Hans-Peter Kiem

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COS Expertise®
Fred Hutchinson Cancer Research Center
Transplantation Biology
Clinical Research
Full Member
University of Washington
Markey Molecular Medicine Center
Investigator
University of Washington
School of Medicine
Medicine
Professor
University of Washington
School of Medicine
Pathology
Adjunct Professor
Professional Headshot of Hans-Peter Kiem

Mailing Address

Fred Hutchinson Cancer Research Center
1100 Fairview Avenue N., D1-100
P.O. Box 19024
Seattle, Washington 98109-1024
United States

Contact Information

hkiem@fhcrc.org

Qualifications

Dr.Med., University of Ulm, Medicine, 1988.
M.D., University of Ulm, Medicine, 1987.

Expertise and Research Interests

Conducting Preclinical and Clinical Studies of Gene Therapy
Hematopoietic stem cells (HSCs) are attractive targets for gene therapy because of their ability to permanently reconstitute the hematopoietic and immune systems after transplant. Many different congenital and acquired diseases could be treated by introducing new genes into stem cells. In fact, in certain diseases with a selective advantage of genetically modified cells such as severe combined immunodeficiency (SCID), stem cell gene therapy has already been successfully applied to affected patients. These studies, however, have also demonstrated potential side effects of stem cell gene therapy when some patients developed leukemia in part due to retroviral insertional mutagenesis. These findings have led to a shift in emphasis in the gene therapy field from efficacy to safety. Thus, significant efforts have been devoted to improve not only stem cell gene transfer efficiency but also safety. Unfortunately, mouse studies have not been predictive of stem cell gene transfer in large animals. We have recently shown in a direct comparison that distinct repopulating cells engraft in the NOD/SCID versus the nonhuman primate model, suggesting NOD/SCID repopulating cells are more differentiated than nonhuman primate repopulating cells. Thus, we have focused on stem cell gene transfer studies in clinically relevant large animals and have identified factors resulting in increased gene transfer, including lentiviral vectors (Horn et al, Blood 2004). The relatively high gene transfer levels, >20% in peripheral blood and marrow cells, obtained with these conditions suggest the potential for therapeutic efficacy in diseases affecting the hematopoietic system, especially in diseases with selective advantages for corrected cells. Future clinical gene therapy efforts are aimed at patients with Fanconi anemia. A major clinical problem in these patients is marrow failure, and phenotypically corrected cells should have a selective advantage over uncorrected cells.
For most genetic diseases, gene-corrected cells do not have selective advantages, and in vivo selection strategies will be required. To that end, we have used drug resistance genes for in vivo selection and chemo-protection. Using the methylguanine methyltransferase (MGMT) gene, which confers resistance to alkylating agents such as BCNU and temozolomide, we demonstrated efficient in vivo selection and, more importantly, chemo-protection of hematopoietic stem cells (Neff et al, JCI 2003). Based on these data, we are preparing a clinical study in patients with brain tumors. Patients will receive temozolomide and BCNU, and since a major and dose-limiting side effect of this treatment is myelosuppression, we propose to genetically protect stem cells with MGMT, which should allow for more intensive and effective chemotherapy. We also showed protection of allogeneic stem cells from chemotherapy-induced myelosuppression, suggesting this technology could be applied to facilitate nonmyeloablative allogeneic HCT.
We have also made progress in expanding repopulating cells using the transcription factor HOXB4, which expanded CD34+ cells ex vivo and significantly improved engraftment after myeloablative conditioning compared to control cells (Zhang et al, PlosMedicine 2006). We have also initiated studies with ES cells from nonhuman primates and are testing whether we can direct the differentiation to hematopoietic stem/progenitor cells. More recently, we have discovered that dogs given HOXB4-transduced cells developed leukemia about 500 days after HCT and are studying the events that led to leukemia (Zhang et al, JCI 2008). We anticipate using dogs to study novel mechanisms of leukemogenesis and novel treatment approaches for leukemia.
We are also performing studies to use RNAi technology to inhibit HIV infection of stem cells and are currently exploring these strategies in a nonhuman primate model of AIDS.

Keywords

COS Keywords:

Cell Biology, Cell Transplantation, Gene Therapy, Hematology, Oncology, Stem Cells.

Additional Terms:

Stem Cell Biology, Stem Cell Gene Transfer, Transplantation.

Languages

(Reading, Writing, Speaking)

German: (Fluent, Fluent, Fluent)

