Overview
My translational research program investigates the aberrant immunologic mechanisms underlying lung complications after hematopoietic cell transplantation, relapse, and graft failure. In the field of lung complications, we have performed studies that refined the diagnosis of lung chronic graft versus host disease. Our prospective interventional trials led to the current standard of care therapy for this disease. Current work focuses on elucidating disease pathogenesis and identifying new targeted therapies. Leveraging this work in lung cGVHD, we are now also interrogating another devastating transplant lung complications, diffuse alveolar hemorrhage, to understand the immune/endothelial dysregulation and targetable pathways.
Our work on novel imaging and blood biomarkers of graft failure culminated in a funded R01 project with a multicenter clinical trial. We have also developed a minimal residual disease test for acute leukemia after transplant and investigated the failure of immunosurveillance in relapse after transplant. Finally, our group is working to optimize, clinically test, and use correlates to understand novel immunotherapies for acute leukemia. Collectively, these efforts are focused on my long term goal—to improve the outcome for patients with the most devastating complications of hematopoietic cell transplant.
- Schoettler ML and Dandoy C, Harris A, Chan M, Tarquinio K, Jodele S, Qayed M, Kamat P, Petrillo T, Perez J, Higham C, Dvorak CC, Zinter M and Williams KM. Alveolar Hemorrhage in Children after Hematopoietic Cellular Therapy: Risk Factors for Non-Relapse Related Mortality and Response Rates to Inhaled Agents. Accepted to Frontiers in Oncology, July 2023, ahead of press.
- Schoettler M, Davila B, Berkenkamp L, Chonat S, Rotz S, Simon D, Jacobsohn D, Graf E, Cheng J, Rossi C, Hammers YA, Rytting H, Williams KM. Pulmonary manifestations and vascular changes in pediatric transplant associated thrombotic microangiopathy. Journal of Transplant and Cellular Therapy,2022 29(1):45.e1-45.e8.
- Stanojevic M and Grant M, Vesely SK, Kanakry C, Nazarian J, Knoblach S, Panditharatna E, Panchapakesan K, Gress RE, Holter Chakrabarty J, Williams KM. Peripheral blood marker of residual acute leukemia after hematopoietic cell transplantation using multi-plex digital droplet PCR. Frontiers in Immunology 2022; 13:999298.
- Williams KM and Inamoto Y, Im A, Hamilton B, Koreth J, Arora M, Pusic I, Mays JW, Carpenter PA, Luznik L, Reddy P, Ritz J, Greinix H, Paczesny S, Blazar BR, Pidala J, Cutler C, Wolff D, Schultz KR, Pavletic SZ, Lee SJ, Martin PJ, Socie G and Sarantopoulos S. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-host Disease: I. The 2020 Etiology and Prevention Working Group. Journal of Transplantation and Cellular Therapy 2021, 27(6):452-466.
- Williams KM. Non-infectious lung complications of hematopoietic cell transplantation. American Society of Hematology Education Program, 2021, (1):578-586.
- Williams KM, Pavletic SZ, Lee SJ, Martin PJ, Farthing DE, Hakim FT, Rose J, Manning-Geist BL, Gea-Banacloche JC, Comis LE, Cowen EW, Justus DG, Baird K, Cheng G, Avila D, Steinberg SM, Mitchell SA, Gress RE Prospective phase II trial of montelukast to treat bronchiolitis obliterans syndrome after hematopoietic cell transplant and investigation into BOS pathogenesis. Journal of Transplantation and Cellular Therapy, 2022, 28(5):264e1-e9.
- Williams KM and Holter Chakrabarty J, Lindenberg L, Duong Q, Vesely S, Nguyen CT, Havlicek JP, Kurdziel K, Gea-Banacloche J, Lin FI, Avila DN, Selby G, Kanakry CG, Li S, Scordino T, Adler S, Bollard CM, Choyke P, and Gress RE. Imaging of subclinical haemopoiesis after stem-cell transplantation in patients with haematological malignancies: a prospective pilot study. Lancet Haematolog. 2018. 5(1):44-52.
- Williams KM, Chien JW, Gladwin MT, Pavletic SZ. Bronchiolitis Obliterans After Allogeneic Hematopoieitc Stem Cell Transplantation- An Increasingly Recognized Manifestation of Chronic Graft-versus-Host Disease. Journal of American Medical Association. 2009. 302(2):206-214.
1R01HL146668-01
PI: Williams
08/26/2019-07/31/2025 (covid ext.),
Blood and Imaging Biomarkers of Engraftment
1R01 HL162661-01
PI: Yanik
8/17/2022-07/31/2026
Parametric Response Mapping (PRM) for the detection of chronic lung injury in hematopoietic cell transplant recipients
Peachbowl LegACy Fund
PI: Williams
January 2020-12/31/2025
CD19/22 CARPOOL: Phase I Trial of CD19/22 Chimeric Antigen Receptor Protocol with Objective of Tolerability in relapse/refractory ALL