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: 412-641-7557

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
Cancer Genomics
Systems Biology of Cancer
Hormone Signaling and Action
Photo of Adrian Lee, PhD

The goal of the Lee laboratory is translational breast cancer research. The laboratory has two main areas of focus.

The first involves targeting the insulin-like growth factor pathway in breast cancer. A major emphasis is upon the downstream signaling intermediates the insulin receptor substrates (IRSs) analyzing interactions with steroid hormone receptors (ER and PR), role in normal mouse mammary gland development, mechanisms of transformation of mammary epithelial cells in vitro and in mouse models, and roles in human breast cancer. These studies include a systems biology approach to understanding the pathway that includes use of transcriptomics (RNA-seq) and proteomics (Reverse Phase Protein Arrays).

The second area of research is the role of massively parallel sequencing in precision cancer genomic medicine. This work includes basic studies on mutations in breast cancer and then methods (both technical and computational) to apply this in the clinical setting. Studies examine tumor heterogeneity and molecular changes during progression, with a particular focus on DNA and RNA structural rearrangements in metastasis. Analysis includes use of long-insert mate-pair, whole genome, whole exome and RNA-sequencing which have all been completed on a set of 20 tissues to allow an unprecedented integrated view of genomic and transcriptomic changes during progression. Genomic alterations are measured in blood (circulating-free DNA) using targeted sequencing and ddPCR. Computational methods are being developed and optimized for analyzing clonal architecture, evolutionary genomic change, and refinement of structural rearrangements. The laboratory has also developed a breast cancer specific next-generation sequencing test for clinical sequencing and developing a computational architecture for integration of patient genomic and phenotypic data for research and clinical (Oracle Translational Research Center) use.

http://adrianleelab.com/

 

 





Important Publications
Li Z, Levine KM, Bahreini A, Wang P, Chu D, Park BH, Oesterreich S and Lee AV. Upregulation of IRS1 enhances IGF1 response in Y537S and D538G ESR1 mutant breast cancer cells. Endocrinology. 2017 Sep 27. doi: 10.1210/en.2017-00693. [Epub ahead of print]
Priedigkeit N, Watters RJ, Lucas PC, Basudan A, Bhargava R, Horne W, Kolls JK, Fang Z, Rosenzweig MQ, Brufsky AM, Weiss KR, Oesterreich S and Lee AV. Exome-capture RNA sequencing of decade-old breast cancers and matched decalcified bone metastases. JCI Insight 2:e95703, 2017
Priedigkeit N, Hartmaier RJ, Chen Y, Vareslija D, Basudan A, Watters RJ, Thomas R, Leone JP, Lucas PC,  Bhargava R, Hamilton RL, Chmielecki J, Puhalla SL, Davidson NE, Oesterreich S, Brufsky AM, Young L and Lee AV. Intrinsic subtype switching and acquired ERBB2/HER2 amplifications and mutations in breast cancer brain metastases. JAMA Oncol 3:666-671, 2017.
 
Bahreini A, Levine K, Santana-Santos L, Benos P, Wang P, Andersen C, Oesterreich S and Lee AV. Non-coding single nucleotide variants affecting estrogen receptor binding and activity. Genome Med 8:128, 2016.
Gyanchandani R, Lin Y, Lin HM, Cooper KL, Normolle DP, Brufsky AM, Fastuca M, Crosson W, Oesterreich S, Davidson NE, Bhargava R, Dabbs DJ and Lee AV. Intra-tumor heterogeneity affects gene expression profile test prognostic risk stratification in early breast cancer. Clin Cancer Res 22:5362-5369, 2016. 
Farabaugh SM, Chan BT, Cui X, Dearth RK and Lee AV. Lack of interaction between ErbB2 and insulin receptor substrate signaling in breast cancer. Cell Commun Signal 14:25, 2016. 
Katz TA, Liao S, V Palmieri,, Dearth RK, Pathiraja TN, Huo Z, Shaw P, Small S, Davidson NE, Peters DG, Tseng G,  Oesterreich S and Lee AV. Targeted DNA methylation screen in the mouse mammary genome reveals a parity-induced hypermethylation of IGF1R which persists long after parturition.  Cancer Prev Res 8:1000-1009, 2015.
 
 
Casa AJ, Hochbaum D, Sreekumar S, Oesterreich S and Lee AV. The estrogen receptor alpha nuclear localization sequence is critical for fulvestrant-induced degradation of the receptor. Mol Cell Endocrinol 415:76-86, 2015.
 

STUDENT NEWS


UPCOMING EVENTS
6/29/2018 9:00 AM Graduate Student Summer Seminar
Graduate Student Summer Seminar presented by Stephanie Mutchler and Gregory Buchan


7/13/2018 9:00 AM Graduate Student Summer Seminar
Graduate Student Summer Seminar presented by Braulio Bonilla and Nicholas Todd


7/20/2018 9:00 AM Graduate Student Summer Seminar
Graduate Student Summer Seminar presented by Joshua Lorenz-Guertin and Victoria Veroli


Pharmacology and Chemical Biology Event Calendar

Program Achievements

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

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 two consecutive years




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