Trainee and Tech First Thursdays #6

This month, we chat with Nicole Sivetz , a PhD candidate in the Semir Beyaz lab at Cold Spring Harbor Laboratory . Nicole is investigating how inflammation impacts the ability of immune cells to either promote or restrict the spread of pancreatic cancer to the liver, and through this work aims to identify new potential therapeutic strategies that may boost anti-tumor immunity.

As President of CSHL Women in Science and Engineering (WiSE), Nicole was involved in fostering a sustainable and supportive community that adapts to the changing needs of its members while actively working to break down systemic barriers faced by women in science.

You started undergraduate research as early as your freshman year, before coming to CSHL. What sparked that early interest in research, and how did those experiences influence your decision to pursue a PhD?

As a child, I enjoyed learning about the natural world by watching Animal Planet on TV and visiting local zoos with my parents. When I was first introduced to more advanced subjects during high school, like anatomy and biochemistry, I found myself devouring our textbook reading assignments and was enthralled by the knowledge that there was a molecular basis to the world around us. It was, therefore, an easy decision for me to choose biology as my major when it was time to enroll in undergraduate courses. However, I didn't really know what would happen next – all I knew was that I really liked biology! I learned my college sponsored a summer research program before I graduated from high school, so I figured I should apply to make some extra money and try something new. Despite not having any prior research experience, I applied to two projects – one involved monitoring zebra mussels in the Hudson River, and the other focused on developing splice-switching therapies for brain cancer. It was truly pure luck that I was selected for the latter, which marked the beginning of my career in biomedical research. As I progressed through college, I kept pushing myself outside of my comfort zone to be exposed to different 'flavors' of science, from shadowing doctors to interning with a pharmaceutical company. Through this approach, I found opportunities to speak with a wide variety of mentors, and our conversations helped me realize that pursuing a PhD would best develop my skills as a critical thinker and prepare me for a career in research. My scientific interests would be very different today if I had worked on another research project that first summer before starting college, but I think my story is quite representative of how the trajectory of a scientific career can be – there's certainly a degree of careful planning involved, but it's also a serendipitous combination of being in the right place at the right time. The most important thing is to make the most of a current situation by learning as much as you can from it and reflect as you move forward.

Your LinkedIn bio says?you draw insight and inspiration from a variety of biological lenses to ultimately translate basic biological research into more effective cancer immunotherapies.?Could you tell me more about that approach?

My interest in approaching cancer from different scientific perspectives can be greatly attributed to my time spent in CSHL's highly interdisciplinary environment. Cancer is a complex, whole-body disease that operates across multiple biological scales - from molecular signals secreted between cells, up to the level of systemic immune responses acting across major organs. I have always felt the greatest sense of excitement and invigoration whenever I have been able to connect my own research to knowledge from other fields that are considered to be unrelated to cancer, such as plant biology or neuroscience. We can uncover more meaningful biological insights by considering cancer from these diverse viewpoints. For example, applying physics to cancer enables us to study how mechanical forces impact immune cell trafficking in biological tissues, or how different cancer treatments penetrate solid tumors. Artificial intelligence enhances our ability to integrate and identify new patterns from large-scale and multi-parametric data. Regarding the development of cancer treatments specifically, this approach is especially critical because cancer already “considers” all these different aspects simultaneously as the disease evolves to evade the immune system and acquire resistance to therapy. By integrating insights from different scientific disciplines, we will develop more effective therapeutic strategies that address multiple aspects of the disease in parallel. This is especially important as we work to better understand why certain immunotherapies work well in some patients but not others, with the ultimate goal of developing therapeutic strategies that can achieve both durable and robust responses for all.

Even without a formal leadership role, what are some specific actions individuals can take to foster equity and inclusion for women and underrepresented groups in science?

