Suresh S Ramalingam

Emory University, Atlanta, Georgia, United States

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Publications (252)1784.13 Total impact

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    ABSTRACT: Reports have suggested improvements in dosimetry, toxicity, and quality of life with intensity modulated radiation therapy in locally advanced non-small cell lung cancer. The selection criterion for those patients who may benefit is unclear. This study sought to identify subgroups of patients who may derive survival benefit from intensity modulated radiation therapy (IMRT) compared with 3D conformal radiation therapy (3DCRT).
    No preview · Article · Feb 2016 · Clinical Lung Cancer
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    ABSTRACT: We tested and clinically validated a targeted next-generation sequencing (NGS) mutation panel using 80 formalin-fixed, paraffin-embedded (FFPE) tumor samples. Forty non-small cell lung carcinoma, 30 melanoma, and 30 gastrointestinal (12 colonic, 10 gastric, and 8 pancreatic adenocarcinoma) FFPE samples were selected from laboratory archives. After appropriate specimen and nucleic acid quality control, 80 NGS libraries were prepared using the Illumina TruSight tumor (TST) kit and sequenced on the Illumina MiSeq. Sequence alignment, variant calling, and sequencing quality control were performed using vendor software and laboratory-developed analysis workflows. TST generated ≥500× coverage for 98.4% of the 13,952 targeted bases. Reproducible and accurate variant calling was achieved at ≥5% variant allele frequency with 8 to 12 multiplexed samples per MiSeq flow cell. TST detected 112 variants overall, and confirmed all known single-nucleotide variants (n = 27), deletions (n = 5), insertions (n = 3), and multinucleotide variants (n = 3). TST detected at least one variant in 85.0% (68/80), and two or more variants in 36.2% (29/80), of samples. TP53 was the most frequently mutated gene in non-small cell lung carcinoma (13 variants; 13/32 samples), gastrointestinal malignancies (15 variants; 13/25 samples), and overall (30 variants; 28/80 samples). BRAF mutations were most common in melanoma (nine variants; 9/23 samples). Clinically relevant NGS data can be obtained from routine clinical FFPE solid tumor specimens using TST, benchtop instruments, and vendor-supplied bioinformatics pipelines.
    No preview · Article · Jan 2016 · The Journal of molecular diagnostics: JMD
  • S S Ramalingam · K O'Byrne · M Boyer · T Mok · P A Jänne · H Zhang · J Liang · I Taylor · E I Sbar · L Paz-Ares
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    ABSTRACT: Background The irreversible epidermal growth factor receptor (EGFR) inhibitors have demonstrated efficacy in NSCLC patients with activating EGFR mutations, but it is unknown if they are superior to the reversible inhibitors. Dacomitinib is an oral, small-molecule irreversible inhibitor of all enzymatically active HER family tyrosine kinases.
    No preview · Article · Jan 2016 · Annals of Oncology
  • Suchita Pakkala · Suresh S. Ramalingam

    No preview · Article · Jan 2016 · Current Opinion in Oncology

  • No preview · Article · Jan 2016 · International journal of radiation oncology, biology, physics
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    ABSTRACT: The treatment of patients with metastatic non-small cell lung cancer (NSCLC) is slowly evolving from empirical cytotoxic chemotherapy to personalized treatment based on specific molecular alterations. Despite this 10-year evolution, targeted therapies have not been studied adequately in patients with resected NSCLC who have clearly defined actionable mutations. The advent of next-generation sequencing has now made it possible to characterize genomic alterations in unprecedented detail. The efforts begun by The Cancer Genome Atlas project to understand the complexities of the genomic landscape of lung cancer will be supplemented further by studying a large number of tumor specimens. The Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST) is an NCI-sponsored national clinical trials network (NCTN) initiative to address the needs to refine therapy for early-stage NSCLC. This program will screen several thousand patients with operable lung adenocarcinoma to determine whether their tumors contain specific molecular alterations [epidermal growth factor receptor mutation (EGFR) and anaplastic lymphoma kinase rearrangement (ALK)], making them eligible for treatment trials that target these alterations. Patients with EGFR mutation or ALK gene rearrangement in their tumor will be randomized to placebo versus erlotinib or crizotinib, respectively, after completion of their standard adjuvant therapy. ALCHEMIST will also contain a large discovery component that will provide an opportunity to incorporate genomic studies to fully understand the clonal architecture, clonal evolution, and mechanisms of resistance to therapy. In this review, we describe the concept, rationale, and outline of ALCHEMIST and the plan for genomic studies in patients with lung adenocarcinoma. Clin Cancer Res; 21(24); 5439-44. ©2015 AACR.
