Tumor Initiation and Maintenance Program

fluorescently stained skin cancer sample

How cancer begins

Cells become cancerous after acquiring a series of mutations in their DNA, which occur as a result of exposure to radiation, cigarette smoke, dietary components or a genetic predisposition.

Mutations may intensify or eliminate the messages cells use to grow, stop growing or die. Cells then begin to divide too often and are unable to die, forming tumors. Identifying the mutations, signals and mechanisms that promote and sustain tumors creates new opportunities to target human cancer.

Director's statement

We’ve brought together scientists with expertise in developmental and stem cell biology with investigators who focus on RNA biology and the signaling pathways that regulate cell growth and cell fate. The diversity of our faculty members, along with our shared interests in what drives cancer cell growth, is fostering strong interactions that will lead to breakthrough treatments for brain, breast and prostate cancers, as well as melanoma and leukemia.

– Robert Wechsler-Reya, Ph.D., Program Director

Appointments

Publications

EGFR-Pak Signaling Selectively Regulates Glutamine Deprivation-Induced Macropinocytosis.

Lee SW, Zhang Y, Jung M, Cruz N, Alas B, Commisso C

Dev Cell 2019 Aug 5 ;50(3):381-392.e5

Lsd1 as a therapeutic target in Gfi1-activated medulloblastoma.

Lee C, Rudneva VA, Erkek S, Zapatka M, Chau LQ, Tacheva-Grigorova SK, Garancher A, Rusert JM, Aksoy O, Lea R, Mohammad HP, Wang J, Weiss WA, Grimes HL, Pfister SM, Northcott PA, Wechsler-Reya RJ

Nat Commun 2019 Jan 18 ;10(1):332

Gut microbiota dependent anti-tumor immunity restricts melanoma growth in Rnf5-/- mice.

Li Y, Tinoco R, Elmén L, Segota I, Xian Y, Fujita Y, Sahu A, Zarecki R, Marie K, Feng Y, Khateb A, Frederick DT, Ashkenazi SK, Kim H, Perez EG, Day CP, Segura Muñoz RS, Schmaltz R, Yooseph S, Tam MA, Zhang T, Avitan-Hersh E, Tzur L, Roizman S, Boyango I, Bar-Sela G, Orian A, Kaufman RJ, Bosenberg M, Goding CR, Baaten B, Levesque MP, Dummer R, Brown K, Merlino G, Ruppin E, Flaherty K, Ramer-Tait A, Long T, Peterson SN, Bradley LM, Ronai ZA

Nat Commun 2019 Apr 2 ;10(1):1492

Translational reprogramming marks adaptation to asparagine restriction in cancer.

Pathria G, Lee JS, Hasnis E, Tandoc K, Scott DA, Verma S, Feng Y, Larue L, Sahu AD, Topisirovic I, Ruppin E, Ronai ZA

Nat Cell Biol 2019 Nov 18 ;

Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma.

Suzuki H, Kumar SA, Shuai S, Diaz-Navarro A, Gutierrez-Fernandez A, De Antonellis P, Cavalli FMG, Juraschka K, Farooq H, Shibahara I, Vladoiu MC, Zhang J, Abeysundara N, Przelicki D, Skowron P, Gauer N, Luu B, Daniels C, Wu X, Forget A, Momin A, Wang J, Dong W, Kim SK, Grajkowska WA, Jouvet A, Fèvre-Montange M, Garrè ML, Nageswara Rao AA, Giannini C, Kros JM, French PJ, Jabado N, Ng HK, Poon WS, Eberhart CG, Pollack IF, Olson JM, Weiss WA, Kumabe T, López-Aguilar E, Lach B, Massimino M, Van Meir EG, Rubin JB, Vibhakar R, Chambless LB, Kijima N, Klekner A, Bognár L, Chan JA, Faria CC, Ragoussis J, Pfister SM, Goldenberg A, Wechsler-Reya RJ, Bailey SD, Garzia L, Morrissy AS, Marra MA, Huang X, Malkin D, Ayrault O, Ramaswamy V, Puente XS, Calarco JA, Stein L, Taylor MD

Nature 2019 Oct ;574(7780):707-711

Recurrent non-coding U1-snRNA mutations drive cryptic splicing in Shh medulloblastoma.

Suzuki H, Kumar SA, Shuai S, Diaz-Navarro A, Gutierrez-Fernandez A, De Antonellis P, Cavalli FMG, Juraschka K, Farooq H, Shibahara I, Vladoiu MC, Zhang J, Abeysundara N, Przelicki D, Skowron P, Gauer N, Luu B, Daniels C, Wu X, Forget A, Momin A, Wang J, Dong W, Kim SK, Grajkowska WA, Jouvet A, Fèvre-Montange M, Garrè ML, Rao AAN, Giannini C, Kros JM, French PJ, Jabado N, Ng HK, Poon WS, Eberhart CG, Pollack IF, Olson JM, Weiss WA, Kumabe T, López-Aguilar E, Lach B, Massimino M, Van Meir EG, Rubin JB, Vibhakar R, Chambless LB, Kijima N, Klekner A, Bognár L, Chan JA, Faria CC, Ragoussis J, Pfister SM, Goldenberg A, Wechsler-Reya RJ, Bailey SD, Garzia L, Morrissy AS, Marra MA, Huang X, Malkin D, Ayrault O, Ramaswamy V, Puente XS, Calarco JA, Stein L, Taylor MD

Nature 2019 Oct 9 ;

Nilotinib, an approved leukemia drug, inhibits smoothened signaling in Hedgehog-dependent medulloblastoma.

Chahal KK, Li J, Kufareva I, Parle M, Durden DL, Wechsler-Reya RJ, Chen CC, Abagyan R

PLoS One 2019 ;14(9):e0214901

The role of TP53 in acute myeloid leukemia: Challenges and opportunities.

Barbosa K, Li S, Adams PD, Deshpande AJ

Genes Chromosomes Cancer 2019 Dec ;58(12):875-888

Resolving medulloblastoma cellular architecture by single-cell genomics.

Hovestadt V, Smith KS, Bihannic L, Filbin MG, Shaw ML, Baumgartner A, DeWitt JC, Groves A, Mayr L, Weisman HR, Richman AR, Shore ME, Goumnerova L, Rosencrance C, Carter RA, Phoenix TN, Hadley JL, Tong Y, Houston J, Ashmun RA, DeCuypere M, Sharma T, Flasch D, Silkov A, Ligon KL, Pomeroy SL, Rivera MN, Rozenblatt-Rosen O, Rusert JM, Wechsler-Reya RJ, Li XN, Peyrl A, Gojo J, Kirchhofer D, Lötsch D, Czech T, Dorfer C, Haberler C, Geyeregger R, Halfmann A, Gawad C, Easton J, Pfister SM, Regev A, Gajjar A, Orr BA, Slavc I, Robinson GW, Bernstein BE, Suvà ML, Northcott PA

Nature 2019 Aug ;572(7767):74-79

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