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Heasley Lab


Professor and Chair, Department of Craniofacial Biology

Contact Information:
Department of Craniofacial Biology
School of Dental Medicine
Mail Stop 8120, RC1-South, Room L18 11100
12801 E. 17th Ave.
Aurora, CO  80045
Phone: 303-724-4578
Fax: 303-724-4580
Email: lynn.heasley@ucdenver.edu


Research Interests:

My lab investigates autocrine and paracrine signaling through receptor tyrosine kinases, both as oncogene drivers and as acquired or intrinsic resistance mechanisms to targeted therapeutics. Our studies reveal that multiple families of receptor tyrosine kinases engage in autocrine growth stimulation in lung cancer, head and neck cancer and malignant mesothelioma cell lines. Moreover, our studies highlight specific receptor tyrosine kinases for their functioning within a co-activation network such that clinically-relevant tumor cell killing requires treatment with combinations of inhibitors, not monotherapy. Our experimental strategy involves functional genomics approaches to define signaling components functioning within the network and pharmacological approaches to identify inhibitors that can be translated to clinical applications.  We rely on molecular studies with cultured cancer cell lines and in vivo approaches with immune deficient mice bearing orthotopically implanted cancer cell lines to pre-clinically validate promising therapeutics.


Current Trainees:

Emily Kleczko, Cancer Biology graduate student

 

 

 

Publications:

 

Marek, L., Ware, K., Fritzsche, A., Hercule, P., Helton, W.R., Smith, J.E., McDermott, L.A., Coldren, C.D., Nemenoff, R.A., Merrick, D.T., Helfrich, B.A., Bunn, P.A., Jr., and Heasley, L.E. (2009) FGF and FGFR-mediated autocrine signaling in non-small cell lung cancer cells.  Mol. Pharmacol., 75:196-207. PMCID: PMC2669785

Kono, S.A., Marshall, M.E., Ware, K.E., and Heasley, L.E. (2009) The fibroblast growth factor receptor signaling pathway as a mediator of intrinsic resistance to EGFR-specific tyrosine kinase inhibitors in non-small cell lung cancer.  Drug Resist. Updat. 12:95-102. PMCID: PMC2763047

Ware, K.E., Marshall, M.E., Heasley, L.R., Marek, L., Hinz, T.K., Hercule, P., Helfrich, B.A., and Heasley, L.E. (2010) Rapidly acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in NSCLC cell lines through de-repression of FGFR2 and FGFR3 expression. PLoS ONE, 5(11):e14117. PMCID: PMC2994708

Marshall, M.E., Hinz, T.K., Kono, S.A., Singleton, K.R., Bichon, B., Ware, K.E., Marek, L., Frederick, B.A., Raben, D. and Heasley, L.E. (2011) Fibroblast growth factor receptors are components of autocrine signaling networks in head and neck squamous cell carcinoma cells. Clin. Cancer Res. 17:5016-5025. PMCID: PMC3149730
 
Kono SA, Heasley LE, Doebele RC, Camidge DR. (2012) Adding to the mix: Fibroblast growth factor and platelet-derived growth factor receptor pathways as targets in non-small cell lung cancer. Curr Cancer Drug Targets 12:107-23. PMCID: PMC3418220

Linger RMA, Cohen RA, Cummings CT, Sather, S, Migdall-Wilson J, Middleton DHG, Lu X, Barón AE, Franklin WA, Merrick DT, Jedlicka P, DeRyckere D, Heasley LE, and Graham DK (2012) Mer or Axl receptor tyrosine kinase inhibition promotes apoptosis, blocks growth, and enhances chemosensitivity of human non-small cell lung cancer. Oncogene PMCID: PMC3502700
 
Ware KE, Hinz TK, Marek L, Helfrich BA, Astling D, Tan AC, and Heasley, LE. (2013) A mechanism of resistance to gefitinib mediated by cellular reprogramming and the acquisition of an FGF2-FGFR1 autocrine growth loop. Oncogenesis 2:e39. PMCID: PMC3641357
 
Singleton KR, Kim J, Hinz TK, Marek LA, Casas-Selves M, Hatheway C, Tan AC, DeGregori J, Heasley LE. (2013) A receptor tyrosine kinase network comprised of FGFRs, EGFR, ERBB2 and MET drives growth and survival of head and neck squamous carcinoma cell lines.  Mol Pharmacol 83(4):882-93. PMCID: PMC3608435
 
Göke F, Bode M, Franzen A, Kirsten R, Goltz D, Göke A, Sharma R, Boehm D, Vogel W, Wagner P, Lengerke C, Kristiansen G, Kirfel J, Van Bremen T, Bootz F, Heasley LE, Schröck A, Perner S. (2013) Fibroblast growth factor receptor 1 amplification is a common event in squamous cell carcinoma of the head and neck. Mod Pathol. Epub ahead of print, PMID: 23619603