    No preview · Article · Dec 2015 · Clinical Cancer Research

  • No preview · Conference Paper · Dec 2015
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    ABSTRACT: Background: The discovery of oncogenic drivers has ushered in a new era for lung cancer, but the role of these mutations in different racial/ethnic minorities has been understudied. The Lung Cancer Mutation Consortium 1 (LCMC1) database was investigated to evaluate the frequency and impact of oncogenic drivers in lung adenocarcinomas in the racial/ethnic minority patient population. Methods: Patients with metastatic lung adenocarcinomas from 14 US sites were enrolled in the LCMC1. Tumor samples were collected from 2009 through 2012 with multiplex genotyping performed on 10 oncogenic drivers (KRAS, epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase (ALK) rearrangements, ERBB2 [formerly human epidermal growth factor receptor 2], BRAF, PIK3CA, MET amplification, NRAS, MEK1, and AKT1). Patients were classified as white, Asian, African American (AA), or Latino. The driver mutation frequency, the treatments, and the survival from diagnosis were determined. Results: One thousand seven patients were included. Whites represented the majority (n = 838); there were 60 AAs, 48 Asians, and 28 Latinos. Asian patients had the highest rate of oncogenic drivers with 81% (n = 39), and they were followed by Latinos with 68% (n = 19), whites with 61% (n = 511), and AAs with 53% (n = 32). For AAs, the EGFR mutation frequency was 22%, the KRAS frequency was 17%, and the ALK frequency was 4%. Asian patients were most likely to receive targeted therapies (51% vs 27% for AAs). There were no significant differences in overall survival. Conclusions: Differences were observed in the prevalence of oncogenic drivers in lung adenocarcinomas and in subsequent treatments among racial groups. The lowest frequency of drivers was seen for AA patients; however, more than half of AA patients had a driver, and those treated with targeted therapy had outcomes similar to those of other races. Cancer 2015. © 2015 American Cancer Society.
    No preview · Article · Dec 2015 · Cancer
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    Preview · Article · Nov 2015
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    ABSTRACT: Background: The last 3 decades have witnessed limited therapeutic advances in small cell lung cancer (SCLC) management. This study evaluated real-world trends in the use of systemic therapies and the impact on patient outcomes in the United States. Methods: The Surveillance, Epidemiology, and End Results-Medicare database was used to find patients diagnosed with SCLC between 1985 and 2005. The 1985-1990 period served as the baseline for a temporal analysis conducted at 5-year intervals (1985-1990, 1991-1995, 1996-2000, and 2001-2005). Cox proportional models were used to estimate the effect of chemotherapy on survival. Results were validated with a propensity-matched analysis. Results: There were 47,351 eligible patients: 52% were male; the median age was 71 years; and 87% were white, 7% were black, and 1.4% were Asian. The proportion of patients treated with chemotherapy was low but increased over time (38%, 55%, 50%, and 53%; P < .001). Race, diagnosis period, age, stage, and location of residence significantly predicted chemotherapy use. Females (51%), Asians (53%), and rural residents (60%) were more likely to receive chemotherapy. The median overall survival with and without chemotherapy was 9.6 and 3.6 months, respectively. Linear trend analyses showed a modest reduction in the impact of chemotherapy on survival for patients treated with chemotherapy versus untreated patients (hazard ratios [HRs], 0.59, 0.61, 0.64, and 0.62; P < .001) but an overall trend of improved survival for treated (HRs, 1.0, 1.03, 1.00, and 0.96; P = .005) and untreated patients (HRs, 1.0, 0.99, 0.94, and 0.92; P < .001). There was no survival difference between patients treated with carboplatin and patients treated with cisplatin (HR, 0.99; confidence interval [CI], 0.81-1.19; P = .875). Additional therapy beyond platinum-based chemotherapy was associated with a survival benefit (HR, 0.78; CI, 0.75-0.81; P < .001). Conclusions: Chemotherapy use was associated with a survival benefit in Medicare patients with SCLC treated in a real-world setting. Cancer 2015. © 2015 American Cancer Society.
