Scientific Research

AT_Cell_Reports_Small.jpg

Exploring the interactions between tumor suppressor genes, metabolism, and cell death in cancer

Research

Doctoral Dissertation: The role of p53 in Ferroptosis

Laboratory of Dr. Scott Dixon, Stanford University.

Ferroptosis is an oxidative, iron-dependent form of non-apoptotic cell death that occurs due to the lethal accumulation of toxic lipid reactive oxygen species (ROS). The stabilization of the p53 tumor suppressor protein and its downstream transcriptional target CDKN1A (p21), promote cell survival under conditions of metabolic stress that trigger ferroptosis in human and murine cancer cells. This work further supports the role of p53 as a mediator of cellular stress responses and metabolic adaptation.

Publications

1. Tarangelo, A. & Dixon, S.J. (2016) Nanomedicine: An iron age for cancer therapy. Nature Nanotech. 11.

2. Tarangelo, A., Magtanong, L., Li, Y., Bieging-Rolett, K., Yi, J., Attardi, LD., Dixon, SJ. (2018) p53 suppresses metabolic stress-induced ferroptosis in cancer cells. Cell Reports. 22 (3).

3. Tarangelo, A., Dixon, SJ. (2018) The p53-p21 pathway inhibits ferroptosis during metabolic stress. Oncotarget. 9 (37)

4. Magtanong, L., Ko, PJ., To, M., Cao, JY., Forcina, G., Tarangelo, A. ... Dixon, S.J. Exogenous Monounsaturated Fatty Acids Suppress Non-Apoptotic Cell Death. Cell Chemical Biology. Cell Chemical Biology (In Press).

Post-Baccalaureate: Amplification of E2F transcriptional activity in Rb-family Deficient hepatocellular carcinoma

Laboratory of Dr. Patrick Viatour, Children's Hospital of Philadelphia/ University of Pennsylvania

The Rb-family of tumor suppressors (Rb, p107, p130) are functionally lost in the majority of human hepatocellular carcinomas. Rb-family loss leads to the enhanced transcription of numerous genes implicated in tumor initiation and progression. In the absence of the Rb-family, the activity of the E2F1 transcription factor becomes progressively amplified. E2F1 accumulation allows for the recruitment of a chromatin-remodeling complex that enhances chromatin accessibility. Subsequent remodeling of the chromatin landscape enhances the transcriptional output of key genes that drive cancer progression. These target genes include many metabolic enzymes implicated in glycolytic metabolism. This work defines a transcriptional and epigenetic mechanism by which Rb-family loss leads to the progressive acquisition of oncogenic phenotypes, such as the Warburg Effect.

Publications

1. Tarangelo, A., Lo, N., Teng, R., Kim, E., Le, L., Watson, D., Furth EE., Raman, P., Ehmer, U., Viatour, P. (2015). Recruitment of Pontin/Reptin by E2f1 amplifies E2f transcriptional response during cancer progression. Nature Communications, 6.

2. Kim, E., Cheng, Y., Bolton-Gillespie, E., Cai, X., Ma, C., Tarangelo, A., Le, L. Jambhekar, M., Raman, P., Hayer, KE., Wertheim, G., Speck, NA., Tong, W., Viatour, P. (2017) Rb family proteins enforce the homeostasis of quiescent hematopoietic stem cells by repressing Socs3 expression. J. Exp. Med. 20160719.

Curriculum Vitae

Education

2014- Present               

Stanford University, Stanford, CA
Ph.D. Candidate, Program in Cancer Biology
National Science Foundation Graduate Research Fellow (NSF GRFP)
NIH/NCI Predoctoral to Postdoctoral Transition Fellow (F99/K00)

2009-2012                    

University of Pennsylvania, Philadelphia, PA
B.A., summa cum laude, Phi Beta Kappa
Double major with honors in Biology and in Visual Studies

2008-2009                   

Haverford College, Haverford, PA

Fellowships

2018

NIH/NCI Predoctoral to Postdoctoral Transition Award Recipient (F99/K00)

NIH/NCI Ruth L. Kirschstein National Research Service Award Individual Predoctoral Fellowship Recipient (F31)

2015

National Science Foundation Graduate Research Fellowship Program (GRFP) Recipient

Honors and Awards

2017

Oral Presentation Award, Fusion Conference on Cell Death, Cell Stress, and Metabolism, Cancun, Mexico

Oral Presentation Award, Stanford Cancer Biology Annual Retreat, San Jose, CA

2014                               

Poster Presentation Award, Children’s Hospital of Philadelphia Discovery to Innovation Poster Day, Philadelphia, PA

2012 

Phi Beta Kappa Society Member, Delta Chapter, University of Pennsylvania

Recipient of Charles Willson Peale Prize in Visual Studies, Department of Visual Students, University of Pennsylvania

Presentations

2018                                      

Tarangelo, A., Magtanong, L., Bieging-Rolett, K., Li, Y., Yi, J., Attardi, LD., Dixon, SJ. The p53-p21 axis suppresses metabolic stress-induced ferroptosis (September 30th, 2018). American Association for Cancer Research Conference on Metabolism and Cancer, Brooklyn, New York. (Oral presentation and poster presentation)

