Major Lectureships and Seminars
- “Studies on Alloreactivity and Tolerance After Peripheral Blood and Cord Blood Transplantation: Is There a Tipping Point?” University of Pittsburgh Cancer Institute, Cancer Immunology Program Seminars, Pittsburgh, PA., April 2016
- “Lung Transplantation in Tandem with Bone Marrow Transplantation from Partially HLA-matched Deceased Donors: Clinical and Mechanistic Studies,” 2016 STI Scientific Retreat, Pittsburgh, PA., November 2016
- “Reduced Intensity Transplantation is Effective for Multiple Genetic Diseases: The Pittsburgh Protocol,” Dubai-Arab Medical Congress, 2017
- “Reduced Intensity Unrelated Donor Transplantation for Non-Malignant Diseases: A Journey Towards Combined Organ and Marrow Transplantation,” Hematology grand rounds, UPMC Shadyside Hospital, UPCI, Pittsburgh, PA., March, 2017
- “Mechanisms of Tolerance Following HLA-Mismatched Cord Blood Grafts: A Journey Towards Tandem Cadaveric Organ + Marrow Transplantation,” grand rounds, Memorial Sloan Kettering Cancer Center, New York, NY, June 2017
- “Mechanisms of Tolerance Following HLA-Mismatched Cord Blood Grafts: A Journey Towards Tandem Cadaveric + Organ Marrow Transplantation,” UPMC Children’s Hospital of Pittsburgh Molecular Medicine Research Seminar, June 2017
Professional Affiliations/Society Memberships
- American Society of Hematology
- American Society for Blood and Marrow Transplantation
- American Association of Immunologists
- Society for Pediatric Research (SPR)
- Clinical Immunology Society (CIS)
- Federation of Clinical Immunology Society (FOCIS)
- Fellow, American Academy of Pediatrics
- International Society for Cellular Therapy
Education & Training
- MD: Semmelweis Medical University Budapest, Hungary
- Residency: Bellevue Hospital Center New York, NY
- Fellowship: Memorial Sloan-Kettering Cancer Center New York, NY
Paul Szabolcs is a physician-scientist whose clinical and research interests are focused on the biology of donor-derived cellular immunity and modulating alloreactivity in recipients of allogeneic hematopoietic cell transplantation (HCT). The overall goal of his effort is to develop novel diagnostic and therapeutic approaches to accurately diagnose, predict, and therapeutically accelerate post-transplant immune reconstitution without increasing GVHD. He has developed a research program to elucidate mechanisms essential for successful tolerance. These studies will help to develop novel immunotherapy interventions. He continued to focus on unrelated cord blood transplantation (UCBT) as the dominant clinical scenario and laboratory model. His work has continued to influence the global field of transplantation medicine, especially the translational science of HLA-mismatched bone marrow transplantation as it is applied in tandem with solid organ transplantation.
Graft Engineering and Immunotherapy after UCBT. The Szabolcs lab studied HCT recipient and donor pairs to analyze the development of protective immunity and to modulate T-cell responses toward amplifying leukemia reactive T cells. Szabolcs and Xiaohua Chen studied active mechanisms responsible for development of tolerance in HLA-mismatched cord blood recipients. This research aims at developing innovative immunomodulatory strategies relevant to multiple disease categories.
Immune Reconstitution after Cord Blood Transplant. Szabolcs and Chen performed correlative studies of T-cell immune reconstitution in ongoing clinical trials utilizing UCBT to identify the predictors of clinical outcomes. Since late 2012, the research has increasingly focused on elucidating mechanisms of tolerance in mixed chimerism and understanding the role of regulatory T cells in those with tolerance and those without, namely suffering from GVHD.
