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Researcher of the Month

November 2020

Natalie LoNatalie Lo

Majors: Biology, Sociology; Women in Science & Engineering (WISE) program, Class of 2021

Research Mentor:  Dr. Hyungjin Kim, Department of Pharmacological Sciences

          “I think having a mentor is one of the best experiences I’ve had with research.”- Natalie Lo

Natalie Lo is one of 4 Stony Brook undergraduates to receive the Sass Foundation-Arena Scholars* award recognizing research potential in URECA Summer applicants working in the field of cancer biology.

As a member of the research group of Dr. Hyungjin Kim (Pharmacological Sciences) since May 2019, Natalie works on characterizing the interaction of TIMELESS (TIM) in the DNA Damage Response (DDR) pathway and its role in the DNA replication fork protection in conjunction with PARP1. She is a co-author of the lab’s recently published Nature Communications paper titled: “SDE2 integrates into the TIMELESS-TIPIN complex to protect stalled replication forks.”  When in-person laboratory work was suspended due to COVID, Natalie took the opportunity to conduct extensive literature search and review on recent characterizations of the regulatory roles TIM plays at both active and stalled replication forks, to enhance her understanding of the project and to prepare her return to wet work in the lab. She notes: “During the school year,  I don't have that much time to sit and read 30 to 60 papers. But during the summer I was able to actually sit down and comb through the material to figure out everything that there is to know about TIMELESS which was really helpful!“

Majoring in both Biology and Sociology in the Women and Science in Engineering (WISE) honors program, Natalie got involved in research from the get-go. In her freshman year, she was a member of the 2018 International Genetically Engineered Machine (iGEM ) Team—the student-led research team that worked to engineer cyanobacteria to fix atmospheric carbon dioxide and generate sucrose that could be used for biofuels or plastics; and returned from the Giant Jamboree competition in Boston in fall 2018 with Stony Brook's first Gold Medal. 

Natalie continued her involvement with iGEM as a 2019 Teaching Assistant; and has also served as a Teaching Assistant for CHE 152, CHE 331/332 (General and Organic Chemistry), BIO 320 (Genetics), and SOC 340 (Sociology of Human Reproduction). Natalie currently works as a Medical Assistant (Sing Chan Endoscopy) and as a Port Jefferson EMS Volunteer; has volunteered at Stony Brook University Medical Center on the Surgical Critical Care Floor and has also shadowed a doctor at Weill Cornell Medicine. On campus, Natalie is also involved as a writer for Stony Brook Young Investigators Review, and is a team member of the Stony Brook Badminton Team and Badminton Club. Her long -term goal is to pursue an MD/PhD.

Natalie is a graduate of Syosset High School, where she participated in the school’s robust research program, conducted neuro-related research on Alzheimer’s disease at SUNY Old Westbury and participated in high school research competitions (Siemens, NYSSEF, LISEF). Her current hobbies include: badminton, baking, and reading. Below are excerpts of her interview with Karen Kernan, URECA Director. 

*The 2020 Sass Foundation-Arena Scholars awardees include: Navid Ashrafi (Mentor: Dr. Chiara Luberto, Physiology & Biophysics); Gabriella Baraks (Mentors: Dr. Kenneth Shroyer and Dr. Luisa Escobar, Pathology); Natalie Lo (Mentor: Dr. Hyungjin Kim, Pharmacology); and Shivasuryan Vummidi (Mentor: Dr. John Haley, Pathology).  

The Interview:

KarenTell me about your research.

Natalie Lo

Natalie: Currently, I'm in a DNA repair lab in the Pharmacology Department, the Kim Lab. During DNA replication, the replisome composed of helicases and DNA polymerases can potentially make mistakes that lead to an accumulation of DNA lesions.  The DNA Damage response detects DNA lesions to promote cell cycle arrest and DNA repair. We are currently trying to understand the parts and mechanisms of DNA repair pathways, specifically its relation to the fork protection complex (FPC) in the replication fork. The protein that I'm working with is called TIMELESS (TIM), which was actually originally found in Drosophila (fruit flies) and has a role in circadian rhythm. Some researchers found that it actually had some protective mechanisms in the DNA repair, and recently we uncovered in our lab that it actually interacts with a replication stress regulator called SDE2 and our ongoing studies indicate that it also interacts with another protein known as PARP1 which is involved in replication fork protection and recovery of the replication fork through fork stalling. Our project is trying to characterize the interaction between these two proteins and see what the effects are in the DNA repair pathway and in the fork protection complex.

