Loren Walensky

Loren Walensky, MD, PhD



Associate Professor of Pediatrics

    Contact: 617-632-6794
  • Fax: 617-582-8240

Medical Services

Specialties

  • Hematology Oncology

Departments

  • Hematology / Oncology
  • Medicine

Programs

  • Hematology / Oncology
  • Hematology / Oncology
To schedule an appointment: Call 617-632-6794 or Request an Appointment

Experience and Education

Education

Medical School

Johns Hopkins University School of Medicine,

Baltimore, MD

Pediatrics, Boston Combined Residency Program

Boston Children's Hospital/Boston Medical Center,

Boston, MA

Fellowship, Pediatric Hematology/Oncology

Boston Children's Hospital/Dana-Farber Cancer Institute,

Boston, MA

Certifications

  • Pediatrics, Pediatric Hematology/Oncology

Publications

Publications powered by Harvard Catalyst Profiles
  1. Wachter F, Morgan AM, Godes M, Mourtada R, Bird GH, Walensky LD. Mechanistic validation of a clinical lead stapled peptide that reactivates p53 by dual HDM2 and HDMX targeting. Oncogene. 2016 Oct 10.
  2. Edwards AL, Meijer DH, Guerra RM, Molenaar RJ, Alberta JA, Bernal F, Bird GH, Stiles CD, Walensky LD. Challenges in Targeting a Basic Helix-Loop-Helix Transcription Factor with Hydrocarbon-Stapled Peptides. ACS Chem Biol. 2016 Oct 4.
  3. Carpio MA, Michaud M, Zhou W, Fisher JK, Walensky LD, Katz SG. Reply to Fernandez-Marrero et al.: Role of BOK at the intersection of endoplasmic reticulum stress and apoptosis regulation. Proc Natl Acad Sci U S A. 2016 Feb 2; 113(5):E494-5.
  4. Carpio MA, Michaud M, Zhou W, Fisher JK, Walensky LD, Katz SG. BCL-2 family member BOK promotes apoptosis in response to endoplasmic reticulum stress. Proc Natl Acad Sci U S A. 2015 Jun 9; 112(23):7201-6.
  5. Zhang T, Walensky LD, Saghatelian A. A nonapoptotic role for BAX and BAK in eicosanoid metabolism. ACS Chem Biol. 2015 Jun 19; 10(6):1398-403.
  6. Barclay LA, Wales TE, Garner TP, Wachter F, Lee S, Guerra RM, Stewart ML, Braun CR, Bird GH, Gavathiotis E, Engen JR, Walensky LD. Inhibition of Pro-apoptotic BAX by a noncanonical interaction mechanism. Mol Cell. 2015 Mar 5; 57(5):873-86.
  7. Ljubicic S, Polak K, Fu A, Wiwczar J, Szlyk B, Chang Y, Alvarez-Perez JC, Bird GH, Walensky LD, Garcia-Ocaña A, Danial NN. Phospho-BAD BH3 mimicry protects ß cells and restores functional ß cell mass in diabetes. Cell Rep. 2015 Feb 3; 10(4):497-504.
  8. Perry JA, Kiezun A, Tonzi P, Van Allen EM, Carter SL, Baca SC, Cowley GS, Bhatt AS, Rheinbay E, Pedamallu CS, Helman E, Taylor-Weiner A, McKenna A, DeLuca DS, Lawrence MS, Ambrogio L, Sougnez C, Sivachenko A, Walensky LD, Wagle N, Mora J, de Torres C, Lavarino C, Dos Santos Aguiar S, Yunes JA, Brandalise SR, Mercado-Celis GE, Melendez-Zajgla J, Cárdenas-Cardós R, Velasco-Hidalgo L, Roberts CW, Garraway LA, Rodriguez-Galindo C, Gabriel SB, Lander ES, Golub TR, Orkin SH, Getz G, Janeway KA. Complementary genomic approaches highlight the PI3K/mTOR pathway as a common vulnerability in osteosarcoma. Proc Natl Acad Sci U S A. 2014 Dec 23; 111(51):E5564-73.
