van Berlo Lab

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Jop working in the lab

The van Berlo lab works to uncover the biological pathways that regulate cardiac regeneration. Over the past decade it has become clear that the heart contains a small fraction of cells, called stem cells or progenitor cells, which are undifferentiated and retain the capacity to become cardiomyocytes. Other labs have isolated these progenitor cells and shown their ability to form new myocytes in cell culture. We are working to determine whether these cells actively make new myocytes in the living mouse heart at baseline, and after injury. Furthermore, we are working toward uncovering the pathways that regulate whether progenitor cells differentiate down the cardiomyocyte lineage or other cardiac lineages.

The overall aim of the lab is to find new ways of stimulating cardiac regeneration that can be translated to human patient care.

Research Interests

Role of cardiac progenitor cells in vivo during cardiac development

Cardiac regeneration is the main focus of the van Berlo lab. We use genetic mouse models to visualize and interrupt cardiac progenitor cell function in vivo. There are currently a number of different clinical trials using human cardiac progenitor cells. Although the initial results appear encouraging, we actually don’t know the role of these progenitor cells in vivo. Many questions remain such as do these CPCs actually contribute to cardiac renewal and regeneration. Which CPC population has the highest potential in vivo? What are signaling pathways employed by CPCs to differentiate into various cardiac lineages. Which are the main sources of cardiac renewal, cardiomyocytes or CPCs?
We have developed new mouse models that allow genetic lineage tracing of cardiac progenitor cells in vivo. Moreover, we will unravel the signaling pathways in CPCs in vivo using a combination of immunohistochemistry, high-throughput sequencing and cell culture.

Define new regulators of cardiac hypertrophy

It is clear that cardiac hypertrophy is an important risk factor for sudden cardiac death and that it adversely affects hypertension outcome and may lead to heart failure. Furthermore, we know quite a bit about the different players that can result in cardiac hypertrophy. However, we lack an integrated overview of how cardiomyocytes deal with the various stimuli that drive cardiac hypertrophy. We will employ a comprehensive and systematic approach to study the effect of individual genes on the development of cardiac hypertrophy. This will allow us to built signaling networks and unravel nodal points that may be targeted for therapy.

Explore the role of alternative splicing in the development/progression of cardiac disease.

The relatively new field of alternative splicing in cardiomyocytes is the third focus in the lab. Although a couple of splicing factors are known to cause cardiomyopathy when deleted, there are hardly any studies that address the role of alternative splicing in the development and progression of cardiac disease. Here, we will use genetic mouse models, in combination with molecular techniques to uncover the importance of various splicing factors in the heart. The goal is to determine the role of alternative splicing in disease progression, but also to find new regulators of alternative splicing.

Publications

A complete list of publications can be found here: Experts@Minnesota / Jop van Berlo

  1. Van Berlo JH, Kanisicak O, Maillet M, Vagnozzi RJ, Karch J, Lin SCJ, Middleton RC, Marbán E, Molkentin JD. C-kit+ cells minimally contribute cardiomyocytes to the heart. Nature. 2014 May 7.
  2. Elrod JW and van Berlo JH. Unraveling the complexities of cardiac remodeling and hypertrophy – high-content screening and computational modeling. J Mol Cell Cardiol. 2014 Apr 15.
  3. Van Berlo JH, Aronow BJ, Molkentin JD. Parsing the roles of the transcription factors GATA-4 and GATA-6 in the adult cardiac hypertrophic response. PLoS One 2013 Dec 31;8(12):e84591.
  4. Van Berlo JH, Maillet M, Molkentin JD. Signaling effectors underlying pathologic growth and remodeling of the heart. J Clin Invest. 2013 Jan 2;123(1):37-45.
  5. Maillet M, van Berlo JH, Molkentin JD. Molecular basis of physiological heart growth: fundamental concepts and new players. Nat Rev Mol Cell Biol. 2012 Dec 12;14(1):38-48.

Lab Members

Jop van Berlo, Principal Investigator, jvanberl@umn.edu

Ingrid Bender, Assistant Scientist, ikbender@umn.edu

Zhongming Chen, Research Associate, chen4579@umn.edu

Dogacan Yucel, Research Associate, dyucel@umn.edu

Sadiq Umar, Post-Doctoral Associate, sumar@umn.edu

Natsumi Nemoto, Research Technician, nemot008@umn.edu

Yellamilli Amritha, Graduate Student, yella007@umn.edu

Daniel Sorensen, Graduate Student, soren871@umn.edu

Chetana Guthikonda, Undergraduate Student, guthi004@umn.edu

Thomas Hodges, Undergraduate Student, hodge210@umn.edu

Delaney Peterson, Undergraduate Student, pete9830@umn.edu

Jessica Shaklee, Undergraduate Student, shakl001@umn.edu