This summer, you received one of the SASS foundation awards to support your summer research activities. How does your research relate to cancer research, broadly?

If replication fork protection mechanisms fail, DNA lesions caused by replication stress will accumulate which leads to the stalling of the replication fork and eventually to genomic instability, potentially resulting in the development of cancer cells. If we're able to elucidate the mechanisms between the proteins that are involved in the the DNA damage response pathway, we’re able to target these specific proteins, and see if they can be possibly used for cancer therapeutics. One method utilized is called synthetic lethality which takes advantage of the inherent DDR deficiencies found in cancer cells. If a cancer cell has a mutation in one DDR pathway, it relies on other DDR pathways for survival. Cancer treatments essentially utilize drugs that inhibit the important substrates needed in these alternative pathways to exploit this dependence in cancer cells. Currently, Olaparib which is a PARP1 inhibitor is approved as a anticancer drug to effectively kill BRCA1/BRCA2 cells found in breast and ovarian cancers.  

How did you first get involved in research activities at Stony Brook?

I started doing research during high school at SUNY Old Westbury, so when I entered Stony Brook, I knew I wanted to continue research since it was such an important part of my high school career. During my freshman year, someone in my chemistry class advertised an opportunity to become involved with iGEM, and I just thought, “Why not just try it?” And that's how I started doing research in college. iGEM was an incredible experience – and was really unique in being a student-led research experience. iGEM not only developed my sense of collaboration and cooperation by encouraging members to brainstorm and solve issues amongst ourselves, but also has fostered a sense of leadership within me.

That was in 2018— the year iGEM got Stony Brook’s first gold medal?

Yes, that was exciting….really fun!

And then how did you make the transition to the current lab you are in?

After doing iGEM, I knew I wanted to continue doing research, and that I was interested in synthetic biology. So I just looked online at the different labs that were available—I think on the Undergraduate Biology website. At the time, I was taking Genetics (BIO 320) and we had just recently finished a unit on BRCA2 and were learning about DNA repair mechanisms that my lab studies.  I saw that the Kim lab actually works with BRCA2, the Fanconia Anemia pathway and components of the Fork Protection Complex.  So, I emailed Dr. Kim and I asked to meet with him. During our meeting, he explained more about the work the lab was doing. I was really interested, and knew I wanted to learn more. So soon after that, in spring of sophomore year, I joined the Kim lab.

What do you most enjoy about your current work in the Kim lab?

I think having a mentor is one of the best experiences I’ve had with research. When I was in iGEM, a lot of what we did was trial and error -- trying to do our own research design. Although we had a really helpful group of advisors for iGEM, most of the feedback was perhaps once a month and a lot of the trouble-shooting that we did came from students bouncing ideas back off of each other. Now that I’m in the Kim lab, I'm paired up with a post doc, Dr. Julie Rageul. This is a very different experience since I'm able to ask someone who's been in the field for more than ten years advice and she’s able to tell me a lot of things and teach me a lot. I’m also learning a lot of new methods and techniques, such as cell culturing and coimmunoprecipitation assays.  My postdoc mentor is definitely really helpful with teaching me things and with helping me understand the concepts behind the project.  If I have any questions, whether small or big, she’ll sit down and take the time to review everything with me to make sure that we’re on the same page and that I understand everything about the process. That’s really helped me. Additionally, my PI Dr. Kim, helps provide a lot of great feedback on our project when discussing the project development and direction. 

What do you get out of doing research that you wouldn't get from just your classes alone?

I think there’s a difference between knowing what's in the textbook (knowing the pathways) vs actually doing the research and actually figuring out…: Say, “If I use siRNA and I knock down this protein, what am I supposed to see?”  When you’re in classes, you're learning and essentially absorbing information, but you're not able to apply the information. When you're doing hands-on-research, you're able to apply and think about how an experiment should be set up based on the knowledge that you already have. It’s different in that it allows me to connect more to the material and to actually understand and process the information a lot more.