    No preview · Article · Oct 2015 · Cancer
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    George Miles · James Rae · Suresh S Ramalingam · John Pfeifer
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    ABSTRACT: Personalized oncology, or more aptly precision oncogenomics, refers to the identification and implementation of clinically actionable targets tailored to an individual patient's cancer genomic information. Banking of human tissue and other biospecimens establishes a framework to extract and collect the data essential to our understanding of disease pathogenesis and treatment. Cancer cooperative groups in the United States have led the way in establishing robust biospecimen collection mechanisms to facilitate translational research, and combined with technological advances in molecular testing, tissue banking has expanded from its traditional base in academic research and is assuming an increasingly pivotal role in directing the clinical care of cancer patients. Comprehensive screening of tumors by DNA sequencing and the ability to mine and interpret these large data sets from well-organized tissue banks have defined molecular subtypes of cancer. Such stratification by genomic criteria has revolutionized our perspectives on cancer diagnosis and treatment, offering insight into prognosis, progression, and susceptibility or resistance to known therapeutic agents. In turn, this has enabled clinicians to offer treatments tailored to patients that can greatly improve their chances of survival. Unique challenges and opportunities accompany the rapidly evolving interplay between tissue banking and genomic sequencing, and are the driving forces underlying the revolution in precision medicine. Molecular testing and precision medicine clinical trials are now becoming the major thrust behind the cooperative groups' clinical research efforts.
    Preview · Article · Oct 2015 · Seminars in Oncology
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    ABSTRACT: Objectives: Linifanib, a potent and selective inhibitor of the tyrosine kinase activity of vascular endothelial growth factor and platelet-derived growth factor receptors, has clinical activity in advanced non-small cell lung cancer (NSCLC) both as monotherapy in the relapsed setting or with carboplatin and paclitaxel in the first-line setting. Though benefit was observed in unselected patient populations, identification of predictive biomarkers is critical for further development of this novel agent. Materials and methods: Data from 4 randomized studies in relapsed NSCLC with linifanib (n=116) or other treatments (n=125) were examined in an exploratory analysis to identify a biomarker profile predictive of favorable survival. Results: A signature combining the established tumor markers carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (CYFRA 21-1) was predictive of a favorable outcome. This signature was associated with improved survival in patients receiving linifanib monotherapy (hazard ratio [HR]=0.51 vs signature negative; p=0.002), but not in those receiving other anti-cancer treatments (p=0.716). This signature was validated on baseline plasma samples from patients enrolled in a randomized trial of daily linifanib 7.5mg, linifanib 12.5mg, or placebo added to first-line carboplatin and paclitaxel chemotherapy for advanced, nonsquamous NSCLC. Only linifanib-treated signature-positive patients had significant improvement in progression-free survival (PFS). Median PFS with placebo was 5.2 months versus 10.2 months (HR=0.49, p=0.049) for those receiving linifanib 7.5mg, and 8.3 months (HR=0.38, p=0.029) for linifanib 12.5mg. Overall survival for signature-positive patients was 11.3 months with placebo, 12.5 months with linifanib 7.5mg (HR=1.02, p=0.758), and 17.4 months with linifanib 12.5mg (HR=0.54, p=0.137). Conclusion: This baseline plasma biomarker signature is associated with improved outcome in advanced NSCLC patients receiving linifanib. Utility of the biomarker signature in patient selection for linifanib therapy in NSCLC merits evaluation in larger, prospective trials that are powered to detect a survival benefit.
