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Bertal H. Aktas, Ph.D., D.V.M.

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Mentoring
Available: 10/26/20, Expires: 05/31/22

Taxane and anthracycline classes of agents are used as mono-therapy but more frequently in combination with targeted therapies for the treatment hormone refractory breast cancer. Like many solid tumors, breast cancers relay on regulated integrated stress response for survival. As such, they are very sensitive to perturbations of IRS regulators. My group has developed various agents that perturb integrated stress response and shown in preliminary studies that these agents may synergise with anthracyclines.

The goal of this project is to establish potential synergy between taxanes and IRS perurbants using cellular and organoid models of breast cancer.


Research
The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
  1. R21AI154196 (AKTAS, BERTAL H.) May 19, 2020 - Apr 30, 2022
    NIH/NIAID
    Protein Synthesis Inhibitors as anti-T. Cruzi agents
    Role: Principal Investigator
  2. R01CA152312 (AKTAS, BERTAL H.) Aug 15, 2011 - Jun 30, 2016
    NIH/NCI
    Targeting Endoplasmic Reticulum Stress Response for Cancer Therapy
    Role: Principal Investigator
  3. R21AG032546 (AKTAS, BERTAL H.) May 15, 2009 - Apr 30, 2011
    NIH/NIA
    Molecular adn Chemical Biology of Integrated ER Stre
    Role: Principal Investigator

Bibliographic
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
  1. Liu F, Dai S, Feng D, Qin Z, Peng X, Sakamuri SSVP, Ren M, Huang L, Cheng M, Mohammad KE, Qu P, Chen Y, Zhao C, Zhu F, Liang S, Aktas BH, Yang X, Wang H, Katakam PVG, Busija DW, Fischer T, Datta PK, Rappaport J, Gao B, Qin X. Distinct fate, dynamics and niches of renal macrophages of bone marrow or embryonic origins. Nat Commun. 2020 05 08; 11(1):2280. PMID: 32385245.
    Citations: 1     Fields:    Translation:AnimalsCells
  2. Zhang Q, Du R, Reis Monteiro Dos Santos GR, Yefidoff-Freedman R, Bohm A, Halperin J, Chorev M, Aktas BH. New activators of eIF2a Kinase Heme-Regulated Inhibitor (HRI) with improved biophysical properties. Eur J Med Chem. 2020 Feb 01; 187:111973. PMID: 31881453.
    Citations:    Fields:    Translation:HumansCells
  3. Liu F, Dai S, Feng D, Peng X, Qin Z, Kearns AC, Huang W, Chen Y, Ergün S, Wang H, Rappaport J, Bryda EC, Chandrasekhar A, Aktas B, Hu H, Chang SL, Gao B, Qin X. Versatile cell ablation tools and their applications to study loss of cell functions. Cell Mol Life Sci. 2019 Dec; 76(23):4725-4743. PMID: 31359086.
    Citations: 4     Fields:    Translation:HumansAnimalsCells
  4. Aktas BH, Upcin B, Henke E, Padmasekar M, Qin X, Ergün S. The Best for the Most Important: Maintaining a Pristine Proteome in Stem and Progenitor Cells. Stem Cells Int. 2019; 2019:1608787. PMID: 31191665.
    Citations:    
  5. Persaud L, Mighty J, Zhong X, Francis A, Mendez M, Muharam H, Redenti SM, Das D, Aktas BH, Sauane M. IL-24 Promotes Apoptosis through cAMP-Dependent PKA Pathways in Human Breast Cancer Cells. Int J Mol Sci. 2018 Nov 12; 19(11). PMID: 30424508.
    Citations: 3     Fields:    Translation:HumansCells
  6. Nandigama R, Upcin B, Aktas BH, Ergün S, Henke E. Restriction of drug transport by the tumor environment. Histochem Cell Biol. 2018 Dec; 150(6):631-648. PMID: 30361778.
    Citations: 3     Fields:    Translation:HumansAnimals
  7. Zhong X, Persaud L, Muharam H, Francis A, Das D, Aktas BH, Sauane M. Eukaryotic Translation Initiation Factor 4A Down-Regulation Mediates Interleukin-24-Induced Apoptosis through Inhibition of Translation. Cancers (Basel). 2018 May 22; 10(5). PMID: 29786657.
    Citations: 2     
  8. Machado FC, Franco CH, Dos Santos Neto JV, Dias-Teixeira KL, Moraes CB, Lopes UG, Aktas BH, Schenkman S. Identification of di-substituted ureas that prevent growth of trypanosomes through inhibition of translation initiation. Sci Rep. 2018 03 20; 8(1):4857. PMID: 29559670.
