MSTP/MCP Student Kristen Lozada Soto Successfully Defends Her PhD Thesis
By Lynn McCain | December 19
Congratulations to Dr. Kristen Lozada Soto, who successfully defended her thesis Claudin-23 Regulates Intestinal Epithelial Barrier Function and Mucosal Wound Repair on Monday, December 9, 2024, marking a significant milestone in her journey to becoming a physician scientist. As a Medical Scientist Training Program (MSTP) fellow at the University of Michigan, her doctoral work has unveiled exciting new insights into the mechanisms by which a tight junction protein, Claudin-23, regulates intestinal epithelial barrier function and mucosal wound repair. When reflecting about her PhD research contributions she states “it is so exciting to envision how this work can help pave the way for identifying novel therapeutic targets for people with ‘leaky gut’ or those with compromised wound repair, as is typically the case in people with inflammatory bowel disease (IBD). This is exactly why I love training to become a physician-scientist - we get to connect the dots between discoveries and real patient care.”
Growing up in Puerto Rico as the daughter of two physicians, Dr. Lozada Soto's passion for discovery was kindled early through hands-on scientific exploration at home in the shape of unique science fair projects or even pretending to be a doctor as she played with her friends. Later during her undergraduate years at the University of Puerto Rico-Rio Piedras, she pursued research on colorectal cancer epidemiology in Puerto Rico natives in the laboratory of Dr. Marcia Cruz-Correa, one of the island’s few women physician scientists. It was here where Kristen first considered the possibility of a combined career in medicine and research. To solidify this decision, she pursued a Post-Baccalaureate Research Education Program (PREP) Scholar in the laboratory of Dr. George Dubyak at Case Western Reserve University where she fine-tuned her wet-bench skills and hypothesis driven research.
As a PREP scholar, Lozada Soto worked on determining innate immune pathways that regulate the assembly of inflammasome signaling platforms for caspase 1 activation and IL-β1 secretion in macrophages and dendritic cells in the context of crystal-induced inflammation. “My project centered around characterizing the signaling network that couples lysosomal membrane permeability to NLRP3 inflammasome activation and cell death in macrophages. I loved how my research was directly linked to the pathophysiology behind crystal-induced inflammation of joints and arteries, as is the case for gout and atherosclerosis, respectively.” This experience cemented her resolve to pursue a career as a physician-scientist and she applied to medical school as an MSTP student and was accepted at Michigan.
Under the mentorship of Drs. Asma Nusrat and Charles Parkos, Kristen alongside research investigator, Dr. Arturo Raya-Sandino, made key observations about Claudin-23 (CLDN23), an atypical tight junction protein in intestinal epithelial cells. She explained that “Claudins are like molecular zippers that create pores or barriers to seal the spaces between intestinal cells, selectively preventing harmful substances from entering the body while allowing ions and water to pass through.” She explained that there are many members of the Claudin protein family, however CLDN23 is special. "Claudin-23 is a unique member of the claudin protein family that helps strengthen the intestinal barrier in an unexpected way. Through extensive laboratory studies and collaborations with experts at Syracuse University and Emory University, we discovered that Claudin-23 works like a molecular plug by partnering with other claudins (Claudin-3 and Claudin-4) to seal off tiny passages between intestinal cells. This tight sealing is particularly important in the colon, where we need strong protection against the trillions of bacteria and other substances that live in our gut."
Her innovative research was published in the high impact journal, Nature Communications, as a co-first author with Dr. Arturo Raya-Sandino. The scientific community has also recognized her work through multiple presentations at scientific conferences, including the Gordon Research Conference on Signaling by Adhesion Receptors and the American Society of Investigative Pathology (ASIP) Annual Meeting. Her research excellence has been recognized through several prestigious awards, including the highly competitive NIH Ruth L. Kirschstein National Research Service Award (F30), the A.D. Sobel Trainee Scholar Award at ASIP, and the MCP Student Research Award. She was also awarded best oral presentation at the 21st Annual Pathology Research Symposium. Additionally, she has been supported by the NIH Training in Basic and Translational Digestive Sciences T32 fellowship, highlighting her potential as an emerging leader in the field.
During her PhD journey, Dr. Lozada Soto embraced another exciting chapter - motherhood. The birth of her son Iker became a source of additional motivation and inspiration. "Showing my son that perseverance and passion are key to achieving one's dreams became an integral part of my PhD journey," she reflects. With support from her mentors, particularly Dr. Nusrat, she successfully integrated her roles as a scientist and mother. She added that “sometimes integrating these roles meant that I brought the research home with me; other days, Iker joined me in the lab. If he wants to, I’d love to see him grow up to be a researcher like his mommy,” she added with a smile.
The future is bright for Kristen. She eagerly anticipates working with patients in the clinic and continuing to pursue research. “I still have several more years of training ahead of me. However, I rarely think about the length of my training as I enjoy what I am doing day by day. I knew it would be a journey, but I’m so glad I decided to pursue this path” Her mentor, Dr. Asma Nusrat shared this limerick to summarize Kristen’s journey:
In the realm of knowledge so vast,
Stood Kristen, determined and steadfast.
Her thesis, a light,
With rigor and might,
In her defense, she triumphed at last!
Citation:
Raya-Sandino, A., Lozada-Soto, K.M., Rajagopal, N. et al. Claudin-23 reshapes epithelial tight junction architecture to regulate barrier function. Nat Commun 14, 6214 (2023). https://doi.org/10.1038/s41467-023-41999-9
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