Year: 2022

Two of our graduate students, Cynthia Tang and Jack Zheng, received the Rucker Family Fellowship! This is a great honor and a wonderful recognition of Cynthia and Jack’s accomplishments as PhD candidates in Nutritional Biology. Dr. Rucker was and still is one of my most valued mentors. When I was a graduate student in the program Dr. Rucker was still actively involved in research and teaching, and was doing wonderful work in the discovery and characterization of the impacts of PQQ on human health. Dr. Rucker was ahead of his time and was a strong supporter and advocate of my work in the area of what was then called “personalized nutrition” and is now referred to as Precision Nutrition. This was at a time when this concept of personalizing nutrition was not generally appreciated or accepted in the broader nutrition community. Dr. Rucker’s support was invaluable in helping me to achieve my goals and dreams. It is therefore even more of an honor to have some of my own students now receiving recognition in the form of the Rucker Family Fellowship  for their work.

Cynthia is a computational guru who is exploring the contributions of glycosylation pathways in the etiology of Alzheimer’s disease, and how nutritional components may be involved in regulating these pathways. She is using cutting edge computational biology tools to explore the complex regulatory networks of glycosylation machinery in the human brain integrating RNA sequencing and -omic data. She is also interested in the interconnections between glycosylation and lipid metabolism and how this impacts brain health.

Jack is reviving the use of a tried but true imaging technology to study the most complex and difficult class of nanoparticles, high-density lipoproteins (HDL). Although electron microscopy (EM) is not new, it is still one of the only ways to “see” these tiniest of nanoparticles, which are only 5-12 nm in diameter, and therefore too small to image using most other techniques. EM is traditionally considered too cumbersome and difficult to image more than a few samples at a time. Jack is developing methods to use EM to image hundreds of clinical samples, including tens of thousands of HDL particles for every sample, to understand the biological variability in particle size and morphology.

Congratulations Cynthia and Jack!!

In our newly published narrative review in the special issue “Alzheimer’s disease- 115 Years After Its Discovery” in the journal Biomedicines we discuss the ins and outs of cholesterol handling in microglia, the immune cells of the brain, and discuss implications for Alzheimer’s disease.

In this review article we explore what is known about the effects of high and low cholesterol concentrations on microglia phenotype and function, and areas of research that still need to be explored to better understand this aspect of biology. Given the importance of microglia in driving the neuroinflammation that is associated with neurodegenerative diseases like Alzheimer’s disease, improving microglia function and decreasing microglia-associated inflammation are priority targets for finding new, effective treatments for Alzheimer’s disease. Understanding the role of cholesterol in this process may be a key for finding therapeutic solutions.

High density lipoproteins (HDL) are difficult to study: with a diameter range of 5-12nm they are too small to be studied by many tools that are routinely used to count, characterize and image other nanoparticles such as extracellular vesicles and cells, yet they are multi-molecular complexes that perform a wide array of functions which are dependent on their structure and composition. Despite more than 60 years of research, predominantly in the cardiovascular field due to the importance of HDL in clearing excess cholesterol arterial plaques, we understand very little about the complex biology of HDL particles and their myriad critical functions. We all know that not enough HDL is bad (low HDL-cholesterol is a part of the diagnostic criteria for metabolic syndrome), but recently it was found that too much HDL may also be bad (HDL-cholesterol concentrations >100 mg/dL are linked with higher mortality). What’s more, the amount of HDL in circulation (measured as HDL-cholesterol) only explains about 40% of the variability in the ability of HDL to perform their flagship function of cholesterol efflux, or removal of cholesterol from lipid-loaded macrophages. This means that measuring HDL as the amount of cholesterol carried in the particles is really only telling us a very small piece of the story. And it turns out that HDL composition – the proteins, lipids, lipid soluble components, and even RNA that they transport – HDL structure, and HDL particle size distribution, are all critical factors in how these particles do their jobs of protecting us from infection, blocked arteries, hyper inflammatory responses, and a number of additional functions. Yet we do not know how to improve HDL and truly even how to measure them. In the recently funded grant from the National Institutes of General Medical Sciences, the Zivkovic Lab will develop and optimize new technologies to study HDL particles and their complex biology so that we can harness this vast army of nanoparticles (over 6 quadrillion particles in every millimeter of plasma!) to improve and optimize health.