Bio

Honors & Awards


  • New Investigator Award, American Society for Blood and Marrow Transplantation (2015)
  • Best Abstract Award for Basic Science Research, American Society for Blood and Marrow Transplantation (2014)
  • Dr. Mildred Scheel Postdoctoral Fellowship, Deutsche Krebshilfe (2012)

Professional Education


  • Postdoctoral Research Fellow, Stanford University, Bone Marrow Transplantation (2012)
  • Residency, Eberhard Karls University of Tübingen, Internal Medicine (2010)
  • Doctor of Medicine, Universitat Ulm (2010)

Stanford Advisors


Research & Scholarship

Current Research and Scholarly Interests


Specific areas of active research include immunoregulation and immunologic reconstitution following allogeneic hematopoietic cell transplantation (HCT) to develop novel adoptive transfer strategies which induce immunologic tolerance, prevent graft-versus-host disease (GVHD), and augment graft-versus-tumor (GVT) effects to cure cancer.

Publications

Journal Articles


  • Third party CD4+ invariant natural killer T cells protect from murine GVHD lethality. Blood Schneidawind, D., Baker, J., Pierini, A., Buechele, C., Luong, R. H., Meyer, E. H., Negrin, R. S. 2015

    Abstract

    Graft-versus-host disease (GVHD) is driven by extensive activation and proliferation of alloreactive donor T cells causing significant morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). Invariant natural killer T (iNKT) cells are a potent immunoregulatory T-cell subset in both humans and mice. Here, we explored the role of adoptively transferred third party CD4(+) iNKT cells for protection from lethal GVHD in a murine model of allogeneic HCT across major histocompatibility barriers. We found that low numbers of CD4(+) iNKT cells from third party mice resulted in a significant survival benefit with retained graft-versus-tumor (GVT) effects. In vivo expansion of alloreactive T cells was diminished while displaying a Th2-biased phenotype. Notably, CD4(+) iNKT cells from third party mice were as protective as CD4(+) iNKT cells from donor mice although third party CD4(+) iNKT cells were rejected early after allogeneic HCT. Adoptive transfer of third party CD4(+) iNKT cells resulted in a robust expansion of donor CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) that were required for protection from lethal GVHD. However, in vivo depletion of myeloid-derived suppressor cells (MDSCs) abrogated both Treg expansion and protection from lethal GVHD. Despite the fact that iNKT cells are a rare cell population, the almost unlimited third party availability and feasibility of in vitro expansion provide the basis for clinical translation.

    View details for DOI 10.1182/blood-2014-11-612762

    View details for PubMedID 25795920

  • CD4+ invariant natural killer T cells protect from murine GVHD lethality through expansion of donor CD4+CD25+FoxP3+ regulatory T cells. Blood Schneidawind, D., Pierini, A., Alvarez, M., Pan, Y., Baker, J., Buechele, C., Luong, R. H., Meyer, E. H., Negrin, R. S. 2014; 124 (22): 3320-3328

    Abstract

    Dysregulated donor T cells lead to destruction of host tissues resulting in graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). We investigated the impact of highly purified (>95%) donor CD4(+) invariant natural killer T (iNKT) cells on GVHD in a murine model of allogeneic HCT. We found that low doses of adoptively transferred donor CD4(+) iNKT cells protect from GVHD morbidity and mortality through an expansion of donor CD4(+)CD25(+)FoxP3(+) regulatory T cells (Treg). These Treg express high levels of the Ikaros transcription factor Helios and expand from the Treg pool of the donor graft. Furthermore, CD4(+) iNKT cells preserve T cell-mediated graft-versus-tumor (GVT) effects. Our studies reveal new aspects of the cellular interplay between iNKT cells and Treg in the context of tolerance induction after allogeneic HCT and set the stage for clinical translation.

