Kimberly Brown Dahlman, Ph.D.
Research Assistant Professor of Cancer Biology
Director and Project Management Officer, Innovative Translational Research Shared Resource
Vanderbilt University Medical Center
772 Preston Research Building
Nashville, TN 37232
The VICC Innovative Translational Research Shared Resource (ITR) was established in July 2008 to support collaborative research efforts, thereby setting a unique precedent in the field of cancer research by providing a means and method for laboratory and clinical investigators to work together to develop their ideas into new treatment approaches for cancer patients.
The VICC Innovative Translational Research Shared Resource (ITR) was established in July 2008 to support collaborative research efforts, thereby setting a unique precedent in the field of cancer research by providing a means and method for laboratory and clinical investigators to work together to develop their ideas into new treatment approaches for cancer patients. The organization of the laboratory will facilitate collaboration of clinician-scientists with active clinical practices with basic scientists, leveraging the skills and attributes of each. In this collaborative laboratory, the most advanced laboratory techniques, new relevant animal models for cancer, and treatment approaches emphasizing the uniqueness of each patient’s tumor for personalized therapy will lead to discoveries that could be more quickly translated to patient care, saving lives and improving outcomes. Vanderbilt-Ingram physicians and scientists have determined that the most promising research approach emphasizes tailored molecular therapy (personalized cancer treatment) with a focus on inhibiting tumor progression and metastasis. This can best be achieved by defining the molecular changes present in an individual patient’s tumor and monitoring the response of the tumor to treatment, not only based on tumor shrinkage but also treatment effectiveness at the molecular level. The information gained from monitoring will drive subsequent research and help shape the formulation of new treatments for patients. An integral part of this process is the characterization of the features of each patient’s tumor. Vanderbilt-Ingram researchers have found that the greatest impact comes from discoveries made as a result of direct contact with patients and their particular form of the disease. By integrating laboratory studies in the ITR, and monitoring procedures with therapies in the clinic, clinicians are assisted in making the right choices for the most effective drugs to use for each particular patient.
- B.S. Biology (Honors) 1995-99 Lafayette College, Easton, PA
- Ph.D. Cancer Biology 2000-06 Vanderbilt University, Nashville, TN
- Postdoctoral Fellow 2007-10 Memorial Sloan-Kettering Cancer Center
The mission of the Innovative Translational Research Shared Resource (ITR) is to advance the translation of basic and clinical research into improved clinical therapies by facilitating clinical discoveries and managing laboratory and clinical data exchange between researchers. The ITR is part of the Personalized Cancer Medicine Initiative that aims to tailor cancer therapies to each cancer patient by characterizing the molecular changes present in an individual's tumor, building a treatment regimen based on those changes, and monitoring the response to those therapies at the molecular level. The laboratory is collaborating with clinical and laboratory investigators at VICC to guide the initiation and completion of pre-clinical research and Phase I and Phase II correlative studies in melanoma, leukemia, lymphoma, head and neck squamous cell carcinoma, graft versus host disease, and breast, pancreas, and lung cancer. The ITR is preparing and housing DNA and RNA from human tumors and blood cells for genetic analysis utilizing Vanderbilt Shared Resources or outside resources. The laboratory is investigating tumor genome alterations by PCR and sequencing, SNaPShot genotyping, whole genome or transcriptome sequencing, microarray, DNA methylation, and gene copy number analysis. In addition, the laboratory is preparing, collecting, and storing whole blood for serum cytokine assays to measure target inhibition, tumor response, and side effects of clinical compounds.
- Dahlman, KB, Xia, J, Hutchinson, K, Ng, C, Hucks, D, Jia, P, Atefi, M, Su, Z, Branch, S, Lyle, P, Hicks, DJ, Bozon, V, Glaspy, JA, Rosen, N, Solit, DB, Netterville, JL, Vnencak-Jones, CL, Sosman, JA, Ribas, A, Zhao, Z, Pao, W BRAF L597 mutations in melanoma are associated with sensitivity to MEK inhibitors. Cancer Discov, 2012.
- Shi, H, Moriceau, G, Kong, X, Lee, MK, Lee, H, Koya, RC, Ng, C, Chodon, T, Scolyer, RA, Dahlman, KB, Sosman, JA, Kefford, RF, Long, GV, Nelson, SF, Ribas, A, Lo, RS Melanoma whole-exome sequencing identifies (V600E)B-RAF amplification-mediated acquired B-RAF inhibitor resistance. Nat Commun, 3724, 2012.
- Dahlman, KB, Parker, JS, Shamu, T, Hieronymus, H, Chapinski, C, Carver, B, Chang, K, Hannon, GJ, Sawyers, CL Modulators of prostate cancer cell proliferation and viability identified by short-hairpin RNA library screening. PLoS One, 7(4), e34414, 2012.
- Shi, H, Moriceau, G, Kong, X, Koya, RC, Nazarian, R, Pupo, GM, Bacchiocchi, A, Dahlman, KB, Chmielowski, B, Sosman, JA, Halaban, R, Kefford, RF, Long, GV, Ribas, A, Lo, RS Preexisting MEK1 exon 3 mutations in V600E/KBRAF melanomas do not confer resistance to BRAF inhibitors. Cancer Discov, 2(5), 414-24, 2012.
