Olson Laboratory

In coordination with these clinical efforts, my clinical research program seeks to retrospectively and prospectively assess outcomes for patients undergoing HSCT due to inherited and acquired bone marrow failure syndromes, defined and stratified by distinct cytogenetic abnormalities. Our ultimate goal is to develop targeted clinical trials which will serve to define optimal treatment strategies for patients with distinct genetic and immunologic etiologies of bone marrow failure.

The goal of my laboratory research program is to improve HSCT outcomes by identifying methods to decrease the incidence of graft failure following HSCT, which is a particularly critical challenge in the setting of transplant for non-malignant conditions such as bone marrow failure. We are specifically examining methods to enhance donor hematopoietic stem cell (HSC) engraftment efficiency following HSCT through enhancement of the functions of specialized areas of the bone marrow microenvironment, known as hematopoietic stem cell niches. We are currently testing therapeutic strategies that can be applied to enhance niche activity and receptivity for donor stem cells, which could be utilized to improve donor engraftment efficiency following clinical HSCT.

  • The role of germline genetic predisposition syndromes in the development of pediatric myelodysplastic syndrome and acute myeloid leukemia
  • Patterns of HLA allele expression and clonal evolution in acquired aplastic anemia, and how these findings may serve as biomarkers for disease response as well as clues to the underlying immune basis of this disease
  • Investigation of how intrinsic pathways governing hematopoietic stem cell niche function can be harnessed to improve the efficiency and durability of donor engraftment after hematopoietic stem cell transplantation, particularly in the context of bone marrow failure syndromes.
  • Clinical trials of novel conditioning and T cell depletion strategies to improve survival and decrease allo-immune complications for patients with non-malignant hematologic disorders undergoing hematopoietic stem cell transplantation.

Location: Abramson Research Center, ARC 303

People

Timothy Olson, MD, PhD

Photo of Timothy Olson, MD, PhD
Principal Investigator

Dr. Olson's clinical efforts focus on pediatric hematopoietic stem cell transplantation (HSCT), with a specific emphasis on HSCT for patients with inherited and acquired bone marrow failure.

Ji Zha, PhD

Ji Zha, PhD
Postdoctoral Fellow

Dr. Ji Zha is a postdoctoral fellow in Dr. Timothy Olson’s laboratory. She is currently studying on the cellular and molecular roles of hematopoietic stem cell (HSC) niche in donor HSC engraftment following hematopoietic stem cell transplantation (SCT) in mouse models of inherited bone marrow failure, including Fanconi Anemia, Shwachman Diamond Syndrome, and Dyskeratosis Congenita.

Joseph Oved, MD

Joseph Oved, MD
Postdoctoral Fellow

Dr. Oved is a Pediatric Hematology/Oncology fellow and a postdoctoral fellow in Dr. Timothy Olson’s laboratory. His clinical interests involve hematopoietic stem cell transplant, cell therapies and bone marrow failure. He is currently working on developing novel lentiviral gene therapies for inherited bone marrow failure conditions.

Lori Kunselman

Lori Kunselman
Research Technician

Lori Kunselman joined the Bone Marrow Failure Center in September 2014. As a research assistant, her role is to support Dr. Tim Olson in his research of engraftment efficiency in HSCT murine models. She is responsible for maintaining the conditional knockout mouse models of IGF and PDGF, as well as models of inherited bone marrow failure such as Fanconi Anemia, Shwachman Diamond Syndrome, and Dyskeratosis Congenita.

Research

  • The role of germline genetic predisposition syndromes in the development of pediatric myelodysplastic syndrome and acute myeloid leukemia
  • Patterns of HLA allele expression and clonal evolution in acquired aplastic anemia, and how these findings may serve as biomarkers for disease response as well as clues to the underlying immune basis of this disease
  • Investigation of how intrinsic pathways governing hematopoietic stem cell niche function can be harnessed to improve the efficiency and durability of donor engraftment after hematopoietic stem cell transplantation, particularly in the context of bone marrow failure syndromes.
  • Clinical trials of novel conditioning and T cell depletion strategies to improve survival and decrease allo-immune complications for patients with non-malignant hematologic disorders undergoing hematopoietic stem cell transplantation.

Publication Highlights

Babushok DV, Duke JL, Xie HM, Stanley N, Atienza J, Perdigones N, Nicholas P, Ferriola D, Li Y, Huang H, Ye W, Morrissette JJD, Kearns J, Porter DL, Podsakoff GM, Eisenlohr LC, Biegel JA, Chou ST, Monos DS, Bessler M, Olson TS. Somatic HLA Mutations Expose the Role of Class I-Mediated Autoimmunity in Aplastic Anemia and its Clonal Complications. Blood Adv. 2017 Oct 10;1(22):1900-1910. PMID: 28971166.