    View details for DOI 10.1182/blood-2014-05-576017

    View details for PubMedID 25293774

  • Regulatory T cells and natural killer T cells for modulation of GVHD following allogeneic hematopoietic cell transplantation BLOOD Schneidawind, D., Pierini, A., Negrin, R. S. 2013; 122 (18): 3116-3121

    Abstract

    Alloreactivity of donor lymphocytes leads to graft-versus-host disease (GVHD) contributing to significant morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). Within the past decade, significant progress has been made in elucidating the mechanisms underlying the immunologic dysregulation characteristic of GVHD. The recent discoveries of different cell subpopulations with immune regulatory function has led to a number of studies aimed at understanding their role in allogeneic HCT and possible application for the prevention and treatment of GVHD and a host of other immune-mediated diseases. Preclinical animal modeling has helped define the potential roles of distinct populations of regulatory cells that have progressed to clinical translation with promising early results.

    View details for DOI 10.1182/blood-2013-08-453126

    View details for Web of Science ID 000326503200010

    View details for PubMedID 24068494

  • The H3K4-Methyl Epigenome Regulates Leukemia Stem Cell Oncogenic Potential. Cancer cell Wong, S. H., Goode, D. L., Iwasaki, M., Wei, M. C., Kuo, H. P., Zhu, L., Schneidawind, D., Duque-Afonso, J., Weng, Z., Cleary, M. L. 2015

    Abstract

    The genetic programs that maintain leukemia stem cell (LSC) self-renewal and oncogenic potential have been well defined; however, the comprehensive epigenetic landscape that sustains LSC cellular identity and functionality is less well established. We report that LSCs in MLL-associated leukemia reside in an epigenetic state of relative genome-wide high-level H3K4me3 and low-level H3K79me2. LSC differentiation is associated with reversal of these broad epigenetic profiles, with concomitant downregulation of crucial MLL target genes and the LSC maintenance transcriptional program that is driven by the loss of H3K4me3, but not H3K79me2. The H3K4-specific demethylase KDM5B negatively regulates leukemogenesis in murine and human MLL-rearranged AML cells, demonstrating a crucial role for the H3K4 global methylome in determining LSC fate.

    View details for DOI 10.1016/j.ccell.2015.06.003

    View details for PubMedID 26190263

  • Treatment with agonistic DR3 antibody results in expansion of donor Tregs and reduced graft-versus-host disease. Blood Kim, B. S., Nishikii, H., Baker, J., Pierini, A., Schneidawind, D., Pan, Y., Beilhack, A., Park, C. G., Negrin, R. S. 2015

    Abstract

    The paucity of regulatory T cells limits clinical translation to control aberrant immune reactions including graft-versus-host disease. Recent studies showed that the agonistic antibody to DR3 (αDR3) expanded CD4(+)FoxP3(+) Tregs in vivo. We investigated whether treating donor mice with a single dose of αDR3 could alleviate acute GVHD in a MHC-mismatched bone marrow transplantation model. αDR3 induced selective proliferation of functional Tregs. CD4(+) T cells isolated from αDR3-treated mice contained higher numbers of Tregs and were less proliferative to allogeneic stimuli. In vivo GVHD studies confirmed that Tregs from αDR3-treated donors expanded robustly and higher frequencies of Tregs within donor CD4(+) T cells were maintained, resulting in improved survival. Conventional T cells derived from αDR3-treated donors showed reduced activation and proliferation. Serum levels of pro-inflammatory cytokines (IFNγ, IL-1β and TNFα) and infiltration of donor T cells into GVHD target tissues (gastrointestinal tract and liver) were decreased. T cells from αDR3-treated donors retained graft-versus-tumor effects. In conclusion, a single dose of αDR3 alleviates acute GVHD while preserving GVT effects by selectively expanding and maintaining donor Tregs. This novel strategy will facilitate the clinical application of Treg based therapies.

    View details for DOI 10.1182/blood-2015-04-637587

    View details for PubMedID 26063163

  • Donor Requirements for Regulatory T Cell Suppression of Murine Graft-versus-Host Disease. Journal of immunology (Baltimore, Md. : 1950) Pierini, A., Colonna, L., Alvarez, M., Schneidawind, D., Nishikii, H., Baker, J., Pan, Y., Florek, M., Kim, B. S., Negrin, R. S. 2015

