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Heather Desaire - Keith Wilner Chair
Dr. Heather Desaire Madeline Isom, Aleesa Chua, Dr. Heather Desaire, Leah Pfeifer, Hanna Nguyen, Dr. Eden Go
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Heather Desaire
Istarted life in Burdett, Kansas, population, 200. My parents were high school teachers – my mom taught English, and my dad taught Physical Education. Eventually, Dad gave up his gym shoes and went into sales. As a result, we moved first to California, then Ohio. As a high school student in Ashland, Ohio, I enjoyed my math classes but did not immediately fall in love with chemistry. I was, on more than one occasion, moved to the back of the classroom for talking too much and distracting my fellow classmates. My chemistry teacher even sent me to the principal’s office once for violating the dress code because I had worn shorts to school.
After such an inauspicious start in my eventual field, I had a lucky break, thanks to the principal of the elementary school where my mother was teaching at the time. Principal Mark suggested I join his daughter, who was also a high school student, and take the Honors General Chemistry class at Ashland University during my senior year. This second experience with chemistry was much more enjoyable, as the ideas of chemistry came to life; and thinking, not memorizing, was the currency of the classroom. This class inspired me to become a chemistry major in college, and eventually, a professor.
I attended Grinnell College in Grinnell, Iowa for my undergraduate studies. In addition to learning a lot of chemistry there, I learned how much an engaged professor could positively influence students. After a decentbut-not-impressive first semester in college, my academic advisor and organic chemistry professor, Mary Mader, told me that I needed higher grades if I wanted to get into top graduate schools. This advice was not only absolutely accurate, it provided the motivation and encouragement necessary to realize that such a path was possible, with a little more effort. In addition to being hard on me when I needed it, Professor Mader also helped me land a full-tuition scholarship covering my last two years at Grinnell; these funds made such a difference. They likely kept me from having to transfer to a more affordable school.
I did a number of different summer research stints as an undergrad. I spent a summer at Harvey Mudd college, where, at the time, men outnumbered women by about 10 to 1. I struggled through a summer of synthetic chemistry in Laramie, Wyoming, where I thankfully learned that synthesis was not my thing. Finally, I spent a summer at Kimberly Clark in Neenah, Wisconsin, where my goal for the summer was to develop better ways to test the absorbency of diapers.
In 1997, I moved to Oakland, CA, to attend graduate school at the University of California, Berkeley. Even back then, Berkeley had student housing problems. I eventually found a very convenient studio apartment that was less than a block away from the following amenities: a gun store, a liquor store, an hourly motel, a funeral parlor, a church, and the subway (BART) station. Of all the luxurious amenities mentioned, the BART station was the only one I ever entered.
I began doing mass spectrometry research on carbohydrates under the guidance of Professor Julie Leary. Two things immediately attracted me to this line of work: First, it was fascinating that one could use an instrument designed to weigh things (the mass spectrometer) to distinguish diastereomers, molecules with the same weight and functional groups. The second highly appealing aspect of the work was that mass spectrometers are so sensitive, the samples to be analyzed always were prepared and loaded into new (disposable) Eppendorf tubes – this meant that there was no dishwashing to be done, a point that clearly established
Dr. Heather Desaire, Madeline Isom
the superiority of mass spectrometry research over synthetic chemistry.
I applied for my faculty position at the University of Kansas while I was finishing up my graduate studies. I am immensely grateful that the faculty at KU could see past my lack of experience and that they offered me a job. I spent about seven months, between the completion of my graduate studies and the start of my position at KU, working at a contract research organization in Kansas City that specialized in supporting the pharmaceutical industry.
Figuring out how to obtain grant funding proved to be quite challenging for me, as it is for most new professors. It took me 10 tries at submitting external grant proposals before I got one funded. The winning proposal described analyses of glycosylation on HIV vaccine candidates. This line of work opened up opportunities for my group to collaborate with the preeminent HIV vaccine developers in the US, and these studies and collaborations have been a significant component of my research program for the past twenty years.
The initial HIV grant we received primarily described methods development work: Our main goal was to develop a robust strategy to characterize the glycans (sugar molecules) on the Env protein in a glycosylation sitespecific manner. The protein has ~30 different sites where glycans were attached, and we thought that being able to discriminate the glycans at each site would ultimately provide more useful information than cutting them all off the protein first and then analyzing them, which was the prevailing strategy at the time for glycosylation analysis of proteins. Analyzing the glycans in this site-specific approach was more challenging, though, and it took several
Aleesa Chua, Madeline Isom, Dr. Heather Desaire years to develop the methods needed to do this efficiently. Eventually, we were able to use the approach we developed to demonstrate that many of the early vaccine candidates did not accurately represent the glycosylation on native forms of the protein that they were supposed to emulate, and this work, along with similar findings in the HIV field about the early vaccine candidates, caused a shift in HIV vaccine design towards strategies that generated more native forms of the vaccine candidate proteins.
More recently, we were able to apply these same strategies to analyzing the glycosylation on the S glycoprotein, which is the primary component in the SARS-CoV-2 vaccine. Because we had spent years developing, testing, and validating a workflow that produces a highly reliable assessment of the glycosylation on multiply glycosylated proteins (in our HIV work), we were able to apply these same strategies to this new viral protein, which is also heavily glycosylated. In addition to characterizing the glycans on a native form of this protein, we showed that many other researchers, who were also analyzing glycosylation on the SARS-CoV-2 glycoprotein, were getting incomplete and inaccurate information. Their analyses relied on a commercial product to analyze the glycosylation from the mass spectrometry data, and we showed that this software produces more false positives than true positives and only assigns about one in three of cont. next page
Dr. Keith D. Wilner earned his B.A. in chemistry at KU in 1978 and is currently the Oncology Clinician Leader and Global Clinical Lead for Pfizer Global Research and Development. At KU, Keith carried out undergraduate research in the labs of Profs. Givens and Christofferson and he credits this and his other experiences at KU with “...setting him on the path to a successful career.” “I have been very fortunate to work in an area that is amazingly rewarding and having an impact on patients’ lives.” Keith established the Chair to help “...pay KU back...” for setting him on his career trajectory.
As discussed in the last newsletter, The Keith D. Wilner Chair in Chemistry is a rotating Chair that will be awarded every three years to a deserving faculty member. During their 3-year term, each awardee will hold the title of the Keith D. Wilner Chair in Chemistry and receive $15,000 a year in support for their scholarly activities. When the invested endowment grows to a sufficient level, the Wilner Chair will be converted to a permanent endowed professorship and used to attract a faculty member at the Distinguished Professor level.
