Department of Pediatrics

Education

• AA, Ulster County Community College, 1997
• BS, Mount Allison University, 2000
• PhD, University of Pennsylvannia, 2007

Training

• Post-doctoral Fellowship, Harvard Medical School - Brigham and Women's Hospital, 2008 - 2009
• Post-doctoral Fellowship, Harvard Medical School - Massachusetts General Hospital, 2009 - 2012

Honors and Awards

• Mount Allison University Entrance Scholarship, 1997 - 1998
• Academic All-Canadian - Basketball, 2000
• Monica Shander Award for Outstanding Pre-Doctoral Research (Wistar Institute), 2006
• International Society of Experimental Hematology (ISEH) Eugene Goldwasser Fellowship, 2011 - 2012
• American Society of Hematology (ASH) Junior Scholar Award, 2014 - 2016
• American Cancer Society Research Scholar Award, 2019 - 2022

Recent Publications view all (44)

1. Zhang Y, Truong B, Fahl SP, Martinez E, Cai KQ, Al-Saleem ED, Gong Y, Liebermann DA, Soboloff J, Dunbrack R, Levine RL, Fletcher S, Kappes D, Sykes SM, Shapiro P, Wiest DL. The ERK2-DBP domain opposes pathogenesis of a mouse JAK2V617F-driven myeloproliferative neoplasm. Blood. 2022;140(4):359-373. PMID:35436326 
2. Maifrede S, Le BV, Nieborowska-Skorska M, Golovine K, Sullivan-Reed K, Dunuwille WMB, Nacson J, Hulse M, Keith K, Madzo J, Caruso LB, Gazze Z, Lian Z, Padella A, Chitrala KN, Bartholdy BA, Matlawska-Wasowska K, Di Marcantonio D, Simonetti G, Greiner G, Sykes SM, Valent P, Paietta EM, Tallman MS, Fernandez HF, Litzow MR, Minden MD, Huang J, Martinelli G, Vassiliou GS, Tempera I, Piwocka K, Johnson N, Challen GA, Skorski T. TET2 and DNMT3A Mutations Exert Divergent Effects on DNA Repair and Sensitivity of Leukemia Cells to PARP Inhibitors. Cancer Res. 2021. PMID:34215619 
3. Di Marcantonio D, Martinez E, Kanefsky JS, Huhn JM, Gabbasov R, Gupta A, Krais JJ, Peri S, Tan Y, Skorski T, Dorrance A, Garzon R, Goldman AR, Tang HY, Johnson N, Sykes SM. ATF3 coordinates serine and nucleotide metabolism to drive cell cycle progression in acute myeloid leukemia. Mol Cell. 2021;81(13):2752-2764.e6. PMID:34081901 
4. Stanek TJ, Gennaro VJ, Tracewell MA, Di Marcantonio D, Pauley KL, Butt S, McNair C, Wang F, Kossenkov AV, Knudsen KE, Butt T, Sykes SM, McMahon SB. The SAGA complex regulates early steps in transcription via its deubiquitylase module subunit USP22. EMBO J. 2021;e102509. PMID:34155658 
5. Nacson J, Di Marcantonio D, Wang Y, Bernhardy AJ, Clausen E, Hua X, Cai KQ, Martinez E, Feng W, Callén E, Wu W, Gupta GP, Testa JR, Nussenzweig A, Sykes SM, Johnson N. BRCA1 Mutational Complementation Induces Synthetic Viability. Mol Cell. 2020;78(5):951-959.e6. PMCID:PMC7418109  PMID:32359443 
6. Peshkova IO, Aghayev T, Fatkhullina AR, Makhov P, Titerina EK, Eguchi S, Tan YF, Kossenkov AV, Khoreva MV, Gankovskaya LV, Sykes SM, Koltsova EK. IL-27 receptor-regulated stress myelopoiesis drives abdominal aortic aneurysm development. Nat Commun. 2019;10(1):5046. PMCID:PMC6834661  PMID:31695038 
7. Di Marcantonio D, Sykes SM. Flow Cytometric Analysis of Mitochondrial Reactive Oxygen Species in Murine Hematopoietic Stem and Progenitor Cells and MLL-AF9 Driven Leukemia. J Vis Exp. 2019;(151). PMCID:PMC7239511  PMID:31545325 
8. Sykes SM. NCAM1 supports therapy resistance and LSC function in AML. Blood. 2019;133(21):2247-2248. PMID:31122937 
