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Stephen C. Mack, PhD
Stephen C. Mack, PhD

Stephen C. Mack, PhD

Associate Member, St. Jude Faculty

Departments

Education

BSc (Laboratory Medicine and Pathobiology) – University of Toronto, Toronto
PhD (Laboratory Medicine and Pathobiology) – University of Toronto, Toronto
Fellowship (Stem Cell Biology) – Cleveland Clinic, Cleveland, Ohio

Research Interests

  • Brain tumors
  • Gene regulation
  • Brain development
  • Developmental therapeutics

Selected Publications

Chen CCL, Deshmukh S, Jessa S, Hadjadj D, Lisi V, Andrade AF, Faury D, Jawhar W, Dali R, Suzuki H, Pathania M, A D, Dubois F, Woodward E, Hébert S, Coutelier M, Karamchandani J, Albrecht S, Brandner S, De Jay N, Gayden T, Bajic A, Harutyunyan AS, Marchione DM, Mikael LG, Juretic N, Zeinieh M, Russo C, Maestro N, Bassenden AV, Hauser P, Virga J, Bognar L, Klekner A, Zapotocky M, Vicha A, Krskova L, Vanova K, Zamecnik J, Sumerauer D, Ekert PG, Ziegler DS, Ellezam B, Filbin MG, Blanchette M, Hansford JR, Khuong-Quang DA, Berghuis AM, Weil AG, Garcia BA, Garzia L, Mack SC, Beroukhim R, Ligon KL, Taylor MD, Bandopadhayay P, Kramm C, Pfister SM, Korshunov A, Sturm D, Jones DTW, Salomoni P, Kleinman CL, Jabado N. Histone H3.3G34-Mutant Interneuron Progenitors Co-opt PDGFRA for Gliomagenesis. Cell Nov;183(6):1617-1633.e22, 2020. PMID 33259802

Khazaei S, De Jay N, Deshmukh S, Hendrikse LD, Jawhar W, Chen CCL, Mikael LG, Faury D, Marchione DM, Lanoix J, Bonneil É, Ishii T, Jain SU, Rossokhata K, Sihota TS, Eveleigh R, Lisi V, Harutyunyan AS, Jung S, Karamchandani J, Dickson BC, Turcotte R, Wunder JS, Thibault P, Lewis PW, Garcia BA, Mack SC, Taylor MD, Garzia L, Kleinman CL, Jabado N. H3.3 G34W Promotes Growth and Impedes Differentiation of Osteoblast-Like Mesenchymal Progenitors in Giant Cell Tumor of Bone. Cancer Discov Dec;10(12):1968-1987, 2020. PMID 32967858

Mack SC, Bertrand KC. Sub-group, Sub-type, and Cell-type Heterogeneity of Ependymoma. Cancer Cell July;38(1):15-17, 2020. PMID 32663463

Michealraj KA, Kumar SA, Kim LJY, Cavalli FMG, Przelicki D, Wojcik JB, Delaidelli A, Bajic A, Saulnier O, MacLeod G, Vellanki RN, Vladoiu MC, Guilhamon P, Ong W, Lee JJY, Jiang Y, Holgado BL, Rasnitsyn A, Malik AA, Tsai R, Richman CM, Juraschka K, Haapasalo J, Wang EY, De Antonellis P, Suzuki H, Farooq H, Balin P, Kharas K, Van Ommeren R, Sirbu O, Rastan A, Krumholtz SL, Ly M, Ahmadi M, Deblois G, Srikanthan D, Luu B, Loukides J, Wu X, Garzia L, Ramaswamy V, Kanshin E, Sánchez-Osuna M, El-Hamamy I, Coutinho FJ, Prinos P, Singh S, Donovan LK, Daniels C, Schramek D, Tyers M, Weiss S, Stein LD, Lupien M, Wouters BG, Garcia BA, Arrowsmith CH, Sorensen PH, Angers S, Jabado N, Dirks PB, Mack SC*, Agnihotri S*, Rich JN*, Taylor MD*. Metabolic Regulation of the Epigenome Drives Lethal Infantile Ependymoma. Cell May;181(6):1329-1345.e24, 2020. PMID 32445698 * denotes co-corresponding author.

