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Collaborations Creating Change

Women’s Health Research at Yale encourages faculty from different fields to collaborate and use their combined expertise to answer real-world health questions more effectively. Investigators with similar interests share data and utilize their diverse knowledge and perspectives to further research and advance science.

Sex Differences in Alzheimer’s Disease:

Drs. Hongyu Zhao, Stephen Strittmatter, and Le Zhang

WHRY-investigator Dr. Hongyu Zhao, a public health epidemiologist and statistical modeler who employs novel analytical techniques in assessing large collections of health data, discovered evidence of genetic sex differences in Alzheimer’s Disease (AD). This was of great interest scientifically, and yet WHRY and Dr. Zhao agreed that the sex-specific findings had to be explored further in collaboration with neuroscientists who were pursuing the human investigation in AD.

WHRY had an ongoing collaboration with neuroscientist Dr. Stephen Strittmatter, who focuses on understanding the genetic basis for brain-based intracellular differences that place women at higher risk for AD. In studying human brains of both women and men with AD, Dr. Strittmatter with his junior faculty colleague Dr. Le Zhang found sex-specific intracellular differences that appear to drive the inflammation and degeneration found in AD. They then wanted to understand if these sex-specific molecular and cellular changes could uncover diagnostic biomarkers and targets for therapy, which requires examination of large-scale data.

WHRY brought Dr. Zhao’s findings to Dr. Strittmatter so that these researchers could use their complementary expertise to pursue the genetic underpinnings for AD and advance therapeutic drug response. This work produced feasibility data that led to a $2.5 million NIH grant for Drs. Zhao and Strittmatter to study this area of work. Dr. Zhang also was awarded a separate grant from the Alzheimer’s Disease Research Center to pursue research with Dr. Zhao as a mentor.

Influence of Metabolism on Immune Response to Covid-19:

Drs. Akiko Iwasaki and Caroline Johnson

Metabolomics is the study of chemical byproducts, called metabolites, that are produced in the process of metabolism as cells produce energy. Dr. Caroline Johnson is an expert in this technology and, as a WHRY-Investigator, has used metabolomics to explore sex differences in risk for colon cancer. This is accomplished by analyzing the metabolites found in those with cancer compared to those without cancer, and tracing the upstream metabolic pathways involved in the end product.

Dr. Akiko Iwasaki is an expert immunobiologist who, as a WHRY-Investigator demonstrated how the immune response to the SARS-COV-2 virus, which causes Covid-19, is different in women and men. Given that the immune system is regulated in part by metabolites, WHRY connected these two experts to examine sex differences in the metabolic process that could influence the immune response to SARS-COV-2.

Drs. Iwasaki and Johnson uncovered a sex-specific link between a metabolic pathway and immune response finding that men who more severely ill had higher kynurenic acid (KA) to kynurenine (K) ratios, which caused more inflammation and lower t-cell immune responses. Women, however, had KA to K ratios that were favorable for higher t-cell immune responses. This discovery added to the important data necessary to understand the action of the SARS-COV-2 virus and the observed sex-specific health outcomes.