Steven Artandi

Clinical Focus

• Cancer> Hematology
• Medical Oncology

Honors and Awards

• Fellow, American Association for the Advancement of Science (AAAS) (2008)

Professional Education

Postdoctoral Advisees

Jinkuk Choi , Jae-Il Park , Marina Shkreli , Luis Francisco Zirnberger Batista

Graduate & Fellowship Program Affiliations

• Cancer Biology
• Medicine

Web Site Links

• Artandi lab home page

Current Research Interests

Telomeres, the nucleotide repeats that cap the ends of eukaryotic chromosomes, serve critical roles in promoting cell viability and in maintaining chromosomal stability. In humans, telomeres shorten progressively with cell division and aging because DNA polymerase cannot fully replicate the extreme ends of chromosomes. Critical telomere shortening and loss of the protective telomere capping function in cell culture initiates senescence and crisis responses that profoundly alter chromosome stability, cell cycle progression and survival. Expression of telomerase, the reverse transcriptase that synthesizes telomere repeats, is sufficient to lengthen and stabilize telomeres, thus enabling cells to proliferate in an unlimited fashion. Telomerase is expressed in stem cells and progenitor cells in self-renewing tissues, is downregulated with differentiation and upregulated in the vast majority of human cancers. In the Artandi lab, we are interested in unraveling the molecular and cellular mechanisms according to which telomeres and telomerase modulate stem cell function and carcinogenesis.

TERT and STEM CELLS

Telomerase is comprised of two subunits: TERT, the telomerase reverse transcriptase, and TERC, the telomerase RNA component. In stem cell and progenitor cell compartments, TERT serves a critical role in maintaining telomere length and function to support tissue homeostasis. However, TERT serves an additional function in stem cells, distinct from its role in telomere lengthening. Using a conditional transgenic mouse system, we recently showed that TERT can promote proliferation of quiescent epidermal stem cells. Induction of TERT in mouse skin caused a rapid transition in hair follicle from the resting phase (telogen) to the active phase (anagen) of the hair follicle cycle and robust hair growth. We showed that this novel function for TERT was independent of TERC and therefore independent of TERT's previously understood role in telomere synthesis....

Clinical Trials

• Phase II Cont. IV of ON 01910.Na in MDS w/ Trisomy 8/Intermed-1, 2/High Risk Recruiting

Publications

• Telomeres and telomerase in cancer. Artandi SE, DePinho RA. Carcinogenesis. 2010; 31 (1): 9-18
• A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis. Venteicher AS, Abreu EB, Meng Z, McCann KE, Terns RM, Veenstra TD, Terns MP, Artandi SE. Science. 2009; 323 (5914): 644-8
• Telomerase modulates Wnt signalling by association with target gene chromatin. Park JI, Venteicher AS, Hong JY, Choi J, Jun S, Shkreli M, Chang W, Meng Z, Cheung P, Ji H, McLaughlin M, Veenstra TD, Nusse R, McCrea PD, Artandi SE. Nature. 2009; 460 (7251): 66-72
• Reverse transcribing the code for chromosome stability. Artandi SE, Cooper JP. Mol Cell. 2009; 36 (5): 715-9
• TCAB1: driving telomerase to Cajal bodies. Venteicher AS, Artandi SE. Cell Cycle. 2009; 8 (9): 1329-31