9. Nacson J, Krais JJ, Bernhardy AJ, Clausen E, Feng W, Wang Y, Nicolas E, Cai KQ, Tricarico R, Hua X, DiMarcantonio D, Martinez E, Zong D, Handorf EA, Bellacosa A, Testa JR, Nussenzweig A, Gupta GP, Sykes SM, Johnson N. BRCA1 Mutation-Specific Responses to 53BP1 Loss-Induced Homologous Recombination and PARP Inhibitor Resistance. Cell Rep. 2018;25(5):1384. PMCID:PMC6296467  PMID:30380426 
10. Rudat S, Pfaus A, Cheng YY, Holtmann J, Ellegast JM, Bühler C, Marcantonio DD, Martinez E, Göllner S, Wickenhauser C, Müller-Tidow C, Lutz C, Bullinger L, Milsom MD, Sykes SM, Fröhling S, Scholl C. RET-mediated autophagy suppression as targetable co-dependence in acute myeloid leukemia. Leukemia. 2018;32(10):2189-2202. PMID:29654265 
11. Masselli E, Carubbi C, Cambò B, Pozzi G, Gobbi G, Mirandola P, Follini E, Pagliaro L, Di Marcantonio D, Bonatti F, Percesepe A, Sykes SM, Aversa F, Vitale M. The -2518 A/G polymorphism of the monocyte chemoattractant protein-1 as a candidate genetic predisposition factor for secondary myelofibrosis and biomarker of disease severity. Leukemia. 2018;32(10):2266-2270. PMCID:PMC6170394  PMID:29568096 
12. Nacson J, Krais JJ, Bernhardy AJ, Clausen E, Feng W, Wang Y, Nicolas E, Cai KQ, Tricarico R, Hua X, DiMarcantonio D, Martinez E, Zong D, Handorf EA, Bellacosa A, Testa JR, Nussenzweig A, Gupta GP, Sykes SM, Johnson N. BRCA1 Mutation-Specific Responses to 53BP1 Loss-Induced Homologous Recombination and PARP Inhibitor Resistance. Cell Rep. 2018;24(13):3513-3527.e7. PMCID:PMC6219632  PMID:30257212 
13. Maifrede S, Nieborowska-Skorska M, Sullivan-Reed K, Dasgupta Y, Podszywalow-Bartnicka P, Le BV, Solecka M, Lian Z, Belyaeva EA, Nersesyan A, Machnicki MM, Toma M, Chatain N, Rydzanicz M, Zhao H, Jelinek J, Piwocka K, Sliwinski T, Stoklosa T, Ploski R, Fischer T, Sykes SM, Koschmieder S, Bullinger L, Valent P, Wasik MA, Huang J, Skorski T. Tyrosine kinase inhibitor-induced defects in DNA repair sensitize FLT3(ITD)-positive leukemia cells to PARP1 inhibitors. Blood. 2018;132(1):67-77. PMCID:PMC6034642  PMID:29784639 
14. Di Marcantonio D, Martinez E, Sidoli S, Vadaketh J, Nieborowska-Skorska M, Gupta A, Meadows JM, Ferraro F, Masselli E, Challen GA, Milsom MD, Scholl C, Fröhling S, Balachandran S, Skorski T, Garcia BA, Mirandola P, Gobbi G, Garzon R, Vitale M, Sykes SM. Protein Kinase C Epsilon Is a Key Regulator of Mitochondrial Redox Homeostasis in Acute Myeloid Leukemia. Clin Cancer Res. 2018;24(3):608-618. PMCID:PMC5796864  PMID:29127121 
15. Maifrede S, Martinez E, Nieborowska-Skorska M, Di Marcantonio D, Hulse M, Le BV, Zhao H, Piwocka K, Tempera I, Sykes SM, Skorski T. MLL-AF9 leukemias are sensitive to PARP1 inhibitors combined with cytotoxic drugs. Blood Adv. 2017;1(19):1467-1472. PMCID:PMC5728460  PMID:29296788 
16. Nieborowska-Skorska M, Sullivan K, Dasgupta Y, Podszywalow-Bartnicka P, Hoser G, Maifrede S, Martinez E, Di Marcantonio D, Bolton-Gillespie E, Cramer-Morales K, Lee J, Li M, Slupianek A, Gritsyuk D, Cerny-Reiterer S, Seferynska I, Stoklosa T, Bullinger L, Zhao H, Gorbunova V, Piwocka K, Valent P, Civin CI, Muschen M, Dick JE, Wang JC, Bhatia S, Bhatia R, Eppert K, Minden MD, Sykes SM, Skorski T. Gene expression and mutation-guided synthetic lethality eradicates proliferating and quiescent leukemia cells. J Clin Invest. 2017;127(6):2392-2406. PMCID:PMC5451241  PMID:28481221 