  9. Bird GH, Irimia A, Ofek G, Kwong PD, Wilson IA, Walensky LD. Stapled HIV-1 peptides recapitulate antigenic structures and engage broadly neutralizing antibodies. Nat Struct Mol Biol. 2014 Dec; 21(12):1058-67.
  10. Bird GH, Boyapalle S, Wong T, Opoku-Nsiah K, Bedi R, Crannell WC, Perry AF, Nguyen H, Sampayo V, Devareddy A, Mohapatra S, Mohapatra SS, Walensky LD. Mucosal delivery of a double-stapled RSV peptide prevents nasopulmonary infection. J Clin Invest. 2014 May; 124(5):2113-24.
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  12. Walensky LD, Bird GH. Hydrocarbon-stapled peptides: principles, practice, and progress. J Med Chem. 2014 Aug 14; 57(15):6275-88.
  13. Bird GH, Gavathiotis E, LaBelle JL, Katz SG, Walensky LD. Distinct BimBH3 (BimSAHB) stapled peptides for structural and cellular studies. ACS Chem Biol. 2014 Mar 21; 9(3):831-7.
  14. Lee S, Braun CR, Bird GH, Walensky LD. Photoreactive stapled peptides to identify and characterize BCL-2 family interaction sites by mass spectrometry. Methods Enzymol. 2014; 544:25-48.
  15. Szlyk B, Braun CR, Ljubicic S, Patton E, Bird GH, Osundiji MA, Matschinsky FM, Walensky LD, Danial NN. A phospho-BAD BH3 helix activates glucokinase by a mechanism distinct from that of allosteric activators. Nat Struct Mol Biol. 2014 Jan; 21(1):36-42.
  16. Edwards AL, Gavathiotis E, LaBelle JL, Braun CR, Opoku-Nsiah KA, Bird GH, Walensky LD. Multimodal interaction with BCL-2 family proteins underlies the proapoptotic activity of PUMA BH3. Chem Biol. 2013 Jul 25; 20(7):888-902.
  17. Varadarajan S, Vogler M, Butterworth M, Dinsdale D, Walensky LD, Cohen GM. Evaluation and critical assessment of putative MCL-1 inhibitors. Cell Death Differ. 2013 Nov; 20(11):1475-84.
  18. Walensky LD. Direct BAKtivation. Nat Struct Mol Biol. 2013 May; 20(5):536-8.
  19. Hilgendorf KI, Leshchiner ES, Nedelcu S, Maynard MA, Calo E, Ianari A, Walensky LD, Lees JA. The retinoblastoma protein induces apoptosis directly at the mitochondria. Genes Dev. 2013 May 1; 27(9):1003-15.
  20. Walensky LD. Playing fullBAK. Cell Cycle. 2013 May 1; 12(9):1333-4.
  21. Walensky LD. Protein-protein interactions: A PUMA mechanism unfolds. Nat Chem Biol. 2013 Mar; 9(3):141-3.
  22. Leshchiner ES, Braun CR, Bird GH, Walensky LD. Direct activation of full-length proapoptotic BAK. Proc Natl Acad Sci U S A. 2013 Mar 12; 110(11):E986-95.
  23. Cohen NA, Stewart ML, Gavathiotis E, Tepper JL, Bruekner SR, Koss B, Opferman JT, Walensky LD. A competitive stapled peptide screen identifies a selective small molecule that overcomes MCL-1-dependent leukemia cell survival. Chem Biol. 2012 Sep 21; 19(9):1175-86.
  24. Katz SG, Fisher JK, Correll M, Bronson RT, Ligon KL, Walensky LD. Brain and testicular tumors in mice with progenitor cells lacking BAX and BAK. Oncogene. 2013 Aug 29; 32(35):4078-85.
