Joshua Mendell, M.D., PH.D. |  |
Contact | Education | Interests | Research | Activities | Publications |
- 1996, B.A., Cornell University
- 2001, Ph.D., Johns Hopkins University
- 2003, M.D., Johns Hopkins University
Our research focuses on a recently described class of small regulatory RNAs known as microRNAs. These ~18-25 nucleotide long RNA molecules regulate the stability or translational efficiency of target mRNAs. It is estimated that at least 30% of human transcripts are regulated by microRNAs. Accumulating evidence demonstrates that these molecules play essential roles in normal physiology and are commonly dysregulated in human disease states such as cancer. We have developed tools that allow the analysis of expression of all known microRNAs simultaneously and we are applying these methodologies to study microRNA expression and function in physiologic and pathophysiologic states.
Recently, we identified a group of microRNAs that are directly regulated by the oncogenic transcription factor c-Myc. This was the first mammalian transcription factor shown to control microRNA expression. Furthermore, our studies suggested that these microRNAs play an important role in tumorigenesis. We also recently discovered a microRNA that exhibits regulated expression during the cell-cycle. Ongoing studies in my laboratory aim to further elucidate how these microRNAs are regulated, functionally dissect the specific pathways regulated by these microRNAs, and characterize additional microRNAs that act as oncogenes and tumor suppressors.
- Post-transcriptional regulation of gene expression
- microRNA biogenesis and function
- Characterization of microRNA dysfunction in pathologic states
- Preceptor, Human Genetics and Molecular Biology Graduate Program
- Co-organizer, Molecular Mechanisims of Disease course
- Lecturer, Molecular Biology and Genomics Course
Chang TC, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH, Feldmann G, Yamakuchi M, Ferlito M, Lowenstein CJ, Arking DE, Beer MA, Maitra A, and Mendell JT. (2007). Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell, 26: 745-752.
Hwang HW, Wentzel EA, Mendell JT. (2007) A Hexanucleotide element directs microRNA nuclear import. Science, 315:97-100.
Kent OA, Mendell JT. (2006). A small piece of the cancer puzzle: microRNAs as oncogenes and tumor suppressors. Oncogene, 25(46):6188-96.
Dews M, Homayouni A, Yu D, Murphy D, Sevignani C, Wentzel E, Furth EE, Lee WM, Enders GH, Mendell JT, Thomas-Tikhonenko A. (2006). Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nature Genetics, 38(9):1060-5.
Hwang, HW and Mendell JT. (2006). MicroRNAs in cell proliferation, cell death, and tumorigenesis. British Journal of Cancer, 94(6):776-80.
O’Donnell KA, Wentzel EA, Zeller KI, Dang CV, and Mendell JT. (2005). c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435: 839-843 [Featured in a News and Views by Meltzer, PS (2005) Nature 435:745-746]
Mendell JT, Sharifi NA, Meyers JL, Martinez-Murrillo F, Dietz HC. (2004). Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise. Nature Genetics 36(10):1073-1078. [Featured in Research Highlights, Nature Reviews Genetics, November 2004]
Mendell JT, ap Rhys CMJ, Dietz HC. (2002). Separable Roles for rent1/hUpf1 in Altered Splicing and Decay of Nonsense Transcripts. Science 298: 419-422. [Featured in a Perspective piece by Moore, MJ (2002) Science 298:370-371]
Mendell JT, Dietz HC. (2001). When the Message Goes Awry: Disease-Producing Mutations that Influence mRNA Content and Performance. Cell 107: 411-414.
Mendell JT, Medghalchi SM, Lake RG, Noensie EN, Dietz HC. (2000). Novel Upf2p Orthologues Suggest a Functional Link Between the Translation Initiation and Nonsense Surveillance Complexes. Molecular and Cellular Biology 20(23):8944-8957.
Mendell JT, Paniker SG, Tsao CY, Feng B, Sahenk Z, Marzluf GA, Mendell JR. (1998). Novel compound heterozygous laminin ?2-chain gene (LAMA2) mutations in congenital muscular dystrophy. Human Mutation 12(2):135.
Joshua Mendell, M.D., PH.D.
Johns Hopkins University
Institute of Genetic Medicine
Broadway Research Building
733 N. Broadway, Room #471
Baltimore, MD 21205
Phone: 410-502-0430
Fax: 410-502-1853
E-Mail: jmendell@jhmi.edu
