Sophie Shifman
Education:
B.A. Rutgers University (2018)
Current Position:
4th Year MSTP
2nd Year Graduate Student
Advisor:
Stella Tsirka, PhD
Graduate Program:
Molecular & Cellular Pharmacology
Research Interest:
Cells and the brain are two things I find fascinating. My research experience in both cancer biology and neuroscience has driven my aspiration to combine the two fields in my future work as a physician scientist. My previous research has focused on elucidating the effects of antidepressant on neurogenesis in the hippocampus of female mice across their reproductive cycle, on revealing cellular mechanisms of resistance to therapy in various cancer histologies via the MAPK and PI3K pathways, and on investigating new approaches in targeted and combinational therapies for tumors resistant to conventional treatment. Going forward, my work will focus on exploring the interactions between cancer cells and myeloid cells in the brain tumor microenvironment in glioblastoma, a malignant brain tumor with a dismal prognosis. In studying how cancer cells reprogram immune cells, such as microglia, bone marrow-derived macrophages (BMDMs), T cells, etc. in their environment to their own benefit using both human and mouse cell as well as in vivo murine models, and characterizing cancer stem cell propagation and autophagy as part of the inevitable process leading to relapse after initial treatment, we aim to shed light on mechanisms of resistance to the current standard of care of GBM and how to potentially overcome them.
Publications:
Rosen EY, Won HH, Zheng Y, Cocco E, Selcuklu D, Gong Y, Friedman ND, de Bruijn I, Sumer O, Bielski CM, Savin C, Bourque C, Falcon C, Clarke N, Jing X, Meng F, Zimel C, Shifman S, Kittane S, Wu F, Ladanyi M, Ebata K, Kherani J, Brandhuber BJ, Fagin J, Sherman EJ, Rekhtman N, Berger MF, Scaltriti M, Hyman DM, Taylor BS, Drilon A. The evolution of RET inhibitor resistance in RET-driven lung and thyroid cancers. Nat Commun. 2022 Mar 18;13(1):1450. doi: 10.1038/s41467-022-28848-x. Erratum in: Nat Commun. 2022 Apr 5;13(1):1936. PMID: 35304457; PMCID: PMC8933489.
Cocco E, Lee JE, Kannan S, Schram AM, Won HH, Shifman S, Kulick A, Baldino L, Toska E, Arruabarrena-Aristorena A, Kittane S, Wu F, Cai Y, Arena S, Mussolin B, Kannan R, Vasan N, Gorelick AN, Berger MF, Novoplansky O, Jagadeeshan S, Liao Y, Rix U, Misale S, Taylor BS, Bardelli A, Hechtman JF, Hyman DM, Elkabets M, De Stanchina E, Verma CS, Ventura A, Drilon A, Scaltriti M. TRK xDFG Mutations Trigger a Sensitivity Switch from Type I to II Kinase Inhibitors. Cancer Discov. January 1 2021 (11) (1) 126-141; DOI: 10.1158/2159-8290.CD-20-0571
Li BT, Michelini F, Misale S, Cocco E, Baldino L, Cai Y, Shifman S, Tu HY, Myers ML, Xu C, Mattar M, Khodos I, Little M, Qeriqi B, Weitsman G, Wilhem CJ, Lalani AS, Diala I, Freedman RA, Lin NU, Solit DB, Berger MF, Barber PR, Ng T, Offin M, Isbell JM, Jones DR, Yu HA, Thyparambil S, Liao WL, Bhalkikar A, Cecchi F, Hyman DM, Lewis JS, Buonocore DJ, Ho AL, Makker V, Reis-Filho JS, Razavi P, Arcila ME, Kris MG, Poirier JT, Shen R, Tsurutani J, Ulaner GA, de Stanchina E, Rosen N, Rudin CM, Scaltriti M. HER2-Mediated Internalization of Cytotoxic Agents in ERBB2 Amplified or Mutant Lung Cancers. Cancer Discov. 2020 May;10(5):674-687. doi: 10.1158/2159- 8290.CD-20-0215. Epub 2020 Mar 25. PMID: 32213539; PMCID: PMC7196485.
Yohn CN, Shifman S, Garino A, Diethorn E, Bokka L, Ashamalla SA, Samuels BA. Fluoxetine effects on behavior and adult hippocampal neurogenesis in female C57BL/6J mice across the estrous cycle. Psychopharmacology (Berl). 2020 May;237(5):1281- 1290. doi: 10.1007/s00213-020-05456-5. Epub 2020 Jan 21. PMID: 31965254; PMCID: PMC7196514.
Rosen EY, Goldman DA, Hechtman JF, Benayed R, Schram AM, Cocco E, Shifman S, Gong Y, Kundra R, Solomon JP, Bardelli A, Scaltriti M, Drilon A, Iasonos A, Taylor BS, Hyman DM. TRK Fusions Are Enriched in Cancers with Uncommon Histologies and the Absence of Canonical Driver Mutations. Clin Cancer Res. 2020 Apr 1;26(7):1624-1632. doi: 10.1158/1078-0432.CCR-19-3165. Epub 2019 Dec 23. PMID: 31871300; PMCID: PMC7124988.
Cocco E, Schram AM, Kulick A, Misale S, Won HH, Yaeger R, Razavi P, Ptashkin R, Hechtman JF, Toska E, Cownie J, Somwar R, Shifman S, Mattar M, Selçuklu SD, Samoila A, Guzman S, Tuch BB, Ebata K, de Stanchina E, Nagy RJ, Lanman RB, Houck-Loomis B, Patel JA, Berger MF, Ladanyi M, Hyman DM, Drilon A, Scaltriti M. Resistance to TRK inhibition mediated by convergent MAPK pathway activation. Nat Med. 2019 Sep;25(9):1422-1427. doi: 10.1038/s41591-019-0542-z. Epub 2019 Aug 12. PMID: 31406350; PMCID: PMC6736691.
Toska E, Castel P, Chhangawala S, Arruabarrena-Aristorena A, Chan C, Hristidis VC, Cocco E, Sallaku M, Xu G, Park J, Minuesa G, Shifman SG, Socci ND, Koche R, Leslie CS, Scaltriti M, Baselga J. PI3K Inhibition Activates SGK1 via a Feedback Loop to Promote Chromatin-Based Regulation of ER-Dependent Gene Expression. Cell Rep. 2019 Apr 2;27(1):294-306.e5. doi: 10.1016/j.celrep.2019.02.111. PMID: 30943409; PMCID: PMC6503687.
Cocco E, Javier Carmona F, Razavi P, Won HH, Cai Y, Rossi V, Chan C, Cownie J, Soong J, Toska E, Shifman SG, Sarotto I, Savas P, Wick MJ, Papadopoulos KP, Moriarty A, Cutler RE Jr, Avogadri-Connors F, Lalani AS, Bryce RP, Chandarlapaty S, Hyman DM, Solit DB, Boni V, Loi S, Baselga J, Berger MF, Montemurro F, Scaltriti M. Neratinib is effective in breast tumors bearing both amplification and mutation of ERBB2 (HER2). Sci Signal. 2018 Oct 9;11(551):eaat9773. doi: 10.1126/scisignal.aat9773. PMID: 30301790; PMCID: PMC6498841.
