Madeline Shea was born in 1956 in Washington, D.C. and spent her childhood in the northeastern United States. Madeline’s father was a physicist. Her mother was very interested in science, but due to the lack of financial means to pursue higher education, she found other outlets for her creativity and great spatial reasoning skills. She taught these skills, including basic geometry and algebra, to Madeline at an early age. Together they created many household items, including sewing without a pattern and building Madeline’s bedroom furniture. Both parents encouraged her academic growth and development. “They stressed independence, self-sufficiency and always urged me to go above and beyond what was required - to set my own standards for achievement… They gave me the greatest gift – a love of learning,” remembers Madeline. They also taught her to never accept the norm – always look to improve on it.
Madeline’s curiosity was evident as a young child. She was interested in putting together and disassembling mechanical things, collecting rocks, investigating bugs, gardening, and camping. She was also an avid reader. While working as a librarian’s helper in the elementary school, she remembers reading the biographies of Abigail Adams, Clara Barton, Mary Mapes Dodge, Jane Addams, Louisa May Alcott, and Marie Curie. This literature gave her an appreciation of women pursuing an independent career. “Unconsciously, it helped me realize that I could aspire to a career beyond those that were commonly acceptable at the time,” she says.
Her public school years - the 1960’s and early 1970’s – were a period of radical changes for female students. California Institute of Technology began admitting women undergraduates in 1970, and Madeline was accepted to the university in 1973. Madeline started her undergraduate career interested in a broad spectrum of subjects and the interfaces between these fields. Although she majored in chemistry, she took additional classes in modern physics, applied mathematics, genetics, and developmental biology and graduated with a Bachelor of Science in 1977. She applied to a mix of PhD programs, including chemistry, biochemistry, molecular biology, and biophysics. After much reflection, she chose biophysics because of its interdisciplinary nature.
In 1978, Madeline started graduate school in the T.C. Jenkins Department of Biophysics at Johns Hopkins University and conducted rotations oriented towards structural biology, particularly electron microscopy. Through coursework, Madeline became interested in the work conducted in Gary K. Ackers’s laboratory on transport theory, allostery and protein behavior. Madeline joined his group for her PhD studies, initially studying tobacco mosaic virus (TMV) coat protein assembly with calorimetry before switching to a new project in the laboratory – understanding the operator-repressor interactions that regulate the bacteriophage lambda lysogenic-to-lytic growth switch. “The ability to monitor individual sites in a multi-site DNA operator region using DNase footprinting was akin to having a Maxwell’s demon telling us about occupancy at each site. This gave rise to my theoretical thesis that began with creation of a partition function for cI, cro and RNA polymerase binding to the operators and divergent promoters, and led to predicting the time-course of lysogeny and induction of lysis based on free energies and rate constants,” remembers Madeline. She obtained her PhD in biophysics in 1984. During her graduate work, she also contributed to the development of quantitative DNase I footprinting to evaluate cooperativity in protein-DNA interactions. Her postdoctoral studies in the same department diverged into cryo-electric focusing studies of protein-ligand interactions, to probe allosteric regulation of hemoglobin and its deviation from the classical MWC model.
In 1989, Madeline established her laboratory at the University of Iowa’s Carver College of Medicine, in the Department of Biochemistry. Since then, she has developed a vibrant lab and contributed broadly to the educational system of the University of Iowa. Madeline is now well known for her effective leadership, for her thorough, careful approach to research, and for her innovation and dedication as a teacher. She has served as Director of Undergraduate Studies and Honors Advisor and held positions of Vice Chair, Interim Head, and Founding Director of the FUTURE in Biomedicine Program. She is very passionate about “promoting STEM careers for talented young people who may not realize what opportunities exist, and often do not know that they will be supported while going to graduate school.” She is also committed to several other outreach programs, including some for students who are extraordinarily talented and have disabilities. Madeline aspires for all people to have opportunities for meaningful and respectful inclusion in the community. She is a highly active member of the Biophysical Society, having served over the years on Council, the Executive Board, as Chair of the Membership Committee, and supporting CPOW events. Madeline’s current laboratory projects include calcium-mediated control of voltage-dependent sodium channel and regulation of calcineurin. The voltage-dependent sodium channels are important to human health – especially brain and muscle – because they control the upstroke of an action potential. Multiple forms of epilepsy arise from various mutations in several of the isoforms. Another isoform is important in pain perception. This family of channels is the target of pharmacological agents (sodium channel blockers) that bind on the external side or in the membrane-spanning pore. In addition, Madeline’s group and her collaborators are examining several other targets of calmodulin, including several receptors and channels.
