Paul Orchard, M.D.

Associate Professor of Pediatrics
Medical Director, Inherited Metabolic and Storage Disease Bone Marrow Transplantation Program
Mayo Mail Code 366
420 Delaware St. SE
Minneapolis, MN 55455
Phone: (612) 626-2961
Fax: (612) 626-4074
orcha001@umn.edu
Preferred method of contact:  Phone

Dr. Orchard is an Associate Professor of Pediatrics in the Division of Hematology-Oncology and Blood and Marrow Transplantation. He is the Medical Director of the Inherited Metabolic and Storage Disease Bone Marrow Transplantation Program.

Dr. Orchard received his M.D. degree from the Brown University Program in Medicine in 1984, and completed his training in Pediatrics at the University of Wisconsin in Madison in 1987. He did his fellowship training in Hematology-Oncology and Bone Marrow Transplantation in Minnesota, and joined the faculty at the University of Minnesota in 1990. He is board certified in Pediatrics and Hematology/Oncology.

Dr. Orchard has been interested 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 focus has been gene therapy approaches in association with transplantation or other cellular therapies. 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. Additional activities include a role as co-chair of the Institutional Review Board of the National Marrow Donor Program (NMDP) and participation in the University of Minnesota Data and Safety Monitoring Council (DSMC), the Children's Oncology Group and the Pediatric Blood and Marrow Transplantation Consortium.

Dr. Orchard has published over 50 research manuscripts in medical journals, including: New England Journal of Medicine, Blood, Bone Marrow Transplantation, Journal of Bone and Mineral Research and Nature Genetics.

• 1982 CIBA Award Winner for Medical Student Community Service
• 1984 Sigma Xi, Scientific Research Society, Brown University School of Medicine
• 1987-88 American Cancer Society Clinical Fellowship Award
• 1987 Elected Outstanding Pediatric Resident, Univ. of Wisconsin Medical Students
• 1988 Elected Outstanding Fellow, University of Minnesota Residents
• 1990 Third Place Award, Pediatric Fellow Research Symposium
• 1993-96 Recipient, American Cancer Society Career Development Award
• 1994-96 Recipient, Irvine McQuarrie Research Scholar Award
• 1994-95 Recipient, Jundt Research Award
• 1998-00 Recipient, Amy Strelzer-Manasevit Scholar's Award (1 of 2 National Awards)

1. Hematopoietic Cell Transplantation of Genetic Disorders
• Transplant related toxicity and graft failure
• Use of reduced intensity preparative regimens
• Risk factors affecting outcomes following transplantation
2. Osteopetrosis
• Biology and genetics of osteopetrosis
• Correlations of clinical and genetic parameters to outcome and prognosis
• Hematopoietic transplantation and other therapies
3. Gene Therapy
• T cell engineering with "suicide genes" for transplantation
• Infusions of mismatched T cells with following genetic manipulation
• Treatment of genetic and metabolic diseases with gene therapy
4. Development of Alternative Cellular Therapy
• Use of mesenchymal stem cells for genetic diseases
• Infusions of immunologically active cell populations

Selected Recent Publications

Huang X, Wilber AC, Bao L, Tuong D, Tolar J, Orchard PJ, Levine BL, June CH, McIvor RS, Blazar BR, Zhou X.  Stable Gene Transfer and Expression in Human Primary T-Cells by the Sleeping Beauty Transposon System.  Blood 107:483-491, 2006.

Fraser C, Charnas L, Orchard P.  Central Pontine Myelinolysis Following Bone Marrow Transplantation Complicated by Severe Hepatic Veno-occlusive Disease.  Bone Marrow Transplantation 36:733-744, 2005.

McKenna DH, Kadidlo DM, Miller JS, Orchard PJ, Wagner JE, McCullough J.  The Minnesota Molecular and Cellular Therapeutics Facility: A State-of-the-Art Biotherapeutics Engineering Laboratory.  Transfus Med Rev. 19:217-228, 2005.

Laudi N, Arora M, Burns LJ, Miller JS, McGlave PB, Barker JN, Ramsay NK, Orchard PJ, MacMillan ML, Weisdorf DJ.  Long-term Follow-up After Autologous Hematopoietic Stem Cell Transplantation for Low-grade Non-Hodgkin Lymphoma.  Biology of Blood and Marrow Transplantation 11:129-135, 2005.

 Steward CG, Blair A, Moppett J, Clarke E, Virgo P, Lankester A, Burger SR, Sauer MG, Flanagan AM, Pamphilon DH, Orchard PJ.  High Peripheral Blood Progenitor Cell Counts Enable Autologous Backup Before Stem Cell Transplantation for Malignant Infantile Osteopetrosis.  Biology of Blood and Marrow Transplantation 11:115-121, 2005.

Miller JS, Soignier Y, Panoskaltsis-Mortari A, McNearney SA, Yun GH, Fautsch SK, McKenna D, Le C, De For TE, Burns LJ, Orchard PJ, Blazar BR, Wagner JE, Slungaard A, Weisdorf DJ, Okazaki IJ, McGlave PB.  Successful Adoptive Transfer and In Vivo Expansion of Human Haploidentical NK Cells in Patients with Cancer.  Blood 105:3051-7, 2005.

