Stepfanie Lam

Stepfanie Lam
Mentor: Dr. Margaret Wallace
College of Medicine
 
"What initially sparked my interest in research was how intrigued I was how a change in a single codon in the DNA can cause major diseases. Moreover, I was fascinated by the genetics section, translation and transcription in particular, of my AP Biology course in high school which also led me to pursue a degree in Microbiology. In addition, I am interested in studying cancer because it has personally affected my family. It came as a shock to all of us when a member of my family was diagnosed with pancreatic cancer. She passed away four months later. This project brings all these reasons together. Research offers me intellectual vitality and hands on experience that cannot be found in the classroom. By participating in research, I hope to improve the lives of individuals with my contributions to the scientific world."

Major

Microbiology

Minor

N/A

Research Interests

  • Molecular Genetics
  • Cancer
  • Bioinformatics

Academic Awards

  • UF University Scholars Program
  • Howard Hughes Medical Institute (HHMI) Science for Life Intramural Award
  • Creativity in the Arts & Sciences Event (CASE) Award winner
  • Alumni Scholarship

Organizations

  • Prism-UF Honors Magazine
  • Centerpoint Christian Fellowship
  • Multicultural Association of Pre-Health Students

Volunteer

  • Equal Access Clinic
  • Camp Boggy Creek
  • Gainesville TOPSoccer

Hobbies and Interests

  • Tennis
  • Reading
  • Photography/Digital Imaging
  • Cooking

Research Description

Mechanisms of PTEN Inactivation in NF1 Malignant Peripheral Nerve Sheath Tumors
Neurofibromatosis 1 (NF1) is an autosomal dominant tumor condition caused by mutations in the NF1 tumor suppressor gene, occurring in 1/3500 worldwide. It mainly affects the nervous system, skin, eyes, and bone. Clinically, the main feature is benign Schwann cell tumors called neurofibromas. Most are small and cutaneous but some can occur on large peripheral nerves, with a 20% risk of transforming into malignant peripheral nerve sheath tumors (MPNSTs). Additionally, genomics projects have determined that somatic NF1 gene mutation is common in lung cancer and brain cancer, even in people who don’t have NF1. Over the past year and a half, I have been working in Dr. Wallace’s lab examining the DNA and RNA from a series of MPNST samples as well as matched germline DNA, in order to look for somatic mutations in the PTEN gene. This gene was chosen because it was found that loss of PTEN in an NF1 mouse model led to MPNST formation, but has not been well characterized in human MPNSTs. I was able to identify deletions in some, but not all MPNSTs. Therefore we hypothesize that hypermethylation of the PTEN gene promoter is involved in some MPNSTs, as a different way to inactivate this gene. My specific aim is to do an epigenetic methylation study of the PTEN promoter in MPNSTs that do not have deletions. This will include the MPNSTs as well as some neurofibromas for contrast. This data will help me understand whether epigenetic inactivation of PTEN might also be contributing to human MPNSTs. A system from the Zymo corporation will be used to treat the DNA with sodium bisulfite to modify methylated cytosines, which will then be studied with the use of two approaches. One will examine five key cytosines in the -1325 to -1300 region by PCR followed by cloning and sequencing, and the other will examine key cytosines in the -298 to -143 region using methyl-specific PCR. This will enable me to screen for methylation at two important parts of the promoter. In addition, half of the tumors have cell lines established, which I will test to see if any methylation pattern is retained in the cultured cells. This experiment will give me a chance to learn tissue culture and cell biology. If I find methylation in some cell cultures, I hope to try testing the cells with de-methylating agents to see if tumorigenic properties or PTEN gene expression are affected. This work will contribute to our understanding of the involvement of the PTEN gene/protein in MPNSTs, providing an opportunity to develop therapies targeting it.