Explore Research Innovation at the David Geffen School of Medicine
Michael Robert Yeaman, PhDProfessor of Medicine, David Geffen School of Medicine at UCLA
Medical Science Investigator, Harbor-UCLA Medical Center / LABioMed
Dr. Michael Yeaman studies natural processes and patterns to develop interventions that fight pathogens, overcome antibiotic resistance, and optimize immune health. His discovery of a universal structure in antimicrobial molecules illuminated a new world of disease-fighting possibilities.
By understanding the interplay of immunity and infection, Dr. Yeaman can design balanced, sustainable strategies that heal patients while mitigating aggressive disease response and resistance. He strives to develop vaccines and anti-infectives that incorporate personalized techniques to reduce the prevalence and devastation of human disease.
By looking at molecules in three dimensions instead of linear sequences, Dr. Yeaman discovered clinically significant biological themes that changed the way we study and fight infection.
Discovery: Immune System Molecules Have the Same Structure Across Species
Dr. Yeaman found that all life's innate "antibiotic" molecules have the exact same shape, whether they are found in a sea urchin or a human being. He looked for the shape in undefined antimicrobials and discovered antimicrobial properties. Beautifully efficient, nature had used the same structure to confer defensive mechanisms across the evolutionary continuum. Read more in Multidimensional Signatures in Antimicrobial Peptides, published in Proceedings of the National Academy of Sciences of the United States.
Implication: Researchers can borrow nature's antibiotic structure to develop novel interventions.
Discovery: Bacteria and Fungi Use the Same Molecular Structure to Infect Hosts
Dr. Yeaman uncovered similar infection mechanisms in Staphylococcus bacteria and Candida fungus. Both pathogens cause serious, highly resistant infections in humans.
Implication: Researchers can use one vaccine to protect against both Staphylococcus bacteria and Candida fungus.
Early clinical trials of the first cross-kingdom vaccines suggest they are safe and effective. Read more in NDV-3, a Recombinant Alum-Adjuvanted Vaccine for Candida and Staphylococcus Aureus, is Safe and Immunogenic in Healthy Adults, published in Vaccine.
"We’ve found that bacteria and fungi have evolved in a very specific way to exploit the human host, and so we vaccinated against the common denominator, and it protects against both organisms," says Dr. Yeaman.
Dr. Yeaman is developing anti-infectives to mitigate antibiotic resistance by circumnavigating the mechanisms that make pathogens resist in the first place. The treatments incorporate small molecules designed to:
Dr. Yeaman hopes these treatments will mitigate resistance by lessening the intense kill pressure used by most antibiotics. The therapies focus on an organism's choice to die instead of a drug's ability to kill.
"Whenever you exert pressure to kill an organism, natural selection is such that there will be resistance," says Dr. Yeaman.
Dr. Yeaman believes the next big breakthroughs in immune health will come not only from studying pathogens, antibiotics, and immune systems separately, but also from studying the interactions between them. He is part of a pioneering collaboration with Harbor-UCLA, the David Geffen School of Medicine at UCLA, and Duke University that examines the intersection between the human host, the Staphylococcus aureus bacteria, and the antibiotic used.
Backed by $10 million in National Institutes of Health funding, the collaborators hope to develop biomarkers to help practitioners detect the unique vulnerabilities and best treatments for patients on an individualized basis.
"We’re moving into an era of personalized and precision medicine where we cannot just look at a human as a human or a staph bacterium as a staph bacterium—each individual within any category can have statistically significant differences," says Dr. Yeaman.
The immune system is core to human health; it's functionality has implications in everything from bacterial infections to cancer. By studying immune system function on an individualized level, Dr. Yeaman hopes to detect even more patterns we can leverage to improve outcomes in human disease.
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Harbor-UCLA Medical Center