Loren Walensky, MD, PhD
Attending Physician, Dana-Farber/Boston Children's Cancer and Blood Disorders Center; Director, Harvard/MIT MD-PhD Program
Professor of Pediatrics, Harvard Medical School
Image
Loren Walensky, MD, PhD
Attending Physician, Dana-Farber/Boston Children's Cancer and Blood Disorders Center; Director, Harvard/MIT MD-PhD Program
Professor of Pediatrics, Harvard Medical School
Medical Services
Languages
English
Education
Medical School
Johns Hopkins University School of Medicine
Baltimore
MD
Residency
Pediatrics
Boston Combined Residency Program (BCRP)
Boston
MA
Fellowship
Pediatric Hematology-Oncology
Boston Children's Hospital/Dana-Farber Cancer Institute
Boston
MA
Certifications
American Board of Pediatrics (Hematology-Oncology)
Professional History
Dr. Loren Walensky received his MD and PhD degrees from Johns Hopkins University School of Medicine in 1997. He trained at the Boston Combined Residency Program in pediatrics, completed a fellowship in pediatric hematology-oncology at Dana-Farber and Boston Children's Hospital, and is board-certified in pediatric hematology/oncology. Dr. Walensky joined Dana-Farber as an attending physician in pediatric hematology/oncology in 2003 and founded his cancer chemical biology research laboratory in 2006. His research involves the development of highly specific and stable “stapled peptides” that preserve the structure of biologically-active peptide helices, maximizing their potential as novel tools to elucidate oncogenic pathways and as prototype therapies for cancer. A stapled peptide drug based on his research is currently undergoing clinical testing in a diversity of human cancers. Dr. Walensky is currently Principal Investigator and Attending Physician in the Department of Pediatric Oncology at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center; Professor of Pediatrics at Harvard Medical School; and Director of the Harvard/MIT MD-PhD Program.
Publications
Bridging Medicine and Society-A Call to Expand the Pipeline of Physician-Social Scientists. View Abstract
Application Overload - A Call to Reduce the Burden of Applying to Medical School. View Abstract
US Science in Peril. View Abstract
Dissecting the neuroprotective interaction between the BH4 domain of BCL-w and the IP3 receptor. View Abstract
Dispelling the myth: comparable duration and impact of research training for MD-PhD and PhD graduates. View Abstract
Covalent inhibition of pro-apoptotic BAX. View Abstract
A stapled lipopeptide platform for preventing and treating highly pathogenic viruses of pandemic potential. View Abstract
Targeting MCL-1 triggers DNA damage and an anti-proliferative response independent from apoptosis induction. View Abstract
Preclinical models for prediction of immunotherapy outcomes and immune evasion mechanisms in genetically heterogeneous multiple myeloma. View Abstract
Inhibition of FOXP3 by stapled alpha-helical peptides dampens regulatory T cell function. View Abstract
MCL-1 is a master regulator of cancer dependency on fatty acid oxidation. View Abstract
Structural basis for defective membrane targeting of mutant enzyme in human VLCAD deficiency. View Abstract
Generation of Potent and Stable GLP-1 Analogues Via "Serine Ligation". View Abstract
Correction: Phase I Trial of ALRN-6924, a Dual Inhibitor of MDMX and MDM2, in Patients with Solid Tumors and Lymphomas Bearing Wild-type TP53. View Abstract
Glucose metabolism and pyruvate carboxylase enhance glutathione synthesis and restrict oxidative stress in pancreatic islets. View Abstract
The conformational stability of pro-apoptotic BAX is dictated by discrete residues of the protein core. View Abstract
Characterizing Native and Hydrocarbon-Stapled Enfuvirtide Conformations with Ion Mobility Mass Spectrometry and Hydrogen-Deuterium Exchange. View Abstract
Binding and transport of SFPQ-RNA granules by KIF5A/KLC1 motors promotes axon survival. View Abstract
Targeting a helix-in-groove interaction between E1 and E2 blocks ubiquitin transfer. View Abstract
A redox switch regulates the structure and function of anti-apoptotic BFL-1. View Abstract
Homogeneous Oligomers of Pro-apoptotic BAX Reveal Structural Determinants of Mitochondrial Membrane Permeabilization. View Abstract
Hydrocarbon-Stitched Peptide Agonists of Glucagon-Like Peptide-1 Receptor. View Abstract
Identification of a Covalent Molecular Inhibitor of Anti-apoptotic BFL-1 by Disulfide Tethering. View Abstract
Glucose-dependent partitioning of arginine to the urea cycle protects ß-cells from inflammation. View Abstract
Identification of a Structural Determinant for Selective Targeting of HDMX. View Abstract