- Su, Y, Vilgelm, AE, Kelley, MC, Hawkins, O, Liu, Y, Boyd, KL, Kantrow, S, Splittgerber, R, Short, SP, Sobolik-Delmaire, T, Zaja-Milatovic, S, Dahlman, KB, Amiri, KI, Jiang, A, Lu, P, Shyr, Y, Stuart, D, Levy, SE, Sosman, JA, Richmond, A RAF265 Inhibits the Growth of Advanced Human Melanoma Tumors. Clin Cancer Res, 2012.
- Lovly, CM, Dahlman, KB, Fohn, LE, 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, AJ, Sosman, J, Pao, W Routine multiplex mutational profiling of melanomas enables enrollment in genotype-driven therapeutic trials. PLoS One, 7(4), e35309, 2012.
- Bivona, TG, Hieronymus, H, Parker, J, Chang, K, Taron, M, Rosell, R, Moonsamy, P, Dahlman, K, Miller, VA, Costa, C, Hannon, G, Sawyers, CL FAS and NF-ÎºB signalling modulate dependence of lung cancers on mutant EGFR. Nature, 471(7339), 523-6, 2011.
- Poulikakos, PI, Persaud, Y, Janakiraman, M, Kong, X, Ng, C, Moriceau, G, Shi, H, Atefi, M, Titz, B, Gabay, MT, Salton, M, Dahlman, KB, Tadi, M, Wargo, JA, Flaherty, KT, Kelley, MC, Misteli, T, Chapman, PB, Sosman, JA, Graeber, TG, Ribas, A, Lo, RS, Rosen, N, Solit, DB RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E). Nature, 480(7377), 387-90, 2011.
- 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, Brown, KD, Laquerre, S, McArthur, GA, Sosman, JA, Nathanson, KL, Herlyn, M 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(6), 683-95, 2010.
- Brown, KA, Ham, AJ, Clark, CN, Meller, N, Law, BK, Chytil, A, Cheng, N, Pietenpol, JA, Moses, HL Identification of novel Smad2 and Smad3 associated proteins in response to TGF-beta1. J Cell Biochem, 105(2), 596-611, 2008.
- Brown, KA, Pietenpol, JA, Moses, HL A tale of two proteins: differential roles and regulation of Smad2 and Smad3 in TGF-beta signaling. J Cell Biochem, 101(1), 9-33, 2007.
- Bonine-Summers, AR, Aakre, ME, Brown, KA, Arteaga, CL, Pietenpol, JA, Moses, HL, Cheng, N Epidermal growth factor receptor plays a significant role in hepatocyte growth factor mediated biological responses in mammary epithelial cells. Cancer Biol Ther, 6(4), 561-70, 2007.
- Barbieri, CE, Tang, LJ, Brown, KA, Pietenpol, JA Loss of p63 leads to increased cell migration and up-regulation of genes involved in invasion and metastasis. Cancer Res, 66(15), 7589-97, 2006.
- Cheng, N, Bhowmick, NA, Chytil, A, Gorksa, AE, Brown, KA, Muraoka, R, Arteaga, CL, Neilson, EG, Hayward, SW, Moses, HL Loss of TGF-beta type II receptor in fibroblasts promotes mammary carcinoma growth and invasion through upregulation of TGF-alpha-, MSP- and HGF-mediated signaling networks. Oncogene, 24(32), 5053-68, 2005.
- Xie, L, Law, BK, Chytil, AM, Brown, KA, Aakre, ME, Moses, HL Activation of the Erk pathway is required for TGF-beta1-induced EMT in vitro. Neoplasia, 6(5), 603-10, 2004.
- Brown, KA, Aakre, ME, Gorska, AE, Price, JO, Eltom, SE, Pietenpol, JA, Moses, HL Induction by transforming growth factor-beta1 of epithelial to mesenchymal transition is a rare event in vitro. Breast Cancer Res, 6(3), R215-31, 2004.
- Brown, K, Bhowmick, NA Linking TGF-beta-mediated Cdc25A inhibition and cytoskeletal regulation through RhoA/p160(ROCK) signaling. Cell Cycle, 3(4), 408-10, 2004.
- Brown, KA, Roberts, RL, Arteaga, CL, Law, BK Transforming growth factor-beta induces Cdk2 relocalization to the cytoplasm coincident with dephosphorylation of retinoblastoma tumor suppressor protein. Breast Cancer Res, 6(2), R130-9, 2004.
- Bhowmick, NA, Ghiassi, M, Aakre, M, Brown, K, Singh, V, Moses, HL TGF-beta-induced RhoA and p160ROCK activation is involved in the inhibition of Cdc25A with resultant cell-cycle arrest. Proc Natl Acad Sci U S A, 100(26), 15548-53, 2003.
- Yen, CJ, Beamer, BA, Negri, C, Silver, K, Brown, KA, Yarnall, DP, Burns, DK, Roth, J, Shuldiner, AR Molecular scanning of the human peroxisome proliferator activated receptor gamma (hPPAR gamma) gene in diabetic Caucasians: identification of a Pro12Ala PPAR gamma 2 missense mutation. Biochem Biophys Res Commun, 241(2), 270-4, 1997.