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James L. Labelle

Associate Professor
jlabelle1@uchicago.edu
Websites
Research Summary
The major goal of the laboratory is to dissect and pharmacologically target intracellular proteins to induce cancer cell death and manipulate the immune response. We are currently applying new research tools and prototype therapeutics that we, and others, have developed to target the BCL-2 family of proteins and other cell signaling proteins in immune cells. A large part of our lab focuses on using portions of the actual proteins, or peptides, as drugs and biological tools to uncover specific molecular pathways in diseased and normal cells. Peptide-based therapeutics have enormous potential for immune modulation and direct cancer treatment but have traditionally lacked efficient stabilization and delivery within patients, and thereby, have had limited clinical applications. To are working to overcome these barriers within the lab and through collaboration with nanotechnologists and chemical engineers. Overall, we are committed to translation of our findings to pediatric and adult patients with cancer and immune system disease. While performing research at the University of Chicago, we are in close proximity to scientists, clinicians, and patients and are deeply committed to working collaboratively with these groups to make significant inroads in treating those suffering from refractory disease.
Keywords
bcl-2 Genes, Regulatory T Cells, Graft Versus Host Disease, Immunomodulatory Therapies
Education
  • Dana-Farber Cancer Institute/BCH, Boston, MA, Postdoctoral fellowship, Walensky Lab Cancer Chemical Biology 06/2012
  • Dana-Farber Cancer Institute/BCH, Boston, MA, Clinical Fellow Pediatric Hematology/Oncology 06/2009
  • Boston Children's Hospital (BCH), Boston, MA, Intern/Resident Pediatrics 06/2006
  • Medical College of Wisconsin, Milwaukee, WI, MD/PhD Medicine/Immunology 06/2003
  • Lawrence University, Appleton, WI, BA Biology 06/1994
Biosciences Graduate Program Association
Awards & Honors
  • 1992 - Engstrom Scholars Award
  • 1994 - Botanical Society of America Merit Award
  • 1994 - Phi Sigma Award in Biology
  • 2001 - First Place, Research Trainee Award
  • 2004 - Proctor and Gamble Teaching and Tomorrow Award
  • 2006 - Senior Resident Teaching Award
  • 2007 - Lauri Strauss Leukemia Foundation Research Award
  • 2010 - Leukemia and Lymphoma Society Special Fellow Award
  • 2011 - AACR-Aflac Scholar-in-Training Award
  • 2012 - Cancer Research Foundation Young Investigator's Award
  • 2013 - James B. Nachman Fellow
  • 2014 - Hyundai Hope on Wheels Scholar Award
  • 2014 - United-4a Cure Research Award
  • 2015 - Comer Children's Hospital Development Board Award
  • 2016 - AbbVie-UChicago Collaboration in Oncology Award
  • 2016 - Hoogland Lymphoma Pilot Project Award
  • 2018 - Hyundai Hope on Wheels Scholar Award
Publications

  1. Desai AV, Applebaum MA, Karrison TG, Oppong A, Yuan C, Berg KR, MacQuarrie K, Sokol E, Hall AG, Pinto N, Wolfe I, Mody R, Shusterman S, Smith V, Foster JH, Nassin M, LaBelle JL, Bagatell R, Cohn SL. Efficacy of post-induction therapy for high-risk neuroblastoma patients with end-induction residual disease. Cancer. 2022 Jun 06. View in: PubMed

  2. Siddiqui A, Pinto N, Applebaum MA, Mak GZ, Cunningham JM, LaBelle JL, Nassin ML. The addition of autologous stem cell transplantation to neoadjuvant chemotherapy, radiation, and HIPEC for patients with unresectable desmoplastic small round cell tumor: a single center case series. Int J Surg Oncol (N Y). 2020 Dec; 5(6). View in: PubMed

  3. Tian Y, Tirrell MV, LaBelle JL. Harnessing the Therapeutic Potential of Biomacromolecules through Intracellular Delivery of Nucleic Acids, Peptides, and Proteins. Adv Healthc Mater. 2022 Jun; 11(12):e2102600. View in: PubMed

  4. McKee MN, Palama BK, Hall M, LaBelle JL, Bohr NL, Hoehn KS. Racial and Ethnic Differences in Inpatient Palliative Care for Pediatric Stem Cell Transplant Patients. Pediatr Crit Care Med. 2022 Jun 01; 23(6):417-424. View in: PubMed

  5. Khanna S, Mackin AG, Dao DT, Komati R, Morocco PC, LaBelle JL, Shah HA, Blair MP. Exudative Retinal Detachment Following Chimeric Antigen Receptor T-Cell Therapy in Relapsed B-Cell Acute Lymphoblastic Leukemia. Ophthalmic Surg Lasers Imaging Retina. 2022 02; 53(2):113-115. View in: PubMed

