Joshua T. Mendell Explained

Joshua T. Mendell is an American molecular biologist who is a professor of molecular biology at the University of Texas Southwestern Medical Center, where he is a Howard Hughes Medical Institute Investigator. Before moving to UT Southwestern, Mendell was a Howard Hughes Medical Institute early career scientist[1] at Johns Hopkins School of Medicine. His molecular biology research examines microRNA (miRNA) regulation and function, with particular emphasis on miRNAs and cancer.

Training and career

Mendell began working in a molecular biology laboratory when he was a teenager and continued to perform laboratory research as an undergraduate at Cornell University.[1] He graduated with a BA in 1996 and was a member of the Delta Phi fraternity. Mendell pursued a Ph.D. and M.D. at Johns Hopkins University, receiving the degrees in 2001 and 2003 respectively. He remained at Johns Hopkins as a faculty member before moving to University of Texas Southwestern Medical Center in 2011.

Research

Mendell and members of his research group investigate post-transcriptional gene regulation. As a graduate student with Harry (Hal) Dietz at Johns Hopkins, Mendell researched how cells recognize and degrade messenger RNA molecules with early stop codons, a process known as nonsense mediated decay.[2] [3] [4] [5] [6] Mendell's interest in RNA led him into the field of microRNA.[1]

In 2005, Mendell reported in the journal Nature that a gene often mutated in cancer cells, c-Myc, influences the expression of several miRNAs encoded in a cluster on human chromosome 13. These miRNAs in turn affect the expression of a c-Myc-induced transcription factor, E2F1. This research demonstrated a potentially important role for miRNAs in the development of cancer. Mendell has followed up on this work with publications in high-impact journals including Nature Genetics,[7] [8] PNAS,[9] Molecular Cell,[10] Nature,[11] [12] and Cell,[13] among others.

In 2009, Mendell reported in the journal Cell that treating mice with therapeutic levels of specific miRNAs could suppress development of liver cancer.[14] The publication generated media interest,[15] [16] [17] including an article in The Times asking, "Is there a secret to eternal youth?"[18]

Mendell has also published numerous review articles on miRNA regulation and function.[19] [20] [21]

Family

Mendell credits his father, Ohio State University neurologist Jerry Mendell, with influencing his early interest and involvement in molecular biology research,[1] and Mendell's first scientific publication was co-written with his father and other researchers.[22]

Mendell generated data on c-Myc and miRNAs in collaboration with Kathryn O'Donnell. Mendell and O'Donnell are now married and continue to work together on miRNA-related projects.[1]