Publications

  • Wang H, Cao H, Wohlfahrt M, Kiem HP, Lieber A (Jul 2008) Tightly regulated gene expression in human hematopoietic stem cells after transduction with helper-dependent Ad5/35 vectors., Experimental hematology, 36 (7), 823-31 Abstract
  • Trobridge GD, Beard BC, Gooch C, Wohlfahrt M, Olsen P, Fletcher J, Malik P, Kiem HP (Jun 2008) Efficient transduction of pigtailed macaque hematopoietic repopulating cells with HIV-based lentiviral vectors., Blood, 111 (12), 5537-43 Abstract
  • Furlong T, Kiem HP, Appelbaum FR, Carpenter PA, Deeg HJ, Doney K, Flowers ME, Mielcarek M, Nash RA, Storb R, Martin PJ (May 2008) Sirolimus in combination with cyclosporine or tacrolimus plus methotrexate for prevention of graft-versus-host disease following hematopoietic cell transplantation from unrelated donors., Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 14 (5), 531-7 Abstract
  • Zhang XB, Beard BC, Trobridge GD, Wood BL, Sale GE, Sud R, Humphries RK, Kiem HP (Apr 2008) High incidence of leukemia in large animals after stem cell gene therapy with a HOXB4-expressing retroviral vector., The Journal of clinical investigation, 118 (4), 1502-10 Abstract
  • Piasecki JC, Beagles K, Beard BC, Riddell S, Kiem HP (Jan 2008) Induction of transgene-specific cytotoxic T lymphocyte responses after transplantation of gene-modified CD34+ cells despite nonablative immunosuppressive conditioning., Human gene therapy, 19 (1), 103-7 Abstract
  • Bonfim CM, de Medeiros CR, Bitencourt MA, Zanis-Neto J, Funke VA, Setubal DC, Ruiz J, Sanders JE, Flowers ME, Kiem HP, Storb R, Pasquini R (Dec 2007) HLA-matched related donor hematopoietic cell transplantation in 43 patients with Fanconi anemia conditioned with 60 mg/kg of cyclophosphamide., Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 13 (12), 1455-60 Abstract
  • Sangiolo D, Lesnikova M, Nash RA, Jensen MC, Nikitine A, Kiem HP, Georges GE (Nov 2007) Lentiviral vector conferring resistance to mycophenolate mofetil and sensitivity to ganciclovir for in vivo T-cell selection., Gene therapy, 14 (21), 1549-54 Abstract
  • Shepherd BE, Kiem HP, Lansdorp PM, Dunbar CE, Aubert G, LaRochelle A, Seggewiss R, Guttorp P, Abkowitz JL (Sep 2007) Hematopoietic stem-cell behavior in nonhuman primates., Blood, 110 (6), 1806-13 Abstract
  • Shepherd BE, Kiem HP, Lansdorp PM, Dunbar CE, Aubert G, LaRochelle A, Seggewiss R, Guttorp P, Abkowitz JL (Sep 2007) Hematopoietic stem-cell behavior in nonhuman primates., Blood, 110 (6), 1806-13 Abstract
  • Wohlfahrt ME, Beard BC, Lieber A, Kiem HP (Sep 2007) A capsid-modified, conditionally replicating oncolytic adenovirus vector expressing TRAIL Leads to enhanced cancer cell killing in human glioblastoma models., Cancer research, 67 (18), 8783-90 Abstract
  • Zhang XB, Schwartz JL, Humphries RK, Kiem HP (Aug 2007) Effects of HOXB4 overexpression on ex vivo expansion and immortalization of hematopoietic cells from different species., Stem cells (Dayton, Ohio), 25 (8), 2074-81 Abstract
  • Beard BC, Dickerson D, Beebe K, Gooch C, Fletcher J, Okbinoglu T, Miller DG, Jacobs MA, Kaul R, Kiem HP, Trobridge GD (Jul 2007) Comparison of HIV-derived lentiviral and MLV-based gammaretroviral vector integration sites in primate repopulating cells., Molecular therapy : the journal of the American Society of Gene Therapy, 15 (7), 1356-65 Abstract
  • Jung CW, Beard BC, Morris JC, Neff T, Beebe K, Storer BE, Kiem HP (Jul 2007) Hematopoietic stem cell engraftment: a direct comparison between intramarrow and intravenous injection in nonhuman primates., Experimental hematology, 35 (7), 1132-9 Abstract
  • Neff T, Gerull S, Peterson LJ, Kiem HP (May 2007) Improved short-term engraftment of lentivirally versus gammaretrovirally transduced allogeneic canine repopulating cells., The journal of gene medicine, 9 (5), 357-61 Abstract
  • Ying SX, Seal S, Abbassi N, Hockenbery DM, Kiem HP, Li X, Pagel JM, Gopal AK, Deeg HJ (May 2007) Differential effects of bexarotene on intrinsic and extrinsic pathways in TRAIL-induced apoptosis in two myeloid leukemia cell lines., Leukemia & lymphoma, 48 (5), 1003-14 Abstract
  • Gerull S, Beard BC, Peterson LJ, Neff T, Kiem HP (May 2007) In vivo selection and chemoprotection after drug resistance gene therapy in a nonmyeloablative allogeneic transplantation setting in dogs., Human gene therapy, 18 (5), 451-6 Abstract
  • Beard BC, Keyser KA, Trobridge GD, Peterson LJ, Miller DG, Jacobs M, Kaul R, Kiem HP (May 2007) Unique integration profiles in a canine model of long-term repopulating cells transduced with gammaretrovirus, lentivirus, or foamy virus., Human gene therapy, 18 (5), 423-34 Abstract
  • Aker M, Tubb J, Groth AC, Bukovsky AA, Bell AC, Felsenfeld G, Kiem HP, Stamatoyannopoulos G, Emery DW (Apr 2007) Extended core sequences from the cHS4 insulator are necessary for protecting retroviral vectors from silencing position effects., Human gene therapy, 18 (4), 333-43 Abstract
