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Department of Medicine

Department of Medicine

  Division of Hematology/Oncology

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photo Timothy F. Burns, MD, PhD

Assistant Professor of Medicine

Department of Medicine

Division of Hematology/Oncology

University of Pittsburgh Cancer Institute

Email: burnstf@upmc.edu

Phone: 412-623-7770

Contact
Office: Hillman Cancer Center Research Pavilion,
5117 Centre Avenue, Office: Suite 2.18e Lab: 2.7
Pittsburgh, PA 15213
 
Phone: 412-623-7770
Fax: 412-623-7798
E-mail: burnstf@upmc.edu
Administrative Assistant:
Carmella Campbell
Address: Hillman Cancer Center Research Pavilion
Room 2.18
Pittsburgh, PA 15213
Email: campbellcm@upmc.edu
Phone: 412-623-7770
Fax: 412-623-7768
Education and Training
Education
BS with Honors, Cornell University, 1996
M.D./Ph.D., University of Pennsylvania, 2005
Training
Osler Medical Residency, Johns Hopkins Hospital, 2008
Fellowship in Medical Oncology, Johns Hopkins Hospital, 2012
Research Interest
My research and clinical interests revolve around the development of targeted therapies for KRAS-mutant NSCLC as well as novel strategies to overcome resistance to targeted therapies. The first line of research in my laboratory focuses on the role of the epithelial–mesenchymal transition transcription factor TWIST1 in oncogene-driven NSCLC. We have demonstrated the TWIST1 is essential for lung tumorigenesis for several key oncogenic drivers including KRAS mutant, EGFR mutant and MET mutant/amplified NSCLC. Furthermore, we have demonstrated that TWIST1 overexpression leads to resistance to EGFR and MET targeted therapies. We are currently examining the mechanism(s) through which this occurs and developing therapeutic combinations to overcome this resistance. Importantly, we have developed a novel TWIST1 inhibitor which serves a tool compound for our therapeutic studies and serves as the basis for our current drug screening efforts in order to develop a TWIST1 inhibitor that we can translate to the clinic. The second line of research in my lab focuses on studying the mechanisms of resistance to the Hsp90 inhibitor, ganetespib in KRAS-mutant NSCLC so that we can use to develop rationally designed Hsp90 inhibitor combination for the clinic which can prevent or overcome resistance. Of note, we have recently demonstrated that the ERK-p90RSK-CDC25C pathway plays a key role in resistance to Hsp90 inhibitors through bypass of a G2/M checkpoint. These data suggest that the combination of an ERK inhibitor with an Hsp90 inhibitor maybe effective in KRAS mutant NSCLC and we hope to test this combination in early phase trials soon.
Clinical Interest
Lung cancer is the leading cause of cancer death in the United States and worldwide. Recent advances in the treatment of NSCLC have come from recognition that NSCLC is not a single disease entity, but rather a collection of distinct molecularly driven neoplasms. This paradigm is typified by the recent progress made in the treatment of patients with EGFR-mutant and EML4-ALK translocation-driven adenocarcinomas of the lung with tyrosine kinase inhibitors targeting these oncogenes. Unfortunately, little progress has been made in the treatment of patients with the most frequently observed driver oncogene, mutant KRAS. KRAS is mutated in approximately 25% of all NSCLC, and patients with this mutation have an increased risk of recurrence in early stage disease and have a worse prognosis with metastatic disease.
Publications
For my complete bibliography, Click Here.
Selected Publications:
Chatterjee, S., Huang, E.H., Christie, I., Burns, T.F. Reactivation of the p90RSK-CDC25C pathway leads to bypass of the ganetespib induced G2/M arrest and mediates acquired resistance to ganetespib in KRAS mutant NSCLC. Molecular Cancer Therapeutics. 2017; In Press: XXX.
Chatterjee, S., Huang, E.H., Christie, I., Kurland, B.F., Burns, T.F. Acquired resistance to the Hsp90 inhibitor, ganetespib in KRAS mutant NSCLC is mediated via reactivation of the ERK-p90RSK-mTOR signaling network. Molecular Cancer Therapeutics. 2017; 16(5): 793.
Somasundaram, A., Burns, T.F. The next generation of immunotherapy: keeping lung cancer in check. Journal of hematology & oncology. 2017; 10(1): 87.
Yochum, Z.A., Socinski, M.A., Burns, T.F. Paradoxical functions of ZEB1 in EGFR-mutant lung cancer: tumor suppressor and driver of therapeutic resistance. Journal of Thoracic Disease. 2016; 8(11): E1528-E1531.
Chatterjee, S., Bhattacharya, S., Socinski, M.A., Burns, T.F. HSP90 inhibitors in lung cancer: promise still unfulfilled. Clinical advances in hematology & oncology. 2016; 14(5): 346-56.
Bhattachary, S., Socinski, M.A., Burns, T.F. KRAS mutant lung cancer: progress thus far on an elusive therapeutic target. Clinical and translational medicine. 2015; 4(1): 35.
Gajula RP, Chettiar ST, Williams RD, Nugent K, Kato Y, Wang H, Malek R, Taparra K, Cades J, Annadanam A, Yoon AR, Fertig E, Firulli BA, Mazzacurati L, Burns TF, Firulli AB, An SS, Tran PT. Structure-function studies of the bHLH phosphorylation domain of TWIST1 in prostate cancer cells. Neoplasia. 2015; 17(1): 16-31.
Somasundaram A, Socinski MA, Burns TF. Personalized treatment of EGFR mutant and ALK-positive patients in NSCLC. Expert opinion on pharmacotherapy. 2014; 15(18): 2693-708.
Burns TF, Dobromilskaya I, Murphy SC, Gajula RP, Thiyagarajan S, Chatley SN, Aziz K, Cho YJ, Tran PT, Rudin CM. Inhibition of TWIST1 leads to activation of oncogene-induced senescence in oncogene-driven non-small cell lung cancer. Molecular cancer research. 2013; 11(4): 329-38.
Tran PT, Shroff EH, Burns TF, Thiyagarajan S, Das ST, Zabuawala T, Chen J, Cho YJ, Luong R, Tamayo P, Salih T, Aziz K, Adam SJ, Vicent S, Nielsen CH, Withofs N, Sweet-Cordero A, Gambhir SS, Rudin CM, Felsher DW. Twist1 suppresses senescence programs and thereby accelerates and maintains mutant Kras-induced lung tumorigenesis. Plos genetics. 2012; 8(5): 31002650.
Notable Achievements
Young Investigators Award, ASCO, 2010
Merit Award, IASCL 11th annual Targeted Therapies for the Treatment of Lung Cancer Meeting, 2010
Merit Award, ASCO Annual Meeting, 2011
Scholar in Training Award, AACR Annual Meeting, 2012
Scholar Award, V Foundation, 2013
Junior Faculty, University of Pittsburgh School of Medicine Research Day Award, 2014; 2015
Sidney Kimmel Foundation for Cancer Reseach Kimmel Scholar Award, 2015
Doris Duke Clinical Scientist Development Award, 2016
ASCI Young Physician-Scientist Award, 2016