Ana Maria Cuervo, MD PhD Professor of Developmental and Molecular Biology and of Medicine; co-director of the Einstein Institute for Aging Research Albert Einstein College of Medicine Research Summary: Our research program focuses on selective autophagy and the connections of this basic cellular process with aging and agerelated disorders (namely neurodegeneration, metabolic disorders and cancer).
Address: Albert Einstein College of Medicine Jack and Pearl Resnick Campus 1300 Morris Park Avenue Chanin Building, Room 504 Bronx, NY 10461 Email:
[email protected]
Our main programmatic goals revolve around three aspects of the autophagic process and aim: 1) to perform the molecular dissection of different autophagic pathways; 2) to discover new physiological functions of different types of autophagy and 3) to fully understand the reasons for autophagic malfunctioning in aging and the contribution of this age-dependent decline to diseases of aging. Our studies have been instrumental to advance our understanding of selective mammalian autophagy and the relevance of this fundamental cellular process in aging and agerelated disorders. Our major discoveries have occurred at three levels: A) Molecular dissection of autophagy: we have 1) identified the molecular machinery that mediates translocation of substrates into lysosomes via chaperone-mediated autophagy (CMA); 2) discovered a new type of autophagy, endosomal microautophagy (e-Mi) [2], which represents a new site of interaction between endocytic and autophagic pathways; 3) demonstrated a functional integration among autophagic pathways and the establishment of compensatory mechanisms when one of them fails B) Physiology of autophagy: we have demonstrated new functions 1) for macroautophagy: in lipid metabolism through macrolipophagy, in ciliogenesis and in intercellular communication and 2) for CMA: in the defense against oxidative stress and the modulation of proteostasis and cellular energetic balance
C) Autophagy in aging and disease: we have identified a functional decline on CMA with age that, when prevented in rodents, maintains their cellular homeostasis and preserves their organs’ function until late in life. This age-dependent decrease in CMA could explain in part the aggravating effect of aging in pathologies with a connection to CMA, specifically 1) neurodegeneration: we provided the first evidence that a compromise in CMA underlies the pathogenesis of Parkinson’s disease, and have subsequently proven to be true for other neurodegenerative disorders; and 2) oncogenesis: we identified the dependence of most malignantly transformed cells on CMA and demonstrated the anti-tumoral effect of blocking CMA in cancer cells. Selected Publications: 1. Rodriguez-Navarro JA, Kaushik S, Koga H, Dall’Armi, Shui G, Wenk MR, Di Paolo G, Cuervo AM*, Inhibitory effect of dietary lipids on chaperone-mediated autophagy. Proc. Natl. Acad. Sci. 109: E705-14, 2012. 2. Pampliega O, Orhon I, Patel B, Sridhar S, Diaz-Carretero A, Beau I, Codogno P, Satir B, Satir P, Cuervo AM* Functional interaction between autophagy and ciliogenesis. Nature 502:194-200, 2013 3. Schneider JL, Suh Y, Cuervo AM*. Deficient chaperone-mediated autophagy in liver leads to metabolic disregulation. Cell Metab. 20:417-432, 2014 • Featured in News and Views (Cell Metab) 4. Schneider S, Villarroya J, Diaz A, Patel B, Urbanska AM, Thi MM, Villarroya F, Santambrogio L, Cuervo AM*. Loss of hepatic chaperone-mediated autophagy accelerates proteostasis failure in aging. Aging Cell, 14:249-64, 2015. 5. Kaushik, S. Cuervo AM*. Degradation of lipid droplet-associated proteins by chaperone-mediated autophagy facilitates lipolysis. Nat. Cell. Biol. 17: 759-70, 2015 • Featured in Perspective (Cell Metabolisml) 6. Arias E., Koga H, Diaz A, Mocholi E, Patel B, Cuervo AM*. Lysosomal mTORC2/PHLPP1/Akt regulate chaperone-mediated
autophagy. Mol. Cell 59, 1-15, 2015
More about Ana Maria Cuervo: http://www.einstein.yu.edu/faculty/8784/ana-maria-cuervo/