Olson TS, Caselli A, Otsuru S, Hofmann TJ, Williams R, Paolucci P, Dominici M, Horwitz EM. Megakaryocytes promote murine osteoblastic HSC niche expansion and stem cell engraftment after radioablative conditioning. Blood. 2013 Jun 27;121(26):5238-49. doi: 10.1182/blood-2012-10-463414. Epub 2013 May 10. PMID: 23667055.

Betensky M, Babushok D, Roth JJ, Mason, PJ, Biegel JA, Busse TM, Li Y, Lind C, Papazoglou A, Monos D, Podsakoff G, Bessler M, and Olson TS. Clonal evolution and clinical significance of copy number neutral loss of heterozygosity of chromosome arm 6p in acquired aplastic anemia.. Cancer Genet. 2016 Jan-Feb;209(1-2):1-10. doi: 10.1016/j.cancergen.2015.10.002. Epub 2015 Oct 30. PMID: 26702937 .

Oved JH, Wang Y, Barrett DM, Levy EM, Huang Y, Monos DS, Grupp SA, Bunin NJ, Olson TS. CD3+/CD19+ depleted matched and mismatched unrelated donor hematopoietic stem cell transplant with targeted T cell addback is associated with excellent outcomes in pediatric patients with non-malignant hematologic disorders. Biol Blood Marrow Transplant. pii: S1083-8791(18)30612-8. doi: 10.1016/j.bbmt.2018.10.003. [Epub ahead of print] PMID: 30312755.

Babushok DV, Bessler M, Olson TS. Genetic predisposition to myelodysplastic syndrome and acute myeloid leukemia in children and young adults. Leuk Lymphoma. 2016;57(3):520-36. doi: 10.3109/10428194.2015.1115041. Epub 2015 Dec 23. PMID: 26693794.

Articles

Peter Kurre, MD, Appointed Director of the Comprehensive Bone Marrow Failure Center

Wednesday, January 30, 2019 Full Article: view

Photo of Peter Kurre, MDPeter Kurre, MD, joined Children’s Hospital of Philadelphia (CHOP) as Director of the Comprehensive Bone Marrow Failure Center on August 31, 2018. In collaboration with bone marrow failure (BMF) experts at the Perelman School of Medicine at the University of Pennsylvania, the center has built an international reputation of excellence in consultation and treatment of patients with BMF disorders, currently following well over 200 patients. Dr. Kurre will lead a world-renowned, multidisciplinary team in developing new therapies for BMF syndromes and in basic research to understand the causes of these syndromes.

Olson Clinical Trial #5

Wednesday, January 30, 2019 Full Article: view

TransIT Study (#16-013471, NCT02845596) Unrelated Donor Transplant versus Immune Therapy in Pediatric Severe Aplastic Anemia (Pulsiper/Williams, North American Pediatric Aplastic Anemia Consortium)

Olson Clinical Trial #3

Wednesday, January 30, 2019 Full Article: view

CHP 894 (IRB 08‐005659, NCT01050855) Reduced Intensity Conditioning (RIC) Regimen for Patients with Non‐Malignant Disorders

Olson Clinical Trial #6

Wednesday, January 30, 2019 Full Article: view

Eltrombopag Study (#17-014047, NCT03025698) A Phase II, open-label, non-controlled, intra-patient dose-escalation study to characterize the pharmacokinetics after oral administration of Eltrombopag in pediatric patients with refractory, relapsed or treatment naïve severe aplastic anemia or recurrent aplastic anemia (Novartis)

Olson Clinical Trial #1

Sunday, February 3, 2019 Full Article: view

CHP 14BT057 (IRB 14‐011465, NCT02928991) Pilot Study of Fludarabine‐based Conditioning for Matched Related Donor Bone Marrow Transplantation in Patients with Acquired and Inherited Bone Marrow Failure Syndromes

Olson Clinical Trial #4

Wednesday, January 30, 2019 Full Article: view

Telomere diseases SCT Trial (IRB 17‐014074, NCT01659606): Radiation‐ and alkylator‐free hematopoietic cell transplantation for bone marrow failure due to dyskeratosis congenita / telomere disease (Agarwal, Boston Children’s Hospital)

Olson Clinical Trial #2

Saturday, February 2, 2019 Full Article: view

CHP 16BT052 (IRB 16‐012881, NCT03047746) Unrelated and Partially Matched Related Donor Peripheral Stem Cell Transplant w/ TCRαβ depletion for patients with Bone Marrow Failure Syndromes