Department of Medicine
Faculty Profiles by Division

Department of Medicine

Faculty Profiles

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photo Timothy F. Burns, MD, PhD

Hematology/Oncology

Associate Professor of Medicine

Associate Program Director for Research, Hematology/Oncology Fellowship Program

Department of Medicine

Division of Hematology-Oncology

UPMC Hillman Cancer Center

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 for EGFR-mutant and MET-altered NSCLC. My two main research themes are 1) novel pre-clinical target validation and drug development (TWIST1 in oncogene driven NSCLC and TKI resistance); and 2) elucidating mechanisms of resistance for targeted inhibitors to develop rationale therapeutic combinations that can be tested in the clinic (Hsp90 and ERK1/2 inhibitors). The first line of research in my laboratory focuses on the role of the EMT transcription factor TWIST1 in oncogene-driven NSCLC. We have demonstrated the TWIST1 is essential for lung tumorigenesis for KRAS mutant, EGFR mutant and MET mutant/amplified NSCLC and TWIST1 overexpression leads to resistance to EGFR and MET TKIs. We are examining the mechanism(s) through which this occurs and developing therapeutic combinations to overcome this resistance. Furthermore, we are exploring whether targeting the HGF-MET-TWIST1 pathway can be an effective strategy for preventing or treating lung brain metastases. 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 to develop a clinical TWIST1 inhibitor. The second line of research in my lab focuses on studying the mechanisms of resistance to targeted agents currently in phase 1 and 2 trials to develop rationale therapeutic combinations in the clinic. This is typified by our previous work with Hsp90 inhibitors and ongoing work on ERK inhibitors.
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, resistance to our current targeted therapies is inevitable. Furthermore, 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. My clinical interests revolve around the development of targeted therapies for KRAS-mutant NSCLC as well as novel strategies to overcome resistance to targeted therapies for EGFR-mutant and MET-altered NSCLC as well as other oncogenic drivers in lung cancer.
Publications
For my complete bibliography, Click Here.
Selected Publications:
Yochum ZA, Cades J, Wang H, Chatterjee S, Simons BW, O'Brien JP,, Khetarpal SK, Lemtiri-Chlieh G, Myers KV, Huang EH, Rudin CM, Tran PT, Burns TF. Targeting the EMT transcription factor TWIST1 overcomes resistance to EGFR inhibitors in EGFR-mutant non-small-cell lung cancer. Oncogene. 2019; 38(5): 656-670.
Han J, Goldstein LA, Hou W, Chatterjee S, Burns TF, Rabinowich H. HSP90 inhibition targets autophagy and induces a CASP9-dependent resistance mechanism in NSCLC. Autophagy. 2018; 14(6): 958-971.
Ancevski, H.K., Friedland, D.M., Villaruz, L.C., Burns, T.F. First-Line Osimertinib in Patients with Treatment-Naive Somatic or Germline EGFR T790M-Mutant Metastatic NSCLC. Journal of thoracic oncology. 2018; 1: e3-e5.
Yochum ZA, Cades J, Mazzacurati L, Neumann NM, Khetarpal SK, Chatterjee S, Wang H,, Attar MA, Huang EH, Chatley SN, Nugent K, Somasundaram A, Engh JA, Ewald AJ, Cho YJ,, Rudin CM, Tran PT, Burns TF. A First-in-Class TWIST1 Inhibitor with Activity in Oncogene-Driven Lung Cancer. Molecular Cancer Research. 2017; 15(12): 1764-1776.
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.
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.
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
American Cancer Socieity Research Scholar Grant, 2018