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



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

FBXO44 promotes DNA replication-coupled repetitive element silencing in cancer cells.

Shen JZ, Qiu Z, Wu Q, Finlay D, Garcia G, Sun D, Rantala J, Barshop W, Hope JL, Gimple RC, Sangfelt O, Bradley LM, Wohlschlegel J, Rich JN, Spruck C

Cell 2020 Dec 18 ;

Triple‑negative breast cancer therapy: Current and future perspectives (Review).

Won KA, Spruck C

Int J Oncol 2020 Dec ;57(6):1245-1261

Functional Precision Medicine Identifies New Therapeutic Candidates for Medulloblastoma.

Rusert JM, Juarez EF, Brabetz S, Jensen J, Garancher A, Chau LQ, Tacheva-Grigorova SK, Wahab S, Udaka YT, Finlay D, Seker-Cin H, Reardon B, Gröbner S, Serrano J, Ecker J, Qi L, Kogiso M, Du Y, Baxter PA, Henderson JJ, Berens ME, Vuori K, Milde T, Cho YJ, Li XN, Olson JM, Reyes I, Snuderl M, Wong TC, Dimmock DP, Nahas SA, Malicki D, Crawford JR, Levy ML, Van Allen EM, Pfister SM, Tamayo P, Kool M, Mesirov JP, Wechsler-Reya RJ

Cancer Res 2020 Dec 1 ;80(23):5393-5407

The RNA m6A reader YTHDF2 maintains oncogene expression and is a targetable dependency in glioblastoma stem cells.

Dixit D, Prager BC, Gimple RC, Poh HX, Wang Y, Wu Q, Qiu Z, Kidwell RL, Kim LJY, Xie Q, Vitting-Seerup K, Bhargava S, Dong Z, Jiang L, Zhu Z, Hamerlik P, Jaffrey SR, Zhao JC, Wang X, Rich JN

Cancer Discov 2020 Oct 6 ;

Rac1 and EGFR cooperate to activate Pak in response to nutrient stress.

Lee SW, Commisso C

Biochem Biophys Res Commun 2020 Dec 10 ;533(3):437-441

Metabolic regulation of EGFR effector and feedback signaling in pancreatic cancer cells requires K-Ras.

Lee SW, Commisso C

Biochem Biophys Res Commun 2020 Dec 10 ;533(3):424-428

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