    Citations: 1     Fields:    Translation:HumansAnimalsCells
  9. Bahnan W, Boucher JC, Gayle P, Shrestha N, Rosen M, Aktas B, Adkins B, Ager A, Khan WN, Schesser K. The eIF2a Kinase Heme-Regulated Inhibitor Protects the Host from Infection by Regulating Intracellular Pathogen Trafficking. Infect Immun. 2018 03; 86(3). PMID: 29311243.
    Citations:    Fields:    Translation:HumansAnimalsCells
  10. Dias-Teixeira KL, Calegari-Silva TC, Medina JM, Vivarini ÁC, Cavalcanti Á, Teteo N, Santana AKM, Real F, Gomes CM, Pereira RMS, Fasel N, Silva JS, Aktas BH, Lopes UG. Emerging Role for the PERK/eIF2a/ATF4 in Human Cutaneous Leishmaniasis. Sci Rep. 2017 12 06; 7(1):17074. PMID: 29213084.
    Citations: 4     Fields:    Translation:HumansAnimalsCells
  11. Burwick N, Aktas BH. The eIF2-alpha kinase HRI: a potential target beyond the red blood cell. Expert Opin Ther Targets. 2017 12; 21(12):1171-1177. PMID: 29063813.
    Citations: 6     Fields:    Translation:HumansAnimalsCells
  12. Yefidoff-Freedman R, Fan J, Yan L, Zhang Q, Dos Santos GRR, Rana S, Contreras JI, Sahoo R, Wan D, Young J, Dias Teixeira KL, Morisseau C, Halperin J, Hammock B, Natarajan A, Wang P, Chorev M, Aktas BH. Development of 1-((1,4-trans)-4-Aryloxycyclohexyl)-3-arylurea Activators of Heme-Regulated Inhibitor as Selective Activators of the Eukaryotic Initiation Factor 2 Alpha (eIF2a) Phosphorylation Arm of the Integrated Endoplasmic Reticulum Stress Response. J Med Chem. 2017 07 13; 60(13):5392-5406. PMID: 28590739.
    Citations: 6     Fields:    Translation:HumansAnimalsCells
  13. Persaud L, Zhong X, Alvarado G, Do W, Dejoie J, Zybtseva A, Aktas BH, Sauane M. eIF2a Phosphorylation Mediates IL24-Induced Apoptosis through Inhibition of Translation. Mol Cancer Res. 2017 08; 15(8):1117-1124. PMID: 28461326.
    Citations: 3     Fields:    Translation:HumansCells
  14. Dias-Teixeira KL, Pereira RM, Silva JS, Fasel N, Aktas BH, Lopes UG. Unveiling the Role of the Integrated Endoplasmic Reticulum Stress Response in Leishmania Infection - Future Perspectives. Front Immunol. 2016; 7:283. PMID: 27499755.
    Citations: 2     Fields:    
  15. Dias-Teixeira KL, Calegari-Silva TC, dos Santos GR, Vitorino Dos Santos J, Lima C, Medina JM, Aktas BH, Lopes UG. The integrated endoplasmic reticulum stress response in Leishmania amazonensis macrophage infection: the role of X-box binding protein 1 transcription factor. FASEB J. 2016 Apr; 30(4):1557-65. PMID: 26678450.
    Citations: 9     Fields:    Translation:HumansAnimalsCells
  16. Aktas BH, Bordelois P, Peker S, Merajver S, Halperin JA. Depletion of eIF2·GTP·Met-tRNAi translation initiation complex up-regulates BRCA1 expression in vitro and in vivo. Oncotarget. 2015 Mar 30; 6(9):6902-14. PMID: 25762631.
    Citations: 2     Fields:    Translation:HumansAnimalsCells
  17. Papadopoulos E, Jenni S, Kabha E, Takrouri KJ, Yi T, Salvi N, Luna RE, Gavathiotis E, Mahalingam P, Arthanari H, Rodriguez-Mias R, Yefidoff-Freedman R, Aktas BH, Chorev M, Halperin JA, Wagner G. Structure of the eukaryotic translation initiation factor eIF4E in complex with 4EGI-1 reveals an allosteric mechanism for dissociating eIF4G. Proc Natl Acad Sci U S A. 2014 Aug 05; 111(31):E3187-95. PMID: 25049413.
