LOREN DAVID WALENSKY

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi request reprint Reactivation of the p53 tumor suppressor pathway by a stapled p53 peptide
    Federico Bernal
    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
    J Am Chem Soc 129:2456-7. 2007
  2. ncbi request reprint The challenge of drugging undruggable targets in cancer: lessons learned from targeting BCL-2 family members
    Gregory L Verdine
    Department of Chemistry and Chemical Biology, and Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
    Clin Cancer Res 13:7264-70. 2007
  3. doi request reprint Synthesis and biophysical characterization of stabilized alpha-helices of BCL-2 domains
    Gregory H Bird
    Department of Pediatric Oncology and the Program in Cancer Chemical Biology, Dana Farber Cancer Institute, Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA
    Methods Enzymol 446:369-86. 2008
  4. doi request reprint Dissection of the BCL-2 family signaling network with stabilized alpha-helices of BCL-2 domains
    Kenneth Pitter
    Department of Pediatric Oncology and the Program in Cancer Chemical Biology, Dana Farber Cancer Institute, Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA
    Methods Enzymol 446:387-408. 2008
  5. pmc Brain and testicular tumors in mice with progenitor cells lacking BAX and BAK
    S G Katz
    Department of Pediatric Oncology and the Program in Cancer Chemical Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA
    Oncogene 32:4078-85. 2013
  6. ncbi request reprint Interview: interview with loren d walensky
    Loren D Walensky
    Harvard Medical School, Dana Farber Cancer Institute and Children s Hospital Boston, Mayer Building, Room 664, 450 Brookline Avenue, Boston, MA 02215, USA
    Future Med Chem 4:1537-9. 2012
  7. pmc Stemming Danger with Golgified BAX
    Loren D Walensky
    Department of Pediatric Oncology and the Program in Cancer Chemical Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
    Mol Cell 46:554-6. 2012
  8. pmc Characterization of a core fragment of the rhesus monkey TRIM5α protein
    Alak K Kar
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    BMC Biochem 12:1. 2011
  9. ncbi request reprint A stapled BID BH3 helix directly binds and activates BAX
    Loren D Walensky
    Department of Pediatric Oncology, Dana Farber Cancer Institute and Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 24:199-210. 2006
  10. ncbi request reprint BCL-2 in the crosshairs: tipping the balance of life and death
    L D Walensky
    Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cell Death Differ 13:1339-50. 2006