    Abstract

    Adoptive transfer of freshly isolated natural occurring CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) prevents graft-versus-host disease (GVHD) in several animal models and following hematopoietic cell transplantation (HCT) in clinical trials. Donor-derived Treg have been mainly used, as they share the same MHC with CD4(+) and CD8(+) conventional T cells (Tcon) that are primarily responsible for GVHD. Third party-derived Treg are a promising alternative for cellular therapy, as they can be prepared in advance, screened for pathogens and activity, and banked. We explored MHC disparities between Treg and Tcon in HCT to evaluate the impact of different Treg populations in GVHD prevention and survival. Third-party Treg and donor Treg are equally suppressive in ex vivo assays, whereas both donor and third-party but not host Treg protect from GVHD in allogeneic HCT, with donor Treg being the most effective. In an MHC minor mismatched transplantation model (C57BL/6 → BALB/b), donor and third-party Treg were equally effective in controlling GVHD. Furthermore, using an in vivo Treg depletion mouse model, we found that Treg exert their main suppressive activity in the first 2 d after transplantation. Third-party Treg survive for a shorter period of time after adoptive transfer, but despite the shorter survival, they control Tcon proliferation in the early phases of HCT. These studies provide relevant insights on the mechanisms of Treg-mediated protection from GVHD and support for the use of third-party Treg in clinical trials.

    View details for DOI 10.4049/jimmunol.1402861

    View details for PubMedID 25994967

  • Autologous apoptotic cells preceding transplantation enhance survival in lethal murine graft-versus-host models BLOOD Florek, M., Sega, E. I., Leveson-Gower, D. B., Baker, J., Mueller, A. M., Schneidawind, D., Meyer, E., Negrin, R. S. 2014; 124 (11): 1832-1842
  • Role of Lymphocyte Activation Gene-3 (Lag-3) in Conventional and Regulatory T Cell Function in Allogeneic Transplantation PLOS ONE Sega, E. I., Leveson-Gower, D. B., Florek, M., Schneidawind, D., Luong, R. H., Negrin, R. S. 2014; 9 (1)
  • Allogeneic hematopoietic cell transplantation with reduced-intensity conditioning following FLAMSA for primary refractory or relapsed acute myeloid leukemia. Annals of hematology Schneidawind, D., Federmann, B., Faul, C., Vogel, W., Kanz, L., Bethge, W. A. 2013

    Abstract

    Patients with primary refractory or relapsed acute myeloid leukemia (AML) have a dismal prognosis. We report a retrospective single center analysis of aplasia-inducing chemotherapy using fludarabine, cytarabine, and amsacrine (FLAMSA) followed by reduced-intensity conditioning (RIC) for allogeneic hematopoietic cell transplantation (HCT) in 62 consecutive primary refractory or relapsed AML patients. Two-year event-free survival and overall survival (OS) were 26 and 39 %, respectively. Risk stratification according to cytogenetic and molecular genetic markers showed superior survival in patients in the intermediate-1 risk group (2-year OS 70 %) compared to the intermediate-2 risk (2-year OS 34 %, p?=?0.03) and adverse risk (2-year OS 38 %, p?=?0.06) group. The use of HLA-matched versus HLA-mismatched donors had no significant influence on survival (p?=?0.98). Two-year OS in the elderly subgroup defined by age ?60 years was 31 % compared to 46 % in the group of younger patients <60 years (p?=?0.19). Cumulative incidence of non-relapse mortality at 2 years adjusted for relapse as competing risk was 20 % for patients <60 years and 26 % for older patients (p?=?0.55). Chronic graft-versus-host disease was associated with a statistically significant superior survival (p?

    View details for PubMedID 23652585

  • Allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia and pulmonary mucormycosis TRANSPLANT INFECTIOUS DISEASE Schneidawind, D., Nann, D., Vogel, W., Faul, C., Fend, F., Horger, M., Kanz, L., Bethge, W. 2012; 14 (6): E166-E172

    Abstract

    Mucormycosis is a serious invasive fungal infection in immunocompromised patients. Patients undergoing treatment for hematologic malignancies are predominantly prone to the pulmonary manifestation of mucormycosis. Historically, allogeneic hematopoietic cell transplantation (HCT) in patients suffering from pulmonary mucormycosis (PM) was considered contraindicated owing to mortality rates up to 90%. We present 3 patients with acute myeloid leukemia and PM who were treated with radical surgical debridement combined with high-dose liposomal amphotericin B (LAB), and subsequently underwent successful allogeneic HCT. To date, all 3 patients are in complete remission and show no signs of mucormycosis. Allogeneic HCT in patients with PM seems feasible provided that the infectious focus is completely removed surgically and adequate antifungal pharmacotherapy, such as high-dose LAB or posaconazole, is established.

