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Joshua T. Mendell

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Joshua T. Mendell, M.D., Ph.D., is an associate professor of pediatrics and molecular biology and genetics at the Johns Hopkins School of Medicine, where he is a faculty member of the McKusick-Nathans Institute of Genetic Medicine.[1] Mendell is a Howard Hughes Medical Institute early career scientist[2] and a preceptor for two Johns Hopkins graduate programs. His molecular biology research examines microRNA (miRNA) regulation and function, with particular emphasis on miRNAs and cancer.[1]

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.[2] He graduated with a BA in 1996. 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.[1]

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.[3][4][5][6][7] Mendell's interest in RNA led him into the field of microRNA.[2]

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,[8][9] PNAS,[10] Molecular Cell,[11] Nature,[12][13] and Cell,[14] 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.[15] The publication generated media interest,[16][17][18] including an article in The Times asking, "Is there a secret to eternal youth?"[19]

Mendell has also published numerous review articles on miRNA regulation and function.[20][21][22]

Family

Mendell credits his father, Ohio State University neurologist Jerry Mendell, with influencing his early interest and involvement in molecular biology research,[2] and Mendell's first scientific publication was co-written with his father and other researchers.[23]

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.[2]

Awards and honors

  • Howard Hughes Medical Institute Early Career Scientist Award (2009)
  • Leukemia and Lymphoma Society Scholar (2008)
  • Top Young Investigator of 2007 (Genome Technology Magazine, 2007)
  • Outstanding Young Scientist in the State of Maryland (Allan C. Davis Medal, 2007)
  • Rita Allen Foundation Scholar (2006)
  • March of Dimes Basil O'Connor Scholar (2004)[1]

