- ADJUNCT PROFESSOR Medicine, Hematology and Medical Oncology
- ADJUNCT PROFESSOR Developmental and Regenerative Biology
- ADJUNCT PROFESSOR Oncological Sciences
Transcription Factors Disrupted In Human Cancer-Their Mechanism Of Action And TargetsThe broad goal of my research program is to understand how mutations of transcriptional regulators may set up patterns of aberrant gene expression that yield cancer. This requires a detailed understanding of the normal function of these transcription factors. Such information includes an understanding of the role of these factors in cell growth, differentiation and developmental, the normal DNA binding and transcriptional activity of these proteins, identification of the critical protein partners of the factors and elucidation of the downstream targets of these genes. The mutations that occur in cancer are tragic experiments of nature that may alter critical amino acid residues for the function of the proteins. By modeling the function of both the normal and mutated forms of these factors we hope to better understand the molecular basis of cancer and potentially identify new therapeutic targets and pathways in this disease.
Reciprocal signaling between the ureteric bud (UB -Green) and metanephric mesenchyme (Red) guides kidney development. Factors from the UB, including LIF and FGFs induce condensation of the mesenchyme and may induce the expression of factors like WT1 and Pax2 critical for epithelial differentiation. WT1 may induce the expression of growth factors like amphiregulin, Wnt4 and GDNF which stimulate the UB and mesenchyme. At the same time WT may induce the expression of sprouty a counter-regulatory factor THAT limits the effects of growth factor signaling on the condensing mesenchme.
Benezra M, Chevallier N, Morrison DJ, MacLachlan TK, El-Deiry WS, Licht JD. BRCA1 augments transcription by the NF-kappaB transcription factor by binding to the Rel domain of the p65/RelA subunit. J Biol Chem 2003 Jul 18; 278(29): 26333-26341.
Sirulnik A, Melnick A, Zelent A, Licht JD. Molecular pathogenesis of acute promyelocytic leukaemia and APL variants. Best Pract Res Clin Haematol 2003 Sep; 16(3): 387-408.
McConnell MJ, Chevallier N, Berkofsky-Fessler W, Giltnane JM, Malani RB, Staudt LM, Licht JD. Growth suppression by acute promyelocytic leukemia-associated protein PLZF is mediated by repression of c-myc expression. Mol Cell Biol 2003 Dec; 23(24): 9375-9388.
Gross I, Morrison DJ, Hyink DP, Georgas K, English MA, Mericskay M, Hosono S, Sassoon D, Wilson PD, Little M, Licht JD. The receptor tyrosine kinase regulator Sprouty1 is a target of the tumor suppressor WT1 and important for kidney development. J Biol Chem 2003 Oct 17; 278(42): 41420-41430.
Ahmad KF, Melnick A, Lax S, Bouchard D, Liu J, Kiang CL, Mayer S, Takahashi S, Licht JD, Prive GG. Mechanism of SMRT corepressor recruitment by the BCL6 BTB domain. Mol Cell 2003 Dec; 12(6): 1551-1564.
Johnstone RW, Licht JD. Histone deacetylase inhibitors in cancer therapy: is transcription the primary target?. Cancer Cell 2003 Jul; 4(1): 13-18.
Takahashi S, McConnell MJ, Harigae H, Kaku M, Sasaki T, Melnick AM, Licht JD. The Flt3 Internal Tandem Duplication Mutant Inhibits the Function of Transcriptional Repressors by Blocking Interactions with SMRT. Blood 2004 Feb 24 [Epub ahead of print];.
Chevallier N, Corcoran CM, Lennon C, Hyjek E, Chadburn A, Bardwell VJ, Licht JD, Melnick A. ETO protein of t(8;21) AML is a corepressor for Bcl-6 B-cell lymphoma oncoprotein. Blood 2004 Feb 15 ; 103(4): 1454-1463.
Mason JM, Morrison DJ, Bassit B, Dimri M, Band H, Licht JD, Gross I. Tyrosine Phosphorylation Of Sprouty Proteins Regulates Their Ability to Inhibit Growth Factor Signaling-A Dual Feedback Loop. Mol Biol Cell 2004 May; 15(5): 2176-2188.
Takahashi S, Harigae H, Kaku M, Sasaki T, Licht JD. Flt3 mutation activates p21WAF1/CIP1 gene expression through the action of STAT5. Biochem Biophys Res Commun 2004 Mar 26; 316(1): 85-92.
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.
Dr.Licht is not currently required to report Industry relationships.
Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website. Patients may wish to ask their physician about the activities they perform for companies.
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