    No preview · Article · Oct 2015 · Lung cancer (Amsterdam, Netherlands)
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    Philip J. Webber · Chanhee Park · Min Qui · Suresh S. Ramalingam · Fadlo R. Khuri · Haian Fu · Yuhong Du
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    ABSTRACT: Discovery of effective drug combinations is a promising strategy to improve patient survival. This study explores the impact of heat shock protein 90 (Hsp90) inhibition in combination with focal adhesion kinase (FAK) inhibitor on the growth of non-small cell lung cancer cells (NSCLC cells). Our data show that 17-N-Allylamino-17-demethoxygeldanamycin (17-AAG), a well-studied Hsp90 inhibitor, synergized with FAK inhibitor, PF-573228, on the growth inhibition of NSCLC cells. This combination effect was confirmed using additional chemically distinct Hsp90 inhibitor, STA-9090, which is currently undergoing phase 3 clinical evaluation. Co-treatment of NSCLC cells with Hsp90 and FAK inhibitors significantly enhanced the inhibition on long-term colony formation compared to that with single agent. Inhibition of FAK exacerbated the G2 cell cycle arrest and annexin-V apoptotic staining induced by 17-AAG. Further mechanistic studies revealed that the combination of Hsp90 and FAK inhibitors reduced the activity of canonical proliferative and survival Akt-mTOR signaling, and increased pro-apoptotic caspase activation. Interestingly, FAK inhibition alone induced feedback activation of pro-survival Erk signaling, which was abrogated by co-treatment with Hsp90 inhibitors. Both Hsp90 and FAK inhibitors are undergoing clinical evaluation. Our studies suggest the tandem of Hsp90 and FAK inhibitors may provide an effective treatment option for NSCLC patients.
    Preview · Article · Sep 2015
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    O.B. Alese · S. Kim · Z. Chen · S.S. Ramalingam · T.K. Owonikoko · B.F. El-Rayes
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    ABSTRACT: Background: The liver is a common site of primary and metastatic cancer. Liver-directed therapies are commonly used to treat cancer involving the liver. We report on the patterns, predictors, and outcomes of liver-directed therapies in hospitalized cancer patients in the United States. Methods: Data were obtained from all U.S. states that contributed to the Nationwide Inpatient Sample maintained by the Agency for Healthcare Research and Quality between 2006 and 2010. Univariate and multivariate testing was used to identify factors significantly associated with patient outcome. Results: For the 5-year period of interest, 12,540 patient discharges were identified. Mean age in the sample was 60 years. Primary liver lesions (n = 8840) made up 26.9% of the sample; the remaining cases were metastases. Most procedures were performed in large (79%) urban (98%) hospitals and in patients with insurance (97.9%). The most common intervention was partial hepatectomy (42.7%), followed by open (9.9%), percutaneous (7.2%), and laparoscopic (5.04%) ablation of liver lesions; embolization (9.8%); and liver transplantation (2.64%). The incidence of in-hospital mortality was very low (2.4%), and the complication rate was 12.2%. Complications such as acute liver necrosis, ascites, hepatic coma, hepatorenal syndrome, liver abscess, and high number of comorbid illnesses (>8) accounted for 60% of the in-hospital mortality. Conclusions: The low rate of morbidity and mortality associated with liver-directed therapies in hospitalized cancer patients supports the continuing utility of such procedures in the management of primary and metastatic liver cancer. The patterns of health disparities observed with respect to the use of liver-directed therapies are concerning.