  6. Ludwig LM, Hawley KM, Banks DB, Thomas-Toth AT, Blazar BR, McNerney ME, Leverson JD, LaBelle JL. Venetoclax imparts distinct cell death sensitivity and adaptivity patterns in T cells. Cell Death Dis. 2021 10 27; 12(11):1005. View in: PubMed

  7. Volpatti LR, Wallace RP, Cao S, Raczy MM, Wang R, Gray LT, Alpar AT, Briquez PS, Mitrousis N, Marchell TM, Sasso MS, Nguyen M, Mansurov A, Budina E, Solanki A, Watkins EA, Schnorenberg MR, Tremain AC, Reda JW, Nicolaescu V, Furlong K, Dvorkin S, Yu SS, Manicassamy B, LaBelle JL, Tirrell MV, Randall G, Kwissa M, Swartz MA, Hubbell JA. Polymersomes Decorated with the SARS-CoV-2 Spike Protein Receptor-Binding Domain Elicit Robust Humoral and Cellular Immunity. ACS Cent Sci. 2021 Aug 25; 7(8):1368-1380. View in: PubMed

  8. Harris K, LaBelle JL, Bishop MR. Current Status of CAR T Cell Therapy for Leukemias. Curr Treat Options Oncol. 2021 06 07; 22(7):62. View in: PubMed

  9. Volpatti LR, Wallace RP, Cao S, Raczy MM, Wang R, Gray LT, Alpar AT, Briquez PS, Mitrousis N, Marchell TM, Sasso MS, Nguyen M, Mansurov A, Budina E, Solanki A, Watkins EA, Schnorenberg MR, Tremain AC, Reda JW, Nicolaescu V, Furlong K, Dvorkin S, Yu SS, Manicassamy B, LaBelle JL, Tirrell MV, Randall G, Kwissa M, Swartz MA, Hubbell JA. Polymersomes decorated with SARS-CoV-2 spike protein receptor binding domain elicit robust humoral and cellular immunity. bioRxiv. 2021 Apr 08. View in: PubMed

  10. Ludwig LM, Roach LE, Katz SG, LaBelle JL. Loss of BIM in T cells results in BCL-2 family BH3-member compensation but incomplete cell death sensitivity normalization. Apoptosis. 2020 04; 25(3-4):247-260. View in: PubMed

  11. Kothari S, Artz AS, Lee SM, Fulton N, Park JH, Stock W, Larson RA, Odenike O, Kline J, LaBelle J, Kosuri S, Riedell P, Nakamura Y, Bishop MR, Liu H. Dose escalation prophylactic donor lymphocyte infusion after T-cell depleted matched related donor allogeneic hematopoietic cell transplantation is feasible and results in higher donor chimerism, faster immune re-constitution, and prolonged progression-free survival. Bone Marrow Transplant. 2020 06; 55(6):1161-1168. View in: PubMed

  12. Hadji A, Schmitt GK, Schnorenberg MR, Roach L, Hickey CM, Leak LB, Tirrell MV, LaBelle JL. Preferential targeting of MCL-1 by a hydrocarbon-stapled BIM BH3 peptide. Oncotarget. 2019 Oct 22; 10(58):6219-6233. View in: PubMed

  13. Schnorenberg MR, Bellairs JA, Samaeekia R, Acar H, Tirrell MV, LaBelle JL. Activating the Intrinsic Pathway of Apoptosis Using BIM BH3 Peptides Delivered by Peptide Amphiphiles with Endosomal Release. Materials (Basel). 2019 Aug 12; 12(16). View in: PubMed

  14. Fan Y, Artz AS, van Besien K, Stock W, Larson RA, Odenike O, Godley LA, Kline J, Cunningham JM, LaBelle JL, Bishop MR, Liu H. Outcomes following second allogeneic stem cell transplant for disease relapse after T cell depleted transplant correlate with remission status and remission duration after the first transplant. Exp Hematol Oncol. 2019; 8:1. View in: PubMed

  15. Ludwig LM, Maxcy KL, LaBelle JL. Flow Cytometry-Based Detection and Analysis of BCL-2 Family Proteins and Mitochondrial Outer Membrane Permeabilization (MOMP). Methods Mol Biol. 2019; 1877:77-91. View in: PubMed

  16. Schnorenberg MR, Yoo SP, Tirrell MV, LaBelle JL. Synthesis and Purification of Homogeneous Lipid-Based Peptide Nanocarriers by Overcoming Phospholipid Ester Hydrolysis. ACS Omega. 2018 Oct 31; 3(10):14144-14150. View in: PubMed

