Laboratory of Dr. Rhoda Alani & Dr. Marianne Collard
The Alani Laboratory is focused on understanding the molecular basis of melanoma development and progression. The aim of our lab is to translate basic research findings to better prevention, detection and treatment of melanoma and to directly enhance the lives of patients currently diagnosed with melanoma. For further information, please visit the Alani Collard lab website.
1. Melanoma Biomarkers: Previous studies from our laboratory have allowed us to identify critical molecular pathways associated with melanoma development and progression. Those molecular pathways have also been demonstrated to be specifically altered in primary tissue specimens and serum of patients with melanoma. Current studies is our laboratory seek to evaluate the significance of these molecular markers to develop quantitative tools to improve the diagnostic and prognostic information available for patients diagnosed with melanoma. In addition, new studies are seeking to identify specific predictive biomarkers for patient responses to targeted therapies which would allow for personalized treatments for patients with advanced disease and those with high-risk disease.
Neuropilin-2 Gene Expression Correlates with Malignant Progression in Cutaneous Melanoma. Rossi M, Tuck J, Kim OJ, Panova I, Symanowski JT, Mahalingam M, Riker AI, Alani RM, Ryu B. Br J Dermatol. 2013 Dec 20.
Notch signaling mediates melanoma-endothelial cell communication and melanoma cell migration.Howard JD, Moriarty WF, Park J, Riedy K, Panova IP, Chung CH, Suh KY, Levchenko A, Alani RM. Pigment Cell Melanoma Res. 2013 Sep;26(5):697-707.
MicroRNAs as an emerging target for melanoma therapy.Ryu B, Hwang S, Alani RM. J Invest Dermatol. 2013 May;133(5):1137-9.
Neuropilin-2: a novel biomarker for malignant melanoma? Rushing EC, Stine MJ, Hahn SJ, Shea S, Eller MS, Naif A, Khanna S, Westra WH, Jungbluth AA, Busam KJ, Mahalingam M, Alani RM. Hum Pathol. 2012 Mar;43(3):381-9.
Melanoma biomarkers: current status and vision for the future. Larson AR, Konat E, Alani RM. Nat Clin Pract Oncol. 2009 Feb;6(2):105-17.
2. Epigenetic alterations in melanoma and other malignancies: Our laboratory has had a long-standing interest in defining critical epigenetic alterations in melanoma associated with disease progression and response to therapies. Current research has used novel small molecule inhibitors of the p300 histone acetyltransferase to further define transcriptional mediators of melanoma progression and identify targeted therapies specific to these epigenetic alterations. Therapies are currently being evaluated using in vivo and in vitro model systems in order to optimize therapeutic responses in anticipation of studies in patients.
Selective inhibition of p300 HAT blocks cell cycle progression, induces cellular senescence, and inhibits the DNA damage response in melanoma cells. Yan G, Eller MS, Elm C, Larocca CA, Ryu B, Panova IP, Dancy BM, Bowers EM, Meyers D, Lareau L, Cole PA, Taverna SD, Alani RM. J Invest Dermatol. 2013 Oct;133(10):2444-52.
Dynamic acetylation of all lysine-4 trimethylated histone H3 is evolutionarily conserved and mediated by p300/CBP. Crump NT, Hazzalin CA, Bowers EM, Alani RM, Cole PA, Mahadevan LC. Proc Natl Acad Sci U S A. 2011 May 10;108(19):7814-9.
Virtual ligand screening of the p300/CBP histone acetyltransferase: identification of a selective small molecule inhibitor. Bowers EM, Yan G, Mukherjee C, Orry A, Wang L, Holbert MA, Crump NT, Hazzalin CA, Liszczak G, Yuan H, Larocca C, Saldanha SA, Abagyan R, Sun Y, Meyers DJ, Marmorstein R, Mahadevan LC, Alani RM, Cole PA. Chem Biol. 2010 May 28;17(5):471-82.
Histone acetyltransferase activity of p300 is required for transcriptional repression by the promyelocytic leukemia zinc finger protein. Guidez F, Howell L, Isalan M, Cebrat M, Alani RM, Ivins S, Hormaeche I, McConnell MJ, Pierce S, Cole PA, Licht J, Zelent A. Mol Cell Biol. 2005 Jul;25(13):5552-66.
3. Development of Engineered Model Systems for Cancer Development and Progression: We have had a strong interest in partnering with physical scientists to explore complex cancer networks in more defined and structured ways. In particular, partnerships with colleagues in biomedical engineering have allowed us to develop novel tools to evaluate fundamental mediators of tumor development and progression in a controlled setting. Such systems, while complex in their design, provide specific and quantifiable frameworks for defining cellular and molecular interactions that take place during tumor development, progression, and metastasis. It is expected that these novel tools will allow us to more completely define critical components of the tumor-host microenvironment and mediators of these complex communication networks. Ultimately, this information will be used to develop targeted therapies for specific cancers using a personalized, patient-specific approach.