves around the structure and function of the LIM domain Only-2 protein and its partners. Together with LDB1, TAL1, GATA, and E2A proteins, LMO2 forms a multisubunit complex that is critical for the specification and maintenance of the hematopoietic stem cell. The LMO2-associated complex (that includes GATA1) has a specific role in the differentiation of hematopoietic stem and progenitor cells toward the erythroid lineage. Many erythrocyte structural genes such as ALAS, Band 3, and globins are direct targets of the LMO2 complex. The regulation of these genes involves binding to GATA sites or E boxes within the proximal promoters. Globin gene regulation involves very robust upregulation by proximal promoter binding and looping to the locus control region, a superenhancer located 30 kb upstream. The looping within this locus is regulated by the LMO2/LDB1 complex. Recently, our lab has been studying the assembly of higher order LMO2/LDB1 protein complexes toward a transcriptionally active holocomplex comprised of the proteins listed above. We recently discovered that there is a hierarchy of half-lives for these proteins with LDB1 at the top. LDB1 has the most prolonged turnover and it confers stability upon its indirect and direct binding partners. We have employed a baculoviral expression system to produce significant quantities of these proteins to analyze their in vitro assembly. Most remarkably, we have assembled the LMO2/LDB1 multisubunit complex in vitro. Our future work involves analysis of higher order single particles by cyro EM and analysis of the function of the LMO2 complex upon the globin genes specifically addressing chromosomal looping.

Alexander Dent, Ph.D.

Growth and differentiation of T cells
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My lab studies the regulation of the antibody response, and specifically the T helper cells that are required for helping B cells. Our work has implications for controlling autoimmune diseases such as lupus, and also for helping to develop vaccines that can target infectious diseases as well as cancer cells.

Linda Anne DiMeglio, M.D., MPH

Type 1 diabetes and metabolic bone diseases. Diabetes biomarkers
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The Grant lab focuses on the impact of diabetes on vascular repair mechanisms and the impact of diabetes-induced denervation on bone marrow function. Our studies seek to understand the molecular mechanisms responsible for the phenotypic and functional changes in CD34+ cells that occur in individuals that develop microvascular complication.

Kenneth Dunn, Ph.D.

Kidney microtubules function in diabetic patients
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The research of my laboratory is broadly focused on the development of methods of quantitative microscopy, particularly intravital microscopy.  Current projects include development of fluorescent protein biosensors for in vivo studies, development of methods of automated digital image analysis and intravital microscopy studies of the dynamics of drug-induced liver injury.

Sherif Farag, M.D., Ph.D.

Cord blood and marrow HSC transplantation. NK cell function in transplant recipients
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W. Scott Goebel, M.D, Ph.D.

Mechanisms of engraftment of transduced HSC in sub-myeloablated murine hosts
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My research seeks to develop novel cellular and gene therapies for non-malignant diseases, especially Fanconi anemia. Two patients have been treated with mesenchymal stem cells to enhance hematopoietic engraftment and prevent graft-vs-host disease.  A gene therapy trial for Fanconi type A patients has been funded, with regulatory approval pending.

Samir Gupta, M.D.

HIV and cardiovascular disease
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Dr. Gupta conducts clinical and translational research in new HIV treatment strategies and methods to reduce chronic co-morbidities in HIV-infected persons. He currently holds NIH grants focused on depression treatment to reduce systemic inflammation and improve cardiovascular risk and also on the role of inflammatory monocytes on endothelial colony forming cells. He also supports the research of other groups by performing in vivo vascular imaging and providing clinical samples from HIV-infected patients within the IU Health medical system.

Laura Haneline, M.D.

How mutations in the Fanconi anemia genes perturb HSC function
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Dr. Haneline examines how abnormal intrauterine environments alter fetal stem/progenitor function. Maternal diabetes leads to profound functional deficits in fetal hematopoietic stem/progenitors and endothelial colony forming cells. Current studies are interrogating epigenetic alterations that promote dysregulated gene expression and vasculogenesis. Translational studies evaluate circulating progenitors as biomarkers of endothelial dysfunction.

Roland W. Herzog, Ph.D.

Gene therapy and immune tolerance for hemophilia and in AAV vectors
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My laboratory is developing gene therapies for the X-linked bleeding disorder hemophilia using adenosine-associated viral (AAV) vectors. This approach has the potential for a lasting cure of hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency). In related work we are studying the mechanisms of immune responses to AAV vectors and to the therapeutic coagulation factor proteins to prevent immune rejection of therapy. Furthermore, we are developing immune tolerance protocols for hemophilia based on oral, cell-, gene-, and drug-based immunotherapies.

Melissa Kacena, Ph.D.

Role of osteoblasts in hematopoietic niche. Impact of megakaryocytes on osteogenesis
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Our research focuses on the regulatory interactions between skeletal and hematopoietic cells  in 3 main areas: 1) The effects of megakaryocytes on osteoblast proliferation and bone formation; 2) The regulation of bone regeneration by thrombopoietin; and 3) The regulation of hematopoietic stem cells by osteoblasts, megkaryocytes, and osteal macrophages.