Site-Dependent Cysteine Lipidation Potentiates the Activation of Proapoptotic BAX. View Abstract
Mind the gap: Expediting gender parity in MD-PhD admissions. View Abstract
Design of stapled antimicrobial peptides that are stable, nontoxic and kill antibiotic-resistant bacteria in mice. View Abstract
Targeting BAX to drug death directly. View Abstract
Cheating Death: New Molecules Block BAX. View Abstract
MDM2 and MDM4 Are Therapeutic Vulnerabilities in Malignant Rhabdoid Tumors. View Abstract
Precision Targeting of BFL-1/A1 and an ATM Co-dependency in Human Cancer. View Abstract
Genome-scale CRISPR-Cas9 screen identifies druggable dependencies in TP53 wild-type Ewing sarcoma. View Abstract
Dynamic Regulation of Long-Chain Fatty Acid Oxidation by a Noncanonical Interaction between the MCL-1 BH3 Helix and VLCAD. View Abstract
Iterative optimization yields Mcl-1-targeting stapled peptides with selective cytotoxicity to Mcl-1-dependent cancer cells. View Abstract
Crystal Structures of Anti-apoptotic BFL-1 and Its Complex with a Covalent Stapled Peptide Inhibitor. View Abstract
Paclitaxel Reduces Axonal Bclw to Initiate IP3R1-Dependent Axon Degeneration. View Abstract
Direct Activation of BAX by BTSA1 Overcomes Apoptosis Resistance in Acute Myeloid Leukemia. View Abstract
Extra-mitochondrial prosurvival BCL-2 proteins regulate gene transcription by inhibiting the SUFU tumour suppressor. View Abstract
Allosteric sensitization of proapoptotic BAX. View Abstract
Bim gene dosage is critical in modulating nephron progenitor survival in the absence of microRNAs during kidney development. View Abstract
Mechanistic validation of a clinical lead stapled peptide that reactivates p53 by dual HDM2 and HDMX targeting. View Abstract
Challenges in Targeting a Basic Helix-Loop-Helix Transcription Factor with Hydrocarbon-Stapled Peptides. View Abstract
Selective Covalent Targeting of Anti-Apoptotic BFL-1 by Cysteine-Reactive Stapled Peptide Inhibitors. View Abstract
Biophysical determinants for cellular uptake of hydrocarbon-stapled peptide helices. View Abstract
Allosteric inhibition of antiapoptotic MCL-1. View Abstract
Reply to Fernandez-Marrero et al.: Role of BOK at the intersection of endoplasmic reticulum stress and apoptosis regulation. View Abstract
SWI/SNF-mutant cancers depend on catalytic and non-catalytic activity of EZH2. View Abstract
Generation of multiple reporter ions from a single isobaric reagent increases multiplexing capacity for quantitative proteomics. View Abstract
Cellular Uptake and Ultrastructural Localization Underlie the Pro-apoptotic Activity of a Hydrocarbon-stapled BIM BH3 Peptide. View Abstract
Regulation of mitochondrial ceramide distribution by members of the BCL-2 family. View Abstract
BCL-2 family member BOK promotes apoptosis in response to endoplasmic reticulum stress. View Abstract
A nonapoptotic role for BAX and BAK in eicosanoid metabolism. View Abstract
Inhibition of Pro-apoptotic BAX by a noncanonical interaction mechanism. View Abstract
Phospho-BAD BH3 mimicry protects ß cells and restores functional ß cell mass in diabetes. View Abstract
Direct inhibition of oncogenic KRAS by hydrocarbon-stapled SOS1 helices. View Abstract
Complementary genomic approaches highlight the PI3K/mTOR pathway as a common vulnerability in osteosarcoma. View Abstract
Stapled HIV-1 peptides recapitulate antigenic structures and engage broadly neutralizing antibodies. View Abstract
Mucosal delivery of a double-stapled RSV peptide prevents nasopulmonary infection. View Abstract
Hydrocarbon-stapled peptides: principles, practice, and progress. View Abstract
Repression of BIM mediates survival signaling by MYC and AKT in high-risk T-cell acute lymphoblastic leukemia. View Abstract
Distinct BimBH3 (BimSAHB) stapled peptides for structural and cellular studies. View Abstract
Photoreactive stapled peptides to identify and characterize BCL-2 family interaction sites by mass spectrometry. View Abstract
Mantle cell lymphoma in cyclin D1 transgenic mice with Bim-deficient B cells. View Abstract
A phospho-BAD BH3 helix activates glucokinase by a mechanism distinct from that of allosteric activators. View Abstract
Targeted disruption of the EZH2-EED complex inhibits EZH2-dependent cancer. View Abstract
Multimodal interaction with BCL-2 family proteins underlies the proapoptotic activity of PUMA BH3. View Abstract
Evaluation and critical assessment of putative MCL-1 inhibitors. View Abstract
Direct BAKtivation. View Abstract
The retinoblastoma protein induces apoptosis directly at the mitochondria. View Abstract
Playing fullBAK. View Abstract
Protein-protein interactions: A PUMA mechanism unfolds. View Abstract