The field of biophysics remains Madeline’s passion. She loves connecting results from orthogonal models, inventing new methods, imagining alternative models, and testing them - in short, applying many approaches to answer tough questions. She loves the fundamental nature of the work, knowing that findings about protein energetics, dynamics and structure have many future applications that are critical to advancing civilization. According to Amy Lee, a Professor in the Department of Molecular Physiology and Biophysics and Assistant Dean for Research at the Carver College of Medicine, Madeline participated in organizing new curriculum in Biophysical Chemistry for PhD students. She introduced modules on quantitative analysis of ligand binding, subunit assembly and conformational change, as well as linear and nonlinear data analysis methods. Madeline was the first to incorporate tools for building and visualizing macromolecules using a Silicon Graphics workstation into the curriculum. “For more than 20 years (1989 to 2011), Madeline was the only female tenure-track faculty member in biophysics in her department and became a role model particularly for women. Her pioneering approaches encouraged her colleagues to introduce computer simulations and data analysis exercises within their sections of the Biophysical Chemistry course,” says Lee.
In these teaching roles, Madeline has had an essential impact on graduate students in her department and her lab. One former graduate student from her department, Liskin Swint-Kruse, is now a Professor and Graduate Director at the University of Kansas Medical Center. Swint-Kruse says. “[I] still vividly remember those lectures and use the concepts she taught in my current research… Madeline’s research program is a model for the way science should be conducted. I strive for my lab to maintain the same degree of biophysical rigor in all of our experiments that she models with her beautiful work. The students in her lab receive exquisite training in how to carry out biophysics research.” Madeline has mentored more than 60 undergraduates and post baccalaureate students, as well as many MS and PhD students and postdoctoral fellows. She has invested in their professional training by having them present their work at national conferences such as the Biophysical Society Annual Meeting, and the Gibbs Conference on Biothermodynamics. All of her former graduate trainees pursued academic postdocs, and most have ultimately joined universities, biotechnology companies, or pharmaceutical companies.
Balancing all of the demands of a professional scientist, educator, and mentor with responsibilities at home can sometimes be challenging. For Madeline, the biggest challenge was to face the chronic medical needs of her family. Madeline notes that the skills she developed to conquer difficulties in her career have helped her to withstand other challenging times. “The stamina needed to monitor a fraction collector through the night so that a precious sample from a human patient is safe, or to stay chained to a computer terminal, compiling revised versions of code to compare models for a talk at an upcoming national meeting ... those all-nighters as an undergrad and grad student were good training for what was to come,” she shares. “Critical thinking skills honed in the laboratory, combined with determination, humor, and ability to get by on little sleep have been essential for coping with the course of my children’s development.”
Madeline’s story illustrates how nurturing a love of math and science in one person can exponentially expand to inspire and educate a larger community. Madeline transformed encouragement from her parents into a passion for teaching and research. In turn, she has inspired and educated hundreds of students in her classrooms, her lab, and outreach programs. Many of these former students are now science professionals, passing skills on to the next generation and creating an ever-increasing radius of people inspired by a love of science and an appreciation of the exciting opportunities present at the interface between biology, math, chemistry, and physics. To embrace all the professions she was interested in, Madeline once dreamed of becoming a cosmologist. Although she became a biophysicist instead, she did succeed in creating a “cosmic orbit” of scientists and students.