September 2018: Passegué Lab

Background:

What is the main focus of your lab?

The biology of the blood-forming hematopoietic stem cell (HSC), the mother of all blood cells and a key adult somatic stem cell population. I am a firm believer that this so-called "liquid organ", the blood system, is the most important tissue in the body, and is certainly one of the most fascinating. In my lab, we are interested in understanding the mechanism by which HSCs maintain their functional properties and regulate blood production during regeneration, stress, disease and aging. Recently, we have also started to investigate some developmental aspect of the establishment of the blood system.

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

I got officially hired by the University of California, San Francisco (UCSF) in December 2005, but I didn’t hire my first lab member until March 2006. I took directorship of Columbia Stem Cell Initiative 2 years ago, and my lab relocated to Columbia University last spring. So, I have had my lab for 12 years.

How big is your lab currently?

Since the relocation, my lab consists of four postdocs, a MD/PhD fellow, a graduate student, a lab manager and a junior tech, as well as a variable number rotating students and interns.

Where is your lab located?

It is a moving target. Right now, we are located on the 7th floor of the Hammer Building, but we will be relocating to the new CSCI headquarters on the 11th floor of the Black building sometime in the spring of 2019. Yes, another move, but it will be great to be together with other CSCI labs and facilities, and the view from there is also great!

Current affairs:

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

I think that all of our research projects are exciting, since I really don’t pursue projects that are boring. Each direction has interesting aspects, and it is a changing landscape with different type of excitement depending on the stage of the project. All of our work currently fits under two main directions: 1) emergency myelopoiesis and regenerative processes, and 2) blood aging. Regarding aging biology, one of our big questions is understanding of the interplay between cell-intrinsic and cell-extrinsic deregulations. We are trying to establish how much of the HSC and blood aging phenotypes come from the aging of the bone marrow niche microenvironment, what is driven by changes in HSC metabolism, and how much we can control and manipulate these processes. These questions are addressed by a senior postdoc - Evgenia Verovskaya, and a new graduate student - Paul Dellorusso. Regarding the emergency myeloid regeneration axis, we are digging into the roles of individual cytokines, as I consider them as words that the organism is using in inflammatory conditions to talk to stem and progenitor cells, and trying to understand the vocabulary of signals that are regulating regeneration in stress conditions, and during ontogeny and malignancies. These directions are pursued by two senior postdocs – Yoona Kang and Masayuki Yamashita, a medical fellow - Amélie Collins, and new postdoc - Oakley Olson. Of course, everyone in the lab benefits from the technical expertise of my lab manager- Silvere Pagant, and other staff members.

What are the biggest accomplishments that your lab recently had?

Two Nature publications coming out within the same month last year, which was a great ending of two large stories. Also, relocating my lab from the West coast to the East coast, which was a much bigger undertaking than I anticipated. Glad it is over.

Technology:

What are the model systems that your lab is using?

A lot, really a lot of mice that are either wild type, with large colonies of CD45.1 and CD45.2 C57Bl/6 mice to produce our needed donor and recipient animals, and many different genetic models (too many to name) to modulate the hematopoietic system, death mechanisms, autophagy, inflammation, etc. We are also slowly moving to using human cord blood and bone marrow samples for some questions.

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

Sharing technology is a part of building a community, so yes, we welcome other scientists to learn what we know how to do. We mainly use multiparameter flow cytometry to isolate and analyze defined populations of hematopoietic stem and progenitor cells, coupled with immunofluorescence staining on sorted cells and bone sections, primary cell culture, bone marrow transplantation, molecular investigation of sorted cells including with many Omic approaches including Fluidigm-based microfluidic multiplex qPCR and single cell RNA-Seq analysis. In terms of specialized equipment, we have a Leica cryostat equipped with the CryoJane tape transfer system and tungsten blades for sectioning un-decalcified frozen bones, the Imaris for Cell Biologist imaging software suite, a CBC machine for blood analyses, an AutoMACS cell separator for pre-enrichment approaches before cell sorting, a ViCell cell counter, a Shandon cytospin, an X-Ray mouse irradiator located on the 19th floor of the Black building, as well as an Applied Biosystems ViiATM 7 real time quantitative PCR machines and a Luminex cytokine analyzer that are located and managed by the CSCI Flow Core.

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

We do a heck of a lot of flow cytometry, so first and foremost the CSCI Flow Core. Additionally, mouse facility, histology core in the cancer center, and genomics core.

Who shall be contacted with questions about equipment, resources and training?

