E. Premkumar Reddy

E. Premkumar Reddy is a biologist.

Studies

He obtained his Ph. D. in molecular biology in 1971 from the Regional Research Laboratory and Osmania University, Hyderabad, India.

After post-doctoral training in the United States of America at the UCLA School of Medicine and the National Cancer Institute (NCI).

Professional career

He joined the National Cancer Institute after his post-graduation, with which he was associated till 1984 as the chief of the molecular genetics section.

In 1984, he moved to Hoffman LaRoche Roche Institute of Molecular Biology as a full member and in 1986, he joined the Wistar Institute as their deputy director. In 1992, he was appointed as the Director of the Fels Institute for Cancer Research and Molecular Biology, which is affiliated with Temple University.

He moved to the Mount Sinai School of Medicine in 2010 where he is the Director of Experimental Cancer Therapeutics program and Professor in the Departments of Oncological Sciences and Structural and Chemical Biology. Dr. Reddy served as a member of the board of directors of NIEHS from 1990-1995. In 1993, he was awarded the Scientific Achievement award by the American Cancer Society.

Findings

He made a number of seminal discoveries that provided a clear understanding of the molecular basis of cancer. He cloned and sequenced a number of viral oncogenes which included mos,[1] abl,[2][3] ras,[2][4] fgr,[5] myb,[6][7] myc[8][9] and sis[10][11] oncogenes and their cellular homologues which pinpointed the precise changes that cellular proto-oncogenes undergo to produce cancer-causing viral oncogenes. He extended this work to human cancers and was responsible for the seminal discovery that point mutations in the cellular ras genes result in their oncogenic activation.[12][13] His work also showed the mechanisms associated with the activation of Abl and Myb oncogenes, which are associated with the development of human myelogenous leukemias.[14][15] His recent work on cell cycle regulator, Cdk4 has shown that this gene is very critical for the development of ErbB2 and ras oncogene-induced tumors and inhibition of expression of Cdk4 causes ablation of breast cancers caused by ErbB2 and Ras oncogenes.[16][17] His most recent findings include the generation of A-myb, c-myb and CDK4 null mutant mice[18][19][20][21] and delineation of the apoptotic mechanisms associated with hematopoietic cell death.

His recent work centers around the role of cell cycle and apoptotic genes in cancer progression and as targets for the development of novel anticancer drugs. This work has led to the development of novel therapeutic agents that can differentially induce apoptosis in tumor cells and spare normal cells. One of the drugs developed by his team (ON01910/Estybon/Rigosertib) is currently in Phase III clinical trials and shows promise as a powerful anti-cancer agent, especially for the treatment of Myelo Dysplastic Syndrome (MDS) and pancreatic cancer.[22][23][24][25]

Publications and Journalism

He co-founded the international cancer journal Oncogene in 1986, for which he served as an Editor from 1986 to 2009. In 2010, he founded a new cancer journal named 'Genes & Cancer' for which he serves as the Editor-in-Chief.

Reddy has published over 250 papers. The most notable of his findings are the molecular cloning and sequence determination of a number of viral oncogenes and their cellular homologues.

According to data published in 2000 by the Institute for Scientific Information, which compiled the list of most highly cited authors, Dr. Reddy was amongst the top 0.5% of the most highly cited authors in the world.

