Margaret (Peggy) Wallace, Ph.D.
Professor,
Department of Molecular Genetics & Microbiology
Before beginning her faculty appointment, Margaret Wallace, Ph.D., completed postdoctoral training at Howard Hughes Medical Institute at the University of Michigan. She received her Ph.D. from Indiana University, School of Medicine and B.S from Miami University in Oxford, Ohio.
Dr. Wallace is co-director of the Biomedical Sciences program concentration in genetics.
The main project in the Wallace laboratory is the study of neurofibromatosis type 1 (NF1)—a common dominant condition characterized by overgrowth of neural crest tissues. This progressive condition is caused by mutations in the NF1 tumor suppressor, a large complex gene whose protein is not well understood.
The Wallace lab is using genetic and cell biology approaches to study this condition—a large set of patient samples and data. Tumor-based projects focus on the neurofibroma, a benign Schwann cell tumor that can form on any peripheral nerve including the gut and MPNST (malignant transformation of a neurofibroma associated with a large nerve or nerve bundle). The contributions of other tumor-related genes such as PTEN and SUZ12 are under study at the germline and somatic levels.
Current work involves creating and characterizing immortalized tumor Schwann cell lines, correlating this with clinical information regarding tumor immunohistochemistry, investigating mutation mechanisms and phenotype-genotype analyses including within pedigrees.
What Are Your Current Research Interests And/or What Is a Project You Are Currently Working On?
My lab’s focus is on the genetic makeup and tumor cell biology of neurofibromatosis type 1 (NF1)— a Schwann cell tumor syndrome. We have two projects: (1) developing and studying immortalized tumor Schwann cell lines from excised neurofibromas (those within the skin), and (2) studying MPNST fixed sections with immunohistochemistry while analyzing the results in context of clinical parameters (e.g. survival, tumor grade, etc.) to see if these antibodies can be clinically useful biomarkers. MPNSTs are malignant peripheral nerve sheath tumors, which arise in about 10%-15% of people with NF1, usually from transformation of a benign plexiform neurofibroma to a malignancy.
How Did You Decide on Your Specialty?
In college, I realized that I had a passion for medical science and genetics, but I knew little about medical or graduate school. I entered a Medical Genetics Ph.D. program in a clinical/basic science department at Indiana University, where I could explore genetics research and observe medicine. The grad students attended clinic, grand rounds and went on consults. I soon realized that although I loved the medical science, I didn’t want a doctor’s life, death responsibility or to do procedures on people. Human genetics research has been the perfect combination of those interests for me.
Why Did You Decide to Focus on Cancer?
I started my lab here in 1991 based on my postdoctoral project, NF1. Initially I didn’t have plans to study NF1 tumors, but one of my research subjects told me she was going to have skin neurofibromas removed in a few months. She asked if I would like them for research because her doctor said he was just going to discard them. At that point, nothing was known about neurofibromas except that they were Schwann cell tumors. By incredible luck, another new faculty member in my department, David F. Muir, was a Schwann cell biologist. He said we could try to culture the tumor Schwann cells and perform genetics. Long story short, we developed and studied over 50 neurofibroma cultures as well as MPNST cultures. That was how I moved into studying tumors.
What Excites You About Your Work? What Is Exciting to You About Your Field Right Now?
Knowing that my work is contributing toward research to develop therapies for NF1, which affects 1/3000 people worldwide and have severe impact on quality of life. I would love to see this disorder conquered because I’ve lost numerous research subjects to this condition— one only 15 years old. We’ve shared cells and other samples with labs around the world and have further been involved in many advancements. I am particularly excited about the new approaches that can really move the field forward such as patient IPS cells, single-cell transcriptomics, gene editing and precision medicine.
What Do You like to Do Outside of Work?
Outside of work I perform biomedical research projects that usually span years, sometimes even decades. My “aha” moments are few and far between. Therefore, I enjoy the instant gratification (or nearly so) of home, yard and maintenance projects with my husband, Wayne McCormack. The physical exertion of such work is a nice change of pace from my generally sedentary job as a professor. I also like to read books, do puzzles and enjoy the company of our dogs, fish, turtles and any wildlife that happens to come by. Visiting with family and friends, near and far, is also fun, especially in the form of a family trip exploring another part of the country.