Patrick Nnoromele

Abstract: The ability of cancer to avoid elimination by the immune system contributes to disease progression and treatment resistance. Tumor neoantigens, if any are expressed, can be presented in either an MHC class I-restricted manner to begin induction of a CD8+ T cell-mediated adaptive response or by antigen presenting cells via MHC class II presentation of class II-restricted peptides to CD4+ T cells. Model antigens, such as the chicken egg white protein Ovalbumin, are typically used to study antigen presentation in the generation of a systemic anti-cancer response.  However, the Ovalbumin protein as well as other model antigen proteins can contain both class I- and class II- restricted peptides. In addition, the role of neoantigen localization (cytoplasmic, membrane-bound, or secreted) in the tumor microenvironment may play a role in the strength or characteristics of an immune-mediated anti-cancer response. We hypothesize that different types of antigens (i.e. class I- or class II- or cytoplasmic or membrane-bound) impact immune-mediated anti-tumor responses. To understanding how the type and location of antigens in the tumor microenvironment impacts systemic anti-cancer responses, we designed and generated cytoplasmic and membrane-bound model antigens that contain either class I-, class-II, or both types of MHC-restricted peptide sequences. Briefly, the desired genes were ligated into a pLenti vector, confirmed via Sanger sequencing, and plasmids were transfected into MC38 colorectal cancer cells, which are syngeneic in immunocompetent C57BL/6 mice. Ongoing work will focus on the growth and immunogenicity of these modified colorectal cancer cells in vivo with or without immunotherapy and radiation therapy. Elucidating mechanistic details of antigen presentation in the generation of an anti-tumor immune response will inform therapeutic strategy in cancer patients.

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What does research mean to you?
To me, research is hope. It represents the last boundary between a chaotic, mysterious biological world and clinical medicine. By harnessing the remarkable tools available to us in the modern age of discovery, we can explore and understand the complex physical realities around us with controlled experimentation. With a ton of persistence and a dash of luck, we can translate those findings into therapeutic innovations that will improve patients' lives in countless years to come. This is what excites me about research. 
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Tell us about your journey.
As the son of two humanities professors in a small, rural city in central Kentucky, my entire life was a humanities classroom. However, by my freshman year of high school, I knew that I had more interests in cellular biology than I did in Aristotle or Jane Austin. I set my ambition on becoming a molecular biology professor and full-time researcher. Then, in my sophomore year of high school, my father started to develop symptoms of early-onset dementia, and I had to re-evaluate my priorities. I realized that I could spend my entire life studying the cell and its pathology, but at the end of the day, there will always be people like my father with tangible, immediate needs.
For this reason, I began to pursue both clinical and research opportunities in high school and college. Working in hospitals and taking to patients taught me how much I loved to care for the patient. Exploring cellular mechanisms in my research taught me how much I enjoyed the scientific process and the independent thought it cultivated. For these reasons, I am currently applying to MD/Ph.D. programs, where I hope to garner the education I need to combine my interest in cellular mechanisms with my passion for clinical care.

What was your favorite part about the program? 
I underestimated the amount of independence my lab would provide me. I had the space to read publications, author my hypotheses, and design my own experiments to test them in the lab. I gave presentations on my research during lab meetings and presented papers during our journal clubs. I had the space to grow into my own scientific identity, and I am beyond grateful to have been able to work in an environment like that so early on my career.  

What was the biggest thing you learned from the program?
In science, you must simultaneously possess resilience and flexibility. There are so many things that can and will go wrong in an experiment. The trick is to know when shear tenacity and brute force are needed to bring an experimental design to fruition or when an innovative perspective is required to execute it well. I learned this lesson the hard way when I had to handle a mycoplasma pandemic in my cell cultures that halted my experiments for several months.

 

Advice for Future Green Fellows

​Never underestimate the value of the people around you. Take the time to learn about the people you work with and immerse yourself in the lab culture, not just your research. You won't be disappointed.