Courtney Andersen studies the role of estrogen receptor-alpha in ovarian cancer.
Chris Barnes investigates the structural details by which transcription factor activity regulates RNA Polymerase II during the universal process of eukaryotic gene expression.
Soma Jobaggy studies nitrated fatty acid pharmacology and the antioxidant response in hypertensive end-organ damage.
Allison Nagle studies growth factor receptor signaling in breast cancer.
Adrian Lee, PhD
Professor; Pittsburgh Foundation Chair in Precision Medicine
A412 Magee-Women's Research Institute
204 Craft Avenue, Pittsburgh, PA 15213

Email:
leeav@upmc.edu
Phone: 412-641-8554

Fax: 412-641-2458


Education
BSc (Biochemistry), University of Kent, Canterbury, Kent, England, 1989
PhD, University of Surrey, Guildford, Surrey, England, 1993
Postdoctoral Fellow, University of Texas Health Science Center, San Antonio, 1997


Research Areas
Pharmacology of Cell and Organ Systems
Photo of Adrian Lee, PhD

We are investigating the endocrine regulation of mammary gland development and progression to mammary cancer. Specifically we are interested in interaction between steroid hormones (estrogen and progesterone) with the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis. These endocrine hormones are all critical for normal mammary development, but have also all been implicated in risk for breast cancer and in breast cancer progression.

 

We have shown that IGF-IR and IRSs are hormonally regulated in breast cancer, and we have now found that they are also developmentally and hormonally regulated during normal mammary gland development. We have found in breast cancer cell lines that estrogen can sensitize cells to insulin-like growth factor (IGF) stimulation by increasing expression of many of the IGF signaling components such as the IGF-IR and its downstream signaling intermediates IRS-1 and IRS-2.

 

We have also found that overexpression of IGF-IR, IRS-1, or IRS-2 causes transformation of mammary epithelial cells in culture, combined with epithelial to mesenchymal transition. We have also created transgenic mice that overexpress IGF-IR, IRS-1 or IRS-2 in the mammary gland and all mice develop mammary tumors. Mammary tumors in these mice show multiple cell lineages and expansion of putative mammary stem/progenitor cells. We are currently investigating how these pathways impact upon stem/progenitor cell renewal and cell fate determination.





Important Publications
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.
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.
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.
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.
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.
Hampton OA, P Den Hollander, CA Miller, RA Harris, S Richards, SE Scherer, DM Muzny, RA Gibbs, AV Lee and A Milosavljevic.  A sequence-level map of chromosal breakpoints in the MCF-7 cancer cell line yields insights into the evolution of a cancer genome.  Genome Res 19:167-177, 2009.
Liu S, M Umezu-Goto, M Murph, Y Lu, W Liu, F Zhang, X Cui, G Murrow, K Coombes, W Muller, MC Hung, CM Perou, AV Lee, X Fang and GB Mills.  Expression of autotaxin and lysophosphatidic acid receptors increases mammary tumorigenesis, invasion, and metastases.  Cancer Cell 15:539-550, 2009.

STUDENT NEWS


UPCOMING EVENTS
11/27/2017 8:30 AM Molecular Pharmacology Journal Club
Lloyd Harvey


11/30/2017 12:00 PM Pharmacology & Chemical Biology Seminar Series
Jeffrey L. Brodsky, Ph.D.


12/4/2017 8:30 AM Molecular Pharmacology Journal Club
Andrew Lamade


Pharmacology and Chemical Biology Event Calendar

Program Achievements

Molecular Pharmacology Graduate Program Ranked #2 in National Research Council Rankings

Molecular Pharmacology Graduate Program Ranked #2 in Faculty Scholarly Productivity Index


Outcomes:  Time to disseration, last five graduating clasess:  4.5 years, Completion Rate: 84.8%

Ranked #12 in National of Institute of Health funding of departments of Pharmacology

Ranked in the top 15 in funding for twenty consecutive years




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