Mark Kaplan, Ph.D.

Immunobiology of STAT proteins; cytokines promoting T helper effector functions
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Research in the Kaplan lab focuses on understanding the development and function of T helper cell subsets that impact autoimmunity and allergic disease. The lab is particularly interested in understanding the role of transcription factors during the decision process for acquisition of a specific inflammatory phenotype in the T cell.

Reuben Kapur, Ph.D.

Molecular mechanisms involved in normal and abnormal hematopoiesis
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We study signaling pathways involved in regulating normal hematopoiesis as well as non-malignant hematologic diseases. Specifically, we study how PI3Kinase and Rho family GTPases ROCK and Rap1 contribute to stem and progenitor cell functions. We also study the role of stress MAPKinase pathways in normal and stress hematopoiesis.

Yan Liu, Ph.D.

Role of p53 and Bmi in HSC self-renewal
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The Liu laboratory is interested in investigating the molecular mechanisms that regulate hematopoietic stem cell self-renewal in normal and leukemic hematopoiesis. Research in the Liu lab is currently focused on determining the role of the role of mutant p53 and phosphatase PRL2 in leukemia stem cell self-renewal and leukemogenesis.

Heather O’Leary, Ph.D.

Mechanisms by which the microenvironment regulates normal and malignant stem cells
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The O’Leary laboratory focuses on the mechanisms by which the microenvironment regulates normal and malignant stem cells. More specifically, we are interested in how oxygen tension modifies the phenotype, function, and intracellular signaling of hematopoietic stem cells. Our goals are to better understand the true biology of normal and malignant stem cells in their native environment and utilize this information to bridge the disconnect across diseases between basic biology, pre-clinical models, and clinical success.

Christie Orschell, Ph.D.

Acute and delayed effects of radiation exposure on the hematopoietic system and hematopoietic stem cell biology
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Dr. Orschell is a radiobiologist/experimental hematologist focused on understanding and developing mitigation strategies for the hematopoietic acute radiation syndrome and the delayed effects of acute radiation exposure on the hematopoietic system and others.

Sophie Paczesny, M.D., Ph.D.

T cell regulation in GVHD disease
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Conducting proteomic discovery studies, I have made seminal contributions to identification of biomarkers associated with graft-versus-host disease (GVHD), and validated them in independent cohorts, thus providing the highest level of evidence for their clinical significance. Another research interest is to understand how effective antitumor immunity is generated.

Louis Pelus, Ph.D.

Bioactive cytokines/growth factor control of HSC proliferation & migration
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The Pelus lab focuses on  hematopoietic stem cell  self-renewal, differentiation and trafficking and how these processes  are regulated by the bone marrow niche.  Using genetically modified mice, pharmacological agents and in vivo imaging, the laboratory identified  key roles for prostaglandin E2 and neuropeptide Y in regulation of stem cell function and trafficking and is exploring their roles in  aging and response to radiation exposure.

Karen E. Pollok, Ph.D.

Immunotherapy and DNA repair
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Our research on normal hematopoiesis is to discover mechanistically how human hematopoietic cells respond to genotoxic stress. We are using ex-vivo expanded myeloid precursor cells and humanized bone marrow mouse models to interrogate molecular mechanisms and develop strategies to protect these life-sustaining cells from the deleterious effects of genotoxic stress.

Pratibha Singh, Ph.D.

Understanding how the bone marrow microenvironment/niche regulates hematopoietic stem cell function
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Dr. Singh’s research is focused on understanding how the bone marrow microenvironment/niche regulates hematopoietic stem cell function. Using a combination of genetics, pharmacology and imaging, we have identified key niche factors/mechanisms that critically regulate stem cell maintenance under the steady-state, and hematopoietic regeneration after genotoxic/pathologic stress. We recently discovered a key role for neuropeptide Y, a neural signal in the regulation of bone marrow vascular gateway function, and stem cell trafficking. This work is the basis for investigating the role of neuropeptide Y in stem cell niche restoration and hematopoietic regeneration after genotoxic/pathologic stress such as exposure to ionization radiation/ chemotherapy and diabeties. In addition, we are also exploring whether the regulatory mechanisms involved in healthy stem cells trafficking applies to cancer cell migration and metastasis.

Edward F. Srour, Ph.D.

Hematopoietic microenvironment; cell cycle regulation and engraftment of HSC
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The Srour research focuses on the impact of interactions between hematopoietic stem cells (HSC) and cellular elements of the hematopoietic niche on the maintenance and function of HSC. This research centers on how osteoblasts, osteolineage macrophages, and megakaryocytes maintain the stem cell pool and how CD166 bridges these cells together.

Mervin Yoder, M.D.

Endothelial cell regulation of proliferation and differentiation of HSC
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The Yoder laboratory is focused on identifying the regulatory pathways modulating the cells involved in vascular formation, remodeling, and repair and have identified endothelial colony forming cells (ECFC) as critical elements. We are now focusing on the therapeutic effects of ECFC when implanted in immunodeficient animal models of vascular ischemic injuries.