  • Aker M, Tubb J, Groth AC, Bukovsky AA, Bell AC, Felsenfeld G, Kiem HP, Stamatoyannopoulos G, Emery DW (Apr 2007) Extended core sequences from the cHS4 insulator are necessary for protecting retroviral vectors from silencing position effects., Human gene therapy, 18 (4), 333-43 Abstract
  • Kiem HP, Allen J, Trobridge G, Olson E, Keyser K, Peterson L, Russell DW (Jan 2007) Foamy-virus-mediated gene transfer to canine repopulating cells., Blood, 109 (1), 65-70 Abstract
  • Keyser KA, Beagles KE, Kiem HP (2007) Comparison of mesenchymal stem cells from different tissues to suppress T-cell activation., Cell transplantation, 16 (5), 555-62 Abstract
  • Spence AM, Kiem HP, Partap S, Schuetze S, Silber JR, Peterson RA (Oct 2006) Complications of a temozolomide overdose: a case report., Journal of neuro-oncology, 80 (1), 57-61 Abstract
  • Beard BC, Mezquita P, Morris JC, Kiem HP (Aug 2006) Efficient transduction and engraftment of G-CSF-mobilized peripheral blood CD34+ cells in nonhuman primates using GALV-pseudotyped gammaretroviral vectors., Molecular therapy : the journal of the American Society of Gene Therapy, 14 (2), 212-7 Abstract
  • Deeg HJ, Storer BE, Boeckh M, Martin PJ, McCune JS, Myerson D, Heimfeld S, Flowers ME, Anasetti C, Doney KC, Hansen JA, Kiem HP, Nash RA, O'Donnell PV, Radich JP, Sandmaier BM, Scott BL, Sorror ML, Warren EH, Witherspoon RP, Woolfrey A, Appelbaum FR, Storb R (May 2006) Reduced incidence of acute and chronic graft-versus-host disease with the addition of thymoglobulin to a targeted busulfan/cyclophosphamide regimen., Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 12 (5), 573-84 Abstract
  • Deeg HJ, Storer BE, Boeckh M, Martin PJ, McCune JS, Myerson D, Heimfeld S, Flowers ME, Anasetti C, Doney KC, Hansen JA, Kiem HP, Nash RA, O'Donnell PV, Radich JP, Sandmaier BM, Scott BL, Sorror ML, Warren EH, Witherspoon RP, Woolfrey A, Appelbaum FR, Storb R (May 2006) Reduced incidence of acute and chronic graft-versus-host disease with the addition of thymoglobulin to a targeted busulfan/cyclophosphamide regimen., Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 12 (5), 573-84 Abstract
  • Zhang XB, Beard BC, Beebe K, Storer B, Humphries RK, Kiem HP (May 2006) Differential effects of HOXB4 on nonhuman primate short- and long-term repopulating cells., PLoS medicine, 3 (5), e173 Abstract
  • Placantonakis DG, Bukovsky AA, Aicher SA, Kiem HP, Welsh JP (May 2006) Continuous electrical oscillations emerge from a coupled network: a study of the inferior olive using lentiviral knockdown of connexin36., The Journal of neuroscience : the official journal of the Society for Neuroscience, 26 (19), 5008-16 Abstract
  • Neff, T., Beard, B.C., Kiem, H.P. (2006) Survival of the fittest: in vivo selection and stem cell gene therapy, Blood, 107 (5), 1751-60
  • Kurre, P., Anandakumar, P., Kiem, H.P. (2006) Rapid 1-hour transduction of whole bone marrow leads to long-term repopulation of murine recipients with lentivirus-modified hematopoietic stem cells., Gene Therapy, 13 (4), 369-73
  • Kurre P, Anandakumar P, Kiem HP (Feb 2006) Rapid 1-hour transduction of whole bone marrow leads to long-term repopulation of murine recipients with lentivirus-modified hematopoietic stem cells., Gene therapy, 13 (4), 369-73 Abstract
  • Trobridge, G.D., Miller, D.G., Jacobs, M.A., Allen, J.M., Kiem, H.P., Kaul, R., Russell, D.W. (2006) Foamy virus vector integration sites in normal human cells., PNAS, 103 (5), 1498-503
  • Trobridge GD, Miller DG, Jacobs MA, Allen JM, Kiem HP, Kaul R, Russell DW (Jan 2006) Foamy virus vector integration sites in normal human cells., Proceedings of the National Academy of Sciences of the United States of America, 103 (5), 1498-503 Abstract
  • Nash, R.A., Johnston, L., Parker, P., McCune, J.S., Storer, B., Slattery, J.T., Furlong, T., Anasetti, C., Appelbaum, F.R., Lloid, M.E., Deeg, H.J., Kiem, H.P., Martin, P.J., Schubert, M.M., Witherspoon, R.P., Forman, S.J., Blume, K.G., Storb, R. (2005) A phase I/II study of mycophenolate mofetil in combination with cyclosporine for prophylaxis of acute graft-versus-host disease after myeloablative conditioning and allogeneic hematopoietic cell transplantation, BBMT, 11 (7), 495-505
  • Zanis-Neto, J., Flowers, M.E.D., Medeiros, C.R., Bitencourt, M.A., Bonfirm, C.M., Setubal, D.C., Funke, V., Sanders, J., Deeg, H.J., Kiem, H.P., Martin, P., Leisenring, W., Storb, R., Pasquini, R. (2005) Low-dose cyclophosphamide conditioning for haematopoietic cell transplantation from HLA-matched related donors in patients with Fanconi anaemia, British Journal of Haematology, 130 (1), 99-106