  25. Takada K, Zhu D, Bird GH, Sukhdeo K, Zhao JJ, Mani M, Lemieux M, Carrasco DE, Ryan J, Horst D, Fulciniti M, Munshi NC, Xu W, Kung AL, Shivdasani RA, Walensky LD, Carrasco DR. Targeted disruption of the BCL9/ß-catenin complex inhibits oncogenic Wnt signaling. Sci Transl Med. 2012 Aug 22; 4(148):148ra117.
  26. Walensky LD. Interview with Loren D Walensky. Future Med Chem. 2012 Aug; 4(12):1537-9.
  27. Walensky LD. Stemming danger with Golgified BAX. Mol Cell. 2012 Jun 8; 46(5):554-6.
  28. Gavathiotis E, Reyna DE, Bellairs JA, Leshchiner ES, Walensky LD. Direct and selective small-molecule activation of proapoptotic BAX. Nat Chem Biol. 2012 Jul; 8(7):639-45.
  29. Walensky LD. From mitochondrial biology to magic bullet: navitoclax disarms BCL-2 in chronic lymphocytic leukemia. J Clin Oncol. 2012 Feb 10; 30(5):554-7.
  30. Walensky LD, Gavathiotis E. BAX unleashed: the biochemical transformation of an inactive cytosolic monomer into a toxic mitochondrial pore. Trends Biochem Sci. 2011 Dec; 36(12):642-52.
  31. Bird GH, Crannell WC, Walensky LD. Chemical synthesis of hydrocarbon-stapled peptides for protein interaction research and therapeutic targeting. Curr Protoc Chem Biol. 2011 Sep 1; 3(3):99-117.
  32. Kar AK, Mao Y, Bird G, Walensky L, Sodroski J. Characterization of a core fragment of the rhesus monkey TRIM5a protein. BMC Biochem. 2011 Jan 04; 12:1.
  33. Bird GH, Madani N, Perry AF, Princiotto AM, Supko JG, He X, Gavathiotis E, Sodroski JG, Walensky LD. Hydrocarbon double-stapling remedies the proteolytic instability of a lengthy peptide therapeutic. Proc Natl Acad Sci U S A. 2010 Aug 10; 107(32):14093-8.
  34. Danial NN, Walensky LD, Zhang CY, Choi CS, Fisher JK, Molina AJ, Datta SR, Pitter KL, Bird GH, Wikstrom JD, Deeney JT, Robertson K, Morash J, Kulkarni A, Neschen S, Kim S, Greenberg ME, Corkey BE, Shirihai OS, Shulman GI, Lowell BB, Korsmeyer SJ. Dual role of proapoptotic BAD in insulin secretion and beta cell survival. Nat Med. 2008 Feb; 14(2):144-53.
  35. Bird GH, Bernal F, Pitter K, Walensky LD. Synthesis and biophysical characterization of stabilized alpha-helices of BCL-2 domains. Methods Enzymol. 2008; 446:369-86.
  36. Verdine GL, Walensky LD. The challenge of drugging undruggable targets in cancer: lessons learned from targeting BCL-2 family members. Clin Cancer Res. 2007 Dec 15; 13(24):7264-70.
  37. Bernal F, Tyler AF, Korsmeyer SJ, Walensky LD, Verdine GL. Reactivation of the p53 tumor suppressor pathway by a stapled p53 peptide. J Am Chem Soc. 2007 Mar 7; 129(9):2456-7.
  38. Walensky LD, Pitter K, Morash J, Oh KJ, Barbuto S, Fisher J, Smith E, Verdine GL, Korsmeyer SJ. A stapled BID BH3 helix directly binds and activates BAX. Mol Cell. 2006 Oct 20; 24(2):199-210.
  39. Oh KJ, Barbuto S, Pitter K, Morash J, Walensky LD, Korsmeyer SJ. A membrane-targeted BID BCL-2 homology 3 peptide is sufficient for high potency activation of BAX in vitro. J Biol Chem. 2006 Dec 1; 281(48):36999-7008.