  17. Nassin ML, Nicolaou E, Gurbuxani S, Cohn SL, Cunningham JM, LaBelle JL. Immune Reconstitution Following Autologous Stem Cell Transplantation in Patients with High-Risk Neuroblastoma at the Time of Immunotherapy. Biol Blood Marrow Transplant. 2018 03; 24(3):452-459. View in: PubMed

  18. Acar H, Ting JM, Srivastava S, LaBelle JL, Tirrell MV. Molecular engineering solutions for therapeutic peptide delivery. Chem Soc Rev. 2017 Oct 30; 46(21):6553-6569. View in: PubMed

  19. Acar H, Samaeekia R, Schnorenberg MR, Sasmal DK, Huang J, Tirrell MV, LaBelle JL. Cathepsin-Mediated Cleavage of Peptides from Peptide Amphiphiles Leads to Enhanced Intracellular Peptide Accumulation. Bioconjug Chem. 2017 09 20; 28(9):2316-2326. View in: PubMed

  20. Pu J, Dewey JA, Hadji A, LaBelle JL, Dickinson BC. RNA Polymerase Tags To Monitor Multidimensional Protein-Protein Interactions Reveal Pharmacological Engagement of Bcl-2 Proteins. J Am Chem Soc. 2017 08 30; 139(34):11964-11972. View in: PubMed

  21. Nassin ML, Vergilio JA, Heeney MM, LaBelle JL. Neonatal anemia: Revisiting the enigmatic pyknocyte. Am J Hematol. 2017 Jul; 92(7):717-721. View in: PubMed

  22. Ludwig LM, Nassin ML, Hadji A, LaBelle JL. Killing Two Cells with One Stone: Pharmacologic BCL-2 Family Targeting for Cancer Cell Death and Immune Modulation. Front Pediatr. 2016; 4:135. View in: PubMed

  23. Acar H, Srivastava S, Chung EJ, Schnorenberg MR, Barrett JC, LaBelle JL, Tirrell M. Self-assembling peptide-based building blocks in medical applications. Adv Drug Deliv Rev. 2017 02; 110-111:65-79. View in: PubMed

  24. Darlington WS, Pinto N, Hecktman HM, Cohn SL, LaBelle JL. Stem Cell Transplant-Associated Wernicke Encephalopathy in a Patient with High-Risk Neuroblastoma. Pediatr Blood Cancer. 2015 Dec; 62(12):2232-4. View in: PubMed

  25. 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. View in: PubMed

  26. 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. View in: PubMed

  27. 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 06; 123(6):884-93. View in: PubMed

  28. Meserve EE, Lehmann LE, Perez-Atayde AR, Labelle JL. Cyclophosphamide-associated cardiotoxicity in a child after stem cell transplantation for ß-thalassemia major: case report and review of the literature. Pediatr Dev Pathol. 2014 Jan-Feb; 17(1):50-4. View in: PubMed

  29. 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. View in: PubMed

  30. LaBelle JL, Cunningham JM. Stem cell transplant as an immunomodulatory tool for children with hematologic malignancies. Am Soc Clin Oncol Educ Book. 2013. View in: PubMed

  31. 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. View in: PubMed

  32. 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. View in: PubMed

  33. Gutweiler JR, Labelle J, Suh MY, Misra MV, Ahmed M, Lee EY, Vargas SO, Kim HB, Weldon CB. A familial case of pleuropulmonary blastoma. Eur J Pediatr Surg. 2008 Jun; 18(3):192-4. View in: PubMed

  34. Fishman DS, Manfredi MA, LaBelle JL, Levine JE, Shamberger RC, Rufo PA. Pancreatitis as the initial manifestation of stage IV neuroblastoma. J Pediatr Gastroenterol Nutr. 2007 Jan; 44(1):146-8. View in: PubMed

  35. Rosenblum MD, LaBelle JL, Chang CC, Margolis DA, Schauer DW, Vesole DH. Efficacy of alemtuzumab treatment for refractory T-cell large granular lymphocytic leukemia. Blood. 2004 Mar 01; 103(5):1969-71. View in: PubMed

  36. LaBelle JL, Truitt RL. Characterization of a murine NKT cell tumor previously described as an acute myelogenous leukemia. Leuk Lymphoma. 2002 Aug; 43(8):1637-44. View in: PubMed

  37. LaBelle JL, Hanke CA, Blazar BR, Truitt RL. Negative effect of CTLA-4 on induction of T-cell immunity in vivo to B7-1+, but not B7-2+, murine myelogenous leukemia. Blood. 2002 Mar 15; 99(6):2146-53. View in: PubMed

  38. Johnson BD, Becker EE, LaBelle JL, Truitt RL. Role of immunoregulatory donor T cells in suppression of graft-versus-host disease following donor leukocyte infusion therapy. J Immunol. 1999 Dec 15; 163(12):6479-87. View in: PubMed
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