Grewal SS, Shapiro EG, Krivit W, Charnas L, Lockman LA, Delaney KA, Davies SM, Wenger DA, Rimell FL, Abel S, Grovas AC, Orchard PJ, Wagner JE, Peters C.  Effective Treatment of Alpha-Mannosidosis by Allogeneic Hematopoietic Stem Cell Transplantation.  Journal of Pediatrics 144:569-573, May 2004.

Steward CG, Blair A, Moppett J, Clarke E, Virgo P, Lankester A, Burger SR, Flanagan AM, Pamphilon D, Orchard P. High Peripheral Blood Progenitor Cell Counts Enable Autologous Back-up Before Stem Cell Transplantation for Malignant Infantile Osteopetrosis. Biology of Blood and Marrow Transplantation. 11: 115-21 2004

Tolar J, Teitelbaum S, Orchard PJ. Molecular Etiology of Human Osteopetrosis. New England Journal of Medicine. 351: 2839-49 2004.

Orchard P, Whyte M, Eapen M, Kasow K, Tolar J, Yang S, Mundy G, Key L. Proceedings of the First International Symposium on Osteopetrosis. Journal of Bone and Mineral Research 19:1356-1375, 2004.

Susani L, Pangrazio A, Sobacchi C, Taranta A, Mortier G, Savariravan R, Villa A, Orchard P, Vezzoni P, Albertini A, Frattini A, Pagani F. TCIRG1-Dependent Recessive Osteopetrosis: Mutation Analysis, Functional Identification of the Splicing Defects and in vitro Rescue by U1 snRNA. Human Mutation 24:225-235, Sep. 2004.

Blair HC, Borysenko CW, Villa A, Schlesinger PH, Kalla SE, Yaroslavskiy BB, Garcia-Palacios V, Oakley JI, Orchard PJ. In Vitro Differentiation of CD14 Cells from Osteopetrotic Subjects: Contrasting Phenotypes with TCIRG1, CLCN7, and Attachment Defects. Journal of Bone and Mineral Research 19(8):1329-1338, Aug. 2004.

Peters C, Charnas LR, Tan Y, Ziegler RS, Shapiro EG, DeFor T, Grewal SS, Orchard PJ, Abel SL, Goldman AI, Ramsay NKC, Dusenbery KE, Loes DJ, Lockman LA, Kato S, Aubourg PR, Moser HW, Krivit W. Cerebral X-linked Adrenoleukodystrophy: The International Hematopoietic Cell Transplantation Experience from 1982 to 1999. Prepublished online April 8, 2004; DOI 10.1182/Blood-2003-10-3402.

Frattini A, Pangrazio A, Susani L, Sobacchi C, Mirolo M, Abinun M, Andolina M, Flanagan A, Horwitz EM, Mihci E, Notarangelo LD, Ramenghi U, Teti A, Van Hove J, Vujic D, Young T, Albertini A, Orchard PJ, Vezzoni P, Villa A. Chloride Channel CICN7 Mutations are Responsible for Severe Recessive, Dominant, and Intermediate Osteopetrosis. Journal of Bone and Mineral Research 18(10):1740-1747, November 10, 2003.

Lewis VA, Basso L, Blake N, Salo J, Lund TC, McIvor RS, Orchard PJ. Human Nerve Growth Factor Receptor and Cytosine Deaminase Fusion Genes. Human Gene Therapy 14:1009-1016, 2003.

Burger SR, Kadidlo DM, Basso L, Bostrom N, Orchard PJ. Cellular Engineering of HSV-tk Transduced, Expanded T Lymphocytes for Graft-versus-Host Disease Management. Acta Haematologica 110(2-3):121-131, 2003.

Grewal SS, Krivit W, DeFor TE, Shapiro EG, Orchard PJ, Abel SL, Lockman LA, Ziegler RS, Dusenbery KE, Peters C. Hurler Syndrome: Outcome of Second Hematopoietic Cell Transplantation in Hurler Syndrome. Bone Marrow Transplantation 29:491-496, 2002.

Orchard PJ, Blazar BR, Burger S, Levine B, Basso L, Nelson DMK, Gordon K, McIvor RS, Wagner JE, Miller JS. Clinical-Scale Selection of Anti-CD3/CD28-Activated T Cells After Transduction with a Retroviral Vector Expressing Herpes Simplex Virus Thymidine Kinase and Truncated Nerve Growth Factor Receptor. Human Gene Therapy 13:979-988, 2002.

Sobacchi C, Frattini A, Orchard PJ, Porras O, Tezcan I, et al. The Mutational Spectrum of Human Malignant Autosomal Recessive Osteopetrosis. Human Molecular Genetics 10(17):1767-1773, 2001.

Horwitz, EM, Prockop, DJ, Gordon PL, Koo WWK, Fitzpatrick LA, Neel M, McCarville M, Sussman M, Orchard PJ, Pyeritz RE, Brenner MK. Clinical Responses to Bone Marrow Transplanation in Children with Severe Osteogenesis Imperfecta. Blood 97(5):1227-1231, 2001.

Frattini A*, Orchard PJ*, Sobacchi C, Giliani S, Abinun M, Mattsson JP, Keeling DJ, Andersson A-K, Wallbrandt P, Zecca L, Notarangelo LD, Vezzoni P, Villa A. Defects in TCIRG1 Subunit of the Vacuolar Proton Pump are Responsible for a Subset of Human Autosomal Recessive Osteopetrosis. Nature Genetics 25:343-346, July 2000. *Coprincipal authors.