  • Ni, S., Bernt, K., Gaggar, A., Li, Z.Y., Kiem, H.P., Lieber, A. (2005) Evaluation of biodistribution and safety of adenovirus vectors containing group B fibers after intravenous injection into baboons., Human Gene Therapy, 16 (6), 664-77
  • Beagles, K.E., Peterson, L, Zhang, X., Morris, J., Kiem, H.P. (2005) Cyclosporine inhibits the development of green fluorescent protein (GFP)-specific immune responses after transplantation of GFP-expressing hematopoietic repopulating cells in dogs., Human Gene Therapy, 16 (6), 725-33
  • Neff T, Beard BC, Peterson LJ, Anandakumar P, Thompson J, Kiem HP (Feb 2005) Polyclonal chemoprotection against temozolomide in a large-animal model of drug resistance gene therapy., Blood, 105 (3), 997-1002 Abstract
  • Keyser KA, Morris JC, Kiem HP (2005) Genetically modified CD34+ cells do not contribute to the mesenchymal compartment after autologous transplantation in the baboon., Cytotherapy, 7 (4), 345-52 Abstract
  • Lu H, Zhao Z, Kalina T, Gillespy T 3rd, Liggitt D, Andrews RG, Maloney DG, Kiem HP, Storek J (Jan 2005) Interleukin-7 improves reconstitution of antiviral CD4 T cells., Clinical Immunology (orlando, Fla.), 114 (1), 30-41 Abstract
  • Stewart BL, Storer B, Storek J, Deeg HJ, Storb R, Hansen JA, Appelbaum FR, Carpenter PA, Sanders JE, Kiem HP, Nash RA, Petersdorf EW, Moravec C, Morton AJ, Anasetti C, Flowers ME, Martin PJ (Dec 2004) Duration of immunosuppressive treatment for chronic graft-versus-host disease., Blood, 104 (12), 3501-6 Abstract
  • Platzbecker U, Kurre P, Guardiola P, Ward JL, Radich JP, Kiem HP, Deeg HJ, Fanconi anemia type C-deficient hematopoietic cells are resistant to TRAIL (TNF-related apoptosis-inducing ligand)-induced cleavage of pro-caspase-8, Experimental Hematology, 32(9), 815-21, Sep 2004 Abstract
  • Horn PA, Keyser KA, Peterson LJ, Neff T, Thomasson BM, Thompson J, Kiem HP, Efficient lentiviral gene transfer to canine repopulating cells using an overnight transduction protocol, Blood, 103(10), 3710-6, May 2004 Abstract
  • Placantonakis DG, Bukovsky AA, Zeng XH, Kiem HP, Welsh JP, Fundamental role of inferior olive connexin 36 in muscle coherence during tremor, Proceedings of the National Academy of Sciences of the United States of America., 101(18), 7164-9, May 2004 Abstract
  • Kalina, T, Lu, H, Zhao, Z, Blewitt, E, Dittmer, D.P., Randolph-Habecker, J, Maloney, D.G, Kiem, H.P., Storek, J (2004) De novo generation of CD4 T cells against viruses present in the host during immune reconstitution, Blood, 105 (6), 2410-4
  • Kiem HP, Sellers S, Thomasson B, Morris JC, Tisdale JF, Horn PA, Hematti P, Adler R, Kuramoto K, Calmels B, Bonifacino A, Hu J, von Kalle C, Schmidt M, Sorrentino B, Nienhuis A, Blau CA, Andrews RG, Donahue RE, Dunbar CE, Long-term clinical and molecular follow-up of large animals receiving retrovirally transduced stem and progenitor cells: no progression to clonal hematopoiesis or leukemia, Molecular Therapy : the Journal of the American Society of Gene Therapy, 9(3), 389-95, Mar 2004 Abstract
  • Morris JC, Conerly M, Thomasson B, Storek J, Riddell SR, Kiem HP, Induction of cytotoxic T-lymphocyte responses to enhanced green and yellow fluorescent proteins after myeloablative conditioning, Blood, 103(2), 492-9, Jan 2004 Abstract
  • Neff T, Peterson LJ, Morris JC, Thompson J, Zhang X, Horn PA, Thomasson BM, Kiem H-P, Efficient gene transfer to hematopoietic repopulating cells using concentrated RD114-pseudotype vectors produced by human packaging cells (Letter to the Editor), Molecular Therapy, 9, 157-159, 2004
  • Kurre P, Anandakumar P, Harkey MA, Thomasson B, Kiem H-P, Efficient marking of murine long-term repopulating stem cells targeting unseparated marrow cells at low lentiviral vector particle concentration, Molecular Therapy, 9, 914-922, 2004
  • Horn PA, Morris JC, Neff T, Kiem H-P, Stem cell gene transfer - efficacy and safety in large animals studies, Molecular Therapy, 10, 417-431, 2004
  • Walter RB, Raden BW, Thompson J, Flowers DA, Kiem H-P, Bernstein ID, Linenberger ML, Breast cancer resistance protein (BCRP/ABCG2) does not confer resistance to gemtuzumab ozogamicin and calicheamicin-gamma1 in acute myeloid leukemia cells (Letter to the Editor), Leukemia, 18, 1914-1917, 2004
  • Richard RE, De Claro RA, Yan J, Chien S, von Recum H, Morris J, Kiem H-P, Dalgarno DC, Heimfeld S, Clackson T, Andrews R, Blau CA, Differences in F36VMpl-based in vivo selection among large animal models, Molecular Therapy, 10, 730-740, 2004
  • Morris JC, Kiem H-P, Cytotoxic T-lymphocyte responses to enhanced green and yellow fluorescent proteins after myeloablative conditioning (Response), Blood, 104, 1579, 2004
  • Horn PA, Thomasson BM, Wood BL, Andrews RG, Morris JC, Kiem HP, Distinct hematopoietic stem/progenitor cell populations are responsible for repopulating NOD/SCID mice compared with nonhuman primates, Blood, 102(13), 4329-35, Dec 2003 Abstract