  40. Walensky LD. BCL-2 in the crosshairs: tipping the balance of life and death. Cell Death Differ. 2006 Aug; 13(8):1339-50.
  41. MacGinnitie AJ, Walensky LD, Turvey SE, Orange JS, Bonilla FA, Silverman LB, Oettgen H. Management of an anaphylactoid reaction to methotrexate with a stepwise graded challenge. Pediatr Allergy Immunol. 2003 Oct; 14(5):409-11.
  42. Ramez M, Blot-Chabaud M, Cluzeaud F, Chanan S, Patterson M, Walensky LD, Marfatia S, Baines AJ, Chasis JA, Conboy JG, Mohandas N, Gascard P. Distinct distribution of specific members of protein 4.1 gene family in the mouse nephron. Kidney Int. 2003 Apr; 63(4):1321-37.
  43. Parra M, Gascard P, Walensky LD, Gimm JA, Blackshaw S, Chan N, Takakuwa Y, Berger T, Lee G, Chasis JA, Snyder SH, Mohandas N, Conboy JG. Molecular and functional characterization of protein 4.1B, a novel member of the protein 4.1 family with high level, focal expression in brain. J Biol Chem. 2000 Feb 4; 275(5):3247-55.
  44. Ye K, Compton DA, Lai MM, Walensky LD, Snyder SH. Protein 4.1N binding to nuclear mitotic apparatus protein in PC12 cells mediates the antiproliferative actions of nerve growth factor. J Neurosci. 1999 Dec 15; 19(24):10747-56.
  45. Walensky LD, Blackshaw S, Liao D, Watkins CC, Weier HU, Parra M, Huganir RL, Conboy JG, Mohandas N, Snyder SH. A novel neuron-enriched homolog of the erythrocyte membrane cytoskeletal protein 4.1. J Neurosci. 1999 Aug 1; 19(15):6457-67.
  46. Gascard P, Nunomura W, Lee G, Walensky LD, Krauss SW, Takakuwa Y, Chasis JA, Mohandas N, Conboy JG. Deciphering the nuclear import pathway for the cytoskeletal red cell protein 4.1R. Mol Biol Cell. 1999 Jun; 10(6):1783-98.
  47. Shi ZT, Afzal V, Coller B, Patel D, Chasis JA, Parra M, Lee G, Paszty C, Stevens M, Walensky L, Peters LL, Mohandas N, Rubin E, Conboy JG. Protein 4.1R-deficient mice are viable but have erythroid membrane skeleton abnormalities. J Clin Invest. 1999 Feb; 103(3):331-40.
  48. Peters LL, Weier HU, Walensky LD, Snyder SH, Parra M, Mohandas N, Conboy JG. Four paralogous protein 4.1 genes map to distinct chromosomes in mouse and human. Genomics. 1998 Dec 1; 54(2):348-50.
  49. Walensky LD, Shi ZT, Blackshaw S, DeVries AC, Demas GE, Gascard P, Nelson RJ, Conboy JG, Rubin EM, Snyder SH, Mohandas N. Neurobehavioral deficits in mice lacking the erythrocyte membrane cytoskeletal protein 4.1. Curr Biol. 1998 Nov 19; 8(23):1269-72.
  50. Walensky LD, Dawson TM, Steiner JP, Sabatini DM, Suarez JD, Klinefelter GR, Snyder SH. The 12 kD FK 506 binding protein FKBP12 is released in the male reproductive tract and stimulates sperm motility. Mol Med. 1998 Aug; 4(8):502-14.
  51. Walensky LD, Ruat M, Bakin RE, Blackshaw S, Ronnett GV, Snyder SH. Two novel odorant receptor families expressed in spermatids undergo 5'-splicing. J Biol Chem. 1998 Apr 17; 273(16):9378-87.