    Citations: 23     Fields:    Translation:HumansCells
  18. Mahalingam P, Takrouri K, Chen T, Sahoo R, Papadopoulos E, Chen L, Wagner G, Aktas BH, Halperin JA, Chorev M. Synthesis of rigidified eIF4E/eIF4G inhibitor-1 (4EGI-1) mimetic and their in vitro characterization as inhibitors of protein-protein interaction. J Med Chem. 2014 Jun 26; 57(12):5094-111. PMID: 24827861.
    Citations: 7     Fields:    Translation:HumansCells
  19. Takrouri K, Chen T, Papadopoulos E, Sahoo R, Kabha E, Chen H, Cantel S, Wagner G, Halperin JA, Aktas BH, Chorev M. Structure-activity relationship study of 4EGI-1, small molecule eIF4E/eIF4G protein-protein interaction inhibitors. Eur J Med Chem. 2014 Apr 22; 77:361-77. PMID: 24675136.
    Citations: 3     Fields:    Translation:HumansCells
  20. Yefidoff-Freedman R, Chen T, Sahoo R, Chen L, Wagner G, Halperin JA, Aktas BH, Chorev M. 3-substituted indazoles as configurationally locked 4EGI-1 mimetics and inhibitors of the eIF4E/eIF4G interaction. Chembiochem. 2014 Mar 03; 15(4):595-611. PMID: 24458973.
    Citations: 3     Fields:    Translation:HumansCells
  21. Chen T, Takrouri K, Hee-Hwang S, Rana S, Yefidoff-Freedman R, Halperin J, Natarajan A, Morisseau C, Hammock B, Chorev M, Aktas BH. Explorations of substituted urea functionality for the discovery of new activators of the heme-regulated inhibitor kinase. J Med Chem. 2013 Dec 12; 56(23):9457-70. PMID: 24261904.
    Citations: 11     Fields:    Translation:HumansCells
  22. Aktas BH, Qiao Y, Ozdelen E, Schubert R, Sevinc S, Harbinski F, Grubissich L, Singer S, Halperin JA. Small-Molecule targeting of translation initiation for cancer therapy. Oncotarget. 2013 Oct; 4(10):1606-17. PMID: 24091475.
    Citations: 17     Fields:    Translation:HumansAnimalsCells
  23. Denoyelle S, Chen T, Yang H, Chen L, Zhang Y, Halperin JA, Aktas BH, Chorev M. Synthesis and SAR study of novel 3,3-diphenyl-1,3-dihydroindol-2-one derivatives as potent eIF2·GTP·Met-tRNAiMet ternary complex inhibitors. Eur J Med Chem. 2013 Nov; 69:537-53. PMID: 24095748.
    Citations: 1     Fields:    Translation:HumansAnimalsCells
  24. Bai H, Chen T, Ming J, Sun H, Cao P, Fusco DN, Chung RT, Chorev M, Jin Q, Aktas BH. Dual activators of protein kinase R (PKR) and protein kinase R-like kinase PERK identify common and divergent catalytic targets. Chembiochem. 2013 Jul 08; 14(10):1255-62. PMID: 23784735.
    Citations: 8     Fields:    Translation:HumansCells
  25. Chen L, Aktas BH, Wang Y, He X, Sahoo R, Zhang N, Denoyelle S, Kabha E, Yang H, Freedman RY, Supko JG, Chorev M, Wagner G, Halperin JA. Tumor suppression by small molecule inhibitors of translation initiation. Oncotarget. 2012 Aug; 3(8):869-81. PMID: 22935625.
    Citations: 41     Fields:    Translation:HumansAnimalsCells
  26. Denoyelle S, Chen T, Chen L, Wang Y, Klosi E, Halperin JA, Aktas BH, Chorev M. In vitro inhibition of translation initiation by N,N'-diarylureas--potential anti-cancer agents. Bioorg Med Chem Lett. 2012 Jan 01; 22(1):402-9. PMID: 22153346.
    Citations: 14     Fields:    Translation:HumansAnimalsCells
  27. Chen T, Ozel D, Qiao Y, Harbinski F, Chen L, Denoyelle S, He X, Zvereva N, Supko JG, Chorev M, Halperin JA, Aktas BH. Chemical genetics identify eIF2a kinase heme-regulated inhibitor as an anticancer target. Nat Chem Biol. 2011 Jul 17; 7(9):610-6. PMID: 21765405.
    Citations: 41     Fields:    Translation:HumansAnimalsCells
  28. Domagk D, Mensink P, Aktas H, Lenz P, Meister T, Luegering A, Ullerich H, Aabakken L, Heinecke A, Domschke W, Kuipers E, Bretthauer M. Single- vs. double-balloon enteroscopy in small-bowel diagnostics: a randomized multicenter trial. Endoscopy. 2011 Jun; 43(6):472-6. PMID: 21384320.
