Lipid Leaders - Kelly Hines

Tell us a little bit about yourself.

I’m an Assistant Professor in the Department of Chemistry at University of Georgia. Before I started my own group in 2019, I was a Senior Fellow in Prof. Libin Xu’s group in the Department of Medicinal Chemistry at University of Washington. I completed my PhD with Prof. John McLean at Vanderbilt University in 2014 and did a one-year post-doc in the Mayo Clinic Metabolomics Resource Core before going UW in 2015.

What do you consider the greatest breakthrough in lipid research in recent years?

All the methods for locating double bonds, cyclopropyl modifications, and branching positions in fatty acids are so exciting! That work is taking lipidomics to a whole new depth. Knowing the fatty acid structures to that level allows researchers to connect their mass spec lipid data back to very specific fatty acid synthesis pathways and to physical membrane properties like fluidity.

Did you always envision yourself becoming a scientist? If not, what did you want to be when you grew up? Who influenced you to become a scientist?

I’ve always liked the puzzle-solving nature of science and math. I went into college at University of Florida as an engineering major and came out an analytical chemist! The engineering majors has a separate section of General Chemistry taught by a chemical engineer who brought a lot of case-studies from his own career into the class. It really opened my eyes to the huge reach of chemistry and all its possibilities. Half-way through the second semester, I decided Chemistry was the field for me.

What drove you to focus your attention on ion mobility-mass spectrometry, particularly related to the metabolome and lipidome?

There’s just so much more information you can get out of an IM-MS experiment! The structural separations are really helpful for ID purposes in complex mixtures, but my favorite part is the mobility-aligned tandem MS experiment. When you do CID after mobility separation, the MS/MS spectra are aligned in drift time with the precursor. That makes data-independent MS/MS experiments so much easier to interpret because the spectra from co-eluting lipids or metabolites are each at a different drift time.

Where did your interest in bacterial lipids originate?

From my time at UW. I was already working on lipidomics in Libin’s lab and another faculty member in the School of Pharmacy approached him about doing lipidomics for antibiotic-resistant strains of Staphylococcus aureus. It was well-known that the antibiotic daptomycin targeted the bacterial membrane and that resistance to daptomycin was driven by changes to the abundance of phosphatidylglycerols, lysyl-PGs, diglycosyldiacylglycerols, and cardiolipins. But all that work had been done by 2D-TLC. We knew we could get a similar separation by headgroup using hydrophilic-interaction liquid chromatography (HILIC) plus have all the benefits of IM, MS, and MS/MS for lipid identification.

What do you think are some of the most exciting questions in the field of bacterial lipidomics?

For us, it’s how much bacterial lipids are influenced by the lipid content of their growth environment whether it’s broth, agar, or an infection site in a living organism. Many types of bacteria can use environmentally derived fatty acids in their own membrane lipids. My group is starting to explore just how prevalent this process is, what are the limitations and advantages to the bacteria, and what does it mean for treating bacterial infections with antibiotics.

What are the future implications of understanding the metabolome, lipidome, and genome and how they are integrated, particularly with regard to pathogens?

What we've seen in some of our work in antibiotic resistance is we can’t always or easily predict the effect of a genetic mutation on the molecular phenotype of the organism, especially if there are multiple mutations related to the same pathway. Sometimes it takes looking at the full picture of metabolites, lipids, proteins, and the genome to know what advantage that mutation conveys to the bacteria.

What has been the most interesting discovery you have made as a scientist?

I’m still blown away by our ability to separate phospholipids with branched- and straight-chain fatty acids using liquid chromatography. GC methods to separate anteiso, iso, and straight fatty acids have been around for a long time, but you have to hydrolyze the fatty acids off the glycerol backbone first. All the information about how the fatty acids were combined together and their sn-positions gets lost in the process. We are really just starting to see how important it is to know the BCFA versus SCFA breakdown within and between different types of lipids.

What are your hobbies? What do you like to do outside of the lab?

Our jobs require so much deep-thought and sometimes it’s hard to turn that off. I find myself thinking about our projects all the time. Reading (especially fiction) and yoga really help me turn off that part of my mind and escape for a bit. On the other hand, I love gardening and even mundane things like weeding because my mind can wander while my hands are busy.

Do you have a favorite Avanti product or class of products?

Or perhaps one that you’ve found most useful in your research? We’ve used so many Avanti products in our work! The natural extracts, both the bulk and specific lipid class extracts, have really helped us replicate the complexity of real biological samples for method development.