Adrian Lee, PhD

Professor of Pharmacology and Chemical Biology, University of Pittsburgh

Adrian Lee, PhD

leeav@upmc.edu

Office: A412 Magee
Phone: 412-641-8554 
Fax: 412-641-2458 

Department of Pharmacology and Chemical Biology

Biosketch

University of Kent, Canterbury, UK BSc 05/89 Biochemistry
ICRF, University of Surrey, Guildford, UK PhD 1993 Breast Biology
UT Health Science Center at San Antonio Postdoc 1997 Breast Cancer

I am an established investigator having published over 120 peer-reviewed manuscripts and a history of collaborative efforts (both wet and dry lab). The outstanding environment at the University of Pittsburgh will provide all the necessary facilities and resources needed to complete the research. The goal of my laboratory is translational breast cancer research, particularly research involving human specimens with the ultimate goal of moving basic science discoveries to the clinic. The laboratory has a long standing interest in targeting the insulin-like growth factor (IGF) pathway in breast cancer. This work has been continuously funded by NIH for 14 years and has provided fundamental insight into how IGFs regulate mammary gland development and tumorigenesis in the mouse and the therapeutic importance of this to human breast cancer. For example, we generated transgenic mice overexpression IGF1R or its downstream adaptors IRS1 and IRS2 and showed that all three mouse models developed mammary cancer. We characterized the ability of IGF1R overexpression to transform MCF10A mammary epithelial cells and cause EMT. Important to the clinical translation of IGF1R inhibitors, we developed an IGF gene expression signature that correlates with IGF activity, is repressed by IGF1R inhibitors, and highlighted a TNBC PDX model that is especially sensitive to IGF1R inhibition.

A more recent area of research involves genomic profiling of breast cancer. While at Baylor College of Medicine (BCM), Dr Lee collaborated with Dr. Aleks Milosavljevic and the Human Genome Center to develop new methods to characterize DNA structural rearrangements in breast cancer, and they were the first to map all structural rearrangements at the base pair level in a breast cancer cell line. Since moving to the University of Pittsburgh, Dr. Lee has now transferred these technologies and expanded this line of research. For example, the laboratory has measured ESR1 mutations by ddPCR in 44 primary breast cancers, 72 metastatic brain, 15 metastatic bone, and 32 cfDNA samples. We found a significant rate of mutation (~25% in blood), this work was recently reported in Clinical Cancer Research. Dr. Lee is a well-established investigator with a history of collaborative efforts involving numerous laboratory and clinical researchers.

  1. Gualberto A, M Dolled-Filhart, M Gustavson, J Christiansen, YF Wang, ML Hixon, J Reynolds, S McDonald, A Ang, DL Rimm, CJ Langer, J Blakely, L Garland, LG Paz-Ares, DD Karp and AV Lee. Molecular analysis of non-small cell lung cancer (NSCLC) identifies subsets with different sensitivity to insulin like growth factor I receptor (IGF-IR) inhibition. Clin Cancer Res 16:4654-4665, 2010.
  2. Dearth RK, DA Delgado, JK Hiney, T Pathiraja, S Oesterreich, D Medina, WL Dees and AV Lee. Parity-induced decrease in systemic growth hormone alters mammary gland signaling: A potential role in pregnancy protection from breast cancer. Cancer Prev Res 3:312-321, 2010.
  3. Creighton CJ, X Fu, BT Hennessy, AJ Casa, Y Zhang, AM Gonzalez-Angulo, A Lluch, JW Gray, PH Brown, SG Hilsenbeck, CK Osborne, GB Mills, AV Lee and R Schiff. Proteomic and transcriptomic profiling reveals a link beween the PI3K pathway and lower estrogen-receptor (ER) levels and activity in ER+ breast cancer. Breast Cancer Res 12:R40, 2010.
  4. Hassan AA, TB Chan, KB Hartman, JS Ananta, Y Mackeyev, L Hu, RG Pautler, LJ WIlson and AV Lee. Serine-derivatized gadonanotubes as magnetic nanoprobes for intracellular labeling of breast cancer cells. Contrast Media and Molecular Imaging 5:34-38, 2010.
  5. Migliaccio I, CK Osborne, C Gutierrez, DC Allred, S Mohsin, SG Hilsenbeck and AV Lee. Nuclear IRS-1 predicts tamoxifen response in early breast cancer. Breast Cancer Research and Treatment, in press, 2009.