Srour Lab

The research lab of Edward F. Srour, PhD focuses on the characterization and biology of human and murine hematopoietic stem cells (HSC) and on the interactions between cellular elements of the hematopoietic niche and HSC.

The Srour Lab is examining HSC-Osteoblast (OB) interactions and how these interactions impact the competence of the hematopoietic niche. These studies established that not only are MK required for the support of OB but are also critical for modulating the OB-mediated maintenance of HSC function.

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More recently, the laboratory recognized that osteomacs (OM), a specialized group of bone-resident macrophages are also critical for HSC function and are selectively maintained by MK. The Srour Lab is now focused on better understanding these novel and unique HSC-OB-MK-OM interactions that are fundamental for maintaining the competence of the hematopoietic niche and the functional properties of HSC. State-of-the-art technologies such as CyTOF analysis, flow cytometric analysis and single cell genomics are utilized to conduct these studies.

CD166 as a Critical Marker

Collaborative studies in the Srour Lab recently identified CD166 as a critical marker in the identification of normal HSC and the competence of the hematopoietic niche and in mediating bone lytic disease in multiple myeloma. Loss of CD166 on HSC almost completely abolished the laboratory’s potential to engraft in lethally irradiated recipients. Similarly, the competence of the hematopoietic niche of CD166 deficient mice was compromised illustrating that CD166 is required for both HSC function and the fitness of the niche. Efforts now are directed towards identifying the niche cell type that is most compromised by the loss of CD166 expression. The Srour laboratory also identified CD166 as a critical marker that most likely identifies multiple myeloma initiating cells, mediates disease progression in vivo, and mediates the aggressive and debilitating bone lytic disease that is associated with multiple myeloma.

Recent Publications

2017

Hinge A, Xu J, Javier J, Mose E, Kapur R, Srour EF, Malik P, Aronow BJ, Filippi MD. p190-B RhoGAP and intracellular cytokine signals balance hematopoietic stem and progenitor cell self-renewal and differentiation. Nature Communications 2017 Feb 8;8:14382. doi: 10.1038/ncomms14382. (PMID:28176763).

Mohamad SF, Xu L, Himes ER, Wu H, Alvarez MB, Davis KM, Kacena MA, Srour EF. Osteomacs interact with megakaryocytes and osteoblasts to regulate murine hematopoietic stem cell function. Blood Advances. In Press
2016

Xu L, Mohammad KS, Wu H, Crean C, Poteat B, Cheng Y, Cardoso AA, Machal C, Hanenberg H, Abonour R, Kacena MA, Chirgwin J, Suvannasankha A, Srour EF. Cell Adhesion Molecule CD166 Drives Malignant Progression and Osteolytic Disease in Multiple Myeloma. Cancer Research 76(23):6901-6910, Dec 1, 2016. (PMID:27634757).

Silberstein L, Goncalves KA, Kharchenko PV, Turcotte R, Kfoury Y, Mercier F, Baryawno N, Severe N, Bachand J, Spencer J, Papazian A, Lee D, Chitteti BR, Srour EF, Hoggatt J, Tate T, Lo Celso K, Ono N, Nutt S, Heino J, Sipila K, Shioda T, Osawa M, Lin CP, Hu GF, Scadden DT. Proximity-Based Differential Single-Cell Analysis of the Niche to Identify Stem/Progenitor Cell Regulators. Cell Stem Cell 19(4):530-543, Oct 2016. (PMID: 27524439).
2015

Micanovic R, Chitteti BR, Dagher PC, Srour EF, Khan S, Hato T, Lyle A, Tong Y, Wu XR, El-Achkar TM. Tamm-Horsfall Protein Regulates Granulopoiesis and Systemic Neutrophil Homeostasis. J American Society Nephrology 26(9):2178-2182, Sep 2015. (PMID:25556169).

Mantel CR, O’Leary HA, Chitteti BR, Huang X, Cooper S, Hangoc G, Brustovetsky N, Srour EF, Lee MR, Messina-Graham S, Haas DM, Falah N, Kapur R, Pelus LM, Bardeesy N, Fitamant J, Ivan M, Kim KS, Broxmeyer HE. Enhancing Hematopoietic Stem Cell Transplantation Efficacy by Mitigating Oxygen Shock. Cell 161(7):1553-1565, Jun 18, 2015. (PMID:26073944).

Wang L, Zoetemelk M, Ratliff TL, Myers JD, Chitteti BR, Srour EF, Broxmeyer HE, Jerde TJ. Expansion of prostate epithelial progenitor cells following inflammation of the mouse prostate. American J Physiology. Renal Physiology 308(12):F142-1430, Jun 2015. (PMID:25925259).

Zeng Y, Broxmeyer HE, Staser K, Chitteti BR, Park SJ, Hahn S, Cooper S, Sun Z, Jiang L, Yang X, Yuan J, Kosoff R, Sandusky G, Srour EF, Chernoff J, Clapp DW. Pak2 regulates hematopoietic progenitor cell proliferation, survival, and differentiation. Stem Cells 33(5):1630-1641, May 2015. (PMID:25586960).
2014

Chitteti BR, Kobayashi M, Cheng Y-H, Zhang H, Poteat BA, Broxmeyer HE, Pelus LM, Hanenberg H, Zolman A, Malgorzata K, Carlesso N, Cardoso AA, Kacena MA, Srour EF. CD166 regulates human and murine hematopoietic stem cells and the hematopoietic niche. Blood 124(4):519-529, Jul 24, 2014 (PMID: 24740813).

Wang L, Zhang H, Rodriguez S, Cao L, Parish J, Mumaw C, Zollman A, Kamoka G, Mu J, Chen DZ, Srour EF, Chitteti BR, Hoegenesh H, Boswell S, Manshouri T, Verstovsek S, Kapur R, Cardoso AA, Carlesso N. Notch-dependent repression of miR-155 in the bone marrow niche regulates hematopoiesis in an NF-κB-dependent manner. Cell Stem Cell 15(1):51-65, Jul 3, 2014. (PMID: 24996169).

Faculty Research Team

Edward F. Srour, PhD

Robert J. and Annie S. Rohn Professor of Leukemia Research

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Additional Research Team Members

Other research team members in the Srour Lab include Safa F. Mohamad (PhD Student) and Joydeep Ghosh, PhD (Post-doctoral Fellow).