Serine Avagyan, MD, PhD

Asst Professor in Residence
Pediatrics

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.

Publications: 

Leukemia-derived apelin selects endothelial niche clones to promote tumorigenesis.

bioRxiv : the preprint server for biology

Baron CS, Mitchell O, Avagyan S, Menard R, Yang S, Robertson AL, Potluri R, Shendure J, Madelaine R, McKenna A, Zon LI

Hematopoietic stem cell division is governed by distinct RUNX1 binding partners.

bioRxiv : the preprint server for biology

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

Editorial: Biological aspects of bone marrow failure.

Frontiers in oncology

Diamantopoulos P, Avagyan S, Solomou E

Microenvironmental control of hematopoietic stem cell fate via CXCL8 and protein kinase C.

Cell reports

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

Clonal hematopoiesis and inflammation - the perpetual cycle.

Trends in cell biology

Avagyan S, Zon LI

Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis.

Science (New York, N.Y.)

Avagyan S, Henninger JE, Mannherz WP, Mistry M, Yoon J, Yang S, Weber MC, Moore JL, Zon LI

To T or not to B: germline RUNX1 mutation preferences in pediatric ALL predisposition.

The Journal of clinical investigation

Avagyan S, Brown AL

B-cell acute lymphoblastic leukemia in patients with germline RUNX1 mutations.

Blood advances

Six KA, Gerdemann U, Brown AL, Place AE, Cantor AB, Kutny MA, Avagyan S

Single-cell ATAC-seq reveals GATA2-dependent priming defect in myeloid and a maturation bottleneck in lymphoid lineages.

Blood advances

Avagyan S, Weber MC, Ma S, Prasad M, Mannherz WP, Yang S, Buenrostro JD, Zon LI

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.

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation

Hofmann I, Avagyan S, Stetson A, Guo D, Al-Sayegh H, London WB, Lehmann L

Efficient Transduction of Zebrafish Melanoma Cell Lines and Embryos Using Lentiviral Vectors.

Zebrafish

Fazio M, Avagyan S, van Rooijen E, Mannherz W, Kaufman CK, Lobbardi R, Langenau DM, Zon LI

Stress from Nucleotide Depletion Activates the Transcriptional Regulator HEXIM1 to Suppress Melanoma.

Molecular cell

Tan JL, Fogley RD, Flynn RA, Ablain J, Yang S, Saint-Andr? 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

Hematopoietic stem cell dysfunction underlies the progressive lymphocytopenia in XLF/Cernunnos deficiency.

Blood

Avagyan S, Churchill M, Yamamoto K, Crowe JL, Li C, Lee BJ, Zheng T, Mukherjee S, Zha S

Propranolol as a first-line treatment for diffuse infantile hepatic hemangioendothelioma.

Journal of pediatric gastroenterology and nutrition

Avagyan S, Klein M, Kerkar N, Demattia A, Blei F, Lee S, Rosenberg HK, Arnon R

Prdm16 is a physiologic regulator of hematopoietic stem cells.

Blood

Aguilo F, Avagyan S, Labar A, Sevilla A, Lee DF, Kumar P, Lemischka IR, Zhou BY, Snoeck HW

ATP-binding cassette transporters and HDL suppress hematopoietic stem cell proliferation.

Science (New York, N.Y.)

Yvan-Charvet L, Pagler T, Gautier EL, Avagyan S, Siry RL, Han S, Welch CL, Wang N, Randolph GJ, Snoeck HW, Tall AR

A quantitative trait locus on chr.4 regulates thymic involution.

The journals of gerontology. Series A, Biological sciences and medical sciences

Kumar R, Avagyan S, Snoeck HW

Identification and in vivo analysis of murine hematopoietic stem cells.

Methods in enzymology

Avagyan S, Amrani YM, Snoeck HW

Test of Cairns-Smith's 'crystals-as-genes' hypothesis.

Faraday discussions

Bullard T, Freudenthal J, Avagyan S, Kahr B

Immunokinetics of autoreactive CD4 T cells in blood: a reporter for the "hit-and-run" autoimmune attack on pancreas and diabetes progression.

Journal of autoimmunity

George SK, Preda I, Avagyan S, McEvoy RC, Rapaport R, Brumeanu TD, Casares S

Selection footprint in the FimH adhesin shows pathoadaptive niche differentiation in Escherichia coli.

Molecular biology and evolution

Sokurenko EV, Feldgarden M, Trintchina E, Weissman SJ, Avagyan S, Chattopadhyay S, Johnson JR, Dykhuizen DE