  52. Parra M, Gascard P, Walensky LD, Snyder SH, Mohandas N, Conboy JG. Cloning and characterization of 4.1G (EPB41L2), a new member of the skeletal protein 4.1 (EPB41) gene family. Genomics. 1998 Apr 15; 49(2):298-306.
  53. Walensky LD, Gascard P, Fields ME, Blackshaw S, Conboy JG, Mohandas N, Snyder SH. The 13-kD FK506 binding protein, FKBP13, interacts with a novel homologue of the erythrocyte membrane cytoskeletal protein 4.1. J Cell Biol. 1998 Apr 6; 141(1):143-53.
  54. Walensky LD, Snyder SH. Inositol 1,4,5-trisphosphate receptors selectively localized to the acrosomes of mammalian sperm. J Cell Biol. 1995 Aug; 130(4):857-69.
  55. Cameron AM, Steiner JP, Sabatini DM, Kaplin AI, Walensky LD, Snyder SH. Immunophilin FK506 binding protein associated with inositol 1,4,5-trisphosphate receptor modulates calcium flux. Proc Natl Acad Sci U S A. 1995 Feb 28; 92(5):1784-8.
  56. Walensky LD, Coffey DS, Chen TH, Wu TC, Pasternack GR. A novel M(r) 32,000 nuclear phosphoprotein is selectively expressed in cells competent for self-renewal. Cancer Res. 1993 Oct 1; 53(19):4720-6.
  57. Walensky LD, Roskams AJ, Lefkowitz RJ, Snyder SH, Ronnett GV. Odorant receptors and desensitization proteins colocalize in mammalian sperm. Mol Med. 1995 Jan; 1(2):130-41.
  58. Shen L, Liang F, Walensky LD, Huganir RL. Regulation of AMPA receptor GluR1 subunit surface expression by a 4. 1N-linked actin cytoskeletal association. J Neurosci. 2000 Nov 1; 20(21):7932-40.
  59. Stewart ML, Fire E, Keating AE, Walensky LD. The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer. Nat Chem Biol. 2010 Aug; 6(8):595-601.
  60. Braun CR, Mintseris J, Gavathiotis E, Bird GH, Gygi SP, Walensky LD. Photoreactive stapled BH3 peptides to dissect the BCL-2 family interactome. Chem Biol. 2010 Dec 22; 17(12):1325-33.
  61. Walensky LD, Kung AL, Escher I, Malia TJ, Barbuto S, Wright RD, Wagner G, Verdine GL, Korsmeyer SJ. Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix. Science. 2004 Sep 3; 305(5689):1466-70.
  62. Letai A, Bassik MC, Walensky LD, Sorcinelli MD, Weiler S, Korsmeyer SJ. Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell. 2002 Sep; 2(3):183-92.
  63. LaBelle JL, Katz SG, Bird GH, Gavathiotis E, Stewart ML, Lawrence C, Fisher JK, Godes M, Pitter K, Kung AL, Walensky LD. A stapled BIM peptide overcomes apoptotic resistance in hematologic cancers. J Clin Invest. 2012 Jun; 122(6):2018-31.
  64. Bernal F, Wade M, Godes M, Davis TN, Whitehead DG, Kung AL, Wahl GM, Walensky LD. A stapled p53 helix overcomes HDMX-mediated suppression of p53. Cancer Cell. 2010 Nov 16; 18(5):411-22.
  65. Gavathiotis E, Suzuki M, Davis ML, Pitter K, Bird GH, Katz SG, Tu HC, Kim H, Cheng EH, Tjandra N, Walensky LD. BAX activation is initiated at a novel interaction site. Nature. 2008 Oct 23; 455(7216):1076-81.
  66. Pitter K, Bernal F, Labelle J, Walensky LD. Dissection of the BCL-2 family signaling network with stabilized alpha-helices of BCL-2 domains. Methods Enzymol. 2008; 446:387-408.
