The Innovative Translational Research Shared Resource (ITR) at the Vanderbilt-Ingram Cancer Center partners with oncologists and laboratory and non-laboratory investigators to guide, manage, and facilitate pre-clinical and clinical trial laboratory discoveries.
Since 2010, our mission has been to advance the translation of research into improved anti-cancer therapies.
The ITR is generously supported by the Vanderbilt-Ingram Cancer Center Support Grant, the TJ Martell Foundation, and the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation.
Impact
Since 2010, the ITR has collaborated on 99 research projects with 53 unique investigators across 7 research programs at the Vanderbilt-Ingram Cancer Center, and at other academic institutions in the United States.
These projects have resulted in 35 peer reviewed publications and contributed to the generation of $1.8M in funding for clinical trial correlative research. Furthermore our work has contributed to over 25 grants, awarded to researchers, worth over $43M in direct costs.
This success was founded upon our ability to draw resources together, understand a breadth of research technologies, and engage teams from various backgrounds in a timely manner to achieve common goals.
Since 2010, the ITR has collaborated with investigators in seven VICC research programs including Genome Maintenance, Signal Transduction and Chemical Biology, Host-Tumor Interactions, Cancer Health Outcomes and Control, Translational Research and Interventional Oncology, Gastrointestinal Cancer, and Breast Cancer.
Publications
Laboratory Publications (co-authored)
- Idrees K, Padmanabhan C, Liu E, Guo Y, Gonzalez R, Beauchamp DR, Berlin J, Dahlman K, Shi C (2017). Frequent BRAF mutations suggest a novel oncogenic driver in neuroendocrine carcinoma. Journal of Surgical Oncology. (in press)
- Polosukhina D, Love H, Correa H, Su Z, Dahlman K, Pao W, Moses HL, Arteaga C, Lovvorn HN, Zent R, Clark P (2017). Functional KRAS mutations and a potential role for PI3K/AKT activation in Wilms Tumors. Molecular Oncology. (epub ahead of print).
- Goff LW, Cardin DB, Whisenant JG, Du L, Koyama T, Dahlman KB, Salaria SN, Young RT, Ciombor KK, Gilbert J, Smith SJ, Chan E, Berlin J. (2016). A phase I trial investigating pulsatile erlotinib in combination with gemcitabine and oxaliplatin in advanced biliary tract cancers. Investigational New Drugs. (epub ahead of print).
- Hugo W, Shi H, Sun L, Piva M, Song C, Kong X, Moriceau G, Hong A, Dahlman KB, Johnson DB, Sosman JA, Ribas A, Lo RS. (2015). Non-genomic and immune evolution of melanoma acquiring MAPKi resistance. Cell. (in press).
- Mudigonda TV, Wyman K, Spigel DR, Dahlman KB, Greco FA, Puzanov I, Kelley MC, Hainsworth JD, Sosman JA, Johnson DB. (2015). A Phase II trial of erlotinib and bevacizumab for patients with metastatic melanoma. Pigment Cell Melanoma Research. (in press).
- McGirt LY, Jia P, Baerenwald DA, Duszynski RJ, Dahlman KB, Zic JA, Zwerner JP, Hucks D, Dave U, Zhao Z, Eischen CM. (2015). Whole genome sequencing reveals oncogenic mutations in mycosis fungoides. Blood. (in press).
- Fedorenko IV, Abel EV, Koomen JM, Fang B, Wood ER, Chen YA, Fisher KJ, Iyengar S, Dahlman KB, Wargo JA, Flaherty KT, Sosman JA, Sondak VK, Messina JL, Gibney GT, Smalley KS. (2015). Fibronectin induction abrogates the BRAF inhibitor response of BRAF V600E/PTEN-null melanoma cells. Oncogene. (in press).
- Johnson AS, Crandall H, Dahlman K, Kelley MC. (2015). Preliminary results from a prospective trial of preoperative combined BRAF and MEK-targeted therapy in advanced BRAF mutation-positive melanoma. Journal of the American College of Surgeons. 220: 581-593.
- Moriceau G, Hugo W, Hong A, Shi H, Kong X, Yu CC, Koya RC, Samatar AA, Khanlou N, Braun J, Ruchalski K, Seifert H, Larkin J, Dahlman KB, Johnson DB, Algazi A, Sosman JA, Ribas A, Lo RS. (2015). Tunable-combinatorial mechanisms of acquired resistance limit the efficacy of BRAF/MEK cotargeting but result in melanoma drug addiction. Cancer Cell. (in press).
- Iams WT, Hames ML, Tsai JP, Dahlman KB, Talbott MS, Richards KL, Reddy NM. (2014). Thyroid dysfunction in patients with diffuse large B-cell lymphoma receiving lenalidomide is mediated by TNFalpha. Experimental Hematology. 124: 4438-4438.
