Julien Sage

Administrative Appointments

• Member, Institute for Stem Cell Biology and Regenerative Medicine (2006 - present)

Honors and Awards

• Scholar Award, Damon Runyon Cancer Research Foundation (2005-2008)
• Scholar Award, Leukemia and Lymphoma Society (2009-2014)

Professional Education

Postdoctoral Advisees

Ursula Ehmer,  Phillip Garfin,  Jamie Imam,  Nadine Jahchan,  Michael Kareta,  Pawel Mazur,  Kwon-Sik Park

Graduate & Fellowship Program Affiliations

• Cancer Biology
• Genetics
• Pediatrics

Internet Links

• the Sage lab

Current Research Interests

The accumulation of genetic and epigenetic alterations transforms normal cells into cancer cells. But how does cancer initiate? In the hierarchy from stem cells to terminally differentiated cells present in adult tissues, what cell types have the potential to act as target cells for cancer? And how do these mutant cells become cancer stem cells? Key issues in the cancer field are to identify the target cells for cancer initiation and to determine the nature and consequences of cancer-initiating lesions.

To address these basic questions, we study the mechanisms of action of the retinoblastoma (RB) tumor suppressor gene. RB is a potent tumor suppressor that is mutated in a broad range of human tumors. RB has been implicated in the control of multiple cellular processes, including cell cycle progression, senescence, cell death, chromatin structure, chromosomal stability and cellular differentiation.

A focus of the lab is to identify the cell of origins of various cancers and to determine what function(s) of RB and its two family members p107 and p130 are critical for tumor suppression. In particular, our data indicate that altering the function of RB family members in adult stem cells initiate cancer in several organs and tissues and we are actively investigating the mechanisms underlying these observations.

Because of the role of RB in the control of proper embryonic development and differentiation, and because of accumulating evidence that RB family members interact with chromatin remodeling factors, a second focus of the lab is to investigate the role of RB in embryonic stem cells (from mice and humans) as well as during the reprogramming of iPS cells and during regeneration using the flatworm Schmidtea mediterranea as a model organism. We are particularly interested in investigating links between the basic cell cycle machinery and factors involved in cellular reprogramming as well as lineage fate decisions.

Publications

• Newly identified aspects of tumor suppression by RB. Viatour P, Sage J. Dis Model Mech. 2011 Sep-Oct; 4 (5): 581-5
• A crucial requirement for Hedgehog signaling in small cell lung cancer. Park KS, Martelotto LG, Peifer M, Sos ML, Karnezis AN, Mahjoub MR, Bernard K, Conklin JF, Szczepny A, Yuan J, Guo R, Ospina B, Falzon J, Bennett S, Brown TJ, Markovic A, Devereux WL, Ocasio CA, Chen JK, Stearns T, Thomas RK, Dorsch M, Buonamici S, Watkins DN, Peacock CD, Sage J. Nat Med. 2011; 17 (11): 1504-8
• Characterization of the cell of origin for small cell lung cancer. Park KS, Liang MC, Raiser DM, Zamponi R, Roach RR, Curtis SJ, Walton Z, Schaffer BE, Roake CM, Zmoos AF, Kriegel C, Wong KK, Sage J, Kim CF. Cell Cycle. 2011; 10 (16): 2806-15
• Discovery and preclinical validation of drug indications using compendia of public gene expression data. Sirota M, Dudley JT, Kim J, Chiang AP, Morgan AA, Sweet-Cordero A, Sage J, Butte AJ. Sci Transl Med. 2011; 3 (96): 96ra77
• Functional interactions between retinoblastoma and c-MYC in a mouse model of hepatocellular carcinoma. Saddic LA, Wirt S, Vogel H, Felsher DW, Sage J. PLoS One. 2011; 6 (5): e19758