Modulating autophagy to treat CV disease

Brought to you by the Fondation Leducq Transatlantic Network of Excellence

July 2018: Drs. Nah and Mukai (the Sadoshima Laboratory) received postdoctoral fellowships from the American Heart Association.

June 2018: Drs. Fernandez and Sebti (the Levine laboratory) published a paper in Nature.

Author Correction: Disruption of the beclin 1-BCL2 autophagy regulatory complex promotes longevity in mice. Fernández ÁF, Sebti S, Wei Y, Zou Z, Shi M, McMillan KL, He C, Ting T, Liu Y, Chiang WC, Marciano DK, Schiattarella GG, Bhagat G, Moe OW, Hu MC, Levine B. Nature. 2018 Jun 19. doi: 10.1038/s41586-018-0270-4.

May 2018: Dr. Sciarretta (the Sadoshima laboratory) published a paper in JACC.

Trehalose-Induced Activation of Autophagy Improves Cardiac Remodeling After Myocardial Infarction.Sciarretta S, Yee D, Nagarajan N, Bianchi F, Saito T, Valenti V, Tong M, Del Re DP, Vecchione C, Schirone L, Forte M, Rubattu S, Shirakabe A, Boppana VS, Volpe M, Frati G, Zhai P, Sadoshima J.J Am Coll Cardiol. 2018 May 8;71(18):1999-2010. doi: 10.1016/j.jacc.2018.02.066. PMID: 29724354

Dr. Julio Madrigal-Matute (Cuervo Lab) was recently awarded a two-year AHA Postdoctoral Fellowship to complete his studies on the role of Chaperone-Mediated Autophagy and Atherosclerosis.

Drs. Otsu, Kitsis, and Sadoshima are on the air:

Congratulations to the winners of our Junior Investigator Award:

  1. Drs. Nina Kaludercic (Scorrano Lab) & Julio Madrigal-Matute (Cuervo Lab): "A role for chaperone-mediated autophagy in monoamine oxidases degradation - potential relevance for heart disease
  2. Drs. Federico Pietrocola (Kroemer Lab) & Julio Madrigal-Matute: "CMA and calorie mimetics in the protection against cardiovascular disease-associated metabolic dysregulation
  3. Kimberly Merani (Kitsis Lab): "The role of CMA in the differentiation of cardiac fibroblasts to myofibroblasts"


Dr. Toshiro Saito (Sadoshima Lab) recently competed as one of five finalists for the AHA's prestigious Louis N. and Arnold M. Katz Prize for Young Investigators.

 Dr. Julio Madrigal-Matute and Bianca Sander, September 2016

Dr. Julio Madrigal-Matute and Bianca Sander, September 2016

 Dr. Elke Marsch and Dr. Julio Madrigal-Matute, August 2016

Dr. Elke Marsch and Dr. Julio Madrigal-Matute, August 2016

Recently, the research group of Prof. Ana Maria Cuervo demonstrated that chaperone-mediated autophagy (CMA) is an important regulator of lipid metabolism (Schneider, Suh et al. 2014, Kaushik and Cuervo 2015). Likewise, studies by Dr. Judith Sluimer´s group showed that loss of prolyl hydroxylase (PHD) 1 (Marsch, Demandt et al. 2016) and PHD2 reduces cholesterol levels and alleviates atherosclerotic burden. Presence of a CMA targeting motif in the PHD amino acid sequence, as well as the long half-life of PHD proteins make them a likely target for CMA. We hypothesize that CMA might regulate cholesterol levels, in part through regulated degradation of PHD proteins. Being a member of the Leducq network has enabled an active collaboration between both groups, which has already resulted in two research exchanges of members of the Sluimer group to the Cuervo lab in 2016. Former PhD student Dr. Elke Marsch and new PhD student Bianca Sander provided hands-on help with dissection of tissues from mouse models with genetically modulated CMA and benefitted immensely from Cuervo group’s expertise in CMA. Furthermore, Bianca was able to learn important CMA-related techniques like the usage of a fluorescent CMA reporter assay to monitor this pathway. She performed immunoblot and immunofluorescence analyses of autophagy-related proteins on atherosclerosis samples and is now able to establish those techniques in the Sluimer lab. These short-term exchanges were important to align techniques for atherosclerosis and CMA in both groups. As the project evolves, we anticipate that additional exchanges in between the groups might be required in the future to further implement and standardized methodology and to accelerate data acquisition in this project. The collaboration between Cuervo and Sluimer labs has already generated exciting preliminary data in support of the interplay between CMA and PHDs in cholesterol metabolism and atherosclerosis, which was the basis of the successful acquisition of a prestigious Dr. Dekker career grant from the Dutch Heart Foundation Dekker for Dr. Judith Sluimer.