May 2019: Doege Lab

Background:

What is the main focus of your lab?

We are using human stem cell technology to generate hypothalamic neurons that can model genetic forms of obesity in vitro. Our goal is to understand the molecular mechanisms controlling human body weight. Thanks to large-scale sequencing efforts of our collaborators we now have novel candidate genes which could potentially account for specific instances of human obesity. Importantly, these genes are predominantly expressed in various hypothalamic neuronal populations and thus, we are generating the appropriate patient-specific hypothalamic neuronal cell types using 2D and 3D differentiation approaches.

How long have you had your lab? When did you join Columbia University?

I started my lab in the Naomi Berrie Diabetes Center in 2014 and joined the Columbia Stem Cell Initiative in 2017.

How big is your lab currently?

Steadily growing. We are a team of 6 people, and we are always looking for talent.

Where is your lab located?

We are on the 6th floor of Russ Berrie Medical Science Pavilion surrounded by an amazing array of colleagues and collaborators.

Current affairs:

What are the most exciting projects/directions in the lab at this moment?

We are excited about all our ongoing projects.

Maria Caterina De Rosa, PhD (Associate Research Scientist) is focused on generating neuronal subtypes of the paraventricular nucleus of the human hypothalamus. Among these are those affected by the most common monogenic form of human obesity – mutations in the melanocortin-4 receptor (MC4R).

Our undergraduate student, Jerica Tan (Barnard College) generates human hypothalamic agouti-related peptide (AgRP)-expressing arcuate neurons which participate in control of ingestive behavior. We hope to use them as a tool to screen for appetite-reducing drugs.

Yanjun Xu, PhD (Visiting Postdoctoral Research Scientist from the Helmholtz Center in Munich, Germany) works on the functional role of the transcription factor TBX3 in human body weight regulation. In this collaborative project with the group of Matthias Tschöp (Helmholtz Center), we have been able to assess the impact of TBX3 on human stem cell-derived arcuate-like hypothalamic neurons.

Zhangji Dong, PhD (Berrie Scholar and Visiting Scientist from Nantong University, Nantong, Jiangsu, China) studies the molecular basis of the association of obesity and Alzheimer’s disease.

Daniele Neri, Rotation PhD student (Nutrition and Metabolic Biology) has been analyzing large-scale single-cell RNA sequencing data of the hypothalamus. We aim here to map novel obesity candidate genes to the metabolically relevant cell types.

What are the biggest accomplishments that your lab recently had?

We have been able to demonstrate the utility of human pluripotent stem cells for the modeling of obesity-relevant phenotypes. Maria Caterina just presented her work at the Keystone meeting in Banff, Alberta, Canada on the Functional Neurocircuitry of Feeding and Feeding Disorders. And in collaboration with Matthias Tschoep and colleagues at the Helmholtz Center in Munich, Germany we published on the role of Tbx3 in the regulation of body weight in Nature Metabolism (https://www.nature.com/articles/s42255-018-0028-1.pdf).

Technology:

What are the model systems that your lab is using?

We are creating patient-specific iPSC lines carrying obesity-associated mutations and their isogenic controls.

What are the key techniques that your lab is using? Are you open to training scientists from other labs?

Human pluripotent stem cell culture, CRISPR, hypothalamic neuron differentiation using 2D and 3D approaches, single-cell RNA sequencing using 10X Genomics including data analysis, single-molecule flourescence in situ hybridization (RNAscope). And yes, we are open to training other scientists and currently do so under the auspices of the NIH funded NY Nutrition Obesity Research Center.

What facilities or equipment does your absolutely lab rely upon? Do you use CSCI cores?

We are pretty much live in our tissue culture room. That’s the heart of the lab where all the cool things happen.

Training:

What's your best approach to mentoring trainees in the lab?

Taking lots of time to listen to them, identifying projects suitable to their skills and interests. Positive reinforcement and constructive criticism are the keys to maintaining a productive and educational environment.

Can you recommend courses/lectures in Columbia University that would be most beneficial for students/postdocs?

Come to our Work in Progress Meetings. Actively participate either by presenting your work or asking lots of questions.

What would be your career advice for students/postdocs?

Do what you truly enjoy, find the topic what fascinates you most, and inspires your curiosity. You will be successful if you love what you do.

CSCI:

What was the main reason of you joining CSCI?

It’s a great pleasure to work with the members of the CSCI community, very stimulating scientific atmosphere, great discussions, and of course, all our lab members still talk about the retreat last year.

What do you plan to bring to the CSCI community?

My driven lab members, eager to do their part in moving the field forward. Helping others and learning from them.

Lab management:

Does your lab have any fun traditions?

Breakfast meeting on Tuesday mornings, discussion about anything life or lab in relaxed atmosphere.

What is the key to running a successful lab?

Never forget that science is a team effort. Believe in your people. They are the key to success. Make sure that there is always enough funding so they can do their jobs

What has been your greatest challenge in managing your lab?

It took me quite a while to find my team.

What are the most important recent developments in the stem cell field?

The use of patient-specific stem cells for disease modeling and the move towards translational applications.

Which stem cell conferences does your lab attend?

ISSCR, Keystone, NYSCF conference

 

 

This blog is an initiative of CSCI Trainee Council. If you want to feature your lab, please contact Genia (ev2396@cumc.columbia.edu.)