TAMEST Member Profile: Margaret A. Phillips, Ph.D. (NAS), UT Southwestern Medical Center

TAMEST Member Margaret Phillips, Ph.D. (NAS) has been at UT Southwestern Medical Center since 1992. Currently, she serves as Chair of the Department of Biochemistry with a secondary faculty appointment in the Department of Pharmacology and holds the Sam G. Winstead and F. Andrew Bell Distinguished Chair in Biochemistry. 

Prior to moving to Texas, the native-Californian took a break between her undergraduate and graduate education to work in the pharmaceutical industry. She says her work to develop diagnostics to measure drug levels in serum led her to develop her interests in drug discovery and eventually to combining that interest with her current field of studying parasitic protozoa that cause human disease. 

In 2021, Dr. Phillips was elected to the National Academy of Sciences (NAS) for her groundbreaking work to target metabolic pathways with the goal of developing drugs to treat malaria. Dr. Phillips, who currently sits on the 2023 Edith and Peter O’Donnell Science Award Subcommittee and is herself a former O’Donnell Award Nominator, says the best part of being an academy member is that it gives her a greater voice when trying to lift up and bring recognition to rising research talent. 

TAMEST spoke with Dr. Phillips to find out more about nominating the 2021 O’Donnell Award Recipient in Science and her pioneering work to find treatments for malaria.

Tell us a little about yourself and your work.

I grew up in the San Francisco Bay Area and my father is a Physician-Scientist. He encouraged us when we were growing up to pursue our interests to the fullest extent. I showed an early aptitude and interest in science and math, and he always encouraged me to pursue those. He always said that science and research was the most fun career possible!

I went on to receive my Bachelor’s degree in Biochemistry at The University of California, Davis and after I graduated, I went to work for a small medical diagnostics company.  After that experience, I realized that you need more than a bachelor’s degree if you want to drive your own scientific direction. So, I went back for my Ph.D. at the University of California, San Francisco in Pharmaceutical Chemistry.

Did working in industry between degrees help you have a better understanding of your field?

It was a great experience to spend a couple of years out before going back to finish my education. It really made me realize what kind of science I wanted to do. 

Taking that break meant that when I did go back for my Ph.D., I knew it was what I wanted and not just because I wanted to keep going to school. My Ph.D. program is where I first started researching these single-cell protozoan parasites – which would continue throughout my career.

What was it like to pick up and move to Texas in 1992? 

I grew up entirely in California. When I was interviewing for faculty jobs, I had offers across the country. However, it was the late, great Dr. Alfred G. Gilman, a UT Southwestern Nobel Laureate and Chair of Pharmacology at the time, that made me choose UT Southwestern Medical Center.

Dr. Gilman explained that UT Southwestern is not just collegial, but collaborative and resource heavy. He convinced me that Texas was the place to come, that UT Southwestern was the place to be, and he was just an all-around amazing leader and mentor to me before he passed away in 2015.

I’d never even been to Texas before interviewing for the job! In the end, he was right, and it has just been an incredible research environment to be included in. 

Talk about your biggest research breakthrough at UT Southwestern?

I started my independent lab working on the parasite that causes African sleeping sickness. Around the time I became an Associate Professor, I decided to initiate a new program on malaria, which is caused by Plasmodium species. I was motivated by the importance of malaria and the number of people that are sickened by it every year. Even now, we still have 600,000 people worldwide dying of malaria every year – most of those are children under five and in Africa.

Around the time that I started this program Dr. Steve McKnight who was Chair of the Dept of Biochemistry at that time had the vision to build a high-throughput screening core at UT Southwestern. This enabled me to screen for small molecule inhibitors of an enzyme called dihydroorotate dehydrogenase, which is essential for the synthesis of DNA building blocks called pyrimidine nucleotides in the malaria parasite. It turns out you can get really good selectivity against this enzyme because the active site on the parasite enzyme is quite different to the human enzyme. Long story short, the research advanced to identify a compound that reached clinical development where it was studied in a Phase II human trial in Peru.

