A Conversation with 2007 BSP Wendy Marie Ingram, PhD

AMBF: Prior to college, were you curious about a career in science?

WMI: Both my parents were veterinarians so I was always curious about nature and was fascinated in the way biology could manifest both health and disease. I was personally more interested in the human brain, though, and initially wanted to be a neurologist or psychiatrist. As a pre-med undergrad student, I decided to study both psychology and biochemistry which set the stage for my love affair with research science.

AMBF: What exposure did you have to knowing what research in a laboratory would be like?

WMI: I had no real exposure to lab research, only a bit about diagnostic testing for veterinary medicine. As a freshman, I went to a biochem department event and happened to meet and speak with the Department Head, Dr. Tom Baldwin. It was Dr. Baldwin who encouraged me to explore joining a research lab and introduced me to four labs accepting undergrads. It didn't take long after joining Dr. Matthew Cordes' lab that I remember going to my mom and dad and demanding to know, "Why didn't you tell me research was so interesting!!!" My mother had worked on her masters in ornithology after completing her Doctorate of Veterinary Medicine and had conducted research on bird blood transfusions. Her take away was that "Research is frustrating. You only end up with more questions than you started with." I countered her enthusiastically, "But that's the best part!"

AMBF: When you heard about the Beckman Scholar opportunity, what inspired you to apply?

WMI: I had been working as an undergraduate research assistant in the Cordes Lab for a year and a half when I decided to apply for the Beckman Scholar Program. I had already fallen head over heels for bench research and was absolutely sure that I wanted to come back to the lab following my Junior year abroad in Scotland. There were other less competitive funding opportunities for conducting research, but I decided to apply for the Beckman scholarship because it guaranteed two years and a summer in the lab as well as other opportunities to present my research at the yearly symposium. While I had already had some lab experience, I had never been prompted to research and design my own proposal to defend to a panel of professors. The opportunity was intimidating and exciting and I still vividly remember spending hours in a coffee shop in St. Andrews, Scotland pouring over dozens of articles on the basic biology of HIV, learning about the life cycle and what regions of the RNA mutate and which don't, crafting my research plan to submit with my application. The entire process, including presenting my proposal to the University of Arizona panel of experts, including an RNA biologist, was daunting but exhilarating!

AMBF: What was your research focused on? What were the results?

WMI: The research I conducted as a Beckman Scholar had nothing to do with RNA viruses. I worked on studying the basics of protein evolution using the bacteriophage Cro protein family as a model for sequence, structural, and functional evolution. My first project involved structural characterization of the Cro proteins from the bacteriophages PY54 and N15. These two Cro proteins had unknown structures and from genetic and protein sequences, it was unclear what their primary and secondary protein folding structures may be. My work revealed that both PY54 Cro and N15 Cro had all alpha-helical structures similar to other Cro proteins that did not dimerize in solution, yet surprisingly these demonstrated homo-dimerization, comparable to other Cro proteins like the alpha helix/beta sheet Lambda Cro (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2327278/). In addition to this work, I contributed to three other manuscripts investigating the evolutionary space of the Cro protein family (https://pubmed.ncbi.nlm.nih.gov/21676898/, https://pubmed.ncbi.nlm.nih.gov/18227506/, https://pubmed.ncbi.nlm.nih.gov/16939206/) and also led an independent project investigating the evolutionary avoidance of aggregation-prone sequences in the Arc repressor protein found in the bacteriophage P22, the results of which were published in my masters thesis. This research provided the groundwork for a future PhD student's Doctoral Thesis as well (https://repository.arizona.edu/handle/10150/311174).

AMBF: What was the most memorable part about working with your mentor or working in the laboratory?

WMI: The most memorable part of working with my mentor was the balance between his calm, methodical, contemplative approach to science and his regular demonstration of still being able to marvel at the small wonders of our work. I very distinctly remember the first time we received a digital file with the DNA sequencing results from a plasmid we had submitted to the core sequencing facility. We didn't have access to a plasmid containing the complete sequence of PY54 Cro in an expression vector and therefore had to synthesize our own from four component oligonucleotides we designed ourselves. After using basic molecular biology techniques to ligate and amplify the regions for final insertion into a plasmid, we sent it off for sequencing. When we opened the digital file and aligned the sequence with our design, with perfect match across all 201 nucleotides, he sat back and with true reverence said, "It gets me every time. They have no way of knowing what we sent, what sequence we are expecting. And after sending a few microliters of what could be just pure water, we get this back. It's amazing."

His mentorship also taught me to de-couple my self worth from the research outcome. If an experiment didn't work, don't beat yourself up...just go back through the protocol, step by step and see where you could have gone wrong. If a piece of equipment malfunctioned and lost months of work by dumping my highly purified protein on the refrigerator floor (which it did), it doesn't help to stress over it. After a long pause, "Practice makes perfect," he said. "I guess you are doing it again." There is honestly too much that I've learned from Dr. Cordes to share, but I treasure every lesson.

AMBF: How did the experience change your thinking about science and conducting research?

WMI: The biggest change in my thinking was that I came to believe that we could use laboratory research to better understand and create better approaches to treating the most complicated diseases of the most complicated and important organ we have, our brains. My psychology studies showed me that we knew arguably very little about mental illnesses, neurological diseases, how they manifest, and how treatments work to reverse or mitigate them. It was the incredible opportunity to work in a basic research lab as a Beckman Scholar that opened my eyes to the power of scientific research and the myriad applications and connections that could be discovered.

