Joshua Mendell, MD, PhD

Associate Professor Pediatrics and Molecular Biology and Genetics

Education:

• 1996, B.A., Cornell University
• 2001, Ph.D., Johns Hopkins University
• 2003, M.D., Johns Hopkins University

Main interests:

Our research focuses on a recently described class of small regulatory RNAs known as microRNAs (miRNAs).  These ~18-25 nucleotide long RNA molecules regulate the stability or translational efficiency of target mRNAs.  Mammalian genomes encode at least 500 distinct miRNAs and despite their strong evolutionary conservation, only the functions of a small minority have been characterized in detail.  Accumulating evidence demonstrates that these molecules play essential roles in normal physiology and are commonly dysregulated in human diseases.  My laboratory is using novel in vitro and in vivo models to elucidate fundamental mechanisms of miRNA regulation and function.  We are also applying these tools to understand how aberrant miRNA activity contributes to disease states such as cancer.

Research Interests:

• Post-transcriptional regulation of gene expression
• Regulation of microRNA biogenesis and function
• Physiologic and pathophysiologic functions of microRNAs

Educational Activities:

• Preceptor, Human Genetics and Molecular Biology Graduate Program
• Preceptor, Pathobiology Graduate Program
• Co-director, Molecular Mechanisms of Disease course
• Lecturer, Molecular Biology and Genomics Graduate Course
• Lecturer, Advanced Topics in Human Genetics Graduate Course

Recognition:

• Michael A. Shanoff Research Award, Johns Hopkins University School of Medicine, 2003
• Postdoctoral Basic Science Award, 53^rd American Society of Human Genetics Meeting, 2003
• March of Dimes Basil O’Connor Scholar, 2004
• Rita Allen Foundation Scholar, 2006
• Named the Outstanding Young Scientist in the State of Maryland (Allan C. Davis Medal), 2007
• Named a “Top Young Investigator of 2007” by Genome Technology Magazine, 2007
• Leukemia and Lymphoma Society Scholar, 2008
• Howard Hughes Medical Institute Early Career Scientist Award, 2009
  

Selected Publications:

Kota J, Chivukula RR, O’Donnell KA, Wentzel EA, Montgomery CL, Hwang HW, Chang TC, Clark KR, Mendell JR, Mendell JT. (2009). Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell 137(6):1005-1017.

Hwang HW, Wentzel EA, Mendell JT. (2009). Cell-cell contact globally activates microRNA biogenesis.  Proc. Natl. Acad. Sci.106(17):7016-7021.

Gao P, Tchernyshyov I, Chang TC, Lee YS, Kita K, Ochi T, Zeller KI, De Marzo AM, Van Eyk JE, Mendell JT, Dang CV. (2009).  c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine expression and glutamine metabolism.  Nature 458(7239):762-5.

Chang TC, Zeitels LR, Hwang HW, Chivukula RR, Wentzel EA, Dews M, Jung J, Gao P, Dang CV, Beer MA, Thomas-Tikhonenko A, Mendell JT. (2009). Lin-28B transactivation is necessary for Myc-mediated let-7 repression and proliferation.  Proc. Natl. Acad. Sci. 106(9):3384-9.

Chang TC, Yu D, Lee YS, Wentzel EA, Arking DE, West KM, Dang CV, Thomas-Tikhonenko A, Mendell JT.  (2008). Widespread microRNA repression by Myc contributes to tumorigenesis. Nature Genetics 40:43-50.

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, Mendell JT. (2007).  Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis.  Molecular Cell 26: 745-752.

Hwang HW, Wentzel EA, Mendell JT. (2007). A Hexanucleotide element directs microRNA nuclear import.  Science 315:97-100.

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.

O’Donnell KA, Wentzel EA, Zeller KI, Dang CV, and Mendell JT. (2005). c-Myc-regulated microRNAs modulate E2F1 expression.  Nature 435(7043):839-843.

Invited Reviews

Mendell JT. (2009) Tumors line up for a letdown.  Nature Genetics 41(7):768-9.

Chivukula RR and Mendell JT. (2009). Abate and switch: miR-145 in stem cell differentiation. Cell 137:9-11.

Chivukula RR and Mendell JT. (2008).  Circular reasoning: microRNAs and the cell cycle.  Trends in Biochemical Sciences 33(10):474-481.

Lotterman CD, Kent OA, Mendell JT. (2008). Functional integration of microRNAs into oncogenic and tumor suppressor pathways.  Cell Cycle, 7(16):2493-2499.

Mendell JT. (2008).  miRiad roles for the miR-17-92 cluster in development and disease.  Cell 133(2):217-222.

Chang TC, Mendell JT. (2007). The roles of microRNAs in vertebrate physiology and human disease.  Annual Reviews of Genomics and Human Genetics 8:215-239.

Kent OA, Mendell JT. (2006).  A small piece of the cancer puzzle:  microRNAs as oncogenes and tumor suppressors.  Oncogene 25(46):6188-96.

All Publications

Contact Information:

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: 410-502-0428
Fax: 410-502-1853
E-Mail: jmendell@jhmi.edu