About the Wallace Lab!
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. We are using genetic and cell biology approaches to study this condition, using 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/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 and clinical information with tumor immunohistochemistry, investigating mutation mechanisms, and phenotype-genotype analyses including within pedigrees.
The laboratory also studies the genetic aspects of multifactorial disorders, conditions that do usually do not show Mendelian inheritance but have a genetic susceptibility. This work involves detecting predisposing genetic variants and following up on the underlying mechanisms. One such area is pain, including conditions such as fibromyalgia and development of post-surgical chronic pain.
History
In 1987 Peggy joined the lab of Dr. Francis Collins at the University of Michigan as a post- doctoral fellow, working on NF1. In 1989 she was awarded a Young Investigator Award (YIA) fellowship from the National Neurofibromatosis Foundation (now The Children’s Tumor Foundation, CTF). In July 1990, Peggy, along with a lab at the University of Utah, announced the cloning of the NF1 gene – the first major break-through toward understanding the basis of NF1. A year later, she started her own lab at UF, continuing to study NF1.
30 Years of Discovery
For 30 years, her lab has been funded to study NF1 genetics and tumor biology. This started with funds from UF, but since 1992 has included a variety of agencies: the CTF, the American Cancer Society, the National Institutes of Health, Searle Scholars Program, Children’s Miracle Network, the Department of Defense (NF Research Program), and NTAP (Neurofibromatosis Therapeutic Acceleration Program).
Peggy has always had a strong interest in understanding how the NF1 gene and its variations lead to NF1, why NF1 can be so different between patients even within the same family, how variants lead to neurofibromas and malignant tumors, and why these and other complications are so unpredictable.
Collaborations
Throughout the years in Dr. Wallace’s lab, many excellent young trainees contributed to her work, including two who won YIAs. They have many scientist and physician collaborators, here in Florida, around the country and internationally. Most importantly, over 350 people with NF1 plus their family members have volunteered in the research, contributing samples such as blood, saliva, and tumors removed during surgery, and NF1 clinical information. These contributions have been key in their studies and have helped many other laboratories as well. The CTF has led the way in fostering collaboration among scientists and clinicians which is critical for progress
Expanding Research
On occasion patients with NF2 or schwannomatosis contribute to the research, and our Lab has connected those patients to researchers studying those conditions in more depth. The CTF website lists over 100 cell cultures available for NF research from my lab. Our lab has also sent cell lines to over 60 different laboratories over the years.
Current Interests
We still have work to do, to understand NF1 gene changes and how they relate to NF1 clinical signs. With the adult NF clinic recently established at UF, this lab is now reconnecting with people who contributed years ago. Gathering long- term information, and NF1 gene data, especially within families, is our current project. This can provide a unique opportunity to answer some key questions. If you or a family member participated in our research in the past, or are interested now, please contact Dr. Peggy Wallace: email peggyw@ufl.edu or text/call 352-214-7123.
Challenges
Why has it taken almost 30 years to get the first NF1 drug? NF1 has turned out to be very complicated, scientifically and clinically. So, gathering as much data as possible, through different approaches, is needed to solve NF1 mysteries. In today’s world we have great scientific tools, so there are plenty of great ideas for studies – we just need to find enough money to pay for the work.
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