Joshua T. Mendell

Joshua T. Mendell, M.D., Ph.D., 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. 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
  • 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)

References
  1. HHMI biography
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. Replacing microRNA for cancer treatment. Jenny Lauren Lee, Science News, July 4, 2009
  16. MicroRNA Replacement Therapy May Stop Cancer In Its Tracks Science Daily, June 12, 2009
  17. Cancer May Be Stopped In Its Tracks By MicroRNA Replacement Therapy Medical News Today, June 13, 2009
  18. Dorian Gray: Is there a secret to eternal youth? Anjana Ahuja, The Times, September 8, 2009
  19. 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.
  20. 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.
  21. 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.
  22. 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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