  • Deeg HJ, Gooley TA, Flowers ME, Sale GE, Slattery JT, Anasetti C, Chauncey TR, Doney K, Georges GE, Kiem HP, Martin PJ, Petersdorf EW, Radich J, Sanders JE, Sandmaier BM, Warren EH, Witherspoon RP, Storb R, Appelbaum FR, Allogeneic hematopoietic stem cell transplantation for myelofibrosis, Blood, 102(12), 3912-8, Dec 2003 Abstract
  • Neff T, Horn PA, Peterson LJ, Thomasson BM, Thompson J, Williams DA, Schmidt M, Georges GE, von Kalle C, Kiem HP, Methylguanine methyltransferase-mediated in vivo selection and chemoprotection of allogeneic stem cells in a large-animal model, Journal of Clinical Investigation, 112(10), 1581-8, Nov 2003 Abstract
  • Thomasson B, Peterson L, Thompson J, Goerner M, Kiem HP, Direct comparison of steady-state marrow, primed marrow, and mobilized peripheral blood for transduction of hematopoietic stem cells in dogs, Human Gene Therapy, 14(17), 1683-6, Nov 2003 Abstract
  • Tiede A, Eder M, von Depka M, Battmer K, Luther S, Kiem HP, Ganser A, Scherr M, Recombinant factor VIII expression in hematopoietic cells following lentiviral transduction, Gene Therapy, 10(22), 1917-25, Oct 2003 Abstract
  • Kohn DB, Sadelain M, Dunbar C, Bodine D, Kiem HP, Candotti F, Tisdale J, Riviere I, Blau CA, Richard RE, Sorrentino B, Nolta J, Malech H, Brenner M, Cornetta K, Cavagnaro J, High K, Glorioso J, American Society of Gene Therapy (ASGT), American Society of Gene Therapy (ASGT) ad hoc subcommittee on retroviral-mediated gene transfer to hematopoietic stem cells, Molecular Therapy : the Journal of the American Society of Gene Therapy, 8(2), 180-7, Aug 2003 Abstract
  • Kurre P, Pulsipher M, Woolfrey A, Maris M, Sandmaier B, Kiem HP, Storb R, Reduced toxicity and prompt engraftment after minimal conditioning of a patient with Fanconi anemia undergoing hematopoietic stem cell transplantation from an HLA-matched unrelated donor, Journal of Pediatric Hematology/oncology : Official Journal of the American Society of Pediatric Hematology/oncology., 25(7), 581-3, Jul 2003 Abstract
  • Storek J, Gillespy III T, Lu H, Joseph A, Dawson MA, Gough M, Morris J, Hackman RC, Horn PA, Sale GE, Andrews RG, Maloney DG, Kiem H-P, Interleukin-7 improves CD4 T cell reconstitution after autologous CD34 cell transplantation in monkeys, Blood, 101, 4209-4218, 2003
  • Schmidt M, Glimm H, Wissler M, Hoffmann G, Olsson K, Sellers S, Carbonaro D, Tisdale JF, Leurs C, Hanenberg H, Dunbar CE, Kiem H-P, Karlsson S, Kohn DB, Williams D, Von Kalle C, Efficient characterization of retro-, lenti-, and foamyvector-transduced cell populations by high-accuracy insertion site sequencing, Ann NY Acad Sci, 996, 112-121, 2003
  • Horn PA, Thomasson BM, Wood BL, Andrews RG, Morris JC, Kiem H-P, Distinct hematopoietic stem/progenitor cell populations are responsible for repopulating NOD/SCID mice versus nonhuman primates, Blood, 102, 4329-4335, 2003
  • Kurre P, Morris J, Thomasson B, Kohn DB, Kiem H-P, Scaffold attachment region containing retrovirus vectors improve long-term proviral expression after transplantation of GFP-modified CD34+ baboon repopulating cells, Blood, 102, 3117-3119, 2003
  • Tiede A, Eder M, von Depka M, Battmer K, Luther S, Kiem H-P, Ganser A, Scherr M, Recombinant factor VIII expression in CD34+ and mature hematopoietic cells following lentiviral transduction, Gene Therapy, 10, 1917-1925, 2003
  • Kiem H-P, Anasetti C, Sirolimus and tacrolimus binding proteins: double-edged swords for GVHD prophylaxis, Blood, 102, 1562, 2003
  • Horn PA, Topp MS, Morris JC, Riddell SR, Kiem HP, Highly efficient gene transfer into baboon marrow repopulating cells using GALV-pseudotype oncoretroviral vectors produced by human packaging cells, Blood, 100(12), 3960-7, December 2002 Abstract
  • Horn PA, Morris JC, Bukovsky AA, Andrews RG, Naldini L, Kurre P, Kiem HP, Lentivirus-mediated gene transfer into hematopoietic repopulating cells in baboons, Gene Therapy, 9(21), 1464-71, November 2002 Abstract
  • Horn PA, Morris JC, Bukovsky AA, Andrews RG, Naldini L, Kurre P, Kiem HP (Nov 2002) Lentivirus-mediated gene transfer into hematopoietic repopulating cells in baboons., Gene therapy, 9 (21), 1464-71 Abstract
  • Horn PA, Morris JC, Bukovsky AA, Andrews RG, Naldini L, Kurre P, Kiem HP (Nov 2002) Lentivirus-mediated gene transfer into hematopoietic repopulating cells in baboons., Gene therapy, 9 (21), 1464-71 Abstract
  • Schmidt M, Zickler P, Hoffmann G, Haas S, Wissler M, Muessig A, Tisdale JF, Kuramoto K, Andrews RG, Wu T, Kiem HP, Dunbar CE, von Kalle C, Polyclonal long-term repopulating stem cell clones in a primate model, Blood, 100(8), 2737-43, Oct 2002 Abstract
  • Neff T, Horn PA, Valli VE, Gown AM, Wardwell S, Wood BL, von Kalle C, Schmidt M, Peterson LJ, Morris JC, Richard RE, Clackson T, Kiem HP, Blau CA, Pharmacologically regulated in vivo selection in a large animal, Blood, 100(6), 2026-31, September 2002 Abstract