Donovan LK, Delaidelli A, Joseph SK, Bielamowicz K, Fousek K, Holgado BL, Manno A, Srikanthan D, Gad AZ, Van Ommeren R, Przelicki D, Richman C, Ramaswamy V, Daniels C, Pallota JG, Douglas T, Joynt ACM, Haapasalo J, Nor C, Vladoiu MC, Kuzan-Fischer CM, Garzia L, Mack SC, Varadharajan S, Baker ML, Hendrikse L, Ly M, Kharas K, Balin P, Wu X, Qin L, Huang N, Stucklin AG, Morrissy AS, Cavalli FMG, Luu B, Suarez R, De Antonellis P, Michealraj A, Rastan A, Hegde M, Komosa M, Sirbu O, Kumar SA, Abdullaev Z, Faria CC, Yip S, Hukin J, Tabori U, Hawkins C, Aldape K, Daugaard M, Maris JM, Sorensen PH, Ahmed N, Taylor MD. Locoregional delivery of CAR T cells to the cerebrospinal fluid for treatment of metastatic medulloblastoma and ependymoma. Nat Med Apr;26(5):720-731, 2020. PMID 32341580

Zhu Z, Mesci P, Bernatchez JA, Gimple RC, Wang X, Schafer ST, Wettersten HI, Beck S, Clark AE, Wu Q, Prager BC, Kim LJY, Dhanwani R, Sharma S, Garancher A, Weis SM, Mack SC, Negraes PD, Trujillo CA, Penalva LO, Feng J, Lan Z, Zhang R, Wessel AW, Dhawan S, Diamond MS, Chen CC, Wechsler-Reya RJ, Gage FH, Hu H, Siqueira-Neto JL, Muotri AR, Cheresh DA, Rich JN. Zika Virus Targets Glioblastoma Stem Cells Through a SOX2-Integrin αvβ5 Axis. Cell Stem Cell Feb 6;26(2):187-204e, 2020. PMID 31956038

Jane EP, Premkumar DR, Thambireddy S, Golbourn B, Agnihotri S, Bertrand KC, Mack SC, Myers MI, Chattopadhyay A, Taylor DL, Schurdak ME, Stern AM, Pollack IF. Targeting NAD+ biosynthesis overcomes panobinostat and bortezomib-induced malignant glioma resistance. Mol Cancer Res Jul;18(7):1004-1017, 2020. PMID 32238439

A Arabzade, A J Stuckert, K C Bertrand, S C Mack. Invited Review: The Role and Contribution of Transcriptional Enhancers in Brain Cancer Neuropathology and Applied Neurobiology, 46(1), Feb 2020. PMID 32109328

Morton AR, Dogan-Artun N, Faber ZJ, MacLeod G, Bartels CF, Piazza MS, Allan KC, Mack SC, Wang X, Gimple RC, Wu Q, Rubin BP, Shetty S, Angers S, Dirks PB, Sallari RC, Lupien M, Rich JN, Scacheri PC. Functional Enhancers Shape Extrachromosomal Oncogene Amplifications. Cell Nov;179(6):1330-1341.e13, 2019. PMID 31761532

Krug B, De Jay N, Harutyunyan AS, Deshmukh S, Marchione DM, Guilhamon P, Bertrand KC, Mikael LG, McConechy MK, Chen CCL, Khazaei S, Koncar RF, Agnihotri S, Faury D, Ellezam B, Weil AG, Ursini-Siegel J, De Carvalho DD, Dirks PB, Lewis PW, Salomoni P, Lupien M, Arrowsmith C, Lasko PF, Garcia BA, Kleinman CL, Jabado N, Mack SC. Pervasive H3K27 Acetylation Leads to ERV Expression and a Therapeutic Vulnerability in H3K27M Gliomas. Cancer Cell Sept;36(3):338-339, 2019. PMID 31526762

Dong Z, Zhang G, Qu M, Gimple RC, Wu Q, Qiu Z, Prager BC, Wang X, Kim LJY, Morton AR, Dixit D, Zhou W, Huang H, Li B, Zhu Z, Bao S, Mack SC, Chavez L, Kay SA, Rich JN. Targeting Glioblastoma Stem Cells through Disruption of the Circadian Clock. Cancer Discov Aug;9(11):1556-1573, 2019. PMID 31455674, PMC6983300

Wang X, Yang K, Wu Q, Kim LJY, Morton AR, Gimple RC, Prager BC, Shi Y, Zhou W, Bhargava S, Zhu Z, Jiang L, Tao W, Qiu Z, Zhao L, Zhang G, Li X, Agnihotri S, Mischel PS, Mack SC, Bao S, Rich JN. Targeting pyrimidine synthesis accentuates molecular therapy response in glioblastoma stem cells. Sci Transl Med Aug;11(504), 2019. PMID 31391321