This is an excellent question because individuals can have profound impact on the experiences of women and underrepresented groups in science even without formal authority. Making seemingly small and consistent actions as an individual can very easily make the difference between someone either pursuing their scientific interests or leaving a chosen career path altogether. I believe an important step is (1) to be educated – take time to learn about the invaluable contributions of the women and underrepresented groups that have shaped our modern-day society. Their unique perspectives enriched scientific progress despite facing levels of discrimination and exclusion that sometimes escalated even to the level of endangering personal well-being, and so it is our responsibility to understand both the historical and current barriers that persist to this today for these groups. This action of seeking education may naturally lead to another important step, which is (2) becoming more mindfully present in the work environment – really consider the impact that you as an individual has on others around you and how this contributes to the overall workplace dynamic (whether this be within the context of a small research lab or an entire department). Moreover, consider how these historical and current barriers impact how your fellow peers are treated – both intentionally and unintentionally – in different interpersonal relationships existing within this same workplace dynamic. When building on ideas or prior work, ensure proper attribution is given by saying the name of the respective person, especially if that person is not present in the current conversation. This can be as simple as, “As ‘person X’ said before ...". This highlights the value, both professional and personal, that each individual brings and reinforces their deserved place within that workplace. This process of seeking education and integrating it into your active presence within the workplace should be iterative and can serve as a framework for being more proactive in correcting any personal biases and blind spots regarding systemic barriers that impede women and underrepresented groups in science.

You have been with the amazing CSHL Women in Science and Engineering (WiSE) for 5 years including being President.?What accomplishments are you most proud of, and what challenges do you see for women in science?

During my time in CSHL WiSE leadership, there are certainly several events and programs I am proud of that were organized for both our institutional and local Long Island communities. However, I would like to highlight a more amorphous 'accomplishment', which is sustaining the evolution of our CSHL WiSE organization since it was first formally founded in 2015. CSHL WiSE has always kept trainees at the heart of its mission, and with that comes the challenge of preserving experiences and lessons learned over many periods of member turnover as people move on from our institution. I think one effective strategy that CSHL WiSE leadership employed to combat this was letting the passions, needs, and lived experiences of its community members drive the core activities to ensure that CSHL WiSE remained representative of the people it strives to serve – all while reflecting on the organization’s past. This required continually revisiting the organization’s central mission statement, carefully recording all activities and leadership brainstorming sessions, and collecting community feedback to determine whether our intended impacts were being achieved. I believe this organizational challenge reflects a broader issue that women in science face: the need to preserve and pass on collective knowledge and experiences. As one former CSHL WiSE leader aptly put it, "There is my science time, there is my personal time, and there is my WiSE time." This extra layer of effort, including documenting experiences and maintaining support networks, often falls outside of what is considered 'primary' scientific work. The key challenge is breaking this cycle where each generation of women must individually overcome the same barriers. Instead, we need to better preserve and leverage shared experiences so future generations can build upon progress rather than start from scratch. I believe properly appreciating and investing the efforts done by women – and people of all genders – in this regard would enable more women scientists to focus on their work rather than also having to prove they deserve a seat at the table and/or drive the equitable measures needed to sustain their careers in the long-term.

What’s fueling your?ultimate career goal?

At my core, I am driven by curiosity about the molecular and cellular principles that govern health and disease. There's something profoundly exciting about using the scientific method to uncover these basic biological mechanisms - the careful hypothesis testing, the unexpected discoveries, and those moments when a new finding can shift our collective understanding of how life works at its most fundamental level. I hope to one day be able to impart this sense of curiosity (and how it can be explored using critical thinking and the scientific method) by mentoring young students and interns over the course of my future career. I also hope to carry this appreciation for the power of basic research as I move forward in my career as a scientist in the immuno-oncology industry. As I mentioned before, I am drawn to the approach of combining deep mechanistic insights from multiple disciplines to better understand and treat cancer. I am still not exactly sure what that looks like in the framework of a ‘9-to-5’ job at this point in time, or rather I should say within the realm of the pharmaceutical industry where it is typically considered to be an environment where true basic research is not a primary focus. However, I am most excited right now by the cancer research community’s growing focus on studying cancer as a systemic disease that considers multiple aspects of a patient – and not limited to just interactions between different organ systems and genetics, and but also age, race, gender, socioeconomic status, and access to appropriate care. I look forward to seeing how this paradigm will continue to evolve and translate into more effective cancer treatments, and so my ultimate career goal would be to use my scientific training to help facilitate the incorporation of this new way of thinking into the immuno-oncology industry.

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