    Preview · Article · Sep 2015 · Current Oncology
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    ABSTRACT: Purpose: The American College of Chest Physicians (ACCP) produced an evidence-based guideline on treatment of patients with small-cell lung cancer (SCLC). Because of the relevance of this guideline to American Society of Clinical Oncology (ASCO) membership, ASCO reviewed the guideline, applying a set of procedures and policies used to critically examine guidelines developed by other organizations. Methods: The ACCP guideline on the treatment of SCLC was reviewed for developmental rigor by methodologists. An ASCO Endorsement Panel updated the literature search, reviewed the content, and considered additional recommendations. Results: The ASCO Endorsement Panel determined that the recommendations from the ACCP guideline, published in 2013, are clear, thorough, and based on current scientific evidence. ASCO endorses the ACCP guideline on the treatment of SCLC, with the addition of qualifying statements. Recommendations: Surgery is indicated for selected stage I SCLC. Limited-stage disease should be treated with concurrent chemoradiotherapy in patients with good performance status. Thoracic radiotherapy should be administered early in the course of treatment, preferably beginning with cycle one or two of chemotherapy. Chemotherapy should consist of four cycles of a platinum agent and etoposide. Extensive-stage disease should be treated primarily with chemotherapy consisting of a platinum agent plus etoposide or irinotecan. Prophylactic cranial irradiation prolongs survival in patients with limited-stage disease who achieve a complete or partial response to initial therapy and may do so in similarly responding patients with extensive-stage disease as well. Additional information is available at http://www.asco.org/endorsements/sclc and http://www.asco.org/guidelineswiki.
    No preview · Article · Sep 2015 · Journal of Clinical Oncology
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    ABSTRACT: Background: Recent data have suggested possible oncologic equivalence of sublobar resection with lobectomy for early stage NSCLC.Our aim was to evaluate and compare short and long term survival for these surgical approaches. Methods: This retrospective cohort study utilized the National Cancer Data Base. Patients undergoing lobectomy, segmentectomy,or wedge resection for preoperative clinical T1A N0 NSCLC from 2003-2011 were identified.Overall survival (OS) and 30-day mortality were analyzed using multivariable Cox proportional hazards models,logistic regression models,and propensity score matching.Further analysis of survival stratified by tumor size, facility type, number of lymph nodes examined, and surgical margins was performed. Results: A total of 13,606 patients were identified. After propensity score matching, 987 patients remained in each group. Both segmentectomy and wedge resection were associated with significantly worse OS when compared with lobectomy (HR 1.70 and 1.45, respectively, both p < 0.001), with no difference in 30 day mortality. Median OS for lobectomy, segmentectomy, and wedge resection were 100, 74, and 68 months, respectively (p < 0.001). Finally, sublobar resection was associated with increased likelihood of positive surgical margins, lower likelihood of having more than 3 lymph nodes examined, and significantly lower rates of nodal upstaging. Conclusion: In this large national-level, clinically diverse sample of clinical T1ANSCLC patients, wedge and segmental resectionswere shown to have significantly worse OS compared tolobectomy.Further patients undergoing sublobar resection were more likely to have inadequate lymphadenectomy and positive margins. Ongoingprospective study taking into account LN upstaging and margin status is still needed.
    No preview · Article · Sep 2015 · Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer
  • Srihari Veeraraghavan · Suresh S Ramalingam · Fadlo R Khuri
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    ABSTRACT: As the burden of lung cancer grows dramatically in China, efforts towards prevention and early detection are urgently needed. Implementation of an effective tobacco-control policy will have to go hand-in-hand with other actions.
    No preview · Article · Sep 2015 · Cancer
  • Suresh S. Ramalingam · Fadlo R. Khuri
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    ABSTRACT: Although the burden of lung cancer has started to decline in the United States in recent years, in China, the world's most populous nation, nearly 650,000 new cases are diagnosed each year. These staggering statistics call for urgent action at multiple levels of society to reduce the burden of lung cancer in China.