It's also a great way to just connect with the material that we learn in class on a more personal level. So rather than just knowing general details about all the DNA repair pathways that are involved, I’m now able to specifically work with pathways and understand exactly what they do.   Finally, as mentioned previously, it's also a great opportunity to make new connections and find a lot of people with like-minded passions and interests who are able to help you and mentor you.

Has it helped you in honing your communication skills?

Currently, I don't have much data to present, but I do present at our weekly journal club. Even though I'm not presenting my own research, I'm still learning how to present other people’s research. I prepare a Powerpoint, go through each figure and explain to the lab what the project is about and what the researchers were trying to find. This allows the lab to keep updated on new research, and also allows me to understand what it’s like to communicate research, even though it’s not my own!

What's the most challenging aspect of being involved in research? What advice do you have for other students?

For me, when I was first starting out in the lab, I had a steep learning curve. To combat this, I would spend a lot of time in lab: I would be there from ~9 to 7, trying to learn how to do the experiments properly. Sometimes I would fail and have to re-do them, so it taught me how to learn from my mistakes and grow. I think the long hours were a challenge when I first started out. But now, I’ve learned that being in lab for a long time is helpful because it has given me the chance to improve my skills. And even though it’s sometimes long and tiring, I’m able to improve my skills and make better myself for the future. So my advice is: If you do fail, it’s okay. You can pick yourself up and then just continue. You can always fail, and still learn and move forward. It’s important to think to yourself: “Even though I made this mistake, next time I'll do this better.”

Are you one of the only undergraduates in the lab?

We used to have a lot of undergrads, but most of them have graduated. So right now it’s mostly master’s students and PhD students with everyone having varying levels of experience. But what’s great is that there's always someone I can ask; someone who has more experience or someone who has either maybe already made that mistake or knows how to fix it. A lot of the grad students have been doing this for many years, and have their own helpful tips to pass down. So we pass along the tips and tricks that we use in order to get a good yield or to do one protocol really well.

How big of an effect has COVID had on you and your research this summer?

Because most of my research is wet lab-based (unlike other labs that do modelling or computational work), and we were not able to do in-person work, I spent most of the summer reading journal articles, trying to improve my understanding of TIMELESS’s role in general in DNA repair / DNA replication. Right now, I’m back in lab, so I’m finally able to start doing wet lab research now and actually continue on with this project. So while I wasn’t able to get actual data over the summer, it did help a lot in that I was able to focus a lot of my time and energy to the literature search and reviews. During the school year, I don't have that much time to sit and read 30 to 60 papers. But during the summer I was able to actually sit down and comb through the material to figure out everything that there is to know about TIMELESS which was really helpful! Now that I'm finally able to design experiments, I can remember when I read from the research and build on that for thinking about what to do.

That’s a good outcome! You must be a lot faster and better at reading scientific papers now after this summer.

Yes, when I first started, I had to read over a paper perhaps three times before I was able to understand. But now it's definitely easier.

Has being in WISE also helped you stay focused on research?

I think one of the great things about being in WISE is that I’m surrounded by a lot of women who are like-minded. They’re all really passionate about science. That's really helpful because I meet a lot of people who have the same mindset and together, we’re able to strive towards our goals. I know that if I ever have questions, I have people I can ask who are in the same classes or major. Additionally, the program itself is helpful and I liked having the opportunity in fall of sophomore year through WSE380 to do rotations in different research areas and  get exposure to see different fields to research and what they do.

What are your future plans?

For a really long time, I’ve wanted to go into the medical field, the cardiology field specifically. After doing research in college, I realized that research was a really big part of what I wanted to do for a career. So right now, I’m planning to apply to MD/PhD programs.

I'm taking a gap year (applying next year), and I'm hoping that in my gap year, I can focus on research and on completing the project that I’m currently working on. I really enjoy this field since there’s always more to learn about DNA replication. We know a lot but there’s so much more to learn, and I would like to continue with it.