Reduced-Intensity UCBT for Children with Rare Metabolic and Primary Immune Deficiency (PID) Disorders. Children with PID syndromes, even those who may have significant comorbidities, can be cured with such reduced-toxicity regimens. The CHP BMT&CT medical team works closely with collaborating services, in particular the Program for the Study of Neurodevelopment in Rare Disorders (NDRD) at CHP and Medical Genetics, to identify those who may benefit from HCT. The team offers a novel RIC regimen (ClinicalTrials: NCT01962415) that is testing the hypothesis that it not only can reduce/eliminate transplant-related mortality and achieve superior neurocognitive outcomes compared to traditional myeloablative conditioning for a wide variety of inherited metabolic disorders, including but not limited to Krabbe disease, metachromatic leukodystrophy, and mucopolysaccharidosis syndromes.
In FY17, Szabolcs has focused on a new UPMC initiative called Immune Transplant and Therapy Center (ITTC) where novel auto-transplant protocols will be developed for autoimmune disorders such as IBD, and Scleroderma. With Carella, allogeneic transplant protocols continued to be designed to address HAL-matched donor availability in sickle cell disease (SCD) by offering HLA-mismatched unrelated donor and/or haploidentical transplantation in children and adults. Barnum’s virus-specific T-cell therapy protocol will play a critical support role in this initiative.
Autologous Stem Cell Transplantation with CD34-Selected Peripheral Blood Stem Cells (PBSCs) in Pediatric and Young Adult Patients with Severe Crohn’s Disease and Other Autoimmune Disorders. (ClinicalTrials: NCT0692939) This study continued to evaluate the safety and efficacy of administering high-dose immunotherapy followed by infusion of autologous CD34-selected PBSC in pediatric and young adult patients who are refractory to all other treatment modalities.
Tandem Solid Organ Transplant and T-Cell-Depleted BMT. This new treatment modality was developed to transplant in stages two organs both procured from a partially HLA-matched cadaveric donor. The therapy addresses the unmet need to offer meaningful and high-quality life to children and young adults who have pulmonary or other end organ failure and severe immune deficiency. Szabolcs was the sponsored investigator for this protocol; collaborators came from the Thomas E. Starzl Transplant Institute, Mellon Institute, UPCI, and CHP faculty. The team continued to enroll patients on a protocol titled “Sequential Cadaveric Lung and Bone Marrow Transplant for Primary Immune Deficiency Diseases,” (ClinicalTrials: NCT01852370). One patient received a lung transplant for IL-7R null severe combined immunodeficiency in September of 2015 and received the bone marrow transplant from the same cadaveric donor in January 2016. She was the first patient in the world to engraft with 1 of 8 high resolution HLA-matched cadaveric bone marrow and she successfully weaned off immunosuppression in May 2017. This is also the first case of engraftment and immune reconstitution with a bone marrow graft prepared from vertebral bodies. Adult and pediatric patients with no other life-saving alternatives have come from as far as Texas and Rhode Island to enroll on this research protocol. This work was supported by a National Institute of Allergy and Infectious Diseases (NIAID)/National Institutes of Health (NIH) R34 and UO1 grants to Szabolcs as communicating Co-PI.
Cadaveric Donor Lung and Bone Marrow Transplantation in Immunodeficiency Diseases. 1U01AI125050-01: NIH/NIAID, 07/06/16-06/30/21
For patients with PID who develop the complication of end-stage lung disease, neither bone marrow transplantation (BMT) nor lung transplantation are therapeutic options. This was the first clinical trial to evaluate the safety and efficacy of a combined-tandem strategy for lung transplant followed by BMT to correct the defective immune system, using the same organ donor. The lab will perform tests to determine if BMT restores the ability to fight infection and allows acceptance of the lungs, which would permit eventual withdrawal of all immunosuppression medications in these unique, combined transplant recipients. Ancillary mechanistic studies will test for global and mucosal immune competence and others will test for mechanisms of tolerance. Szabolcs is the communicating PI. John McDyer, MD, UPMC Adult Lung Transplantation is coprincipal investigator. Multiple investigators have joined this translational research proposal from CHP (Geoff Kurland, MD, Marian Michaels, MD, Jay Kolls, MD, PhD), Presbyterian Hospital of UPMC, and the University of Pittsburgh Department of Immunology (Fadi Lakkis M.D., Dario Vignali. Ph.D.)