Direct activation of full-length proapoptotic BAK. View Abstract
A competitive stapled peptide screen identifies a selective small molecule that overcomes MCL-1-dependent leukemia cell survival. View Abstract
Brain and testicular tumors in mice with progenitor cells lacking BAX and BAK. View Abstract
Targeted disruption of the BCL9/ß-catenin complex inhibits oncogenic Wnt signaling. View Abstract
Interview with Loren D Walensky. View Abstract
Stemming danger with Golgified BAX. View Abstract
Direct and selective small-molecule activation of proapoptotic BAX. View Abstract
A stapled BIM peptide overcomes apoptotic resistance in hematologic cancers. View Abstract
From mitochondrial biology to magic bullet: navitoclax disarms BCL-2 in chronic lymphocytic leukemia. View Abstract
BAX unleashed: the biochemical transformation of an inactive cytosolic monomer into a toxic mitochondrial pore. View Abstract
Chemical synthesis of hydrocarbon-stapled peptides for protein interaction research and therapeutic targeting. View Abstract
Tracking BAX once its trigger is pulled. View Abstract
Characterization of a core fragment of the rhesus monkey TRIM5a protein. View Abstract
Photoreactive stapled BH3 peptides to dissect the BCL-2 family interactome. View Abstract
A stapled p53 helix overcomes HDMX-mediated suppression of p53. View Abstract
BH3-triggered structural reorganization drives the activation of proapoptotic BAX. View Abstract
Hydrocarbon double-stapling remedies the proteolytic instability of a lengthy peptide therapeutic. View Abstract
The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer. View Abstract
BAX activation is initiated at a novel interaction site. View Abstract
Dual role of proapoptotic BAD in insulin secretion and beta cell survival. View Abstract
Synthesis and biophysical characterization of stabilized alpha-helices of BCL-2 domains. View Abstract
Dissection of the BCL-2 family signaling network with stabilized alpha-helices of BCL-2 domains. View Abstract
The challenge of drugging undruggable targets in cancer: lessons learned from targeting BCL-2 family members. View Abstract
Reactivation of the p53 tumor suppressor pathway by a stapled p53 peptide. View Abstract
A stapled BID BH3 helix directly binds and activates BAX. View Abstract
A membrane-targeted BID BCL-2 homology 3 peptide is sufficient for high potency activation of BAX in vitro. View Abstract
BCL-2 in the crosshairs: tipping the balance of life and death. View Abstract
Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix. View Abstract
Management of an anaphylactoid reaction to methotrexate with a stepwise graded challenge. View Abstract
Distinct distribution of specific members of protein 4.1 gene family in the mouse nephron. View Abstract
Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. View Abstract
Regulation of AMPA receptor GluR1 subunit surface expression by a 4. 1N-linked actin cytoskeletal association. View Abstract
Molecular and functional characterization of protein 4.1B, a novel member of the protein 4.1 family with high level, focal expression in brain. View Abstract
Protein 4.1N binding to nuclear mitotic apparatus protein in PC12 cells mediates the antiproliferative actions of nerve growth factor. View Abstract
A novel neuron-enriched homolog of the erythrocyte membrane cytoskeletal protein 4.1. View Abstract
Deciphering the nuclear import pathway for the cytoskeletal red cell protein 4.1R. View Abstract
Protein 4.1R-deficient mice are viable but have erythroid membrane skeleton abnormalities. View Abstract
Four paralogous protein 4.1 genes map to distinct chromosomes in mouse and human. View Abstract
Neurobehavioral deficits in mice lacking the erythrocyte membrane cytoskeletal protein 4.1. View Abstract
The 12 kD FK 506 binding protein FKBP12 is released in the male reproductive tract and stimulates sperm motility. View Abstract
Two novel odorant receptor families expressed in spermatids undergo 5'-splicing. View Abstract
Cloning and characterization of 4.1G (EPB41L2), a new member of the skeletal protein 4.1 (EPB41) gene family. View Abstract
The 13-kD FK506 binding protein, FKBP13, interacts with a novel homologue of the erythrocyte membrane cytoskeletal protein 4.1. View Abstract
Inositol 1,4,5-trisphosphate receptors selectively localized to the acrosomes of mammalian sperm. View Abstract
Immunophilin FK506 binding protein associated with inositol 1,4,5-trisphosphate receptor modulates calcium flux. View Abstract
Odorant receptors and desensitization proteins colocalize in mammalian sperm. View Abstract
A novel M(r) 32,000 nuclear phosphoprotein is selectively expressed in cells competent for self-renewal. View Abstract