- Johnson DB, Dahlman, KB, Knol J, Gilbert J, Puzanov I, Means-Powell J, Balko JM, Lovly CM, Murphy BA, Goff LW, Abramson VG, Crispens MA, Mayer IA, Berlin JD, Horn L, Keedy VL, Reddy NM, Arteaga CL, Sosman JA, Pao W. (2014). Enabling a genetically informed approach to cancer medicine: A retrospective evaluation of the impact of comprehensive tumor profiling using a targeted next-generation sequencing panel. Oncologist. 19: 616-622.
- Xia J, Jia P, Hutchinson KE, Dahlman KB, Johnson DB, Sosman J, Pao W, Zhao Z. (2014). A meta-analysis of somatic mutations from next generation sequencing of 241 melanomas: a road map for the study of genes with potential clinical relevance. Molecular Cancer Therapeutics. 13: 1918-1928.
- Abramson VG, Cooper Lloyd M, Ballinger T, Sanders ME, Du L, Lai D, Su Z, Mayer I, Levy M, LaFrance DR, Vnencak-Jones CL, Shyr Y, Dahlman KB, Pao W, Arteaga CL. (2014). Characterization of breast cancers with PI3K mutations in an academic practice setting using SNaPshot profiling. Breast Cancer Research and Treatment. 145: 389-399.
- Meador CB, Micheel CM, Levy MA, Lovly CM, Horn L, Warner JL, Johnson DB, Zhao Z, Anderson IA, Sosman JA, Vnencak-Jones CL, Dahlman KB, Pao W. (2014). Beyond histology: Translating tumor genotypes into clinically effective targeted therapies. Clinical Cancer Research. 20: 2264-2275.
- Rexer BN, Chanthaphaychith S, Dahlman KB, Arteaga CL. (2014). Direct inhibition of PI3K in combination with dual HER2 inhibitors is required for optimal antitumor activity in HER2+ breast cancer cells. Breast Cancer Research. 16: R9.
- Shi H, Hugo W, Kong X, Hong A, Koya RC, Moriceau G, Chodon T, Guo R, Johnson DB, Dahlman KB, Kelley MC, Kefford RF, Chmielowski B, Glaspy JA, Sosman JA, van Baren N, Long GV, Ribas A, Lo RS. Acquired Resistance and clonal evolution in melanoma during BRAF inhibitor therapy. Cancer Discovery. 4: 80-93.
- Wang Q, Jia P, Li F, Chen H, Ji H, Hucks, D, Dahlman KB, Pao W, Zhao Z. (2013) Detecting somatic point mutations in cancer genome sequencing data: a comparison of mutation callers. Genome Medicine. 5: 91.
- Jia P, Jin H, Meador CB, Xia J, Ohashi K, Dahlman KB, Politi K, Zhao Z, Pao W (2013). Next-generation sequencing of paired tyrosine kinase inhibitor-sensitive and -resistant EGFR mutant lung cancer cell lines identifies spectrum of DNA changes associated with drug resistance. Genome Research. 23: 1434-1445.
- Dahlman KB*, Xia J*, Hutchinson K*, Ng C, Hucks D, Jia P, Atefi M, Su Z, Branch S, Lyle P, Hicks D, Bozon V, Glaspy JA, Netterville JL, Venencak-Jones C, Sosman J, Ribas A, Zhao Z, Pao W (2012). BRAF L597 mutations in melanoma are associated with sensitivity to MEK inhibitors. Cancer Discovery. 2: 791-797 *These authors contributed equally. (subject of accompanying editorial Cancer Discovery (2012) 2:766-768)
- Shi H, Moriceau G, Kong X, Koya RC, Nazarian R, Pupo G, Bacchiocchi A, Dahlman KB, Chmielowski B, Sosman JA, Halaban R, Kefford RF, Long GV, Ribas A, Lo RS (2012). Preexisting MEK1 exon 3 mutations in V600E/KBRAF melanomas do not confer resistance to B-RAF inhibitors. Cancer Discovery. 2: 414-424.
- Lovely C*, Dahlman KB*, Fohn L*, Su Z*, Dias-Santagata D, Hicks DJ, Hucks D, Berry, E, Terry C, Duke M Su Y, Sobolik-Delmaire T, Richmond A, Kelley MC, Vnencak-Jones CL, Iafrate JA, Sosman J, Pao W (2012). Routine multiple mutational profiling of melanomas enables enrollment in genotype-driven therapeutic trials. PLoS ONE. 7: e35309. *These authors contributed equally.