Sin-Chan P, Mumal I, Suwal T, Ho B, Fan X, Singh I, Du Y, Lu M, Patel N, Torchia J, Popovski D, Fouladi M, Guilhamon P, Hansford JR, Leary S, Hoffman LM, Mulcahy Levy JM, Lassaletta A, Solano-Paez P, Rivas E, Reddy A, Gillespie GY, Gupta N, Van Meter TE, Nakamura H, Wong TT, Ra YS, Kim SK, Massimi L, Grundy RG, Fangusaro J, Johnston D, Chan J, Lafay-Cousin L, Hwang EI, Wang Y, Catchpoole D, Michaud J, Ellezam B, Ramanujachar R, Lindsay H, Taylor MD, Hawkins CE, Bouffet E, Jabado N, Singh SK, Kleinman CL, Barsyte-Lovejoy D, Li XN, Dirks PB, Lin CY, Mack SC, Rich JN, Huang A. A C19MC-LIN28A-MYCN Oncogenic Circuit Driven by Hijacked Super-enhancers Is a Distinct Therapeutic Vulnerability in ETMRs: A Lethal Brain Tumor. Cancer Cell Jul;36(1):51-67.e7, 2019. PMID 31287992

Gimple RC, Kidwell RL, Kim LJY, Sun T, Gromovsky AD, Wu Q, Wolf M, Lv D, Bhargava S, Jiang L, Prager BC, Wang X, Ye Q, Zhu Z, Zhang G, Dong Z, Zhao L, Lee D, Bi J, Sloan AE, Mischel PS, Brown JM, Cang H, Huan T, Mack SC, Xie Q, Rich JN. Glioma Stem Cell-Specific Superenhancer Promotes Polyunsaturated Fatty-Acid Synthesis to Support EGFR Signaling. Cancer Discov Jun;9(9):1248-1267, 2019. PMID 31201181, PMC6785242

Krug B, De Jay N, Harutyunyan AS, Deshmukh S, Marchione DM, Guilhamon P, Bertrand KC, Mikael LG, McConechy MK, Chen CCL, Khazaei S, Koncar RF, Agnihotri S, Faury D, Ellezam B, Weil AG, Ursini-Siegel J, De Carvalho DD, Dirks PB, Lewis PW, Salomoni P, Lupien M, Arrowsmith C, Lasko PF, Garcia BA, Kleinman CL, Jabado N, Mack SC. Pervasive H3K27 Acetylation Leads to ERV Expression and a Therapeutic Vulnerability in H3K27M Gliomas. Cancer Cell May;35(5):782-797.e8, 2019. PMID 31085178, PMC6521975

Vladoiu MC, El-Hamamy I, Donovan LK, Farooq H, Holgado BL, Sundaravadanam Y, Ramaswamy V, Hendrikse LD, Kumar S, Mack SC, Lee JJY, Fong V, Juraschka K, Przelicki D, Michealraj A, Skowron P, Luu B, Suzuki H, Morrissy AS, Cavalli FMG, Garzia L, Daniels C, Wu X, Qazi MA, Singh SK, Chan JA, Marra MA, Malkin D, Dirks P, Heisler L, Pugh T, Ng K, Notta F, Thompson EM, Kleinman CL, Joyner AL, Jabado N, Stein L, Taylor MD. Childhood cerebellar tumours mirror conserved fetal transcriptional programs. Nature Aug;572(7767):67-73, 2019. PMID 31043743

Mack SC*, Singh I, Wang X, Hirsch R, Wu Q, Villagomez R, Bernatchez JA, Zhu Z, Gimple RC, Kim LJY, Morton A, Lai S, Qiu Z, Prager BC, Bertrand KC, Mah C, Zhou W, Lee C, Barnett GH, Vogelbaum MA, Sloan AE, Chavez L, Bao S, Scacheri PC, Siqueira-Neto JL, Lin CY*, Rich JN*. Chromatin landscapes reveal developmentally encoded transcriptional states that define human glioblastoma. J Exp Med May 6;216(5):1071-1090, 2019. PMID 30948495 * denotes co-corresponding author.

Bertrand KC, Faria CC, Skowron P, Luck A, Garzia L, Wu X, Agnihotri S, Smith CA, Taylor MD, Mack SC, Rutka JT. A functional genomics approach to identify pathways of drug resistance in medulloblastoma. Acta Neuropathol Commun Dec;6(1):146, 2018. PMID 30591080

Khatua S, Mangum R, Bertrand KC, Zaky W, McCall D, Mack SC. Pediatric ependymoma: current treatment and newer therapeutic insights. Future Oncol Nov;14(30):3175-3186, 2018. PMID 30418040

