March 2021: Ciccia Lab

Background:

What is the main focus of your lab?

We work on the cellular processes that protect our genome from DNA damage to prevent the occurrence of cancer and other genetic disorders. In particular, we study DNA repair factors that maintain genome integrity during DNA replication, such as the tumor suppressors BRCA1 and BRCA2. Our goal is to define how DNA repair factors suppress cancer development and identify strategies to target tumors carrying mutations in DNA repair genes.

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

The Ciccia lab opened in January 2014 here at Columbia University.

How big is your lab currently?

Our lab is currently composed of one graduate student, two postdoctoral fellows and two associate research scientists.

Where is your lab located?

Our lab is located in room 301 of the ICRC building.

Current affairs:

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

Thousands of mutations in DNA repair genes, including BRCA1 and BRCA2, have been identified in cancer and genetic syndromes. However, the vast majority of these mutations remains of uncertain clinical significance. To define the functional relevance of mutations, we have recently developed a novel high-throughput screening platform based on CRISPR-dependent base editing that allows us to generate and study thousands of mutations simultaneously. This technology enables us to identify loss-, gain-, and separation-of function mutations, define novel functional domains and interaction surfaces, and classify mutations with pathogenic behavior. We are very excited about the opportunities that this new technology offers us to better understand how mutations in DNA repair genes influence cancer progression and the response to chemotherapy and immunotherapy. We believe that this approach could facilitate the development of cancer therapies tailored to specific mutations. Hopefully we will be able to make significant progress on this front in the coming years!

What are the biggest accomplishments that your lab recently had?

Over the past five years, we have identified three DNA replication factors that cause genome instability in BRCA1/2-deficient cells, and uncovered a novel potential therapy for BRCA1/2-mutant tumors. Moreover, we have identified a new protein that promotes genome integrity, and characterized a DNA replication factor whose loss enhances the response to cancer immunotherapy. In addition to these studies on genome maintenance, we have also developed novel technologies to improve the efficiency of genome editing, disrupt genes through the insertion of stop codons, and detect genome edits without the need of DNA sequencing. Overall, it has been a very exciting time in the lab!

Technology:

What are the model systems that your lab is using? 

We mostly use human and mouse tissue culture cell lines. In addition, we utilize animal models to study tumor progression.

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

We perform analyses of replication fork progression using DNA fiber assays and evaluate the formation of DNA damage using high-content microscopy and assays that detect DNA breaks. We also conduct CRISPR screens using base editing technologies to study the function of nucleotide variants in DNA repair genes.

Are you open to training scientists from other labs?

We have already trained scientists from other labs and are always open to this possibility.

What facilities or equipment does your absolutely lab rely upon?

Our lab relies on the use of microscopy, flow cytometry and next-generation sequencing

Training:

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

I do not think that there is a single best approach to mentoring trainees. Every person has different needs and expectations, so I try to tailor my mentoring to each individual. I have one-on-one meetings with everyone in the lab at least once a week to discuss progresses and challenges, and I make myself always available to meet and discuss during the rest of the week.  

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

I have been very fortunate to train with two leading scientists in the field of genome stability, Steve West (Crick Institute) and Steve Elledge (Harvard Medical School). From them I learned that doing science requires curiosity, passion, dedication and rigor. I now try my best to transmit the same values to my students and postdocs.

Can you recommend courses/lectures in Columbia University that would be most beneficial for students/postdocs? With the ever-increasing number of large-scale studies, I would recommend students and postdocs to take data science courses to become familiar with how to process and analyze large datasets.

What would be your career advice for students/postdocs?

My advice would be to work on a topic that they are very passionate about. The setbacks are around the corner, and without enthusiasm and determination they will not be overcome. Overcoming difficulties might require help from colleagues, so it is important to work together collaboratively.

Are you accepting rotating students at the moment?

Yes, we are accepting rotating students.

Lab Management

What is the key to running a successful lab?

I believe that providing everyone with the opportunity to express their talents and creativity increases the chances of running a successful lab.

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

Starting a new lab comes with the excitement of opening new directions of research. It is also highly rewarding to see the scientific growth and the accomplishments of students and postdocs over the years.  

CSCI:

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

Stem cells have developed unique mechanisms to respond to DNA damage and I have always been interested in understanding how maintenance of genome stability regulates stem cell proliferation and differentiation. CSCI will facilitate our interaction with the stem cell community and allow us to establish collaborations with CSCI labs to study the function of DNA repair factors in stem cell maintenance and differentiation.

What do you plan to bring to the CSCI community?

We plan to bring our expertise in DNA repair and genome editing to the CSCI community to help develop novel cellular and animal models of disease and investigate genetic dependencies in stem cells using high-throughput screening technologies.