    Citations: 54     Fields:    Translation:Humans
  29. Hu W, Ge X, You T, Xu T, Zhang J, Wu G, Peng Z, Chorev M, Aktas BH, Halperin JA, Brown JR, Qin X. Human CD59 inhibitor sensitizes rituximab-resistant lymphoma cells to complement-mediated cytolysis. Cancer Res. 2011 Mar 15; 71(6):2298-307. PMID: 21252115.
    Citations: 30     Fields:    Translation:HumansAnimalsCells
  30. Ziegeler G, Ming J, Koseki JC, Sevinc S, Chen T, Ergun S, Qin X, Aktas BH. Embryonic lethal abnormal vision-like HuR-dependent mRNA stability regulates post-transcriptional expression of cyclin-dependent kinase inhibitor p27Kip1. J Biol Chem. 2010 May 14; 285(20):15408-19. PMID: 20332085.
    Citations: 14     Fields:    Translation:HumansAnimalsCells
  31. Wu G, Chen T, Shahsafaei A, Hu W, Bronson RT, Shi GP, Halperin JA, Aktas H, Qin X. Complement regulator CD59 protects against angiotensin II-induced abdominal aortic aneurysms in mice. Circulation. 2010 Mar 23; 121(11):1338-46. PMID: 20212283.
    Citations: 16     Fields:    Translation:HumansAnimalsCells
  32. Ozel Demiralp D, Aktas H, Akar N. The effect of plasminogen activator inhibitor-1 -675 4G/5G polymorphism on PAI-1 gene expression and adipocyte differentiation. Clin Appl Thromb Hemost. 2008 Oct; 14(4):438-46. PMID: 18160587.
    Citations: 3     Fields:    Translation:HumansAnimalsCells
  33. Tombul M, Guven K, Büyükgüngör O, Aktas H, Durlu TN. Dipotassium maleate with boric acid. Acta Crystallogr C. 2007 Sep; 63(Pt 9):m430-2. PMID: 17762116.
    Citations: 2     Fields:    
  34. Hyberts SG, Heffron GJ, Tarragona NG, Solanky K, Edmonds KA, Luithardt H, Fejzo J, Chorev M, Aktas H, Colson K, Falchuk KH, Halperin JA, Wagner G. Ultrahigh-resolution (1)H-(13)C HSQC spectra of metabolite mixtures using nonlinear sampling and forward maximum entropy reconstruction. J Am Chem Soc. 2007 Apr 25; 129(16):5108-16. PMID: 17388596.
    Citations: 54     Fields:    Translation:AnimalsCells
  35. Moerke NJ, Aktas H, Chen H, Cantel S, Reibarkh MY, Fahmy A, Gross JD, Degterev A, Yuan J, Chorev M, Halperin JA, Wagner G. Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Cell. 2007 Jan 26; 128(2):257-67. PMID: 17254965.
    Citations: 199     Fields:    Translation:HumansAnimalsCells
  36. Gelev V, Aktas H, Marintchev A, Ito T, Frueh D, Hemond M, Rovnyak D, Debus M, Hyberts S, Usheva A, Halperin J, Wagner G. Mapping of the auto-inhibitory interactions of protein kinase R by nuclear magnetic resonance. J Mol Biol. 2006 Dec 01; 364(3):352-63. PMID: 17011579.
    Citations: 18     Fields:    Translation:Cells
  37. Chen H, Fan YH, Natarajan A, Guo Y, Iyasere J, Harbinski F, Luus L, Christ W, Aktas H, Halperin JA. Synthesis and biological evaluation of thiazolidine-2,4-dione and 2,4-thione derivatives as inhibitors of translation initiation. Bioorg Med Chem Lett. 2004 Nov 01; 14(21):5401-5. PMID: 15454234.
    Citations: 7     Fields:    Translation:HumansCells
  38. Natarajan A, Guo Y, Harbinski F, Fan YH, Chen H, Luus L, Diercks J, Aktas H, Chorev M, Halperin JA. Novel arylsulfoanilide-oxindole hybrid as an anticancer agent that inhibits translation initiation. J Med Chem. 2004 Oct 07; 47(21):4979-82. PMID: 15456240.
    Citations: 7     Fields:    Translation:HumansAnimalsCells
  39. Aktas H, Halperin JA. Translational regulation of gene expression by omega-3 fatty acids. J Nutr. 2004 Sep; 134(9):2487S-2491S. PMID: 15333747.
