Research Summary

The goal of the lab is to understand how development of hematopoietic stem cells (HSCs), their clonal composition and competition, and their progeny affect initiation of clonal blood disorders. Clonal blood disorders, including malignant diseases such as myelodysplastic syndromes (MDS) and acute myeloid leukemia, are states of significant disturbance of the balanced clonal output. Focusing on the pathogenesis of pediatric and young adult MDS which are often associated with germline predisposition conditions, our research seeks to identify pathways responsible for establishing early aberrant clonal states and promoting transformation to malignancy. By using techniques of cellular barcoding to gain insight about clone-specific biology in a zebrafish model and primary human cells, our goal is to identify top vulnerabilities in clonal disorders to augment disease-directed therapy and prevent relapse of disease after stem cell transplantation, or perhaps one day prevent the development of MDS in high-risk patients. Such therapies could potentially be broadly applicable in the field of leukemogenesis beyond germline predisposition syndromes.

Research Funding

  • January 1, 2023 - August 31, 2027 - Hematopoietic stem cell clonal diversity in GATA2 deficiency associated blood disorders , Principle investigator . Sponsor: Burroughs Wellcome Foundation Career Award for Medical Scientists, Sponsor Award ID:
  • August 1, 2024 - July 31, 2027 - Pathobiology of maladaptive clonal hematopoiesis driven by monosomy 7 in GATA2 deficiency , PI . Sponsor: Department of Defense Bone Marrow Failure Research Program, Sponsor Award ID:
  • January 1, 2025 - December 31, 2025 - Incidence and persistence of clonal hematopoiesis in pediatric recipients of haploidentical donor stem cell transplantation , PI . Sponsor: UCSF Resource Allocation Program, Sponsor Award ID:

Education

12/2022 - Instructor in Pediatric Oncology, Dana-Farber/Boston Children's Hospital Cancer and Blood Disorders Center
Pediatric Hematology-Oncology fellowship, 06/2017 - Pediatric hematology-oncology-stem cell transplantation, Dana-Farber/Boston Children's Hospital Cancer and Blood Disorders Center
Pediatric internship and residency, 06/2014 - Pediatrics, Children's Hospital of New York-Presbyterian at Columbia University Medical Center
MD, 2011 - , Icahn School of Medicine at Mount Sinai
PhD, 2009 - Hematopoietic stem cell biology, Icahn School of Medicine at Mount Sinai

Honors & Awards

  • Pilot for Early Career Investigators, Resource Allocation Program, UCSF, 2025
  • Bone Marrow Failure Idea Development Award, Department of Defense, 2024-2027
  • Career Awards for Medical Scientists, Burrough Wellcome Foundation, 2023-2027
  • CRAZY8 award (co-PI), Alex's Lemonade Stand Foundation, 2021-2025
  • Early Career Investigator Award, Alex's Lemonade Stand Foundation and RUNX1 Research Program, 2021-2024
  • Boston Combined Residency Program Faculty Teaching Honor Roll, Boston Children's Hospital, 2021
  • Abstract Achievement Award, American Society of Hematology, 2020
  • Rising Star Lecture Series Lecturer, National Institutes of Health, 2019
  • Young Investigator Award, Alex's Lemonade Stand Foundation, 2017-2021
  • Young Investigator Award, EvansMDS, Edward P. Evans Foundation, 2017-2020
  • Pedals for Pediatrics Research Grant, Boston Children's Hospital, 2016-2018
  • Potter Fellowship, Boston Children's Hospital, 2015-2017
  • David Abraham Fellowship, Dana-Farber Cancer Institute, 2015-2017
  • Farley Fund Fellowship Award, Boston Children's Hospital, 2014
  • Bela Schick Pediatric Society Prize, Icahn School of Medicine at Mt Sinai, 2011

