Kimberly Brown Dahlman, Ph.D.
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 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 PL, 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 [print-electronic]. 2012 Sep; 2(9): 791-7. PMID: 22798288, PMCID: PMC3449158, PII: 2159-8290.CD-12-0097, DOI: 10.1158/2159-8290.CD-12-0097, ISSN: 2159-8290.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/22798288.
- 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 [print-electronic]. 2012 May; 2(5): 414-24. PMID: 22588879, PMCID: PMC3594852, PII: 2159-8290.CD-12-0022, DOI: 10.1158/2159-8290.CD-12-0022, ISSN: 2159-8290.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/22588879.
- Su Y, Vilgelm AE, Kelley MC, Hawkins OE, Liu Y, Boyd KL, Kantrow S, Splittgerber RC, Short SP, Sobolik T, Zaja-Milatovic S, Dahlman KB, Amiri KI, Jiang A, Lu P, Shyr Y, Stuart DD, Levy S, Sosman JA, Richmond A. RAF265 inhibits the growth of advanced human melanoma tumors. Clin. Cancer Res [print-electronic]. 2012 Apr 4/15/2012; 18(8): 2184-98. PMID: 22351689, PMCID: PMC3724517, PII: 1078-0432.CCR-11-1122, DOI: 10.1158/1078-0432.CCR-11-1122, ISSN: 1078-0432.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/22351689.
- 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 [print-electronic]. 2012; 7(4): e34414. PMID: 22509301, PMCID: PMC3324507, PII: PONE-D-11-18538, DOI: 10.1371/journal.pone.0034414, ISSN: 1932-6203.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/22509301.
- 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 [print-electronic]. 2012; 7(4): e35309. PMID: 22536370, PMCID: PMC3335021, PII: PONE-D-12-03589, DOI: 10.1371/journal.pone.0035309, ISSN: 1932-6203.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/22536370.
- 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. 2012; 3: 724. PMID: 22395615, PMCID: PMC3530385, PII: ncomms1727, DOI: 10.1038/ncomms1727, ISSN: 2041-1723.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/22395615.
- 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. 2011 Dec 12/15/2011; 480(7377): 387-90. PMID: 22113612, PMCID: PMC3266695, PII: nature10662, DOI: 10.1038/nature10662, ISSN: 1476-4687.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/22113612.
- 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-¿B signalling modulate dependence of lung cancers on mutant EGFR. Nature. 2011 Mar 3/24/2011; 471(7339): 523-6. PMID: 21430781, PMCID: PMC3541675, PII: nature09870, DOI: 10.1038/nature09870, ISSN: 1476-4687.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/21430781.
- 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. 2010 Dec 12/14/2010; 18(6): 683-95. PMID: 21156289, PMCID: PMC3026446, PII: S1535-6108(10)00484-8, DOI: 10.1016/j.ccr.2010.11.023, ISSN: 1878-3686.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/21156289.
- 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. 2008 Oct 10/1/2008; 105(2): 596-611. PMID: 18729074, PMCID: PMC2700048, DOI: 10.1002/jcb.21860, ISSN: 1097-4644.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/18729074.
- 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. 2007 May 5/1/2007; 101(1): 9-33. PMID: 17340614, DOI: 10.1002/jcb.21255, ISSN: 0730-2312.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/17340614.
- 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. 2007 Apr; 6(4): 561-70. PMID: 17495520, PMCID: PMC3395216, PII: 3851, ISSN: 1538-4047.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/17495520.
- 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. 2006 Aug 8/1/2006; 66(15): 7589-97. PMID: 16885358, PII: 66/15/7589, DOI: 10.1158/0008-5472.CAN-06-2020, ISSN: 0008-5472.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/16885358.
- 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. 2005 Jul 7/28/2005; 24(32): 5053-68. PMID: 15856015, PMCID: PMC3074577, PII: 1208685, DOI: 10.1038/sj.onc.1208685, ISSN: 0950-9232.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/15856015.
- 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. 2004 Sep; 6(5): 603-10. PMID: 15548370, PMCID: PMC1531665, DOI: 10.1593/neo.04241, ISSN: 1522-8002.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/15548370.
- Brown K, Bhowmick NA. Linking TGF-beta-mediated Cdc25A inhibition and cytoskeletal regulation through RhoA/p160(ROCK) signaling. Cell Cycle [print-electronic]. 2004 Apr; 3(4): 408-10. PMID: 14752278, PII: 778, ISSN: 1538-4101.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/14752278.
- 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 [print-electronic]. 2004; 6(3): R215-31. PMID: 15084245, PMCID: PMC400675, PII: bcr778, DOI: 10.1186/bcr778, ISSN: 1465-542X.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/15084245.
- 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 [print-electronic]. 2004; 6(2): R130-9. PMID: 14979923, PMCID: PMC400660, PII: bcr762, DOI: 10.1186/bcr762, ISSN: 1465-542X.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/14979923.
- 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 [print-electronic]. 2003 Dec 12/23/2003; 100(26): 15548-53. PMID: 14657354, PMCID: PMC307605, PII: 2536483100, DOI: 10.1073/pnas.2536483100, ISSN: 0027-8424.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/14657354.
- 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. 1997 Dec 12/18/1997; 241(2): 270-4. PMID: 9425261, PII: S0006-291X(97)97798-6, DOI: 10.1006/bbrc.1997.7798, ISSN: 0006-291X.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/9425261.