    No preview · Article · Sep 2015 · Cancer
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    ABSTRACT: BACKGROUND Stereotactic body radiation therapy (SBRT) has demonstrated high rates of local control with low morbidity and has now emerged as the standard of care for medically inoperable, early stage non–small cell lung cancer (NSCLC). However, the impact of lung SBRT on survival in the elderly population is less clear given competing comorbid conditions. An analysis of the National Cancer Data Base (NCDB) was undertaken to determine whether definitive SBRT improves survival relative to observation alone patients ages 70 years and older.METHODS The NCDB, a retrospective national database that captures approximately 70% of all patients treated for cancer, was queried for patients aged 70 years or older with early stage (T1-T3N0M0) NSCLC from 2003 to 2006. Overall survival was compared between patients who received stereotactic body radiotherapy alone and those who received no treatment. An extended Cox proportional hazards model was applied to estimate the treatment effect of SBRT.RESULTSIn total, 3147 patients met the selection criteria for this analysis. SBRT was delivered to 258 patients (8.2%), and 2889 patients (91.8%) received no treatment. There was no significant difference in the distribution of Charlson/Deyo comorbidity index scores between the 2 groups (P = .076). Multivariable analysis revealed improved overall survival with SBRT compared with observation for the entire cohort (hazard ratio, 0.64; P < .001).CONCLUSIONSSBRT is associated with improved survival in elderly patients with early stage NSCLC who have concurrent comorbid conditions compared with observation alone. The current data support the use of SBRT for the treatment of elderly patients with early stage NSCLC who have limiting comorbid conditions. Cancer 2015. © 2015 American Cancer Society.
    Full-text · Article · Sep 2015 · Cancer
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    ABSTRACT: The SQUIRE trial demonstrated that adding necitumumab to chemotherapy for patients with metastatic squamous cell lung cancer (mSqCLC) increased median overall survival by 1.6 months (hazard ratio, 0.84). However, the costs and value associated with this intervention remains unclear. Value-based pricing links the price of a drug to the benefit that it provides and is a novel method to establish prices for new treatments. To evaluate the range of drug costs for which adding necitumumab to chemotherapy could be considered cost-effective. We developed a Markov model using data from multiple sources, including the SQUIRE trial, which compared standard chemotherapy with and without necitumumab as first-line treatment of mSqCLC, to evaluate the costs and patient life expectancies associated with each regimen. In the analysis, patients were modeled to receive gemcitabine and cisplatin for 6 cycles or gemcitabine, cisplatin, and necitumumab for 6 cycles followed by maintenance necitumumab. Our model's clinical inputs were the survival estimates and frequency of adverse events (AEs) described in the SQUIRE trial. Log-logistic models were fitted to the survival distributions in the SQUIRE trial. The cost inputs included drug costs, based on the Medicare average sale prices, and costs for drug administration and management of AEs, based on Medicare reimbursement rates (all in 2014 US dollars). We evaluated incremental cost-effectiveness ratios (ICERs) for the use of necitumumab across a range of values for its cost. Model robustness was assessed by probabilistic sensitivity analyses, based on 10 000 Monte Carlo simulations, sampling values from the distributions of all model parameters. In the base case analysis, the addition of necitumumab to the treatment regimen produced an incremental survival benefit of 0.15 life-years and 0.11 quality-adjusted life-years (QALYs). The probabilistic sensitivity analyses established that when necitumumab cost less than $563 and less than $1309 per cycle, there was 90% confidence that the ICER for adding necitumumab would be less than $100 000 per QALY and less than $200 000 per QALY, respectively. These findings provide a value-based range for the cost of necitumumab from $563 to $1309 per cycle. This study provides a framework for establishing value-based pricing for new oncology drugs entering the US marketplace.
    No preview · Article · Aug 2015

Publication Stats

4k Citations
1,784.13 Total Impact Points

Institutions

  • 2008-2016
    • Emory University
      • Department of Hematology and Medical Oncology
      Atlanta, Georgia, United States
  • 2015
    • University of California, Davis
      Davis, California, United States
  • 2014
    • National Cancer Institute (USA)
      베서스다, Maryland, United States
  • 2013
    • University of Leicester
      Leiscester, England, United Kingdom
  • 2012
    • University of Miami Miller School of Medicine
      Miami, Florida, United States
  • 2011
    • University of Texas Southwestern Medical Center
      Dallas, Texas, United States
  • 2004-2011
    • University of Pittsburgh
      • • Department of Medicine
      • • Department of Pharmacology and Chemical Biology
      • • Division of Hematology/Oncology
      Pittsburgh, Pennsylvania, United States
  • 2007-2008
    • Fox Chase Cancer Center
      Filadelfia, Pennsylvania, United States