    View details for DOI 10.1111/tid.12019

    View details for Web of Science ID 000312149100009

    View details for PubMedID 23075207

  • [Allogeneic stem cell transplantation for acute myeloid leukemia and HIV infection--case 3/2012]. Deutsche medizinische Wochenschrift Schneidawind, D., Dorn, C., Faul, C., Vogel, W., Berg, C., Beck, R., Korn, K., Dittmann, H., Schleicher, J., Erbersdobler, A., Jahn, G., Kanz, L., Bethge, W. 2012; 137 (10): 495-?

    Abstract

    HISTORY AND ADMISSION FINDINGS: A 27-year-old male patient with a past medical history of HIV presented with acute myeloid leukemia for allogeneic hematopoietic stem cell transplantation (HSCT). Highly active anti-retroviral therapy suppressed the viral load below detection threshold. INVESTIGATIONS: There were no contraindications for allogeneic HSCT. TREATMENT AND COURSE: Myeloablative conditioning consisted of total body irradiation and cyclophosphamide. Anti-thymocyte globulin, tacrolimus and mycophenolate mofetil were used for immunosuppression. Combined anti-retroviral therapy (nucleoside and nucleotide analog reverse-transcriptase inhibitor, boostered protease inhibitor, maraviroc and raltegravir) was maintained for allogeneic HSCT and viral load remained below detection threshold. No graft-versus-host disease or serious infectious complications occurred. The patient showed good graft function with stable hematopoiesis. Localized Kaposi's sarcoma was diagnosed six months after allogeneic HSCT and treated successfully with surgical excision and reduction of immunosuppression. Almost one year after allogeneic HSCT, the CD4+ cell count is rising and viral load remains below detection threshold with combined anti-retroviral therapy. Conclusion: Allogeneic HSCT can be safely performed in HIV positive patients. Kaposi's sarcoma is a rare event after allogeneic HSCT and linked to strong immunosuppression.

    View details for DOI 10.1055/s-0031-1299022

    View details for PubMedID 22374660

  • Polyomavirus BK-specific CD8+T cell responses in patients after allogeneic stem cell transplant LEUKEMIA & LYMPHOMA Schneidawind, D., Schmitt, A., Wiesneth, M., Mertens, T., Bunjes, D., Freund, M., Schmitt, M. 2010; 51 (6): 1055-1062

    Abstract

    Polyomavirus BK (BKV) is known as an important etiologic agent in the development of hemorrhagic cystitis (HC) after allogeneic stem cell transplant (SCT). To define T cell epitopes of the BKV proteins VP1 and sT, eight potential HLA-A2-binding peptides were synthesized based on computer algorithms. These peptides were co-incubated with CD8 + T cells from the peripheral blood (PB) of 25 healthy volunteers and seven patients suffering from HC after allogeneic SCT in a mixed-lymphocyte peptide culture (MLPC), which were subsequently screened by enzyme-linked immunospot (ELISPOT) assays and fluorescence-activated cell sorting (FACS) analysis. We found that CD8 + T cells from five of seven (71%) patients with HC presensitized with the BKV peptide VP1 p108 (LLMWEAVTV) specifically recognized T2 cells pulsed with VP1 p108. In contrast, only seven of 25 (28%) healthy volunteers had CD8 + T cells reactive with VP1 p108-pulsed T2 cells. The presence of VP1 p108-specific T cells could be confirmed by FACS analysis. The BKV peptide VP1 p108 seems to play an important role as an immunodominant peptide in the pathogenesis of HC in patients after allogeneic SCT, and might be a promising target for immunotherapies or even strategies to prevent the development of BKV-associated HC.

    View details for DOI 10.3109/10428191003746323

    View details for Web of Science ID 000279485300016

    View details for PubMedID 20370539

Books and Book Chapters


  • Ionisierende Strahlung (Schneidawind D.) Erste Hilfe – Physik und Chemie für Mediziner Schatz, J., Tammer, R. Springer. 2007

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