It was intellectually exciting to be part of something like that. We showed that the compound had the potential for providing a single-dose cure for malaria. We ended up winning a prestigious research award for the discovery, from Medicines for Malaria Venture, and had the opportunity to travel to Tanzania to receive the award and visit malaria field hospitals to see malaria where it is endemic.

I worked with a really great team, and we were able to advance our science from enzymology all the way to a therapy that made it to the clinic and had the potential to really make a difference. It’s because of this discovery that I was elected to the national academies. 

What has it been like to dedicate your career to a disease with such a global impact?

It’s been amazing. However, it also shows you the difficulties in drug discovery. The compound eventually didn’t move forward because of some issues that were found. Yet, the knowledge we gained of the target taught us how to position compounds on that target for the malaria drug portfolio.

We’re continuing to work to identify additional inhibitors that will advance on their own. It is my hope that we will still be able to identify a compound that reaches clinical use for the treatment of malaria.

What was it like to be elected to the National Academy of Sciences for this work?

It was an incredible honor, and one that I share with everybody I work with. You don’t do this kind of science in a vacuum, you do it in a collaborative way with people from different disciplines coming together.

In a drug discovery program, you need Biochemists, Chemists, Pharmacologists, and you also need scientists and physicians who can take these discoveries from the lab and advance them to the clinic.

I feel that one of the great things about being elected to the National Academies is that it makes it easier for me to help the younger people that work with me. It’s important for me to be able to give back to others that I mentor and/or interact with. 

In 2020, you nominated the 2021 Recipient of the Edith and Peter O’Donnell Award in Science. Talk through why you nominated a rising star in research at your institution.

I became chair of the Department of Biochemistry at UT Southwestern in 2016. For that position, mentoring is a big part of the job, as is promoting the people in your department, as well as other young researchers on campus. 

I nominated Dr. Ben Tu for the 2021 O’Donnell award a year prior to becoming an actual TAMEST Member. I did so because I knew about TAMEST, the O’Donnell Awards, and their mission to elevate Texas science and research.

Dr. Tu is just such an amazing scientist and was highly deserving of the award. I wanted to see him win it and was overjoyed when I heard he was the recipient. I’ve had colleagues at UT Southwestern win the award and I’ve seen firsthand the impact it can have in the career trajectory of a rising researcher.

It was gratifying to see Dr. Tu and his work be highlighted.

Why did you decide to join the 2022 O’Donnell Award Science Subcommittee?

For me, having been elected to the national academies, it’s important to give back. I think by sitting on committees like this, it is an opportunity to support the research community.

New this year, is the addition of a second science award. What was your initial thought when you heard the news?

I think the decision to have two yearly science awards instead of rotating between Biological and Physical Sciences every other year was excellent. We have a lot of impressive scientists in both disciplines in Texas and this now provides a great opportunity for more of our brightest young scientists to be recognized for this prestigious award.

Especially being in a medical school, I was always disappointed that the biology awards were only every other year.

What does being a member of TAMEST mean to you?

To start with, it is a great honor to have your research recognized, but the future great discoveries in science are going to come from the next generation. It is important to be mentoring other scientists and inspire young children to get into science as well. These are critical objectives and the reason TAMEST is such an important organization. It gives recognition to that platform, and it makes the public and research community in Texas aware of what science can do and is doing in our state. 

Is there anything else you’d like to add? 

This coronavirus pandemic has really turned things upside down. However, it has also given us the opportunity to observe a real-life experience of the power of science and how it can make an incredible difference in people’s lives. The effort to develop these COVID-19 vaccines is just extraordinary.

The fact that our scientific community developed effective vaccines, and now therapeutics, in such record time is an example of the power of science. This experience highlights how important it is for us, as scientists, to engage and educate the public on the importance of scientific discoveries and the impacts they can have on their lives.

It also shows the importance of nurturing future talent. I think it is important to do that in an inclusive way – in diverse racial and cultural backgrounds – and ensure everyone is brought in to contribute to the scientific mission. The fact we got these vaccines in record time really shows what science can do when everyone pulls together for the greater good.