Egli Lab

Overview of our research programs

Developmental determinants the early embryo

The beginning of life is important because it will impact everything that occurs later. We still know very little about early human embryonic development. This is also why our ability to help the health of the early embryo is nearly inexistent. Abnormal development and failure to develop is very common in our species, and human reproduction is associated with high risks of genetic and developmental abnormalities. We know more about the early development of mice or worms that we know about ourselves. This is a major gap of knowledge and of clinical capabilities and an area we do want to help address. 

Our question is what are the mechanisms that result in abnormal and failed human development, and how can we prevent such adverse events. The promise of these studies is to improve the efficiency of fertility treatments, to reduce the burden of disease-causing genetic change, and increase the chances of parents to have a healthy child.

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Publications on this topic:

• Review on heritable gene editing by Turocy et al. Cell 2020.

• Chromosomal consequences of a DSB in human embryos published in Cell. Zuccaro et al. 2020. PMID: 33125898 ​. Press release here. Read about it in the New York Times, the WIRED, the Wall Street Journal. STAT. Watch the first author Michael Zuccaro present it here.

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Understanding metabolic disease using pluripotent stem cells

An important question of cell biology are the limitations in cell proliferation of different cell types. These limitations determine size and proportions of adult organs, and the ability to regenerate. Beta cells and the cells of the pancreas have a low ability to regenerate, while stem cells have unlimited regenerative potential. What determines these differences, and how can they be exploited for therapeutic use? An important goal of these studies are to develop cell therapies for diabetes. We are now able to generate stem cells from a patient with diabetes, correct a gene, and show that these cells produce and secrete insulin when needed. This should allow the treatment of diabetes with the patient's own cells. 

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Publications related to this subject:

• Bryan Gonzalez, PhD, shows the power of a stem cell model to study diabetes caused by HNF1A deficiency. Read the article in Communications Biology. pdf

• Read the paper published by Lina Sui in JCI insight, showing how reducing replication fork speed promotes endocrine differentiation from pluripotent stem cells and how it controls growth potential.

• PhD student and China Scholarship council scholar Shuangyu Ma publishes proof of principle on gene and cell therapy for diabetes. Read more in Stem Cell Reports

• In this manuscript postdoctoral fellow Lina Sui shows that stem cells matched to a patient with type 1 diabetes, derived by somatic cell nuclear transfer, can be differentiated with high efficiency to beta cells, and can protect mice from diabetes. Read more in Diabetes.

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Genome stability during cell type transitions

We are using somatic cell reprogramming to address a fundamental question of cellular biology. What keeps cells within a specific differentiated state? Our studies identify an important role of genome instability and the cell cycle as the primary obstacle to induced cell type transitions. The origin and type of damage, as well as the repair pathways required to fix the damage are not entirely known. We are studying reprogramming mechanisms in two experimental systems, somatic cell nuclear transfer and induced pluripotency.

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Some notable studies of our lab related to this subject are:

• Giacomo Diedenhofen, MD student, and rotation student Kunheng Cai publish on how to improve homologous recombination with the Ciccia lab: Nature Communications 2019.  

• Ido Sagi, Michael Zuccaro and Joao de Pinho, in a collaboration with the Benvenisty laboratory publish on human pluripotent stem cells containing only a paternal genome. Cell Stem Cell 2019. This study helps understand reproductive tumors and developmental disorders such as Prader-Willi syndrome.

• Daniela Georgieva publishes a new method to sequence replicated DNA using pore sequencing. Read the article in NAR.

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Cell Line Repository

We have an extensive list of various diabetes and control cell lines available in our cell line repository. Please see the Cell Line Repository Tab if you are interested in working with any of our cell lines.

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If you have questions about our research, or would like to learn more, please consult the cell line repository page.

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• Celebrating 20 years of human ES cells: read more in Nature