Silvere Pagant, my lab manager, or Evgenia Verovskaya, one of the postdocs.

Training:

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

I am selecting people, both student and postdocs, who really want to be intellectually involved in their project. I have a motto which is "It is not because you can do it that you should do it". I always ask people to rationalize and justify why they want to do a particular experiment or follow on a specific question. I see working in a lab as an apprenticeship, with a two-way relationship and communication between me and my trainees. They have to have a lot of internal drive to take advantage of my lab where we ask difficult questions. They are really the power behind their project, while I see my role much more as a facilitator to find the resources, both scientifically and financially, to move forward the science. I have an open-door policy and I really value on-on-one discussion time. During lab meetings, I really promote questions and involvement. I also value sending mentees for training to learn skills that they need, connecting them to the right collaborators, etc. I encourage my trainees to develop all the skills needed by become independent researchers including reviewing papers for publications, presenting findings, writing grants, etc. To be successful both grad student or postdoc have to have a very good pair of hands, a great flexible and analytical brain and to be a “writing machine", skills that are all trainable and that I like to develop in my mentees.

Who were your most influential mentors/role models in science and what did you learn from them?

When I was still in Europe as a PhD student and then postdoc, I was very impressed by American-trained scientists and I was looking up to that – their ease in discussion and assurance. When I came to the United States, I was surrounded by people like that - fantastic researchers that really formed an inspiring community, everyone working very hard, and it was a lot of fun. I learn a lot from then to be a better scientist. I also had very influential mentors at every stage of my career that showed me how to be a leader. Their decisions or attitude didn’t always make sense right away, but taught me a lot once I become my own PI. So, in short, both my fellow postdocs and senior mentors influenced me a lot as a scientist and faculty.

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

Of course, all the CSCI programmatic activities – seminar series, work-in-progress (WIP) talks, happy hours and annual retreat. These are events that let the trainees meet internationally renowned scientists, learn about the science conducted in other CSCI labs, and also build the stem cell community though informal events. With the recent creation of the CSCI Trainee Council, I am hoping to develop that further and answer better the need of the students and postdocs in CSCI. Additionally, I highly recommend the course on Stem Cell and Lineage Specification ran by Dieter Egli and Stephen Tsang.

What would be your career advice for students/postdocs?

If I have to give one, you have to do something that motivates you – decide where you want to take your career, and take steps to move towards it. This will allow you to make decisions, and get specific things done early enough to pursue this career choice. 

Are you accepting rotating students at the moment?

Yes.

Lab management:

How do members of your lab celebrate accomplishments?

Champagne in the lab ice buckets is an absolute must.

Does your lab have any fun traditions?

We organize a roast every time someone graduates or leaves the lab. Also, we have an annual lab retreat – while at UCSF, it was winter activity in Tahoe, and now at Columbia – it is summer time at the beach on Fire Island (shark sightings included).

What is the key to running a successful lab?

The boring answer for this question is money. You always need money to do state-of-the-art innovative research. But before the money – it is the people. Your science will be as innovative and exciting as the smart, innovator and motivated people you have hired to do it. So, the main key to success is getting the right people. And then you need money in order to deliver the results, because they all will want to do experiments that cost a fortune.

Stem Cell Directions:

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

First, to see tissue-derived stem cells moving to the clinic and therapy. Second, the fact that we are learning so much about mechanism of regulation of stem cell. In the blood field in particular, the re-emergence of inflammation, and discovery that everything controlling immunity is acting on HSCs and controlling hematopoiesis – this is an exciting new direction.

Which stem cell conferences does your lab attend?

Annual meeting of International Society for Experimental Hematology (ISEH). As the incoming ISEH president, I am bringing ISEH meeting to NYC for 2020, and I highly recommend CSCI community to attend it in two years. Of the New York-based events, NYSCF meeting is great to learn more about translational science and regeneration medicine. And of course, ISSCR.

CSCI:

What was the main reason of joining CSCI? What are the beneficial aspects of CSCI membership for your lab?

As a director, it is my privilege to being able to shape the direction of the outstanding stem cell community at Columbia University.

What do you plan to bring to the CSCI community?

I believe in the importance and power of the CSCI community, and I really encourage participation of all faculties and trainees. And I hope that this blog post can be a good start for getting to know each other.

Emmanuelle Passegué, PhD

Professor of Genetics & Development

Director, Columbia Stem Cell Initiative

A part of this interview was done for the blog of ISEH (www.simplyblood.org). Prof.  Passegué is currently serving as a vice-president of ISEH.