  • Deeg HJ, Storer B, Slattery JT, Anasetti C, Doney KC, Hansen JA, Kiem HP, Martin PJ, Petersdorf E, Radich JP, Sanders JE, Shulman HM, Warren EH, Witherspoon RP, Bryant EM, Chauncey TR, Getzendaner L, Storb R, Appelbaum FR, Conditioning with targeted busulfan and cyclophosphamide for hemopoietic stem cell transplantation from related and unrelated donors in patients with myelodysplastic syndrome, Blood, 100(4), 1201-7, Aug 2002 Abstract
  • Kondo E, Topp MS, Kiem HP, Obata Y, Morishima Y, Kuzushima K, Tanimoto M, Harada M, Takahashi T, Akatsuka Y, Efficient generation of antigen-specific cytotoxic T cells using retrovirally transduced CD40-activated B cells, Journal of Immunology (baltimore, Md. : 1950), 169(4), 2164-71, Aug 2002 Abstract
  • Goerner M, Gooley T, Flowers MED, Sullivan KM, Kiem H-P, Sanders JE, Martin PJ, Storb R, Morbidity and mortality of chronic GVHD after hematopoietic stem cell transplantation from HLA-identical siblings for patients with aplastic or refractory anemias, Biology of Blood and Marrow Transplantation, 8, 47-56, 2002
  • Furlong T, Leisenring W, Storb R, Anasetti C, Appelbaum FR, Carpenter PA, Deeg HJ, Doney K, Kiem H-P, Nash RA, Sanders JE, Witherspoon R, Thompson D, Martin PJ, Psoralen and ultraviolet A irradiation (PUVA) as therapy for steroid-resistant cutaneous acute graft-versus-host disease, Biology of Blood and Marrow Transplantation, 8, 206-212, 2002
  • Kurre P, Morris J, Andrews RG, Kohn DB, Kiem H-P, Kinetics of fluorescence expression in nonhuman primates transplanted with GFP retrovirus-modified CD34 cells, Molecular Therapy, 6, 83-90, 2002
  • Kiem H-P, Rasko JE, Morris J, Peterson L, Kurre P, Andrews RG, Ex Vivo selection for oncoretrovirally transduced green fluorescent protein-expressing CD34-enriched cells increases short-term engraftment of transduced cells in baboons, Human Gene Therapy, 13, 891-899, 2002
  • Kurre P, Anandakumar P, Grompe M, Kiem, H-P, In vivo administration of interferon gamma does not cause marrow aplasia in mice with targeted disruption of FANCC, Experimental Hematology, 30, 1257-1262, 2002
  • Georges GE, Storb R, Bruno B, Brodie SJ, Thompson JD, Taranova AG, Zaucha JM, Little MT, Zellmer E, Moore PF, Gooley T, Sale G, Kiem HP, Sandmaier BM, Lyons RM, Nash RA, Engraftment of DLA-haploidentical marrow with ex vivo expanded, retrovirally transduced cytotoxic T lymphocytes, Blood, 98(12), 3447-55, December 2001 Abstract
  • Goerner M, Horn PA, Peterson L, Kurre P, Storb R, Rasko JE, Kiem HP, Sustained multilineage gene persistence and expression in dogs transplanted with CD34(+) marrow cells transduced by RD114-pseudotype oncoretrovirus vectors, Blood, 98(7), 2065-70, October 2001 Abstract
  • Kurre P, Morris J, Horn PA, Harkey MA, Andrews RG, Kiem HP, Gene transfer into baboon repopulating cells: A comparison of Flt-3 Ligand and megakaryocyte growth and development factor versus IL-3 during ex vivo transduction, Molecular Therapy : the Journal of the American Society of Gene Therapy, 3(6), 920-7, June 2001 Abstract
  • Feinstein L, Sandmaier B, Maloney D, McSweeney PA, Maris M, Flowers C, Radich J, Little MT, Nash RA, Chauncey T, Woolfrey A, Georges G, Kiem HP, Zaucha JM, Blume KG, Shizuru J, Niederwieser D, Storb R, Nonmyeloablative hematopoietic cell transplantation. Replacing high-dose cytotoxic therapy by the graft-versus-tumor effect, Annals of the New York Academy of Sciences, 938, 328-339; discussion, 01 Jun 2001 Abstract
  • McSweeney PA, Niederwieser D, Shizuru JA, Sandmaier BM, Molina AJ, Maloney DG, Chauncey TR, Gooley TA, Hegenbart U, Nash RA, Radich J, Wagner JL, Minor S, Appelbaum FR, Bensinger WI, Bryant E, Flowers ME, Georges GE, Grumet FC, Kiem HP, et al., Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects, Blood, 97(11), 3390-400, June 2001 Abstract
  • Kurre P, Morris J, Miller AD, Kiem HP, Envelope fusion protein binding studies in an inducible model of retrovirus receptor expression and in CD34( ) cells emphasize limited transduction at low receptor levels, Gene Therapy, 8(8), 593-9, April 2001 Abstract
  • Berger C, Huang ML, Gough M, Greenberg PD, Riddell SR, Kiem HP, Nonmyeloablative immunosuppressive regimen prolongs In vivo persistence of gene-modified autologous T cells in a nonhuman primate model, Journal of Virology, 75(2), 799-808, Jan 2001 Abstract
  • Zaucha JA, Yu C, Lothrop CD Jr, Nash RA, Sale G, Georges G, Kiem HP, Niemeyer GP, Dufresne M, Cao Q, Storb R, Severe canine hereditary hemolytic anemia treated by nonmyeloablative marrow transplantation, Biology of Blood and Marrow Transplantation, 7(1), 14-24, 2001 Abstract