17. Zhou C, Martinez E, Di Marcantonio D, Solanki-Patel N, Aghayev T, Peri S, Ferraro F, Skorski T, Scholl C, Fröhling S, Balachandran S, Wiest DL, Sykes SM. JUN is a key transcriptional regulator of the unfolded protein response in acute myeloid leukemia. Leukemia. 2017;31(5):1196-1205. PMCID:PMC5473421  PMID:27840425 
18. Monteith JA, Mellert H, Sammons MA, Kuswanto LA, Sykes SM, Resnick-Silverman L, Manfredi JJ, Berger SL, McMahon SB. A rare DNA contact mutation in cancer confers p53 gain-of-function and tumor cell survival via TNFAIP8 induction. Mol Oncol. 2016;10(8):1207-20. PMCID:PMC5423199  PMID:27341992 
19. Sykes SM. The identity crisis of Hif-1α in HSC biology. Blood. 2016;127(23):2782-4. PMID:27282941 
20. Sykes SM, Kokkaliaris KD, Milsom MD, Levine RL, Majeti R. Clonal evolution of preleukemic hematopoietic stem cells in acute myeloid leukemia. Exp Hematol. 2015;43(12):989-92. PMCID:PMC5492948  PMID:26455528 
21. Di Marcantonio D, Galli D, Carubbi C, Gobbi G, Queirolo V, Martini S, Merighi S, Vaccarezza M, Maffulli N, Sykes SM, Vitale M, Mirandola P. PKCε as a novel promoter of skeletal muscle differentiation and regeneration. Exp Cell Res. 2015;339(1):10-9. PMCID:PMC5130411  PMID:26431586 
22. Limon JJ, So L, Jellbauer S, Chiu H, Corado J, Sykes SM, Raffatellu M, Fruman DA. mTOR kinase inhibitors promote antibody class switching via mTORC2 inhibition. Proc Natl Acad Sci U S A. 2014;111(47):E5076-85. PMCID:PMC4250172  PMID:25385646 
23. 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;3(5):832-40. PMCID:PMC4235746  PMID:25418727 
24. Saez B, Ferraro F, Yusuf RZ, Cook CM, Yu VW, Pardo-Saganta A, Sykes SM, Palchaudhuri R, Schajnovitz A, Lotinun S, Lymperi S, Mendez-Ferrer S, Toro RD, Day R, Vasic R, Acharya SS, Baron R, Lin CP, Yamaguchi Y, Wagers AJ, Scadden DT. Inhibiting stromal cell heparan sulfate synthesis improves stem cell mobilization and enables engraftment without cytotoxic conditioning. Blood. 2014;124(19):2937-47. PMCID:PMC4224192  PMID:25202142 
25. 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;124(1):13-23. PMCID:PMC4190617  PMID:24764564 
26. Gobbi G, Mirandola P, Carubbi C, Masselli E, Sykes SM, Ferraro F, Nouvenne A, Thon JN, Italiano JE Jr, Vitale M. Proplatelet generation in the mouse requires PKCε-dependent RhoA inhibition. Blood. 2013;122(7):1305-11. PMCID:PMC3952532  PMID:23838351 
27. Sykes SM, Scadden DT. Modeling human hematopoietic stem cell biology in the mouse. Semin Hematol. 2013;50(2):92-100. PMCID:PMC3826087  PMID:24216169 
28. Faber K, Bullinger L, Ragu C, Garding A, Mertens D, Miller C, Martin D, Walcher D, Döhner K, Döhner H, Claus R, Plass C, Sykes SM, Lane SW, Scholl C, Fröhling S. CDX2-driven leukemogenesis involves KLF4 repression and deregulated PPARγ signaling. J Clin Invest. 2013;123(1):299-314. PMCID:PMC3533294  PMID:23202735 
29. 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, Armstrong SA. mTOR complex 1 plays critical roles in hematopoiesis and Pten-loss-evoked leukemogenesis. Cell Stem Cell. 2012;11(3):429-39. PMCID:PMC3743253  PMID:22958934 
30. Ferraro F, Lymperi S, Méndez-Ferrer S, Saez B, Spencer JA, Yeap BY, Masselli E, Graiani G, Prezioso L, Rizzini EL, Mangoni M, Rizzoli V, Sykes SM, Lin CP, Frenette PS, Quaini F, Scadden DT. Diabetes impairs hematopoietic stem cell mobilization by altering niche function. Sci Transl Med. 2011;3(104):104ra101. PMCID:PMC3754876  PMID:21998408 