References

  1. ^ a b c d Johns Hopkins School of Medicine faculty webpage Archived 2009-07-01 at the Wayback Machine
  2. ^ a b c d e HHMI biography
  3. ^ Mendell, J. T.; Medghalchi, S. M.; Lake, R. G.; Noensie, E. N.; Dietz, H. C. (2000). "Novel Upf2p Orthologues Suggest a Functional Link between Translation Initiation and Nonsense Surveillance Complexes". Molecular and Cellular Biology. 20 (23): 8944–8957. doi:10.1128/MCB.20.23.8944-8957.2000. PMC 86549. PMID 11073994.
  4. ^ Medghalchi, S. M.; Frischmeyer, P. A.; Mendell, J. T.; Kelly, A. G.; Lawler, A. M.; Dietz, H. C. (2001). "Rent1, a trans-effector of nonsense-mediated mRNA decay, is essential for mammalian embryonic viability". Human Molecular Genetics. 10 (2): 99–105. doi:10.1093/hmg/10.2.99. PMID 11152657.
  5. ^ Mendell, J. T.; Dietz, H. C. (2001). "When the message goes awry: disease-producing mutations that influence mRNA content and performance". Cell. 107 (4): 411–414. doi:10.1016/S0092-8674(01)00583-9. PMID 11719181.
  6. ^ Mendell, J.; Ap Rhys, C.; Dietz, H. (2002). "Separable roles for rent1/hUpf1 in altered splicing and decay of nonsense transcripts". Science. 298 (5592): 419–422. doi:10.1126/science.1074428. PMID 12228722.
  7. ^ Mendell, J.; Sharifi, N.; Meyers, J.; Martinez-Murillo, F.; Dietz, H. (2004). "Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise". Nature Genetics. 36 (10): 1073–1078. doi:10.1038/ng1429. PMID 15448691.
  8. ^ Dews, M.; Homayouni, A.; Yu, D.; Murphy, D.; Sevignani, C.; Wentzel, E.; Furth, E.; Lee, W.; Enders, G.; Mendell, J. T.; Thomas-Tikhonenko, A. (2006). "Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster". Nature Genetics. 38 (9): 1060–1065. doi:10.1038/ng1855. PMC 2669546. PMID 16878133.
  9. ^ Chang, T.; Yu, D.; Lee, Y.; Wentzel, E.; Arking, D.; West, K.; Dang, C.; Thomas-Tikhonenko, A.; Mendell, J. (2008). "Widespread microRNA repression by Myc contributes to tumorigenesis". Nature Genetics. 40 (1): 43–50. doi:10.1038/ng.2007.30. PMC 2628762. PMID 18066065.
  10. ^ 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. (2009). "Lin-28B transactivation is necessary for Myc-mediated let-7 repression and proliferation". Proceedings of the National Academy of Sciences of the United States of America. 106 (9): 3384–3389. Bibcode:2009PNAS..106.3384C. doi:10.1073/pnas.0808300106. PMC 2651245. PMID 19211792.
  11. ^ 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. (2007). "Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis". Molecular Cell. 26 (5): 745–752. doi:10.1016/j.molcel.2007.05.010. PMC 1939978. PMID 17540599.
  12. ^ 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. (2009). "c-Myc suppression of miR-23 enhances mitochondrial glutaminase and glutamine metabolism". Nature. 458 (7239): 762–765. Bibcode:2009Natur.458..762G. doi:10.1038/nature07823. PMC 2729443. PMID 19219026.
  13. ^ Hwang, H.; Wentzel, E.; Mendell, J. (2009). "Cell–cell contact globally activates microRNA biogenesis". Proceedings of the National Academy of Sciences of the United States of America. 106 (17): 7016–7021. Bibcode:2009PNAS..106.7016H. doi:10.1073/pnas.0811523106. PMC 2678439. PMID 19359480.
  14. ^ Chivukula, R.; Mendell, J. (2009). "Abate and switch: miR-145 in stem cell differentiation". Cell. 137 (4): 606–608. doi:10.1016/j.cell.2009.04.059. PMID 19450510.
  15. ^ 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. (2009). "Therapeutic delivery of miR-26a inhibits cancer cell proliferation and induces tumor-specific apoptosis". Cell. 137 (6): 1005–1017. doi:10.1016/j.cell.2009.04.021. PMC 2722880. PMID 19524505.
  16. ^ Replacing microRNA for cancer treatment. Jenny Lauren Lee, Science News, July 4, 2009
  17. ^ MicroRNA Replacement Therapy May Stop Cancer In Its Tracks Science Daily, June 12, 2009
  18. ^ Cancer May Be Stopped In Its Tracks By MicroRNA Replacement Therapy Medical News Today, June 13, 2009
  19. ^ Dorian Gray: Is there a secret to eternal youth? Anjana Ahuja, The Times, September 8, 2009
  20. ^ Hwang, H.; Mendell, J. (2006). "MicroRNAs in cell proliferation, cell death, and tumorigenesis". British Journal of Cancer. 94 (6): 776–780. doi:10.1038/sj.bjc.6603023. PMC 2361377. PMID 16495913.
  21. ^ Kent, O.; Mendell, J. (2006). "A small piece in the cancer puzzle: microRNAs as tumor suppressors and oncogenes". Oncogene. 25 (46): 6188–6196. doi:10.1038/sj.onc.1209913. PMID 17028598.
  22. ^ Mendell, J. (2008). "MiRiad roles for the miR-17-92 cluster in development and disease". Cell. 133 (2): 217–222. doi:10.1016/j.cell.2008.04.001. PMC 2732113. PMID 18423194.
  23. ^ Mendell, J. T.; Panicker, S. G.; Tsao, C. Y.; Feng, B.; Sahenk, Z.; Marzluf, G. A.; Mendell, J. R. (1998). "Novel compound heterozygous laminina2-chain gene (LAMA2) mutations in congenital muscular dystrophy". Human Mutation. 12 (2): 135. doi:10.1002/(SICI)1098-1004(1998)12:2<135::AID-HUMU10>3.0.CO;2-6. PMID 10694916.
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