July 2019: Kousteni Lab

Background:

What is the main focus of your lab?

We study the multiple functions of mesenchymal stem cells of the bone marrow in hematopoietic stem cell (HSC) fate, with an emphasis in the development of myeloid hematological malignancies: Myelodysplasia (MDS) and Acute Myeloid Leukemia (AML). Specifically, we are exploring how extrinsic factors triggered from the bone marrow stroma microenvironment can affect growth of disease-initiating stem cells in MDS or AML as well as the transformation of MDS to AML.

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

I started my lab when I moved to Columbia University in July of 2006.

How big is your lab currently?

Currently, the lab has a research assistant professor, 2 associate research scientists, 3 postdocs and one graduate student. Throughout the years we host trainees from various programs. The summer is our busiest time of the year since we host undergraduate trainees from the SPURS program of the Department of Physiology and Cellular Biophysics for underrepresented students, a teacher trainee from Columbia’s Summer Research Program for Science Teachers, undergraduates from NYIT and visiting scientists or postdocs from various Universities.

Where is your lab located?

Black Building 8th floor Room 1412

Current affairs:

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

Alvaro Cuesta-Dominguez, a post-doctoral fellow, and Andrew Vandenberg, a graduate student, are working in different aspects of a project the goal of which is to identify hematopoietic stem cell intrinsic and extrinsic mechanisms, the latter induced by mesenchymal stem cells, that promote transformation of MDS to AML; they also examine if similar molecular events are observed in disease-initiating pre-MDS stem cells and how they affect transformation to malignant cells. Marta Galan-Diez, an associate research scientist, characterizes cross-talk pathways between leukemia stem cells and mesenchymal stem cells or osteoblasts that affect engraftment and progression of AML. She is also delineating the expression of markers of interest in MDS/AML cells and stromal cells from MDS and AML patients. Ioanna Mosialou, a research assistant professor, traces the identity of stoma cells and how their functions change during MDS development and transformation to AML. She is also asking how these cells can be targeted for therapeutic purposes. Voula Vgenopoulou, a post-doctoral fellow, uses an AML model to study how leukemia stem cells remodel mesenchymal stem cells to promote their engraftment and proliferation. She is also developing xenograft models testing the interaction between stromal and AML cells.

What are the biggest accomplishments that your lab recently had?

Our lab reported a new mechanism for the induction of hematological myeloid malignancies. We identified a stromal cell-triggered pathway that is initiated by activation of -catenin in osteoblast progenitor cells and leads to AML in mice. This pathway is active in one third of AML and MDS patients. Building on these observations, our current work is identifying and characterizing other myeloid-inducing mutations in cells of the bone marrow stroma. Those affect various stages of the diseases, from pathogenesis to transformation of MDS to AML.

Technology:

What are the model systems that your lab is using?

We use several types of genetic mouse models (overexpression, knockout and knockin). The vast majority of them are used in combination with cell-specific Cre lines for conditional gene deletion or activation. Some of these Cre lines are also inducible. We carry several mesenchymal cell and hematopoietic cell-related Cre lines, fluorescent reporter lines, two mouse models of MDS and AML. We also use a system of co-cultures of patient-derived mesenchymal stem cells or osteoblasts with patient-derived MDS or AML cells.

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

We carry out extensive analysis of hematopoietic and stromal cell lineages in samples from mice and humans using flow cytometry, bone and bone marrow histology, generation and analysis of genetic mouse models for hematopoietic deregulation and MDS or AML phenotypes, xenograft models of AML. We are open to training scientists from other labs.

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

We rely on the Flow cytometry core of the CSCI, the X-Ray irradiator of the CSCI, the stem cell core of the CSCI, the Genome Center for our RNAseq and single cell RNAseq experiments, and the transgenic animals core, the histology core and the small animal imaging core of the Cancer Center.

Training:

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

Our lab works on understanding the mechanisms of development and progression of two devastating diseases. The first thing I try to instill to my trainees is care and respect for the patients and their families. If they want to make a difference in the life of patients, they should not be afraid to delve into challenging projects. I try to inspire them with such projects and to cultivate passion for their research. I teach them to have an open mind for new hypotheses even far-reaching ones, and conclusions. To not be afraid to look at their data from different angles. And, to be happy when their hypotheses do not work, because chances are their experiments will lead them to something more novel than the “lost” hypothesis.  I encourage them to read the literature and to discuss as frequently as possible their ideas and results with me and the rest of the group or other relevant groups in the CSCI and the Medical Center.

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

Participating in common group lab meetings where they can present their work and learn how to critically think about the work of others, presenting in the Work in Progress series of the CSCI. A course in basic analyses in system biology would have been prefect if there was one.

What would be your career advice for students/postdocs?

To seek and find their area of interest and pursue their research with passion and commitment. There are no easy or safe roads to take in science, like in life, so it is always better that they love what they do when difficulties arise. To find good mentors, their influence in their professional and personal life will be paramount.

Lab management:

How do members of your lab celebrate accomplishments?

With food and drinks, we also like happy hour.

What is the key to running a successful lab?

There are probably many ways to do this, but for our lab I try to give to trainees stimulating projects and also to involve them in each other’s work. Having a good spirit of collaboration, discussion and teamwork.

What was the most exciting part about starting your new lab?

I could finally choose entirely every project that was meaningful and exciting and had my chance to create a small and hopefully impactful niche.

Which stem cell conferences does your lab attend?

New York Stem Cell Foundation

CSCI:

What was the main reason of you joining CSCI?

To be in a community of stem cell research where people have common interests, critical insight and complementary views and methodologies to promote stem cell work across different fields. To be challenged and inspired by different disciplines within the community. To contribute and benefit from guest and world-class seminar speakers and excellent core facilities.

What do you plan to bring to the CSCI community?

All the above! Plus mentoring WIP participants and contributing to and organizing activities.