Ph.D. Cancer Biology, University of Lisbon Medical School
After a good meal there is a great sense of satisfaction: the body knows it received food and changes metabolism, for example, it releases insulin to help your muscles absorb much needed glucose.
How does the body know that you just ate, and a great supply of nutrients is about to be delivered? Every cell in our body has a multiprotein complex called the mammalian target of rapamycin complex - mTORC1.
Amazingly, mTORC1 senses glucose, amino acids and lipids. In the presence of these nutrients, mTORC1 is activated and re-orchestrates all cellular physiology: cells shift from catabolic (breakdown) to anabolic (synthesis) metabolism. That’s right, after a good meal all our cells know that it’s time to accumulate protein, lipids and make more DNA in case the cell wants to divide.
mTORC1 controls cell division, survival and metabolism and makes sure all these functions happen in a healthy way. But because mTORC1 is such a cellular master regulator, cancer cells very often hijack mTORC1 and make it work permanently. The outcome is uncontrolled cell growth, proliferation, survival, and metabolism – the greatest hallmarks of cancer!
My research aims at deciphering what controls mTORC1, how cancer cells exploit mTORC1, and which drugs can be used to inhibit mTORC1 and treat human cancer.
I received my Ph.D. in Cancer Biology from the Medical School of the University of Lisbon, Portugal in 2008. My PhD research was awarded a prestigious Portuguese government fellowship which allowed me to conduct all my Ph.D. research at the lab of Dr. David M Sabatini, at the Whitehead Institute at MIT.
After my PhD I moved to New York City to pursue postdoctoral studies in Cancer Biology and Neuro-Oncologic Diseases at The Rockefeller University and Hunter College of the City University of New York. During that time I received a grant to complete a Master of Science program in Clinical and Translational Investigation at Weill Cornell Medicine.
I joined SFC in 2021. What an amazing place to teach, serve, and do research with very talented undergraduate students! In my current research, I keep a close collaboration with my former mentor Prof. David Foster of Hunter College and Weill Cornell Medicine. He was an outstanding mentor and now I try to be an outstanding mentor to my undergraduate researchers!
1. * Frias MA, Foster DA. Targeting PLD-dependent production of phosphatidic acid in KRAS-driven pancreatic cancer cells. Research article in preparation.
2. Frias MA, Hatipoglu A, Foster DA. Regulation of mTOR by phosphatidic acid. Trends Endocrinol Metab. 2023 Jan 31:S1043-2760(23)00015-2. doi: 10.1016/j.tem.2023.01.004. Online ahead of print.
3. Hatipoglu A, Menon D, Levy T, Frias MA, Foster DA. Inhibiting glutamine utilization creates a synthetic lethality for suppression of ATP citrate lyase in KRas-driven cancer cells. PLoS One. 2022 Oct 21;17(10):e0276579. doi: 10.1371/journal.pone.0276579. eCollection 2022.
4. Chakraborty S, Utter MB, Frias MA, Foster DA. Cancer cells with defective RB and CDKN2A are resistant to the apoptotic effects of rapamycin. Cancer Lett. 2021 Dec 1;522:164-170. doi: 10.1016/j.canlet.2021.09.020. Epub 2021 Sep 23.
5. Frias MA, Mukhopadhyay S, Lehman E, Walasek A, Utter M, Menon D, Foster DA. Phosphatidic acid drives mTORC1 lysosomal translocation in the absence of amino acids. J Biol Chem. 2020 Jan 3;295(1):263-274. doi: 10.1074/jbc.RA119.010892. Epub 2019 Nov 24.
6. Frias MA. Targeting phosphatidic acid production in cancer cells. M.S. Thesis Dissertation, 2019, Weill Cornell Graduate School of Medical Sciences, New York, NY
Highlighted by J Biol Chem in: https://twitter.com/jbiolchem/status/1198957046323982341
7. Bernfeld E, Menon D, Vaghela V, Zerin I, Faruque P, Frias MA, Foster DA. Phospholipase D-dependent mTOR complex 1 (mTORC1) activation by glutamine. J Biol Chem, 2018, 293(42):16390-16401
8. Menon D, Salloum D, Bernfeld E, Gorodetsky E, Akselrod A, Frias MA, Sudderth J, Chen PH, DeBerardinis R, Foster DA. Lipid sensing by mTOR complexes via de novo synthesis of phosphatidic acid. J Biol Chem, 2017, 292(15):6303-6311
9. Frias MA*, Mukhopadhyay S*, Chatterjee A, Yellen P, Foster DA. The enigma of rapamycin dosage. Mol Cancer Ther, 2016, 15(3):1-7
10. Scheckel C*, Drapeau E*, Frias MA, Park CY, Fak J, Zucker-Scharff I, Kou Y, Haroutunian V, Ma’ayan A, Buxbaum JD, Darnell RB. Regulatory consequences of neuronal ELAV-like binding to coding and non-coding RNAs in human brain. eLife, 2016, 19;5, PII:e10421
11. Mukhopadhyay S, Saqcena M, Chatterjee A, Garcia A, Frias MA, Foster DA. Reciprocal Regulation of AMP-activated protein kinase and phospholipase D. J Biol Chem, 2015, 290(11):6986-6993
12. Foster DA, Salloum D, Menon D, Frias MA. Phospholipase D and the maintenance of phosphatidic acid levels for regulation of mammalian target of rapamycin. J Biol Chem, 2014, 289(33):22583-22588. Review article with 69 citations
13. Le Gendre O, Sookdeo A, Duliepre SA, Utter M, Frias M, Foster DA. Suppression of AKT phosphorylation restores rapamycin-based synthetic lethality in SMAD4-defective pancreatic cancer cells. Mol Cancer Res, 2013, 11(5):474-8. Article featured in the best research papers of 2013 of Molecular Cancer Research
14. Zhang C, Frias MA, Mele A, Ruggiu M, Eom T, Marney CB, Wang H, Licatalosi DD, Fak JJ,Darnell RB. Integrative modeling defines the Nova splicing-regulatory network and its combinatorial controls. Science, 2010, 329(5990):439-443. 241 citations, featured in Editor’s Choice of Science Signaling: H. Pickersgill, Making the final cut. Sci. Signal. 3, ec234 (2010)
15. Frias MA. Identification and characterization of novel molecular components of the mTOR complexes. Ph.D. Thesis Dissertation, 2008, Medical College of the University of Lisbon, Portugal
16. Frias MA, Thoreen CC, Jaffe JD, Schroder W, Sculley T, Carr S, Sabatini DM. mSin1 is necessary
for Akt/PKB phosphorylation, and its isoforms define three distinct mTORC2s. Curr Biol, 2006, 16 (18):1865-1870. 670 citations, featured in a Preview article of Developmental Cell: Polak P, Hall MN. mTORC2 caught in a SINful Akt, Dev Cell, 2006, 11(4):433-4
17. Vegetti W, Van Assche E, Frias A, Verheyen MM, Bonduelle M, Liebaers I, Van Steiteghem A. Correlation between semen parameters and sperm aneuploidy rates investigated by fluorescence in situ hybridization in infertile men. Hum Reprod, 2000, 15 (2): 351-365. 273 citations