  67. Gavathiotis E, Walensky LD. Tracking BAX once its trigger is pulled. Cell Cycle. 2011 Mar 15; 10(6):868-70.
  68. Gavathiotis E, Reyna DE, Davis ML, Bird GH, Walensky LD. BH3-triggered structural reorganization drives the activation of proapoptotic BAX. Mol Cell. 2010 Nov 12; 40(3):481-92.
  69. Kim W, Bird GH, Neff T, Guo G, Kerenyi MA, Walensky LD, Orkin SH. Targeted disruption of the EZH2-EED complex inhibits EZH2-dependent cancer. Nat Chem Biol. 2013 Oct; 9(10):643-50.
  70. Katz SG, Labelle JL, Meng H, Valeriano RP, Fisher JK, Sun H, Rodig SJ, Kleinstein SH, Walensky LD. Mantle cell lymphoma in cyclin D1 transgenic mice with Bim-deficient B cells. Blood. 2014 Feb 6; 123(6):884-93.
  71. Reynolds C, Roderick JE, LaBelle JL, Bird G, Mathieu R, Bodaar K, Colon D, Pyati U, Stevenson KE, Qi J, Harris M, Silverman LB, Sallan SE, Bradner JE, Neuberg DS, Look AT, Walensky LD, Kelliher MA, Gutierrez A. Repression of BIM mediates survival signaling by MYC and AKT in high-risk T-cell acute lymphoblastic leukemia. Leukemia. 2014 Sep; 28(9):1819-27.
  72. Leshchiner ES, Parkhitko A, Bird GH, Luccarelli J, Bellairs JA, Escudero S, Opoku-Nsiah K, Godes M, Perrimon N, Walensky LD. Direct inhibition of oncogenic KRAS by hydrocarbon-stapled SOS1 helices. Proc Natl Acad Sci U S A. 2015 Feb 10; 112(6):1761-6.
  73. Zhang T, Barclay L, Walensky LD, Saghatelian A. Regulation of mitochondrial ceramide distribution by members of the BCL-2 family. J Lipid Res. 2015 Aug; 56(8):1501-10.
  74. Edwards AL, Wachter F, Lammert M, Huhn AJ, Luccarelli J, Bird GH, Walensky LD. Cellular Uptake and Ultrastructural Localization Underlie the Pro-apoptotic Activity of a Hydrocarbon-stapled BIM BH3 Peptide. ACS Chem Biol. 2015 Sep 18; 10(9):2149-57.
  75. Braun CR, Bird GH, Wühr M, Erickson BK, Rad R, Walensky LD, Gygi SP, Haas W. Generation of multiple reporter ions from a single isobaric reagent increases multiplexing capacity for quantitative proteomics. Anal Chem. 2015 Oct 06; 87(19):9855-63.
  76. Kim KH, Kim W, Howard TP, Vazquez F, Tsherniak A, Wu JN, Wang W, Haswell JR, Walensky LD, Hahn WC, Orkin SH, Roberts CW. SWI/SNF-mutant cancers depend on catalytic and non-catalytic activity of EZH2. Nat Med. 2015 Dec; 21(12):1491-6.
  77. Lee S, Wales TE, Escudero S, Cohen DT, Luccarelli J, Gallagher CG, Cohen NA, Huhn AJ, Bird GH, Engen JR, Walensky LD. Allosteric inhibition of antiapoptotic MCL-1. Nat Struct Mol Biol. 2016 Jun; 23(6):600-7.
  78. Bird GH, Mazzola E, Opoku-Nsiah K, Lammert MA, Godes M, Neuberg DS, Walensky LD. Biophysical determinants for cellular uptake of hydrocarbon-stapled peptide helices. Nat Chem Biol. 2016 Oct; 12(10):845-52.
  79. Huhn AJ, Guerra RM, Harvey EP, Bird GH, Walensky LD. Selective Covalent Targeting of Anti-Apoptotic BFL-1 by Cysteine-Reactive Stapled Peptide Inhibitors. Cell Chem Biol. 2016 Sep 22; 23(9):1123-34.
To schedule an appointment: Call 617-632-6794 or Request an Appointment

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