Awards and honors

Notes and References

  1. http://www.hhmi.biz/research/ecs/mendell_bio.html HHMI biography
  2. 11073994. 2000. Mendell . J. T.. Medghalchi . S. M.. Lake . R. G.. Noensie . E. N.. Dietz . H. C.. Novel Upf2p Orthologues Suggest a Functional Link between Translation Initiation and Nonsense Surveillance Complexes. 20. 23. 8944–8957. 86549. Molecular and Cellular Biology. 10.1128/MCB.20.23.8944-8957.2000.
  3. 11152657. 2001. Medghalchi . S. M.. Frischmeyer . P. A.. Mendell . J. T.. Kelly . A. G.. Lawler . A. M.. Dietz . H. C.. Rent1, a trans-effector of nonsense-mediated mRNA decay, is essential for mammalian embryonic viability. 10. 2. 99–105. Human Molecular Genetics. 10.1093/hmg/10.2.99. free.
  4. 11719181. 2001. Mendell . J. T.. Dietz . H. C.. When the message goes awry: disease-producing mutations that influence mRNA content and performance. 107. 4. 411–414. Cell. 10.1016/S0092-8674(01)00583-9. free.
  5. 10.1126/science.1074428. 12228722. 2002. Mendell . J.. Ap Rhys . C.. Dietz . H.. Separable roles for rent1/hUpf1 in altered splicing and decay of nonsense transcripts. 298. 5592. 419–422. Science . 46447414. free.
  6. 10.1038/ng1429. 15448691. 2004. Mendell . J.. Sharifi . N.. Meyers . J.. Martinez-Murillo . F.. Dietz . H.. Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise. 36. 10. 1073–1078. Nature Genetics . free.
  7. 10.1038/ng1855. 16878133. 2006. Dews . M.. Homayouni . A.. Yu . D.. Murphy . D.. Sevignani . C.. Wentzel . E.. Furth . E.. Lee . W.. Enders . G.. Mendell . J. T.. Thomas-Tikhonenko . A.. Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. 38. 9. 1060–1065. 2669546. Nature Genetics .
  8. 10.1038/ng.2007.30. 18066065. 2008. Chang . T.. Yu . D.. Lee . Y.. Wentzel . E.. Arking . D.. West . K.. Dang . C.. Thomas-Tikhonenko . A.. Mendell . J.. Widespread microRNA repression by Myc contributes to tumorigenesis. 40. 1. 43–50. 2628762. Nature Genetics .
  9. 10.1073/pnas.0808300106. 19211792. 2009. Chang . T.. Zeitels . L.. Hwang . H.. Chivukula . R.. Wentzel . E.. Dews . M.. Jung . J.. Gao . P.. Dang . C.. Beer . M. A.. Thomas-Tikhonenko . A.. Mendell . J. T.. Lin-28B transactivation is necessary for Myc-mediated let-7 repression and proliferation. 106. 9. 3384–3389. 2651245. Proceedings of the National Academy of Sciences of the United States of America. 2009PNAS..106.3384C . free.
  10. 10.1016/j.molcel.2007.05.010. 17540599. 2007. Chang . T.. Wentzel . E.. Kent . O.. Ramachandran . K.. Mullendore . M.. Lee . K.. Feldmann . G.. Yamakuchi . M.. Ferlito . M.. Lowenstein . C. J.. Arking . D. E.. Beer . M. A.. Maitra . A.. Mendell . J. T.. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. 26. 5. 745–752. 1939978. Molecular Cell .
  11. 10.1038/nature07823. 19219026. 2009. Gao . P.. Tchernyshyov . I.. Chang . T.. Lee . Y.. Kita . K.. Ochi . T.. Zeller . K.. De Marzo . A.. Van Eyk . J.. Mendell . J. T.. Dang . C. V.. c-Myc suppression of miR-23 enhances mitochondrial glutaminase and glutamine metabolism. 458. 7239. 762–765. 2729443. Nature. 2009Natur.458..762G .
  12. 10.1073/pnas.0811523106. 19359480. 2009. Hwang . H.. Wentzel . E.. Mendell . J.. Cell–cell contact globally activates microRNA biogenesis. 106. 17. 7016–7021. 2678439. Proceedings of the National Academy of Sciences of the United States of America . 2009PNAS..106.7016H . free.
  13. 10.1016/j.cell.2009.04.059. 19450510. 2009. Chivukula . R.. Mendell . J.. Abate and switch: miR-145 in stem cell differentiation. 137. 4. 606–608. Cell . free.
  14. 10.1016/j.cell.2009.04.021. 19524505. 2009. Kota . J.. Chivukula . R.. O'Donnell . K.. Wentzel . E.. Montgomery . C.. Hwang . H.. Chang . T.. Vivekanandan . P.. Torbenson . M.. Clark . K. R.. Mendell . J. R.. Mendell . J. T.. Therapeutic delivery of miR-26a inhibits cancer cell proliferation and induces tumor-specific apoptosis. 137. 6. 1005–1017. 2722880. Cell .
  15. http://www.sciencenews.org/view/generic/id/44613/title/Replacing_microRNA_fo Replacing microRNA for cancer treatment.
  16. https://www.sciencedaily.com/releases/2009/06/090611120732.htm MicroRNA Replacement Therapy May Stop Cancer In Its Tracks
  17. http://www.medicalnewstoday.com/articles/153651.php Cancer May Be Stopped In Its Tracks By MicroRNA Replacement Therapy
  18. http://www.timesonline.co.uk/tol/life_and_style/health/article6825180.ece?print=yes&randnum=1151003209000 Dorian Gray: Is there a secret to eternal youth?
  19. 10.1038/sj.bjc.6603023. 16495913. 2006. Hwang . H.. Mendell . J.. MicroRNAs in cell proliferation, cell death, and tumorigenesis. 94. 6. 776–780. 2361377. British Journal of Cancer .
  20. 10.1038/sj.onc.1209913. 17028598. 2006. Kent . O.. Mendell . J.. A small piece in the cancer puzzle: microRNAs as tumor suppressors and oncogenes. 25. 46. 6188–6196. Oncogene . 36269207.
  21. 10.1016/j.cell.2008.04.001. 18423194. 2008. Mendell . J.. MiRiad roles for the miR-17-92 cluster in development and disease. 133. 2. 217–222. 2732113. Cell .
  22. 10.1002/(SICI)1098-1004(1998)12:2<135::AID-HUMU10>3.0.CO;2-6. Novel compound heterozygous laminina2-chain gene (LAMA2) mutations in congenital muscular dystrophy. 1998. Mendell . J. T.. Panicker . S. G.. Tsao . C. Y.. Feng . B.. Sahenk . Z.. Marzluf . G. A.. Mendell . J. R.. Human Mutation. 12. 2. 135 . 10694916.

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