  • Purton LE, Morris JC, Bernstein ID, Collins SJ, Kiem H-P, All-trans retinoic acid facilitates oncoretrovirus-mediated transduction of hematopoietic repopulating stem cells, Journal of Hematotherapy and Stem Cell Research, 10, 815-825, 2001
  • Bruno B, Goerner M, Nash RA, Storb R, Kiem HP, McSweeney PA, Purififed canine CD34+ Lin- marrow cells transduced with retroviral vectors give rise to long-term multi-lineage hematopoiesis, Biology of Blood and Marrow Transplantation, 7, 543-551, 2001
  • Goerner M, Roecklein B, Torok-Storb B, Heimfeld S, Kiem HP, Expansion and transduction of nonenriched human cord blood cells using HS-5 conditioned medium and FLT3-L, Journal of Hematotherapy and Stem Cell Research, 9(5), 759-65, October 2000 Abstract
  • Shields LE, Kiem HP, Andrews RG, Highly efficient gene transfer into preterm CD34 hematopoietic progenitor cells, American Journal of Obstetrics and Gynecology, 183(3), 732-7, September 2000 Abstract
  • Kurre P, Kiem HP, Progress towards hematopoietic stem cell gene therapy, 2(4), 400-11, August 2000 Abstract
  • Andrews RG, Peterson LJ, Morris J, Potter J, Heyward S, Gough M, Bryant E, Kiem H, Differential engraftment of genetically modified CD34( ) and CD34(-) hematopoietic cell subsets in lethally irradiated baboons, Experimental Hematology, 28(5), 508-18, May 2000 Abstract
  • Berger C, Xuereb S, Johnson DC, Watanabe KS, Kiem HP, Greenberg PD, Riddell SR, Expression of herpes simplex virus ICP47 and human cytomegalovirus US11 prevents recognition of transgene products by CD8( ) cytotoxic T lymphocytes, Journal of Virology, 74(10), 4465-73, May 2000 Abstract
  • Goerner M, Bruno B, McSweeney PA, Buron G, Storb R, Kiem HP, The use of granulocyte colony-stimulating factor during retroviral transduction on fibronectin fragment CH-296 enhances gene transfer into hematopoietic repopulating cells in dogs, Blood, 94(7), 2287-92, 1999 Abstract
  • Storb R, Yu C, Zaucha JM, Deeg HJ, Georges G, Kiem HP, Nash RA, McSweeney PA, Wagner JL, Stable mixed hematopoietic chimerism in dogs given donor antigen, CTLA4Ig, and 100 cGy total body irradiation before and pharmacologic immunosuppression after marrow transplant, Blood, 94(7), 2523-9, 1999 Abstract
  • Storb R, Yu C, Barnett T, Wagner JL, Deeg HJ, Nash RA, Kiem HP, McSweeney P, Seidel K, Georges G, Zaucha JM, Stable mixed hematopoietic chimerism in dog leukocyte antigen-identical littermate dogs given lymph node irradiation before and pharmacologic immunosuppression after marrow transplantation, Blood, 94(3), 1131-6, 1999 Abstract
  • Kiem HP, McSweeney PA, Bruno B, Goerner M, Buron G, Morris J, Storb R, Miller AD, Improved gene transfer into canine hematopoietic repopulating cells using CD34-enriched marrow cells in combination with a gibbon ape leukemia virus-pseudotype retroviral vector, Gene Therapy, 6(6), 966-72, June 1999 Abstract
  • Winkler A, Kiem HP, Shields LE, Sun QH, Andrews RG, Gene transfer into fetal baboon hematopoietic progenitor cells, Human Gene Therapy, 10(4), 667-77, 1999 Abstract
  • Kurre P, Kiem HP, Morris J, Heyward S, Battini JL, Miller AD, Efficient transduction by an amphotropic retrovirus vector is dependent on high-level expression of the cell surface virus receptor, Journal of Virology, 73(1), 495-500, Jan 1999 Abstract
  • Kiem HP, Andrews RG, Morris J, Peterson L, Heyward S, Allen JM, Rasko JE, Potter J, Miller AD, Improved gene transfer into baboon marrow repopulating cells using recombinant human fibronectin fragment CH-296 in combination with interleukin-6, stem cell factor, FLT-3 ligand, and megakaryocyte gr, Blood, 92(6), 1878-86, 1998 Abstract
  • Georges GE, Storb R, Brunvand MW, Kiem HP, Moore PF, Malik P, Ennist D, Nash RA, Canine T cells transduced with a herpes simplex virus thymidine kinase gene: a model to study effects on engraftment and control of graft-versus-host disease, Transplantation, 66(4), 540-4, 1998 Abstract
  • Storb R, Yu C, Deeg HJ, Georges G, Kiem HP, Mcsweeney PA, Nash RA, Sandmaier BM, Sullivan KM, Wagner JL, Walters MC, Current and future preparative regimens for bone marrow transplantation in thalassemia, Annals of the New York Academy of Sciences, 850, 276-87, 1998 Abstract
  • Glimm H, Flugge K, Mobest D, Hofmann VM, Postmus J, Henschler R, Lange W, Finke J, Kiem HP, Schulz G, Rosenthal F, Mertelsmann R, von Kalle C, Efficient serum-free retroviral gene transfer into primitive human hematopoietic progenitor cells by a defined, high-titer, nonconcentrated vector-containing medium, Human Gene Therapy, 9(6), 771-8, 1998 Abstract
  • Kiem HP, Heyward S, Winkler A, Potter J, Allen JM, Miller AD, Andrews RG, Gene transfer into marrow repopulating cells: comparison between amphotropic and gibbon ape leukemia virus pseudotyped retroviral vectors in a competitive repopulation assay in baboons, Blood, 90(11), 4638-45, 1997 Abstract