Xie Q, Wu TP, Gimple RC, Li Z, Prager BC, Wu Q, Yu Y, Wang P, Wang Y, Gorkin DU, Zhang C, Dowiak AV, Lin K, Zeng C, Sui Y, Kim LJY, Miller TE, Jiang L, Lee CH, Huang Z, Fang X, Zhai K, Mack SC, Sander M, Bao S, Kerstetter-Fogle AE, Sloan AE, Xiao AZ, Rich JN. N6-methyladenine DNA Modification in Glioblastoma. Cell Nov;175(5):1228-1243.e20, 2018. PMID 30392959

Cavalli FMG, Hübner JM, Sharma T, Luu B, Sill M, Zapotocky M, Mack SC, Witt H, Lin T, Shih DJH, Ho B, Santi M, Emery L, Hukin J, Dunham C, McLendon RE, Lipp ES, Gururangan S, Grossbach A, French P, Kros JM, van Veelen MC, Rao AAN, Giannini C, Leary S, Jung S, Faria CC, Mora J, Schüller U, Alonso MM, Chan JA, Klekner A, Chambless LB, Hwang EI, Massimino M, Eberhart CG, Karajannis MA, Lu B, Liau LM, Zollo M, Ferrucci V, Carlotti C, Tirapelli DPC, Tabori U, Bouffet E, Ryzhova M, Ellison DW, Merchant TE, Gilbert MR, Armstrong TS, Korshunov A, Pfister SM, Taylor MD, Aldape K, Pajtler KW, Kool M, Ramaswamy V. Heterogeneity within the PF-EPN-B ependymoma subgroup. Acta Neuropathol Jul;136(2):227-237, 2018. PMID 30019219, PMC6373486

Sarvestani SK, Signs SA, Lefebvre V, Mack S, Ni Y, Morton A, Chan ER, Li X, Fox P, Ting A, Kalady MF, Cruise M, Ashburn J, Stiene J, Lai W, Liska D, Xiang S, Huang EH. Cancer-predicting transcriptomic and epigenetic signatures revealed for ulcerative colitis in patient-derived epithelial organoids. Oncotarget Jun;9(47):28717-28730, 2018. PMID 29983891

Pajtler KW, Wen J, Sill M, Lin T, Orisme W, Tang B, Hübner JM, Ramaswamy V, Jia S, Dalton JD, Haupfear K, Rogers HA, Punchihewa C, Lee R, Easton J, Wu G, Ritzmann TA, Chapman R, Chavez L, Boop FA, Klimo P, Sabin ND, Ogg R, Mack SC, Freibaum BD, Kim HJ, Witt H, Jones DTW, Vo B, Gajjar A, Pounds S, Onar-Thomas A, Roussel MF, Zhang J, Taylor JP, Merchant TE, Grundy R, Tatevossian RG, Taylor MD, Pfister SM, Korshunov A, Kool M, Ellison DW. Molecular heterogeneity and CXorf67 alterations in posterior fossa group A (PFA) ependymomas. Acta Neuropathol Jun;136(2):211-226, 2018. PMID 29909548

Pei S, Minhajuddin M, Adane B, Khan N, Stevens BM, Mack SC, Lai S, Rich JN, Inguva A, Shannon KM, Kim H, Tan AC, Myers JR, Ashton JM, Neff T, Pollyea DA, Smith CA, Jordan CT. AMPK/FIS1-Mediated Mitophagy Is Required for Self-Renewal of Human AML Stem Cells. Cell Stem Cell Jun;23(1):86-100.e6, 2018. PMID 29910151

Wang X, Prager BC, Wu Q, Kim LJY, Gimple RC, Shi Y, Yang K, Morton AR, Zhou W, Zhu Z, Obara EAA, Miller TE, Song A, Lai S, Hubert CG, Jin X, Huang Z, Fang X, Dixit D, Tao W, Zhai K, Chen C, Dong Z, Zhang G, Dombrowski SM, Hamerlik P, Mack SC, Bao S, Rich JN. Reciprocal Signaling between Glioblastoma Stem Cells and Differentiated Tumor Cells Promotes Malignant Progression. Cell Stem Cell Apr;22(4):514-528.e5, 2018. PMID 29625067

Wang X, Holgado BL, Ramaswamy V, Mack S, Zayne K, Remke M, Wu X, Garzia L, Daniels C, Kenney AM, Taylor MD. miR miR on the wall, who's the most malignant medulloblastoma miR of them all? Neuro Oncol Feb;20(3):313-323, 2018. PMID 28575493

Khatua S, Song A, Citla Sridhar D, Mack SC. Childhood Medulloblastoma: Current Therapies, Emerging Molecular Landscape and Newer Therapeutic Insights. Curr Neuropharmacol, 16(7):1045-1058, Jan 2018. PMID 29189165

Last update: September 2021

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