AMBF: Where did you go after graduation and where are you now?

WMI: Even though I abandoned my interest in training as a medical doctor, I was still very focused on mental illnesses. Following my research in the Cordes lab, I was sure I wanted to pursue a PhD rather than an MD, but I wasn't sure if I wanted to jump straight into applied neuroscience or get my training in basic sciences. I spent a year between undergrad and grad school working in a schizophrenia research lab led by an MD/PhD Psychiatrist researcher, Dr. Amelia Gallitano. It was this experience that solidified my interest in pursuing a PhD in basic science in order to gain the deepest understanding of basic biology I could. I planned to then apply this knowledge to my ultimate interests in studying the molecular mechanisms of psychiatric illness. After applying to 7 Biochemistry and Molecular Biology programs, I decided on the umbrella Molecular and Cell Biology Department at the University of California Berkeley. I rotated in a biochemistry lab (Tjian), a genetics lab (Eisen), and an immunology lab (Robey), ultimately choosing to pursue a novel and independent project advised jointly by Dr. Eisen and Dr. Robey. My research investigated the behavioral manipulation of mice by the brain parasite Toxoplasma gondii, causing them to lose their innate aversion to cat urine. A combination of behavioral and immunological studies revealed that the parasite causes a permanent behavior change in rodents, even after the parasite is cleared from the brain (https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0075246).

After my PhD, I wanted to gain experience working with human data. I trained in bioinformatics and psychiatric epidemiology as a joint postdoc at Geisinger Health and Johns Hopkins School of Public Health from 2015-2020. I currently work for Geisinger Health as a Research Scientist studying the underlying biological mechanisms of Electroconvulsive Therapy (ECT), designing algorithms that will improve our research of depression using electronic health records, and investigating the longitudinal psychiatric outcomes following operations that involve anesthesia. I also consult for a variety of mental health focused biotech companies. The thing I'm most proud of and excited about next doesn't directly involve lab science. Last year in 2020, I co-founded a nonprofit dedicated to cultivating excellent mental health among academics worldwide, Dragonfly Mental Health. I am serving as CEO and in just a year we have recruited over 180 volunteers from all over the world to join our efforts to combat poor mental health among those who have pursued their graduate education including current students, postdoctoral fellows, faculty and administration. We conduct research, build community, and deliver evidence based programming to create sustainable culture and climate change within academic institutions supportive of mental health.

AMBF: Did you continue doing scientific research?

WMI: Yes, I continue to conduct mainly mental health informatics research. I am currently the Chair of the Mental Health Informatics Working Group for the American Medical Informatics Association (AMIA) and a chapter author in the soon to be released textbook titled "Mental Health Informatics: Enabling a Learning Mental Health Care System". As the Founder and CEO of Dragonfly Mental Health, I am also now engaged in a decidedly different discipline of scientific research as we build the evidence base for effective programing and interventions for improving mental health among academics and researchers.

AMBF: What effect did the Beckman Scholar experience have on your career?

WMI: The Beckman Scholar experience had a huge effect on me as an individual and on my career. The first impact was that receiving the Beckman Scholarship was the first clear indication that I belonged in science. Before that, I felt more like an interloper, someone who didn't quite belong yet. My best friends from undergrad were actually all graduate students and postdocs from my lab! It wasn't until I received the Beckman Scholarship that I gained a sense that even though I was younger and earlier in my career, I was a legitimate scientist.

The second impact was that being a Beckman Scholar showed me the humanity behind scientific discovery. At my first Annual Beckman Symposium, I was gifted by the organization the book, "Arnold O. Beckman: One Hundred Years of Excellence." Up until then, scientists had always been portrayed to me as unidimensional, measured only by their greatest scientific achievements. They had names and sometimes even faces in the textbooks, but none had lives and families that influenced their decisions, their education, their philosophy, their discoveries, and their philanthropy. Reading Dr. Beckman's biography was captivating! We were given a pin with Dr. Beckman's image on it, too, that year and to this day I wear it on my suit lapel at conferences. It reminds me of the whole human beings behind all science and the heart that inspires others to pursue the unknown.

AMBF: Do you have any advice for undergraduates considering a research career?

WMI: My advice to undergraduates is to maintain your curiosity as your guiding light. Curiosity comes from a place that is influenced by your whole being. There may be extremely hard work and long hours and dogged determination that is required for conducting science, but it will all be for naught if you fail to nurture your mind and body and relationships to keep that curiosity burning bright. A scientific research career is not the goal itself, it is merely a method to pursue a great and rewarding life.

AMBF: Did you meet Dr. Beckman in person, and if so, what was most memorable about meeting him?

WMI: Unfortunately I did not have the pleasure of meeting Dr. Beckman as he passed in 2004, three years before I was awarded the scholarship. Receiving his biography, however, was a phenomenal inspiration and I greatly wish I had had the chance to meet him in person.

AMBF: Any final thoughts?

WMI: If Dr. Beckman and the opportunities that the Beckman Scholars program have afforded me taught me anything, it's that the mysteries of the universe would remain hidden if not for the people that pursue them.