  • Glimm H, Kiem HP, Darovsky B, Storb R, Wolf J, Diehl V, Mertelsmann R, Von Kalle C, Efficient gene transfer in primitive CD34 /CD38lo human bone marrow cells reselected after long-term exposure to GALV-pseudotyped retroviral vector, Human Gene Therapy, 8(17), 2079-86, 1997 Abstract
  • Schuening F, Longo WL, Atkinson ME, Zaboikin M, Kiem HP, Sanders J, Scott CR, Storb R, Miller AD, Reynolds T, Bensinger W, Rowley S, Gooley T, Darovsky B, Appelbaum F, Retrovirus-mediated transfer of the cDNA for human glucocerebrosidase into peripheral blood repopulating cells of patients with Gaucher's disease, Human Gene Therapy, 8(17), 2143-60, 1997 Abstract
  • Schuening FG, von Kalle C, Kiem HP, Appelbaum FR, Deeg HJ, Pepe M, Gooley T, Graham TC, Hackman RC, Storb R, Effect of recombinant canine stem cell factor, a c-kit ligand, on hematopoietic recovery after DLA-identical littermate marrow transplants in dogs, Experimental Hematology, 25(12), 1240-5, November 1997 Abstract
  • Dybing J, Lynch CM, Hara P, Jurus L, Kiem HP, Anklesaria P, GaLV pseudotyped vectors and cationic lipids transduce human CD34 cells, Human Gene Therapy, 8(14), 1685-94, 1997 Abstract
  • Kiem HP, Storb R, McDonald GB, Hepatitis-associated aplastic anemia, New England Journal of Medicine, 337(6), 424-5, 1997 Abstract
  • Kiem HP, Myerson D, Storb R, McDonald GB, Spurgeon CL, Leisenring W, Prevalence of hepatitis G virus in patients with aplastic anemia, Blood, 90(3), 1335-6, 1997 Abstract
  • Storb R, Yu C, Wagner JL, Deeg HJ, Nash RA, Kiem HP, Leisenring W, Shulman H, Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation, Blood, 89(8), 3048-54, 1997 Abstract
  • Czerwinski M, Kiem HP, Slattery JT, Human CD34 cells do not express glutathione S-transferases alpha, Gene Therapy, 4(3), 268-70, March 1997 Abstract
  • Kiem HP, Leisenring W, Raff R, Deeg HJ, Schuening FG, Appelbaum FR, Storb R, Failure of recombinant stem cell factor to enhance engraftment of L-leucyl-L-leucine methyl ester treated canine marrow after irradiation, Blood, 88(5), 1896-7, 1996 Abstract
  • Shull R, Lu X, Dube I, Lutzko C, Kruth S, Abrams-Ogg A, Kiem HP, Goehle S, Schuening F, Millan C, Carter R, Humoral immune response limits gene therapy in canine MPS I, Blood, 88(1), 377-9, 1996 Abstract
  • Kiem HP, McDonald GB, Myerson D, Spurgeon CL, Deeg HJ, Sanders JE, Doney K, Appelbaum FR, Sullivan KM, Witherspoon RP, Storb R, Marrow transplantation for hepatitis-associated aplastic anemia: a follow-up of long-term survivors, Biology of Blood and Marrow Transplantation, 2(2), 93-9, May 1996 Abstract
  • Miller AD, Bonham L, Alfano J, Kiem HP, Reynolds T, Wolgamot G, A novel murine retrovirus identified during testing for helper virus in human gene transfer trials, Journal of Virology, 70(3), 1804-9, March 1996 Abstract
  • Kiem HP, Darovsky B, Von Kalle C, Goehle S, Graham T, Miller AD, Storb R, Schuening FG, Long-term persistence of canine hematopoietic cells genetically marked by retrovirus vectors, Human Gene Therapy, 7(1), 89-96, January 1996 Abstract
  • Wagner LA, Kiem HP, McSweeney P, Schuening FG, Storb R, Ostrander EA, Development of a clonality assay for canine hematopoietic stem cells, Blood, 86(8), 3265-7, 1995 Abstract
  • Kiem HP, von Kalle C, Schuening F, Storb R, Gene therapy and bone marrow transplantation, Current Opinion in Oncology, 7(2), 107-14, March 1995 Abstract
  • Barquinero J, Kiem HP, von Kalle C, Darovsky B, Goehle S, Graham T, Seidel K, Storb R, Schuening FG, Myelosuppressive conditioning improves autologous engraftment of genetically marked hematopoietic repopulating cells in dogs, Blood, 85(5), 1195-201, 1995 Abstract
  • von Kalle C, Kiem HP, Goehle S, Darovsky B, Heimfeld S, Torok-Storb B, Storb R, Schuening FG, Increased gene transfer into human hematopoietic progenitor cells by extended in vitro exposure to a pseudotyped retroviral vector, Blood, 84(9), 2890-7, 1994 Abstract
  • Kiem HP, Darovsky B, von Kalle C, Goehle S, Stewart D, Graham T, Hackman R, Appelbaum FR, Deeg HJ, Miller AD, Retrovirus-mediated gene transduction into canine peripheral blood repopulating cells, Blood, 83(6), 1467-73, 1994 Abstract
  • Schmidt-Wolf IG, Negrin RS, Kiem HP, Blume KG, Weissman IL, Use of a SCID mouse/human lymphoma model to evaluate cytokine-induced killer cells with potent antitumor cell activity, Journal of Experimental Medicine, 174(1), 139-49, 1991 Abstract
  • Negrin RS, Kiem HP, Schmidt-Wolf IG, Blume KG, Cleary ML, Use of the polymerase chain reaction to monitor the effectiveness of ex vivo tumor cell purging, Blood, 77(3), 654-60, 1991 Abstract
  • Kiem HP, Nourse J, Saltman DL, Blume KG, Cleary ML, Concurrent activation of c-myc and inactivation of bcl-2 by chromosomal translocation in a lymphoblastic lymphoma cell line, Oncogene, 5(12), 1815-9, December 1990 Abstract

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