Seattle Children's Research Institute

Hans-Peter Kiem, MD, DrMed

NGEC Principal Investigator

Full Member, Clinical Research Division, Fred Hutchinson Cancer Research Center
Investigator, Markey Molecular Medicine Center, University of Washington
Associate Professor, University of Washington School of Medicine
Adjunct Associate Professor of Pathology, University of Washington School of Medicine

Fred Hutchinson Cancer Research Center
1100 Fairview Ave. N., D1-100
PO Box 19024
Seattle, WA 98109-1024
Tel: (206) 667- 4425 Fax: (206) 667-6124
E-mail Dr. Kiem

Dr. Kiem received his DrMed summa cum laude and MD from the University of Ulm in Germany. He did postdoctoral work at Stanford University and his internship and residency at Vanderbilt University as part of the Physician Scientist Track. He then completed an oncology fellowship at the University of Washington and the Fred Hutchinson Cancer Research Center.

Dr. Kiem is the principal investigator for the NGEC in the area of Gene Repair in Canine Immunodeficiency Models.

Awards and honors

  • Fellowship from the Deutsche Krebshilfe (German Cancer Aid): 1988
  • Markey Charitable Trust Award: 1995
  • Editorial Board Memberships: Blood (2002 - present); Molecular Therapy (2003 - present); Gene Therapy (2003 - present)
  • Member, Immunology and Hematopoietic Cell Gene Therapy Committee, American Society of Gene Therapy: 2003 - 2006
  • Chair, Gene Therapy Subcommittee, International Society for Cellular Therapy: 2004
  • Member, Developmental Therapeutics Study Section: 2004 - present
  • Member, American Society of Clinical Investigation: 2005 - present
Hans-Peter Kiem, MD, DrMed “The NGEC provides a unique opportunity to study homing endonuclease-based hematopoietic stem cell gene-repair strategies in a clinically relevant animal model.”
Hans-Peter Kiem, MD, DrMed

Areas of expertise

  • Stem cell biology/transplantation
  • Gene therapy
  • Vector development

Current research interests

  • Characterize HSCs from large animal models
  • Analyze the clonal composition of hematopoiesis after transplantation of gene-modified HSCs
  • Develop novel vector systems for improved gene delivery
  • Study retroviral integration sites and insertional mutaganesis
  • Stem cell expansion and cord blood transplantation
  • Nonhuman primate embryonic stem cells
  • Develop pre-clinical protocols using stem cell gene therapy to facilitate allogeneic nonmyeloablative stem cell transplantation
  • Develop clinical gene therapy protocols for brain tumors, Fanconi anemia and AIDS

NGEC research

Dr. Kiem and his team will initiate studies of LHE-based gene modification in canine hematopoietic stem cells as an initial step towards translation of gene repair of hematopoietic cells to humans. These studies will involve the following specific aims:

  1. The Kiem lab will evaluate initial and stable genomic marking at endogenous and artificial reporter loci in canine hematopoietic stem cells using NIL lentiviral vectors expressing available LHEs.
  2. Using marking conditions established in Aim #1, the Kiem lab will evaluate non-myeloablative conditioning regimens and a “knock in” approach with an in vivo selectable marker system.
  3. Using the methods developed in the above aims, the Kiem lab will pilot gene repair of the naturally-arising canine lymphohematopoietic diseases XSCID and PK deficiency. These studies will involve generation via the NGEC Cell and Virus CORE of appropriate NIL vectors expressing LHEs (designed in Aim #1) which cut at the XSCID and PK loci, followed by use of these vectors for stem cell transduction, and evaluation of the efficacy of correction of the canine XSCID and PK disease phenotypes.

Key lab personnel assisting this work include:

  • Grant Trobridge, PhD, investigator, will assist Dr. Kiem with the overall experimental design and analysis of data, and the testing of the LHE constructs. Dr. Trobridge has extensive experience in molecular virology and gene transfer, including the development of novel retroviral vectors.
  • Nina Munoz, MD, postdoctoral fellow, will work with Dr. Kiem on constructing and testing reporters and non-integrating lentiviruses.
  • Brian Beard, PhD, research associate, will assist in the design and construction of non-integrating lentiviruses.
  • George Sale, MD, investigator, will be involved in histological evaluation of canine tissues.
  • Mark Carter, PhD, research associate, will contribute molecular biology expertise toward the molecular analyses after transplantation of LHE-modified CD34+ cells.
Nina Muñoz, postdoctoral fellow in Hans-Peter Kiem’s lab Nina Muñoz, postdoctoral fellow in Hans-Peter Kiem’s lab

Overview of the Kiem lab

The main focus of the Kiem laboratory is to study stem cell biology and stem cell gene transfer with the goal of developing novel stem cell based treatment strategies for patients with genetic, infectious and malignant diseases.

Selected publications

Horn PA, Morris JC, Bukovsky AA, Andrews RG, Naldini L, Kurre P, Kiem H-P. Lentivirus-mediated gene transfer into hematopoietic repopulating cells in baboons. Gene Ther. 9:1464-1471, 2002.

Neff T, Horn PA, Peterson LJ, Thomasson BM, Thompson J, Williams DA, Schmidt M, Georges GE, Von Kalle C, Kiem H-P. Methylguanine methyltransferase-mediated in vivo selection and chemoprotection of allogeneic stem cells in a large animal model. Journal of Clinical Investigation 112: 1581-1588, 2003.

Horn PA, Keyser KA, Peterson LJ, Neff T, Thomasson BM, Thompson J, Kiem H-P. Efficient lentiviral gene transfer to canine repopulating cells using an overnight transduction protocol. Blood 103: 3710-3716, 2004.

Horn PA, Morris JC, Neff T, Kiem H-P. Stem cell transfer – efficacy and safety in large animal studies. Molecular Therapy 10: 417-431, 2004.

Neff T, Beard BC, Peterson LJ, Anandakumar P, Thompson J, Kiem, H-P. Polyclonal chemoprotection against temozolomide in a large animal model of drug resistance gene therapy. Blood 105: 997-1002, 2005.

Neff,T., Beard,B.C., Kiem,H.-P. Survival of the fittest: in vivo selection and stem cell gene therapy (Review). Blood 107: 1751-1760, 2006.

Trobridge,G.D., Miller,D.G., Jacobs,M.A., Allen,J.M., Kiem,H.-P., Kaul,R., Russell,D.W. Foamy virus vector integration sites in normal human cells. PNAS 103: 1498-1503, 2006.

Zhang XB, Beard BC, Beebe K, Storer B, Humphries RK, Kiem HP. Differential effects of HOXB4 on nonhuman primate short- and long-term repopulating cells. PLoS Med. 2006 May;3(5):e173. Epub 2006 May 2.

Neff,T., Gerull,S., Peterson,L.J., Kiem,H.-P. Improved short-term engraftment of lentivirally versus gammaretrovirally transduced allogeneic canine repopulating cells. J Gene Med. 2007 May;9(5):357-61.

Kiem,H.-P., Allen,J., Trobridge,G., Olson,E., Keyser,K., Peterson,L., Russell, D.W. Foamy virus-mediated gene transfer to canine repopulating cells. Blood. 2007 Jan 1;109(1):65-70. Epub 2006 Sep 12.

Gerull S, Beard BC, Peterson LJ, Neff T, Kiem H-P. In vivo selection and chemoprotection after drug resistance gene therapy in a nonmyeloablative allogeneic transplantation setting in dogs. Hum Gene Ther. 2007 May;18(5):451-6