    Citations: 10     Fields:    Translation:HumansAnimalsCells
  40. Fan YH, Chen H, Natarajan A, Guo Y, Harbinski F, Iyasere J, Christ W, Aktas H, Halperin JA. Structure-activity requirements for the antiproliferative effect of troglitazone derivatives mediated by depletion of intracellular calcium. Bioorg Med Chem Lett. 2004 May 17; 14(10):2547-50. PMID: 15109648.
    Citations: 6     Fields:    Translation:HumansCells
  41. Natarajan A, Fan YH, Chen H, Guo Y, Iyasere J, Harbinski F, Christ WJ, Aktas H, Halperin JA. 3,3-diaryl-1,3-dihydroindol-2-ones as antiproliferatives mediated by translation initiation inhibition. J Med Chem. 2004 Apr 08; 47(8):1882-5. PMID: 15055987.
    Citations: 3     Fields:    Translation:HumansCells
  42. Aktas H, Leibfried-Rutledge ML, First NL. Meiotic state of bovine oocytes is regulated by interactions between cAMP, cumulus, and granulosa. Mol Reprod Dev. 2003 Jul; 65(3):336-43. PMID: 12784256.
    Citations: 2     Fields:    Translation:AnimalsCells
  43. Qin X, Krumrei N, Grubissich L, Dobarro M, Aktas H, Perez G, Halperin JA. Deficiency of the mouse complement regulatory protein mCd59b results in spontaneous hemolytic anemia with platelet activation and progressive male infertility. Immunity. 2003 Feb; 18(2):217-27. PMID: 12594949.
    Citations: 27     Fields:    Translation:HumansAnimalsCells
  44. Palakurthi SS, Aktas H, Grubissich LM, Mortensen RM, Halperin JA. Anticancer effects of thiazolidinediones are independent of peroxisome proliferator-activated receptor gamma and mediated by inhibition of translation initiation. Cancer Res. 2001 Aug 15; 61(16):6213-8. PMID: 11507074.
    Citations: 77     Fields:    Translation:HumansAnimalsCells
  45. Qin X, Miwa T, Aktas H, Gao M, Lee C, Qian YM, Morton CC, Shahsafaei A, Song WC, Halperin JA. Genomic structure, functional comparison, and tissue distribution of mouse Cd59a and Cd59b. Mamm Genome. 2001 Aug; 12(8):582-9. PMID: 11471050.
    Citations: 15     Fields:    Translation:HumansAnimalsCells
  46. Palakurthi SS, Flückiger R, Aktas H, Changolkar AK, Shahsafaei A, Harneit S, Kilic E, Halperin JA. Inhibition of translation initiation mediates the anticancer effect of the n-3 polyunsaturated fatty acid eicosapentaenoic acid. Cancer Res. 2000 Jun 01; 60(11):2919-25. PMID: 10850438.
    Citations: 22     Fields:    Translation:AnimalsCells
  47. Aktas H, Flückiger R, Acosta JA, Savage JM, Palakurthi SS, Halperin JA. Depletion of intracellular Ca2+ stores, phosphorylation of eIF2alpha, and sustained inhibition of translation initiation mediate the anticancer effects of clotrimazole. Proc Natl Acad Sci U S A. 1998 Jul 07; 95(14):8280-5. PMID: 9653178.
    Citations: 31     Fields:    Translation:AnimalsCells
  48. Aktas H, Cai H, Cooper GM. Ras links growth factor signaling to the cell cycle machinery via regulation of cyclin D1 and the Cdk inhibitor p27KIP1. Mol Cell Biol. 1997 Jul; 17(7):3850-7. PMID: 9199319.
    Citations: 92     Fields:    Translation:AnimalsCells
  49. Aktas H, Wheeler MB, Rosenkrans CF, First NL, Leibfried-Rutledge ML. Maintenance of bovine oocytes in prophase of meiosis I by high [cAMP]i. J Reprod Fertil. 1995 Nov; 105(2):227-35. PMID: 8568765.
    Citations: 7     Fields:    Translation:AnimalsCells
  50. Aktas H, Wheeler MB, First NL, Leibfried-Rutledge ML. Maintenance of meiotic arrest by increasing [cAMP]i may have physiological relevance in bovine oocytes. J Reprod Fertil. 1995 Nov; 105(2):237-45. PMID: 8568766.
    Citations: 4     Fields:    Translation:AnimalsCells
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Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.