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Stephen M. Sykes, PhD

Stephen M. Sykes, PhD

Assistant Professor

Adjunct Professor, Lewis Katz School of Medicine, Temple University

Research Program

AML cells prior to FOXO3 inhibition
Effects of FOXO3 inhibition in human AML cells

 

Educational Background

  • PhD, Cell and Molecular Biology, University of Pennsylvania, Philadelphia, PA, 2007
  • BS, Biochemistry, Mount Allison University, Sackville, NB, 2000
  • AAS, Biology, Ulster County Community College, Stone Ridge, NY, 1997

Honors & Awards

  • Junior Scholar, American Society of Hemotology, 2014-2016
  • Tosteson Postdoctoral Fellowship Award, 2011
  • Eugene Goldwasser Fellowship in Hematology, International Society of Hematology, 2011

Research Program

Research Interests

Normal and Malignant Hematopoietic Stem and Progenitor Cells

  • Defining the molecular circuitry that distinguishes leukemia stem and progenitor cells from their healthy counterparts
  • Identifying and targeting critical regulators of redox biology to overcome chemotherapy resistance in acute myeloid leukemia (AML)
  • Targeting ER stress responses to treat certain genetic sub-types of AML
 

Lab Overview

The overall research goals of the lab are to identify and validate molecular pathways that could provide a foundation for designing novel targeted anti-leukemia therapies or enhancing the efficacy of existing chemotherapies. Leukemia cells often hijack molecular pathways that are critical to the regulation of normal HSPCs. Understanding how these pathways are differentially regulated in leukemia versus normal cell development and contribute to chemotherapy resistance provides the most promising strategy for identifying potential therapeutic targets.

As such, our lab focuses on three interdisciplinary directions aimed at:

  • Identifying and delineating molecular events that support leukemia
  • Understanding how these pathways impact both normal and malignant hematopoiesis
  • Validating the therapeutic potential of newly discovered pathways in pre-clinical models of AML

Using this approach, our lab is currently focused on defining how redox biology and stress-activated signaling pathways contribute to leukemogenesis and chemotherapy resistance. Specifically, we are interested in:

  • Understanding how the FOXO family of transcription factors support the differentiation blockade and chemotherapy resistance in AML
  • Determining the role of ER stress signal transduction pathways in healthy and malignant hematopoietic stem and progenitors
  • Elucidating the role of the oncogenic kinase PKC epsilon in AML

People

Chun Zhou, PhD

Room: R297
215-728-3563

Esteban Martinez, BS

Room: R297
215-728-3563

Turan Aghayev, MS

Room: R297
215-728-3563

Daniela Di Marcantonio, MS

Room: R297
215-728-3563

Additional Staff

Victoria Shust, Penn State University

Jake Meadows, University of Pittsburgh

Jesscia Vadaketh

Philipp Kappes

Selected Publications

Sykes SM, Lane SW, Bullinger L, Kalaitzidis D, Yusuf R, Saez B, Ferraro F, Mercier F, Singh H, Brumme KM, Acharya SA, Scholl C, Tothova Z, Attar E, Frohling S, DePinho RA, Gilliland DG, Armstrong SA, Scadden DT (2011). AKT/FOXO signaling enforces reversible differentiation blockade in myeloid leukemias. Cell. 2011 Sep 2;146(5):697-708. PMCID: PMC3826540. PubMed

Placke T, Faber K, Nonami A, Putwain SL, Salih HR, Heidel FH, Krämer A, Root DE, Barbie DA, Krivtsov AV, Armstrong SA, Hahn WC, Huntly BJ, Sykes SM, Milsom MD, Scholl C, Fröhling S. Requirement for CDK6 in MLL-rearranged acute myeloid leukemia. Blood. 2014 Jul 3;124(1):13-23. PubMed

Kalaitzidis D, Sykes SM, Wang Z, Punt N, Tang Y, Ragu C, Sinha AU, Lane SW, Souza AL, Clish CB, Anastasiou D, Gilliland DG, Scadden DT, Guertin DA & SA Armstrong. 2012. mTOR complex 1 plays critical roles in hematopoiesis and Pten-loss-evoked leukemogenesis. Cell Stem Cell. 2012 Sep 7;11(3):429-39. PMCID: PMC3743253. PubMed

Lee D, Sykes SM, Kalaitzidis D, Lane AA, Kfoury Y, Raaijmakers MH, Wang YH, Armstrong SA, Scadden DT. Transmembrane Inhibitor of RICTOR/mTORC2 in Hematopoietic Progenitors. Stem Cell Reports. 2014 Nov 11;3(5):832-40. PMCID: PMC4235746. PubMed

Sykes SM, Mellert HS, Holbert MA, Li K, Marmorstein R, Lane WS, McMahon SB (2006). Acetylation of the p53 DNA-binding domain regulates apoptosis induction. Molecular Cell 24(6):841-851. PMCID: PMC1766330. PubMed

Additional Publications

My NCBI