Lee Research Group

Principal Investigator: Adrian Lee, PhD

The main focus of the laboratory is to understand how insulin‐like growth factors (IGFs) regulate breast transformation, and how this knowledge can be used for successful treatment of patients. This research involves basic studies into the mechanisms of IGF signaling including proteomic and transcriptomic analysis, and comparison to the highly related insulin receptor. The laboratory has created and/or characterized transgenic mice overexpressing most members of the IGF signaling family (IGF‐I, IGF‐IR, IRS1 and IRS2) and all develop mammary tumors. The lab uses knockout mice (IGF‐R fl/fl, and IRS1 and IRS2 germ‐line knockout) to decipher the importance of IGF signaling in initiation and progression of breast cancer. Basic studies are translated into preclinical work using anti‐IGF‐IR antibodies and tyrosine kinase inhibitors in transgenic and xenograft models. Finally, the Lee lab is the central lab for all tissue biomarker studies in clinical trials of the anti‐IGF‐IR antibody Figitumumab (Pfizer).

Dr. Lee’s lab also studies the role of novel nanotechnology agents in the imaging and treatment of early breast cancer. This includes the use of ultrashort carbon nanotubes filled with gadolinium or iron oxide as both imaging (MRI, T1 and T2) and treatment (via thermal ablation using AMF). Recent studies use silicon nanoshells containing gold and iron oxide, and then with anti‐IGF‐IR antibodies, for targeted imaging (IF using gold and MRI using T2 iron oxide) and therapy (via thermal ablation). Finally, the Lee laboratory uses massively parallel sequencing to perform fundamental studies on the role of structural genomic rearrangements in breast cancer.

Lab Members:

Bonita Tak-Yee Chan, PhD

Postdoctoral Fellow
cahnbt@upmc.edu

Yu-Fen Wang

Graduate student
wangy2@upmc.edu

Lab Alumni:
Postdoctoral Fellows

Xiaojiang Cui, PhD

Assistant Professor, John Wayne Cancer Institute, Santa Monica, CA

Jana Divisova PhD

Homemaker, NJ

Robert Dearth, PhD

Assistant Professor,UT Pan Am, Edinburgh, TX

Petra Den Hollander, PhD

Postdoctoral Fellow, UT MD Anderson Cancer Center, Houston, TX

Hyun-Jung Kim
 
Maia Ouspenskia
 
Xiuhua Sun
 

Graduate Students

Beate Litzenburger, PhD

Grünenthal Group. Aachen, Germany

Angelo Casa 

Baylor College of Medicine, Houston, TX

Adam Potter

Baylor College of Medicine, Houston, TX

MD Heme/Onc Fellows

Winston Tan, MD.

Associate Professor, Mayo Clinic, Jacksonville, Florida

Ali Moussa, MD

Physician, Medical Oncologist, Tulsa, Oklahoma

Amy Hassan, MD

Assistant Professor, UT MD Anderson Cancer Center, Houston, TX

Post-baccalaureate Students

David Delgado

UT MD Anderson Cancer Center

Monica Linan

UT Houston

Technicians

ZaWaunyka Lazard

Baylor College of Medicine, Houston, TX

Janice Lising
 
Curtis Thorne
 
Ping Zhang

Baylor College of Medicine, Houston, TX

Summer Students

Jasmeen Dara
 
Kimberley Thomason
 
Marco Vega
 
Andrew Clark
 
Kathryn Connery
 
Tamar Schiff
 
Ilena Ochadsvey
 
Ilyas Patanam

Selected Publications:

  • Lee AV, Zhang P, Ivanova M, et al. Developmental and Hormonal Signals Dramatically alter the
  • Localization and Abundance of Insulin Receptor Substrate Proteins in the Mammary Gland. Endocrinol,
  • 144:2683-94, 2003. PMID:12746333
  • Divisova J, Kuiatse I, Lazard Z, Weiss H, Vreeland F, Hadsell DL, Schiff R, Osborne CK, Lee AV. The
  • growth hormone receptor antagonist pegvisomant blocks both mammary gland development and MCF-7
  • breast cancer xenograft growth. Breast Cancer Res Treat, 98:315-27, 2006. PMID:16541323
  • Dearth RK, Cui X, Kim HJ, Kuiatse I, Lawrence NA, Zhang X, Divisova J, Britton OL, Mohsin S, Allred DC, Hadsell DL, Lee AV. Mammary tumorigenesis and metastasis caused by overexpression of insulin receptor substrate (IRS)-1 or IRS-2. Mol Cell Biol, 26:9302-14, 2006. PMID:17030631,PMC1698542
  • Kim H-J, Litzenburger BC, Cui X, Delgado DA, Grabiner BC, Lin X, Lewis MT, Gottardis MM, Wong T, Attar RM, Carboni JM, and Lee AV. Constitutively active IGF-IR causes transformation and xenograft growth of immortalized mammary epithelial cells, and is accompanied by an epithelial to mesenchymal transition mediated by NF-kappaB and snail. Mol Cell Biol, 27:3165-75, 2007. PMID:17296734, PMC:1899918
  • Hadsell DL, Lawrence N, Kadowaki T, Lee AV. Decreased lactation capacity and altered milk composition in insulin receptor substrate null mice is associated with decreased maternal body mass and reduced insulin dependent phosphorylation of mammary Akt. J Endocrinol, 194:327-36, 2007. PMID 17641282
  • Creighton CJ, Casa A, Lazard Z, Huang S, Tsimelzon A, Hilsenbeck SG, Osborne CK, and Lee AV. Insulinlike growth factor I (IGF-I) activates gene transcription programs strongly associated with poor breast cancer prognosis. J Clin Oncol, 26:4078-85. 2008. PMID: 18757322
  • Litzenburger BC, Kim H-J, Kuiatse I, Carboni JM, Attar RM, Gottardis MM, Fairchild CR, and Lee AV. BMS-536924 reverses IGF-IR-induced transformation of mammary epithelial cells and causes growth inhibition and polarization of MCF-7 cells. Clin Cancer Res 2009; 15: 226-37. PMID: 19118050
  • Hampton OA, Den Hollander P, Miller CA, Harris RA, Richards S, Scherer SE, Muzny DM, Gibbs RA, Lee AV, Milosavljevic A. A sequence-level map of chromosomal breakpoints in the MCF-7 breast cancer cell line yields insights into the evolution of a cancer genome. Genome Res. 2009;19:167-77. PMID: 19056696
  • Migliaccio I, Osborne, CK, Gutierrez C, Allred DC, Mohsin S, Hilsenbeck SG, Lee AV. Nuclear IRS-1
  • predicts tamoxifen response in early breast cancer. In press, Breast Cancer Research and Treatment,
  • 2009
  • Hassan AA, Chan BT, Tran LA, Hartman KB, Ananta JS, Mackeyev Y, Hu L, Pautler RG, Wilson LJ, Lee AV. Serine-derivatized gadonanotubes as magnetic nanoprobes for intracellular labeling. Contrast Media Mol Imaging. 2010 Jan;5(1):34-8.PMID: 20101755
  • Dearth RK, Delgado DA, Hiney JK, Pathiraja T, Oesterreich S, Medina D, Dees WL, Lee AV. Parity induced decrease in systemic growth hormone alters mammary gland signaling: a potential role in
  • pregnancy protection from breast cancer. Cancer Prev Res. 2010 Mar;3(3):312-21
  • Creighton CJ, Fu X, Hennessy BT, Casa AJ, Zhang Y, Gonzalez-Angulo AM, Lluch A, Gray JW, Brown PH, Hilsenbeck SG, Osborne CK, Mills GB, Lee AV, Schiff R. Proteomic and transcriptomic profiling reveals a link between the PI3K pathway and lower estrogen-receptor (ER) levels and activity in ER+ breast cancer. Breast Cancer Res. 2010;12(3):R40.
  • Gualberto A, Dolled-Filhart M, Gustavson M, Christiansen JJ, Wang YF, Hixon ML, Reynolds JM,
  • McDonald S, Ang A, Rimm DL, Langer C, Blakely J, Garland LL, Paz-Ares L, Karp DD, Lee AV. 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. 2010 Jul 29.



 

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