November 2018: Egli Lab
Background:
What is the main focus of your lab?
We are using stem cells to model human disease and understand human genetics. Specifically, we want to understand the connection between cell function and cell proliferation. Abnormalities in cell proliferation – too little or too much – is implicated in the vast majority of human diseases. In diabetes for instance, beta cells have a limited ability to regenerate and do not grow back once they are lost. From reprogramming experiments, we learned that the connection between cell proliferation and cell identity/cell function is made by the cell type specific duplication of the genome. Though the genome is the same in different cell types, it is duplicated in a cell-type specific manner. This is new biology, providing new questions and exciting projects.
How long have you had your lab? When did you join Columbia University?
Almost 5 years, since January 2014.
How big is your lab currently?
We currently have 5 graduate students, 1 post doc, 1 REI (reproduction, endocrinology, infertility) fellow, and 1 MD/PhD student
Where is your lab located?
Russ Berrie, 6th floor
Current affairs:
What are the most exciting projects/directions in the lab at this moment?
The projects in the lab are in two areas: Embryology and early human development. And development of the pancreas, stem cell differentiation to beta cells and genetics of diabetes.
Our projects in embryology include germ line gene editing to fix disease-causing mutations. We are studying genome stability in human embryonic development and reprogramming, and how this understanding can be used to improve the efficiency of both. And we are conducting clinical studies on mitochondrial replacement in human embryos. Our lab is one of very few worldwide working on human eggs and gametes.
In the pancreas, we have several projects related to the genetics of diabetes. We are interested in novel diabetes causing mutations identified by exome sequencing, and non-coding genetic variants with unknown mechanism of action. These studies lead us to new insight into the role of the cell cycle in beta cell differentiation and function.
What are the biggest accomplishments that your lab recently had?
We showed that human stem cells grow and differentiate with just half the genome, with 23 chromosomes. This cell type provides the ability to perform human genetics with the experimental flexibility of yeast cells. (https://www.ncbi.nlm.nih.gov/pubmed/26982723)
One of our most relevant findings is the insight that the duplication of the DNA is not functionally equivalent in different cell types. Though the DNA content is the same, the pattern of duplication has fundamentally important consequences on the ability to proliferate. This insight is relevant to all processes where cell proliferation is relevant, including development, cancer, and regeneration. (https://www.ncbi.nlm.nih.gov/pubmed/28263958)
We also showed that stem cells made from a patient with type 1 diabetes could efficiently differentiate to beta cells and protect mice from diabetes. This is a proof of principle for therapeutic cloning. (https://www.ncbi.nlm.nih.gov/pubmed/28931519)
Technology:
What are the model systems that your lab is using?
We use human stem cell models, and mice to functionally test our stem cells. We have numerous stem cell lines, iPS cell lines and human ES cell lines, from healthy controls and from subjects with diabetes. A complete list of lines can be viewed on our lab web page.
What are the key techniques that your lab is using? Are you open to training scientists from other labs?
Reprogramming, differentiation, CRISPR gene editing, nuclear transfer, and embryology techniques.
What facilities or equipment does your absolutely lab rely upon? Do you use CSCI cores?
We utilize the CSCI flow core frequently. We also work with the Stem Cell Core facility.
Who shall be contacted with questions about equipment, resources and training?
Training:
What's your best approach to mentoring trainees in the lab?
Providing the opportunity to study new questions and perform research at the forefront of science.
Who were your most influential mentors/role models in science and what did you learn from them?
I had great mentors during my PhD studies, pioneers in molecular biology and fundamental discoveries in cell biology. They provide a high standard and a point of reference on what is possible to accomplish in science.
Can you recommend courses/lectures in Columbia University that would be most beneficial for students/postdocs?
Courses related to bioinformatics and genomics are becoming increasingly important.
What would be your career advice for students/postdocs?
Have goals on what you want to accomplish in science.
Lab management:
How do members of your lab celebrate accomplishments?
Great food and lots of laughs
Does your lab have any fun traditions?
Secret Santa in the winter. Hiking and beach trips. Periodic dinners and nights out together.
What is the key to running a successful lab?
Keep at it. Success is not linear, but great things will come out of it.
What was the most exciting part about starting your new lab?
I had previously run a lab at the New York Stem Cell Foundation for several years, so the experience was not entirely new to me.
What has been your greatest challenge in managing your lab?
The transition from the classroom to laboratory thinking is challenging. In the classroom, the incentive is to have varied and diverse interests. The laboratory requires focus and long-term commitment. There are many interesting things one can do, but one often gets further by doing one thing, and addressing one question from multiple angles. It is at the bench where new discoveries are made.
Stem Cell Directions:
What are the most important recent developments in the stem cell field?
The ability to manipulate and interrogate the human genome at will.
Which stem cell conferences does your lab attend?
The annual conference of the International Society for Stem Cell Research
The New York Stem Cell Foundation Annual Research Conference
Other conferences students and postdocs find relevant to their research.
CSCI:
What was the main reason of joining CSCI? What are the beneficial aspects of CSCI membership for your lab?
The colleagues. There are many outstanding scientists right next door, and their knowledge and techniques often prove critical for the next step. Collaborations make all the difference.
What do you plan to bring to the CSCI community?
A dynamic lab with opportunities for collaborations and with much excitement about the discoveries that are being made at CSCI.