- Su Y, Kelley MC, Splittgerber RC, Kantrow S, Short S, Sobolik-Delmaire T, Dahlman KB, Jiang A, Shyr Y, Levy S, Sosman J, Richmond A (2012). RAF265 inhibits the growth of advanced human melanoma independent of BRAF mutation status. Clinical Cancer Research. 18: 2184-2198.
- Shi H, Moriceau G, Kong X, Lee M, Ribas A, Koya R, Ng C, Chodon T, Nelson S, Lee H, Long G, Scolyer R, Kefford R, Sosman J, Dahlman KB, Lo R (2012) Melanoma whole exome sequencing identifies V600EB-RAF amplification-mediated acquired B-RAF inhibitor resistance. Nature Communications. 3: 724.
- Poulikakos, PI, Persaud Y, Janakiraman M, Kong X, Ng C, Moriceau G, Shi H, Atefi M, Titz B, Gabay MT, Salton M, Dahlman KB, Madhavi T, Wargo JA, Flaherty KT, Kelley MC, Misteli T, Chapman PB, Sosman JA, Graeber TG, Ribas A, Lo RS, Rosen N, Solit D (2011). RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E). Nature. 480: 387-390.
- Villanueva J, Vultur A, Lee JT, Somasundaram R, Fukunaga-Kalabis M, Cipolla AK, Wubbenhorst B, Xu X, Gimotty PA, Kee D, Santiago-Walker AE, Letrero R, D’Andrea K, Pushparajan A, Hayden JE, Dahlman KB, Laquerre S, McArthur GA, Sosman JA, Nathanson KL, Herlyn M (2010). Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K. Cancer Cell. 18: 683-695.
Laboratory Publications (not co-authored)
- Martin T, Richter J, Vij R, Cole C. Atanackovic D, Zonder J, Kaufman JL, Bensinger W, Dimopoulos MA, San Miguel J, Zimmerman T, Lendvai N, Hari P, Ocio EM, Gasparetto C, Kumar S, Hsu K, Charpentier E, Strickland SA, Mikhael J. (2015) A dose finding phase II trial of isatuximab (SAR650984, anti-CD38 mAb) as a single agent in relapsed/refractory multiple myeloma. Blood. 126: 509.
- Carroll C, Hunley TE, Guo Y, Cortez D. (2015). A novel splice site mutation in SMARCAL1 results in aberrant exon definition in a child with schimke immunoosseous dysplasia. American Journal of Medical Genetics Part A. 167A: 2260-2264.
- Gonzalez R, Cates JMM, Washington MK, Beauchamp RD, Coffey RJ, Shi C. (2015). Adenoma-like adenocarcinoma: a subtype of colorectal carcinoma with good prognosis, deceptive appearance on biopsy and frequent KRAS mutation. Histopathology. (in press).
- Lovly CM, McDonald T, Chen H, Ortiz-Cuaran S, Heukamp LC, Yan Y, Florin A, Ozretic L, Lim D, Lu W, Chen Z, Chen X, Lu P, Paik PK, Shen R, Jin H, Buettner R, Ansen S, Perner S, Brockmann M, Bos M, Wolf J, Gardizi M, Wright GM, Solomon B, Russell PA, Rogers TM, Suehara Y, Red-Brewer M, Tieu R, de Stanchina E, Wang Q, Zhao Z, Johnson DH, Horn L, Wong KK, Thomas RK, Ladanyi M, Pao W (2014). Rationale for co-targeting IGF-1R and ALK in ALK fusion-positive lung cancer. Nature Medicine. 20: 1027-1034.
- Mayer IA, Abramson VG, Isakoff SJ, Forero A, Balko JM, Kuba MG, Sanders ME, Yap JT, Van den Abbeele AD, Li Y, CAntley LC, Winer E, Arteaga CL (2014). Stand Up to Cancer phase Ib study of pan-phosphoinositide-2-kinase inhibitor buparlisib with letrozole in estrogen receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. Journal of Clinical Oncology.
- Smith S, Tripathi R, Mathias E, Cleveland S, Elliott N, Goodings C, Yi D, Downing J, Mullighan C, Lebeau M, Jenkins N, Copeland N, Davé UP (2012). Lmo2 induces T-cell leukemia by two distinct pathways. (in preparation).
- Liu Y, Hawkins OE, Su Y, Vilgelm AE, Sobolik T, Thu YM, Kantrow S, Splittgerber RC, Short S, Amiri KI, Ecsedy JA, Sosman JA, Kelley MC, Richmond A (2013). Targeting aurora kinases limits tumour growth through DNA damage-mediated senescence and blockade of NF-κB impairs this drug-induced senescence. EMBO Mol Med. 5: 149-166
- Lehmann BD*, Bauer JA*, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, Pietenpol JA (2011). Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. Journal of Clinical Investigation. 121: 2750-2767. *These authors contributed equally.