July 2020: Targoff Lab

Background:

What is the main focus of your lab?

My lab studies the genetic regulation of cardiac development and regeneration.  By using the zebrafish model, we discovered a prominent role of nkx genes in maintaining ventricular identity.  Our findings suggest that molecular mechanisms are necessary both to specify ventricular fate at early developmental stages and to preserve chamber-specific characteristics as morphogenesis proceeds.  We are currently performing a systematic dissection of the molecular, cellular, and temporal mechanisms regulated by nkx genes during cardiac embryogenesis.  Furthermore, we are investigating the requirement of nkx genes for cardiomyocyte regeneration in the adult zebrafish ventricle.  Finally, we have generated dozens of mutants using CRISPR genome editing technology to study novel targets of Nkx transcription factors identified by our RNA-Seq experiments in the zebrafish embryo.  I intend to translate insights from this work back to the fetal, neonatal, and pediatric patients with congenital heart disease for risk stratification and improvement of prognosis and also to the adult patients in need of ventricular cardiomyocyte regeneration. 

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

I arrived at Columbia University following my graduation from Medical School and pursued my Pediatric Residency and Pediatric Cardiology Fellowship at the Children’s Hospital of New York.  Following post-doctoral fellowships in the Division of Molecular Genetics and at the Developmental Genetics Program at the Skirball Institute of Biomolecular Medicine (NYU School of Medicine) in the Yelon lab, I opened my independent laboratory at Columbia University in 2011.

How big is your lab currently?

Currently, there is one post-doctoral fellow, two graduate students, one post-bacclaureate student, and one undergraduate student in the Targoff Lab.

Where is your lab located?

My lab is located in the VP&S building on the 9th floor, room 401.

Current affairs:

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

It has been particularly exhilarating to follow the science where it leads us!  Given our foundational mission to understand the cellular and molecular mechanisms mediated by Nkx2.5, a key causative gene associated with congenital heart disease in humans, several current projects in the lab focus on novel CRISPR mutants that we generated in downstream effectors of Nkx factors.  These zebrafish mutants demonstrate a wide range of phenotypes during embryogenesis and in adulthood.  In addition to uncovering the genetic etiologies of their cardiac defects, we have identified and are working to decipher the mechanisms underlying their abnormalities in craniofacial development and hematopoiesis.

What are the biggest accomplishments that your lab recently had?

We have been working on a project to examine the regenerative properties of an adult rescued nkx2.5 mutant fish that is otherwise embryonic lethal.  Thus, our studies represent the first time this genetic technology has been applied to uncover the requirement for reactivation of the development program following cardiac injury.  We are looking forward to publishing this work in the near future!

In addition, we are proud of our collaborative efforts with the Hillman Lab at the Zuckerman Institute to apply Swept Confocally Aligned Planar Excitation (SCAPE) microscopy to perform high-speed, 3-D imaging of the zebrafish embryo.  The innovative technology allows us to capture cardiac contractility and conduction system abnormalities without a requirement for gating.  This advancement is particularly beneficial for our studies as our CRISPR mutants that exhibit cardiac defects also demonstrate physiologic and functional irregularities that pose challenges for traditional SPIM imaging.

Technology:

What are the model systems that your lab is using? 

We use zebrafish as a model system and carry over 100 different mutant and transgenic lines in our aquatics facility.

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

We would be happy to help train scientists from other labs! 

We use a broad range of techniques – molecular cloning, in situ hydridizaiton, immunohistochemistry, transgenic and mutant generation, lineage tracing, and imaging.  While we perform most of our work in vivo, we also extend our strategies to cell culture when necessary to address particular questions.

What facilities or equipment does your absolutely lab rely upon? 

We use the CSCI core for FACS and cell culture experiments!  Also, we benefit from many different types of microscopy, as I mention above, given the transparent nature of the zebrafish embryo.  However, our pride and joy is the fish facility on the 4th floor of the Black Building.

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

Please feel free to contact me, Kimara Targoff.

Training:

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

I aim to provide structure while allowing the trainees to explore on their own.  Although I (hopefully) am gentle and kind in my critiques, I believe it is clear that I have high expections for each lab member.  Most importantly, I am eager to focus on everyone’s individual strengths to enhance the working environement for the group as a whole.

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

My post-doctoral mentor, Debbie Yelon, was an influential model for me.  She opened my eyes to the world of zebrafish developmental biology and I have never looked back!  I learned so much from her about scientific integrity, asking the right questions, and pursuing the truth vocariously.

My mother also served as an important role model for me!  I observed her love of science and discovery every day during my childhood.  My mother’s commitment to her lab at Rockefeller taught me very early on that her dedication stemmed from pure enjoyment and intellectual satisfaction and not from any sense of obligation.

What would be your career advice for students/postdocs?

I would recommend identifying the elements of science that intrigue and stimulate them personally and making sure that the career path they chose embodies those characteristics.

Are you accepting rotating students at the moment?

Yes.  

Lab management:

How do members of your lab celebrate accomplishments?

We gather as group to celebrate milestone accomplishments for the lab and for individual members.

Does your lab have any fun traditions?

We generally treat ourselves to sweets from bakeries around the city!!!

What is the key to running a successful lab?

I think that there are many different ways to achieve success in a laboratory environment.  However, at this point in my career, I believe that finding the right balance between providing direction and allowing for independence is critical to nuturing trainees and to allowing them to be the best they can be!  Furthermore, it is essential to ensure an appropriate combination of short term/long term and high risk/low risk projects to generate an effective flow of data.

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

I really loved being able to think independently and to design my own research program.  I felt inspired by the intellectual freedom.

CSCI:

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

I was enthusiastic about joining the CSCI as it provides a vital community for my lab members.  Given that we were the only zebrafish lab at Columbia until this year and that very few other labs at Columbia address questions related to cardiac development, it was important for me to establish a scientific home.  The CSCI has offered a nurturing environment, both personally and intellectually, for the Targoff lab with scientists from diverse backgrounds who are likeminded in their pursuits.

What do you plan to bring to the CSCI community?

I hope to bring a spirit of teamwork to the CSCI community.  Furthermore, I believe that our research broadens the CSCI scientific arena with the addition of the zebrafish model system and cardiac developmental and regenerative biology.