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A Passion for Helping Others Leads to a Career in Pathology

By Lynn McCain | May 17 2023

Xinna Li 500.jpgBorn and raised in Northeast China, Dr. Xinna Li, Assistant Research Scientist in the Department of Pathology, has always been passionate about helping others. Her journey began with a childhood fascination with medicine. “I remember as a very young child, bandaging a cut on my brother’s leg. Then, as a teen, my cousin became very ill and I observed how medical treatment could cure illnesses. That is when I realized that I wanted to be a doctor,” recounted Li. Driven by the desire to make a difference, she pursued a medical degree in pediatric hematology from China Medical graduating in 1994. Working at a hospital, she cared for children diagnosed with leukemias, lymphomas, multiple myeloma, and other diseases. “I treated these children with chemotherapy and radiation, and they still died,” Li explained. She yearned for a way to improve their chances of survival.

Determined to find solutions, Li pursued a PhD in molecular biology, which she completed in 2004. In 2002, she migrated to the United States as a Research Fellow under Dr. Roman Dizarski at Indiana University. There, she delved into innate immunity research and mentored undergraduate students. Seeking a vibrant Asian community, she accepted an opportunity to work in Dr. Richard Miller’s laboratory in the Department of Pathology at the University of Michigan in 2008. Over the years, Li’s dedication and success in the Miller Lab led to her promotion as Assistant Research Scientist in 2012.

The Miller Lab focuses on unraveling ways to slow aging processes in mice and potentially extend healthy human lifespan. Li has played a significant role in this research, having published nineteen research articles. Some noteworthy findings from her work include:

  1. The discovery that mutations in the growth hormone receptor (GHR) in mice lead to increased thermogenesis, improved glucose control, and a shift towards anti-inflammatory macrophages in fat tissue. These changes were attributed to interruption of growth hormone (GH)-dependent irisin inhibition. (Aging 2020)
  2. Mice with elevated levels of glycosylphosphatidylinositol-specific phospholipase D1 (GPLD1) levels demonstrate enhanced neurogenesis and cognition. The findings suggest that elevated GPLD1 contributes to the preservation of cognitive function observed in long-lived mutant mice. (Aging Cell 2023)
  3. Use of anti-aging drugs and calorie restriction in young mice result in common changes across various tissues, including increased uncoupling protein UCP1 in fat, a shift from proinflammatory to anti-inflammatory macrophages, elevated muscle fibronectin type III domain-containing protein 5 (FNDC5) and irisin, and higher levels of neurogenesis markers in the brain. These changes are associated with age-related diseases and suggest shared pathways in slow-aging mice. (GeroScience 03/2023)
  4. The lab explored the impact of transient early-life growth hormone exposure on permanent alterations in adipocytes, fat-associated macrophages, liver, muscle, and brain in long-lived mice. The findings indicated that these alterations were not due to hepatic IGF1 production or direct growth hormone effects on adipocytes but rather reflected growth hormone effects on muscle. The changes in adipose tissue differentiation and inflammatory status are suggested to be associated with interrupted growth hormone-dependent irisin inhibition. (FASEB J 2022)
  5. Mice with a global deletion of pregnancy-associated plasma protein-A (PAPP-A) displayed changes resembling other long-lived mice models, including increased UCP1 in adipose tissue, shifts in fat-associated macrophages towards reduced inflammation, elevated muscle FNDC5 and irisin, and higher production of hepatic GPLD1 and plasma GPLD1 associated with neurogenesis. Muscle-specific deletion of PAPP-A resulted in complex and opposing changes compared to global deletion, emphasizing the role of PAPP-A in modulating signals controlled by growth hormone and/or IGF1. (Geroscience 04/2023).

Li’s dedication to the next generation of scientists is seen in her work with the undergraduate students in the laboratory, as she helps guide them in their career aspirations.  Those interested in working with patients and learning more about diagnostics she guides toward medical school. She encourages those passionate about research and discovery to pursue academic research careers, emphasizing the importance of staying informed through reading scientific literature. “I read at least 10 publications a day to keep abreast of the most recent research findings. I examine the data to be sure these are well-done studies and consider how the findings from the best studies could inform my research direction,” explained Li. She credits her mentor, Dr. Roman Dizarski, who practiced the same discipline. “He told me that I have to critically read at least 10 publications daily if I wanted to be a successful scientist.” From her examination of the literature, Li is inspired in her research direction. “I like to pick something that no one else is doing.”

Despite language barriers as a non-native English speaker, Li strives for clear communication. “I know my language is not perfect. I try to speak clearly and write well. I have colleagues who support me in this, but that is my biggest challenge.  People don’t always understand me clearly. Reading the literature also helps me with my English.” Attending Asian Scientific Conferences allows her to connect with her heritage and engage with others in her native Chinese language.

Li finds great joy in her research. “If I could give a person a longer, healthier life, that would be very good.  Not just long life without a memory, but a long, healthy life.” The lab’s findings on the potential of certain drugs, like Acarbose and Metformin, and the benefits of maintaining good body condition through caloric restriction and exercise offer hope for improved lifespan and cognitive function.

Outside of work, Li enjoys running, cooking, drawing, and traveling. “I run for one hour every day, and I have done so for 20 years,” said Li. She derives immense pleasure from cooking authentic foods, expressing herself through art, and exploring new cultures during her travels. She cherishes time spent with her husband and their son, who is pursuing studies at MIT, and looks forward to visiting her 86-year-old father in China.

 
Careers in Pathology faculty experimental pathology immunology
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