31. Lane SW, Wang YJ, Lo Celso C, Ragu C, Bullinger L, Sykes SM, Ferraro F, Shterental S, Lin CP, Gilliland DG, Scadden DT, Armstrong SA, Williams DA. Differential niche and Wnt requirements during acute myeloid leukemia progression. Blood. 2011;118(10):2849-56. PMCID:PMC3172801  PMID:21765021 
32. Sykes SM, Lane SW, Bullinger L, Kalaitzidis D, Yusuf R, Saez B, Ferraro F, Mercier F, Singh H, Brumme KM, Acharya SS, Scholl C, Tothova Z, Attar EC, Fröhling S, DePinho RA, Armstrong SA, Gilliland DG, Scadden DT. AKT/FOXO signaling enforces reversible differentiation blockade in myeloid leukemias. Cell. 2011;146(5):697-708. PMCID:PMC3826540  PMID:21884932 
33. Cornejo MG, Mabialah V, Sykes SM, Khandan T, Lo Celso C, Lopez CK, Rivera-Muñoz P, Rameau P, Tothova Z, Aster JC, DePinho RA, Scadden DT, Gilliland DG, Mercher T. Crosstalk between NOTCH and AKT signaling during murine megakaryocyte lineage specification. Blood. 2011;118(5):1264-73. PMCID:PMC3152494  PMID:21653327 
34. Mellert HS, Stanek TJ, Sykes SM, Rauscher FJ 3rd, Schultz DC, McMahon SB. Deacetylation of the DNA-binding domain regulates p53-mediated apoptosis. J Biol Chem. 2011;286(6):4264-70. PMCID:PMC3039376  PMID:21148320 
35. Parmar K, Kim J, Sykes SM, Shimamura A, Stuckert P, Zhu K, Hamilton A, Deloach MK, Kutok JL, Akashi K, Gilliland DG, D'andrea A. Hematopoietic stem cell defects in mice with deficiency of Fancd2 or Usp1. Stem Cells. 2010;28(7):1186-95. PMCID:PMC2910804  PMID:20506303 
36. Lane SW, Sykes SM, Al-Shahrour F, Shterental S, Paktinat M, Lo Celso C, Jesneck JL, Ebert BL, Williams DA, Gilliland DG. The Apc(min) mouse has altered hematopoietic stem cell function and provides a model for MPD/MDS. Blood. 2010;115(17):3489-97. PMCID:PMC2867262  PMID:20197553 
37. Sykes SM, Stanek TJ, Frank A, Murphy ME, McMahon SB. Acetylation of the DNA binding domain regulates transcription-independent apoptosis by p53. J Biol Chem. 2009;284(30):20197-205. PMCID:PMC2740446  PMID:19494119 
38. Pietsch EC, Sykes SM, McMahon SB, Murphy ME. The p53 family and programmed cell death. Oncogene. 2008;27(50):6507-21. PMCID:PMC2657599  PMID:18955976 
39. Zhang XY, Varthi M, Sykes SM, Phillips C, Warzecha C, Zhu W, Wyce A, Thorne AW, Berger SL, McMahon SB. The putative cancer stem cell marker USP22 is a subunit of the human SAGA complex required for activated transcription and cell-cycle progression. Mol Cell. 2008;29(1):102-11. PMCID:PMC2254522  PMID:18206973 
40. Mellert H, Sykes SM, Murphy ME, McMahon SB. The ARF/oncogene pathway activates p53 acetylation within the DNA binding domain. Cell Cycle. 2007;6(11):1304-6. PMID:17534149 
41. Sykes SM, Mellert HS, Holbert MA, Li K, Marmorstein R, Lane WS, McMahon SB. Acetylation of the p53 DNA-binding domain regulates apoptosis induction. Mol Cell. 2006;24(6):841-51. PMCID:PMC1766330  PMID:17189187 
42. Schnepp RW, Mao H, Sykes SM, Zong WX, Silva A, La P, Hua X. Menin induces apoptosis in murine embryonic fibroblasts. J Biol Chem. 2004;279(11):10685-91. PMCID:PMC2858560  PMID:14688275 
43. Jin S, Mao H, Schnepp RW, Sykes SM, Silva AC, D'Andrea AD, Hua X. Menin associates with FANCD2, a protein involved in repair of DNA damage. Cancer Res. 2003;63(14):4204-10. PMID:12874027 
44. La P, Morgan TA, Sykes SM, Mao H, Schnepp RW, Petersen CD, Hua X. Fusion proteins of retinoid receptors antagonize TGF-beta-induced growth inhibition of lung epithelial cells. Oncogene. 2003;22(2):198-210. PMID:12527889