Research Grants

Collaborators

Detail Information

Publications21

  1. ncbi request reprint Reactivation of the p53 tumor suppressor pathway by a stapled p53 peptide
    Federico Bernal
    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
    J Am Chem Soc 129:2456-7. 2007
  2. ncbi request reprint The challenge of drugging undruggable targets in cancer: lessons learned from targeting BCL-2 family members
    Gregory L Verdine
    Department of Chemistry and Chemical Biology, and Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
    Clin Cancer Res 13:7264-70. 2007
    ....
  3. doi request reprint Synthesis and biophysical characterization of stabilized alpha-helices of BCL-2 domains
    Gregory H Bird
    Department of Pediatric Oncology and the Program in Cancer Chemical Biology, Dana Farber Cancer Institute, Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA
    Methods Enzymol 446:369-86. 2008
    ..Here we describe the chemical synthesis of Stabilized Alpha-Helices of BCL-2 domains or SAHBs, and the analytical methods used to characterize their secondary structure, proteolytic stability, and cellular penetrance...
  4. doi request reprint Dissection of the BCL-2 family signaling network with stabilized alpha-helices of BCL-2 domains
    Kenneth Pitter
    Department of Pediatric Oncology and the Program in Cancer Chemical Biology, Dana Farber Cancer Institute, Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA
    Methods Enzymol 446:387-408. 2008
    ..Here, we describe the in vitro and cell-based methods that exploit SAHB compounds to determine the functional consequences of BH3 interactions in regulating apoptosis...
  5. pmc Brain and testicular tumors in mice with progenitor cells lacking BAX and BAK
    S G Katz
    Department of Pediatric Oncology and the Program in Cancer Chemical Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA
    Oncogene 32:4078-85. 2013
    ..This in vivo model of severe apoptotic blockade highlights the constitutive role of BAX/BAK in long-term regulation of Nestin-positive progenitor cell pools, with loss of function predisposing to adult-onset tumorigenesis...
  6. ncbi request reprint Interview: interview with loren d walensky
    Loren D Walensky
    Harvard Medical School, Dana Farber Cancer Institute and Children s Hospital Boston, Mayer Building, Room 664, 450 Brookline Avenue, Boston, MA 02215, USA
    Future Med Chem 4:1537-9. 2012
    ..Dr Walensky spoke to Isaac Bruce, Commissioning Editor of Future Medicinal Chemistry, about his career in therapeutic peptides, his involvement in collaborations and funding, and the future of peptides as therapy...
  7. pmc Stemming Danger with Golgified BAX
    Loren D Walensky
    Department of Pediatric Oncology and the Program in Cancer Chemical Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
    Mol Cell 46:554-6. 2012
    ..2012) report that hES cells localize a conformationally activated form of proapoptotic BAX to the trans Golgi network, a previously unanticipated launch pad for mitochondrial assault in response to DNA damage...
  8. pmc Characterization of a core fragment of the rhesus monkey TRIM5α protein
    Alak K Kar
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    BMC Biochem 12:1. 2011
    ..2(SPRY) domain. Although structures have been determined for some individual TRIM domains, the structure of an intact TRIM protein is unknown...
  9. ncbi request reprint A stapled BID BH3 helix directly binds and activates BAX
    Loren D Walensky
    Department of Pediatric Oncology, Dana Farber Cancer Institute and Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 24:199-210. 2006
    ..We further demonstrate that membrane targeting of stapled BID BH3 optimizes its ability to activate BAX, supporting a model in which BID directly engages BAX to trigger mitochondrial apoptosis...
  10. ncbi request reprint BCL-2 in the crosshairs: tipping the balance of life and death
    L D Walensky
    Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cell Death Differ 13:1339-50. 2006
    ....
  11. pmc BAX unleashed: the biochemical transformation of an inactive cytosolic monomer into a toxic mitochondrial pore
    Loren D Walensky
    Department of Pediatric Oncology and the Program in Cancer Chemical Biology, Dana Farber Cancer Institute, Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    Trends Biochem Sci 36:642-52. 2011
    ....
  12. pmc The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer
    Michelle L Stewart
    Department of Pediatric Oncology, Dana Farber Cancer Institute and Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA
    Nat Chem Biol 6:595-601. 2010
    ..By leveraging nature's solution to ligand selectivity, we generated an MCL-1-specific agent that defines the structural and functional features of targeted MCL-1 inhibition...
  13. ncbi request reprint Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics
    Anthony Letai
    Howard Hughes Medical Institute, Department of Pathology, Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Cancer Cell 2:183-92. 2002
    ..These data support a two-class model for BH3 domains: BID-like domains that "activate" BAX, BAK and BAD-like domains that "sensitize" by occupying the pocket of antiapoptotic members...
  14. ncbi request reprint Management of an anaphylactoid reaction to methotrexate with a stepwise graded challenge
    Andrew J MacGinnitie
    Division of Allergy Immunology, Children s Hospital, Boston, MA 02446, USA
    Pediatr Allergy Immunol 14:409-11. 2003
    ..Because weekly methotrexate therapy is an important component of continuation chemotherapy for pediatric ALL, a stepwise graded challenge was employed to achieve drug tolerance...
  15. doi request reprint Dual role of proapoptotic BAD in insulin secretion and beta cell survival
    Nika N Danial
    Department of Pathology, Harvard Medical School, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Nat Med 14:144-53. 2008
    ..Furthermore, we show that BAD regulates the physiologic adaptation of beta cell mass during high-fat feeding. Our findings provide genetic proof of the bifunctional activities of BAD in both beta cell survival and insulin secretion...
  16. ncbi request reprint A membrane-targeted BID BCL-2 homology 3 peptide is sufficient for high potency activation of BAX in vitro
    Kyoung Joon Oh
    Howard Hughes Medical Institute, the Department of Pathology and Medicine, Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    J Biol Chem 281:36999-7008. 2006
    ..These results highlight the importance of membrane targeting of the BID BH3 domain in tBID-mediated BAX activation and support a model in which tBID engages BAX to trigger its pro-apoptotic activity...
  17. pmc BH3-triggered structural reorganization drives the activation of proapoptotic BAX
    Evripidis Gavathiotis
    Department of Pediatric Oncology and Program in Cancer Chemical Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 40:481-92. 2010
    ..Our structure-activity analysis of this seminal apoptotic process reveals pharmacologic opportunities to modulate cell death by interceding at key steps of the BAX activation pathway...
  18. pmc Hydrocarbon double-stapling remedies the proteolytic instability of a lengthy peptide therapeutic
    Gregory H Bird
    Department of Pediatric Oncology, Dana Farber Cancer Institute and Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 107:14093-8. 2010
    ..Thus, hydrocarbon double-stapling may unlock the therapeutic potential of natural bioactive polypeptides by transforming them into structurally fortified agents with enhanced bioavailability...
  19. pmc BAX activation is initiated at a novel interaction site
    Evripidis Gavathiotis
    Department of Pediatric Oncology and the Program in Cancer Chemical Biology, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Nature 455:1076-81. 2008
    ..Thus, we have now defined a BAX interaction site for direct activation, establishing a new target for therapeutic modulation of apoptosis...
  20. pmc Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix
    Loren D Walensky
    Howard Hughes Medical Institute, Department of Pediatric Hematology Oncology and Children s Hospital Boston, Massachusetts, USA
    Science 305:1466-70. 2004
    ..Hydrocarbon stapling of native peptides may provide a useful strategy for experimental and therapeutic modulation of protein-protein interactions in many signaling pathways...

Research Grants9

  1. PROTEIN INTERACTION EXTENDS THE CELL DEATH PATHWAY
    LOREN WALENSKY; Fiscal Year: 2006
    ..The current proposal will dissect this pro-apoptotic cascade by identifying the precise downstream molecules that mediate the mitochondrial demise and detailing their mechanism of action. ..
  2. Targeting Apoptosis by Chemical Design
    LOREN WALENSKY; Fiscal Year: 2007
    ..Walensky's development as an independent investigator at the interface of these notable fields. ..
  3. Stapled Antigens for HIV-1 Vaccination
    LOREN WALENSKY; Fiscal Year: 2009
    ....
  4. A Lexicon of Stapled Peptide Helices Engineered to Capture the Protein Interactom
    LOREN WALENSKY; Fiscal Year: 2009
    ....
  5. PROTEIN INTERACTION EXTENDS THE CELL DEATH PATHWAY
    LOREN DAVID WALENSKY; Fiscal Year: 2010
    ..Ultimately, we aim to harness the fresh insights from these studies to generate prototype therapeutics that reactivate BAX-mediated apoptosis in human cancer. ..
  6. Stapled Antigens for HIV-1 Vaccination
    LOREN DAVID WALENSKY; Fiscal Year: 2010
    ....
  7. A Lexicon of Stapled Peptide Helices Engineered to Capture the Protein Interactom
    LOREN DAVID WALENSKY; Fiscal Year: 2010
    ....