Related links

References

  1. ↑ Reddy EP, Smith MJ, Aaronson SA (1981). "Complete nucleotide sequence and organization of the Moloney murine sarcoma virus genome". Science. 214 (4519): 445–50. doi:10.1126/science.6170110. PMID 6170110.
  2. 1 2 Reddy EP, Smith MJ, Srinivasan A (1983). "Nucleotide sequence of Abelson murine leukemia virus genome: Structural similarity of its transforming gene product to other onc gene products with tyrosine-specific kinase activity". Proceedings of the National Academy of Sciences of the United States of America. 80 (12): 3623–7. doi:10.1073/pnas.80.12.3623. PMC 394102Freely accessible. PMID 6304726.
  3. ↑ Oppi C, Shore SK, Reddy EP (1987). "Nucleotide sequence of testis-derived c-abl cDNAs: Implications for testis-specific transcription and abl oncogene activation". Proceedings of the National Academy of Sciences of the United States of America. 84 (23): 8200–4. doi:10.1073/pnas.84.23.8200. PMC 299509Freely accessible. PMID 3317402.
  4. ↑ Reddy EP (1983). "Nucleotide sequence analysis of the T24 human bladder carcinoma oncogene". Science. 220 (4601): 1061–3. doi:10.1126/science.6844927. PMID 6844927.
  5. ↑ Naharro G, Robbins KC, Reddy EP (1984). "Gene product of v-fgr onc: Hybrid protein containing a portion of actin and a tyrosine-specific protein kinase". Science. 223 (4631): 63–6. doi:10.1126/science.6318314. PMID 6318314.
  6. ↑ Rushlow KE, Lautenberger JA, Papas TS, Baluda MA, Perbal B, Chirikjian JG, Reddy EP (1982). "Nucleotide sequence of the transforming gene of avian myeloblastosis virus". Science. 216 (4553): 1421–3. doi:10.1126/science.6283631. PMID 6283631.
  7. ↑ Rosson D, Reddy EP (1986). "Nucleotide sequence of chicken c-myb complementary DNA and implications for myb oncogene activation". Nature. 319 (6054): 604–6. doi:10.1038/319604a0. PMID 3753748.
  8. ↑ Reddy EP, Reynolds RK, Watson DK, Schultz RA, Lautenberger J, Papas TS (1983). "Nucleotide sequence analysis of the proviral genome of avian myelocytomatosis virus (MC29)". Proceedings of the National Academy of Sciences of the United States of America. 80 (9): 2500–4. doi:10.1073/pnas.80.9.2500. PMC 393853Freely accessible. PMID 6302688.
  9. ↑ Watson DK, Reddy EP, Duesberg PH, Papas TS (1983). "Nucleotide sequence analysis of the chicken c-myc gene reveals homologous and unique coding regions by comparison with the transforming gene of avian myelocytomatosis virus MC29, delta gag-myc". Proceedings of the National Academy of Sciences of the United States of America. 80 (8): 2146–50. doi:10.1073/pnas.80.8.2146. PMC 393774Freely accessible. PMID 6300896.
  10. ↑ Devare SG, Reddy EP, Law JD, Robbins KC, Aaronson SA (1983). "Nucleotide sequence of the simian sarcoma virus genome: Demonstration that its acquired cellular sequences encode the transforming gene product p28sis". Proceedings of the National Academy of Sciences of the United States of America. 80 (3): 731–5. doi:10.1073/pnas.80.3.731. PMC 393453Freely accessible. PMID 6298772.
  11. ↑ Chiu IM, Reddy EP, Givol D, Robbins KC, Tronick SR, Aaronson SA (1984). "Nucleotide sequence analysis identifies the human c-sis proto-oncogene as a structural gene for platelet-derived growth factor". Cell. 37 (1): 123–9. doi:10.1016/0092-8674(84)90307-6. PMID 6327048.
  12. ↑ Reddy EP, Reynolds RK, Santos E, Barbacid M (1982). "A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene". Nature. 300 (5888): 149–52. doi:10.1038/300149a0. PMID 7133135.
  13. ↑ Yuasa Y, Srivastava SK, Dunn CY, Rhim JS, Reddy EP, Aaronson SA (1983). "Acquisition of transforming properties by alternative point mutations within c-bas/has human proto-oncogene". Nature. 303 (5920): 775–9. doi:10.1038/303775a0. PMID 6866079.