Selected Publications

  1. Choi JE, Valle R, Long-Boyle J, Garcia BM, Frieden IJ, Pincus LB, Akagi N, Bhargava P, Wen KW, Ozgediz D, Rangaswami A, Chu J, Levinson A, Avagyan S. KIT Inhibitor Therapy in a Pediatric Patient With Systemic Mastocytosis and a Germ Cell Tumor of Shared Clonal Origin. Pediatr Blood Cancer. 2025 Jul; 72(7):e31717.  View on PubMed
  2. Dvorak CC, Cho S, Salinas Cisneros G, Higham CS, Chu J, Winestone LE, Temple WC, Kharbanda S, Shimano KA, Avagyan S, Pauerstein PT, Huang JN, Cheng G, Lalefar N, Aguayo-Hiraldo P, Keizer RJ, Pulsipher MA, Long-Boyle JR. High Melphalan Exposure Increases the Risk of Graft-Versus-Host Disease in Pediatric Patients Undergoing Alpha-Beta T-Cell Depleted Haploidentical Transplantation. Transplant Cell Ther. 2025 Apr 02.  View on PubMed
  3. Dvorak CC, Temple WC, Cisneros GS, Chu J, Winestone LE, Higham CS, Shimano KA, Kharbanda S, Avagyan S, Pauerstein P, Huang JN, Cheng G, Waters E, Winger BA, Cowan MJ, Long-Boyle JR. Younger children with nonmalignant disease have increased incidence of mixed myeloid chimerism after allogeneic hematopoietic cell transplantation with busulfan-based conditioning. Transplant Cell Ther. 2025 Apr; 31(4):259.e1-259.e15.  View on PubMed
  4. Baron CS, Mitchell O, Avagyan S, Menard R, Yang S, Robertson AL, Potluri R, Shendure J, Madelaine R, McKenna A, Zon LI Leukemia-derived apelin selects endothelial niche clones to promote tumorigenesis.  View on PubMed
  5. Robertson AL, Yue L, Choudhuri A, Kubaczka C, Wattrus SJ, Mandelbaum J, Avagyan S, Yang S, Freeman RJ, Chan V, Blair MC, Daley GQ, Zon LI Hematopoietic stem cell division is governed by distinct RUNX1 binding partners.  View on PubMed
  6. Diamantopoulos P, Avagyan S, Solomou E Editorial: Biological aspects of bone marrow failure.  View on PubMed
  7. Binder V, Li W, Faisal M, Oyman K, Calkins DL, Shaffer J, Teets EM, Sher S, Magnotte A, Belardo A, Deruelle W, Gregory TC, Orwick S, Hagedorn EJ, Perlin JR, Avagyan S, Lichtig A, Barrett F, Ammerman M, Yang S, Zhou Y, Carson WE, Shive HR, Blachly JS, Lapalombella R, Zon LI, Blaser BW Microenvironmental control of hematopoietic stem cell fate via CXCL8 and protein kinase C.  View on PubMed
  8. Avagyan S, Zon LI Clonal hematopoiesis and inflammation - the perpetual cycle.  View on PubMed
  9. Avagyan S, Shimamura A Lessons From Pediatric MDS: Approaches to Germline Predisposition to Hematologic Malignancies.  View on PubMed
  10. Avagyan S, Henninger JE, Mannherz WP, Mistry M, Yoon J, Yang S, Weber MC, Moore JL, Zon LI Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis.  View on PubMed
  11. Avagyan S, Brown AL To T or not to B: germline RUNX1 mutation preferences in pediatric ALL predisposition.  View on PubMed
  12. Six KA, Gerdemann U, Brown AL, Place AE, Cantor AB, Kutny MA, Avagyan S B-cell acute lymphoblastic leukemia in patients with germline RUNX1 mutations.  View on PubMed
  13. Avagyan S, Weber MC, Ma S, Prasad M, Mannherz WP, Yang S, Buenrostro JD, Zon LI Single-cell ATAC-seq reveals GATA2-dependent priming defect in myeloid and a maturation bottleneck in lymphoid lineages.  View on PubMed
  14. Hofmann I, Avagyan S, Stetson A, Guo D, Al-Sayegh H, London WB, Lehmann L Comparison of Outcomes of Myeloablative Allogeneic Stem Cell Transplantation for Pediatric Patients with Bone Marrow Failure, Myelodysplastic Syndrome and Acute Myeloid Leukemia with and without Germline GATA2 Mutations.  View on PubMed
  15. Fazio M, Avagyan S, van Rooijen E, Mannherz W, Kaufman CK, Lobbardi R, Langenau DM, Zon LI Efficient Transduction of Zebrafish Melanoma Cell Lines and Embryos Using Lentiviral Vectors.  View on PubMed
  16. Robertson AL, Avagyan S, Gansner JM, Zon LI Understanding the regulation of vertebrate hematopoiesis and blood disorders - big lessons from a small fish.  View on PubMed
  17. Tan JL, Fogley RD, Flynn RA, Ablain J, Yang S, Saint-André V, Fan ZP, Do BT, Laga AC, Fujinaga K, Santoriello C, Greer CB, Kim YJ, Clohessy JG, Bothmer A, Pandell N, Avagyan S, Brogie JE, van Rooijen E, Hagedorn EJ, Shyh-Chang N, White RM, Price DH, Pandolfi PP, Peterlin BM, Zhou Y, Kim TH, Asara JM, Chang HY, Young RA, Zon LI Stress from Nucleotide Depletion Activates the Transcriptional Regulator HEXIM1 to Suppress Melanoma.  View on PubMed
  18. Avagyan S, Zon LI Fish to Learn: Insights into Blood Development and Blood Disorders from Zebrafish Hematopoiesis.  View on PubMed
  19. Avagyan S, Churchill M, Yamamoto K, Crowe JL, Li C, Lee BJ, Zheng T, Mukherjee S, Zha S Hematopoietic stem cell dysfunction underlies the progressive lymphocytopenia in XLF/Cernunnos deficiency.  View on PubMed
  20. Avagyan S, Klein M, Kerkar N, Demattia A, Blei F, Lee S, Rosenberg HK, Arnon R Propranolol as a first-line treatment for diffuse infantile hepatic hemangioendothelioma.  View on PubMed

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