Tarangelo, A., Magtanong, L., Bieging-Rolett, K., Li, Y., Yi, J., Attardi, LD., Dixon, SJ. The p53-p21 axis suppresses metabolic stress-induced ferroptosis (September 15th, 2018). Annual Stanford Cancer Biology Retreat. San Jose, CA. (Oral presentation)

Tarangelo, A., Magtanong, L., Bieging-Rolett, K., Li, Y., Yi, J., Attardi, LD., Dixon, SJ. The p53-p21 pathway suppresses non-apoptotic cell death through metabolic rewiring. (June 25th, 2018). 2nd Annual Stanford ChEM-H Chemical/Biology Interface Retreat. Menlo Park, CA. (Poster presentation)

Tarangelo, A. The adventure beyond your door: Reflections on life, cell death, and grad school. (Mar 1st, 2018). Presentation for approximately 400 prospective graduate students at the Stanford Biosciences Recruitment Welcome Breakfast. (Oral presentation)

2017                                 

Tarangelo, A. & Dixon, S.J. Turning to the dark side: p53 in cancer cell survival and metabolic adaptation. (Nov 17th, 2017). Stanford Biology Department Seminar Series. Stanford, CA. (Oral presentation)

Tarangelo, A., Bieging-Rolett, K., Li, Y., Yi, J., Attardi, LD., Dixon, SJ. The p53-p21 pathway suppresses non-apoptotic cell death through metabolic rewiring. (Sept 15th, 2017). Stanford Cancer Biology Program 40th Annual Conference. San Jose, California. (Poster presentation)

Tarangelo, A. & Dixon, S.J. Turning to the dark side: The role of p53 in survival and metabolic adaptation. (May 30th, 2017). Stanford Cancer Biology Program Seminar (Oral presentation)

Tarangelo, A. & Dixon, S.J. Investigating the role of p53 in non-apoptotic cell death. (Mar. 16th, 2017). FUSION Conference on Cell Death, Cell Stress, and Metabolism. Cancún, Mexico. (Oral presentation, selected for award) 

Tarangelo, A. & Dixon, S.J. Death Metal: The role of p53 in ferroptosis. (Mar. 3rd, 2017). Presentation for incoming students at the Stanford Cancer Biology Recruitment Weekend. (Oral presentation)

2016                                         

Tarangelo, A. & Dixon, S.J. Investigating the role of p53 in non-apoptotic cell death. (Sept. 22nd, 2016). Stanford Cancer Biology Program 39th Annual Conference. San Jose, California. (Oral presentation, selected for award) 

2015                                        

Tarangelo, A. & Dixon, S.J. Investigating the role of p53 in ferroptosis. (Sept. 25th, 2015) Stanford Biology Department Seminar. (Oral presentation) 

Conlon, M., Tarangelo, A., Ko, P., Dixon, S. J.  Regulation of ferroptosis by metabolic and signaling networks. (Sept. 16th, 2015) Cold Spring Harbor Meeting on Cell Death (Poster presentation)

2014                                        

Tarangelo, A., Lo, N., Le, L., Watson, D., Viatour, P.  Recruitment of Pontin/Reptin by E2f1 amplifies E2f transcriptional response during cancer progression. (Feb. 24th, 2014) Children’s Hospital of Philadelphia Discovery to Innovation Poster Day. (Poster presentation, selected for award) 

2012

Tarangelo, A., Kurzweil, V., Oliver, PM. Gastrointestinal microbiota do not significantly contribute to T cell activation or GI inflammation in Ndfip1-cKO mice. University of Pennsylvania 4th Annual Undergraduate Research Symposium, (Feb. 9th, 2012). (Poster presentation)

Outreach and Leadership

2018-2019                         

Stanford Graduate Student Council School, Co-Chair, School of Med. Representative: I serve as Co-Chair of the Graduate Student Council, the branch of Stanford’s student government representing graduate students under the Associated Students of Stanford University (ASSU)

2017-2018 

Admissions Committee Student Member, Stanford Cancer Biology Program: As one of two student members of the admissions committee, I evaluated applicants for admission to the Cancer Biology program for the 2018-2019 academic year. 

2016-2017 

Program Representative, Stanford Biosciences Student Association (SBSA) Executive Committee: I represented the interests of my classmates and advised the direction of SBSA programs and resources.

2015-2016                           

Social Activities Chair, Stanford Biosciences Student Association (SBSA) Executive Committee: I planned monthly events for Stanford Biosciences graduate students to promote community building and student wellness.

2015-2017                           

Graduate Student Volunteer, Stanford Science Pen Pals Program: I wrote letters to underprivileged high school students throughout the southwestern United States to foster interest in STEM careers. 

2014-2017                           

Alumni Volunteer, Alumni Interviewer for the University of Pennsylvania: I served as an alumni interviewer and conduct admissions interviews of high school students applying to the University of Pennsylvania.