  14. ↑ Shen-Ong GL, Potter M, Mushinski JF, Lavu S, Reddy EP (1984). "Activation of the c-myb locus by viral insertional mutagenesis in plasmacytoid lymphosarcomas". Science. 226 (4678): 1077–80. doi:10.1126/science.6093260. PMID 6093260.
  15. ↑ Shore SK, Bogart SL, Reddy EP (1990). "Activation of murine c-abl protooncogene: Effect of a point mutation on oncogenic activation". Proceedings of the National Academy of Sciences of the United States of America. 87 (17): 6502–6. doi:10.1073/pnas.87.17.6502. PMC 54564Freely accessible. PMID 2168550.
  16. ↑ Reddy HK, Mettus RV, Rane SG, Graña X, Litvin J, Reddy EP (2005). "Cyclin-dependent kinase 4 expression is essential for neu-induced breast tumorigenesis". Cancer Research. 65 (22): 10174–8. doi:10.1158/0008-5472.CAN-05-2639. PMID 16288002.
  17. ↑ Reddy HK, Graña X, Dhanasekaran DN, Litvin J, Reddy EP (2010). "Requirement of Cdk4 for v-Ha-ras-Induced Breast Tumorigenesis and Activation of the v-ras-Induced Senescence Program by the R24C Mutation". Genes & cancer. 1 (1): 69–80. doi:10.1177/1947601909358105. PMC 2904236Freely accessible. PMID 20634902.
  18. ↑ Toscani A, Mettus RV, Coupland R, Simpkins H, Litvin J, Orth J, Hatton KS, Reddy EP (1997). "Arrest of spermatogenesis and defective breast development in mice lacking A-myb". Nature. 386 (6626): 713–7. doi:10.1038/386713a0. PMID 9109487.
  19. ↑ Lieu YK, Reddy EP (2009). "Conditional c-myb knockout in adult hematopoietic stem cells leads to loss of self-renewal due to impaired proliferation and accelerated differentiation". Proceedings of the National Academy of Sciences of the United States of America. 106 (51): 21689–94. doi:10.1073/pnas.0907623106. PMC 2787467Freely accessible. PMID 19955420.
  20. ↑ Rane SG, Dubus P, Mettus RV, Galbreath EJ, Boden G, Reddy EP, Barbacid M (1999). "Loss of Cdk4 expression causes insulin-deficient diabetes and Cdk4 activation results in beta-islet cell hyperplasia". Nature Genetics. 22 (1): 44–52. doi:10.1038/8751. PMID 10319860.
  21. ↑ Rane SG, Cosenza SC, Mettus RV, Reddy EP (2002). "Germ line transmission of the Cdk4(R24C) mutation facilitates tumorigenesis and escape from cellular senescence". Molecular and Cellular Biology. 22 (2): 644–56. doi:10.1128/MCB.22.2.644-656.2002. PMC 139741Freely accessible. PMID 11756559.
  22. ↑ Reddy, MV; Venkatapuram, P; Mallireddigari, MR; Pallela, VR; Cosenza, SC; Robell, KA; Akula, B; Hoffman, BS; Reddy, EP (2011). "Discovery of a clinical stage multi-kinase inhibitor sodium (E)-2-{2-methoxy-5-(2',4',6'-trimethoxystyrylsulfonyl)methylphenylamino}acetate (ON 01910.Na): Synthesis, structure-activity relationship, and biological activity". Journal of Medicinal Chemistry. 54 (18): 6254–76. doi:10.1021/jm200570p. PMID 21812421.
  23. ↑ Olnes MJ, Shenoy A, Weinstein B, Pfannes L, Loeliger K, Tucker Z, Tian X, Kwak M, et al. (2012). "Directed therapy for patients with myelodysplastic syndromes (MDS) by suppression of cyclin D1 with ON 01910.Na". Leukemia research. 36 (8): 982–9. doi:10.1016/j.leukres.2012.04.002. PMC 3381873Freely accessible. PMID 22524974.
  24. ↑ Seetharam M, Fan AC, Tran M, Xu L, Renschler JP, Felsher DW, Sridhar K, Wilhelm F, Greenberg PL (2012). "Treatment of higher risk myelodysplastic syndrome patients unresponsive to hypomethylating agents with ON 01910.Na". Leukemia research. 36 (1): 98–103. doi:10.1016/j.leukres.2011.08.022. PMC 3612532Freely accessible. PMID 21924492.
  25. ↑ Ma WW, Messersmith WA, Dy GK, Weekes CD, Whitworth A, Ren C, Maniar M, Wilhelm F, et al. (2012). "Phase I study of Rigosertib, an inhibitor of the phosphatidylinositol 3-kinase and Polo-like kinase 1 pathways, combined with gemcitabine in patients with solid tumors and pancreatic cancer". Clinical Cancer Research. 18 (7): 2048–55. doi:10.1158/1078-0432.CCR-11-2813. PMID 22338014.
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