Bio

Bio


I am currently postdoctoral research fellow pursuing immunotherapy research in the oncology department at Stanford University. My clinical training as a pediatric hematology oncology fellow at Memorial Sloan Kettering Cancer Center highlighted the desperate need for novel therapeutic options for a subtype of aggressive pediatric leukemia, Acute Myeloid Leukemia (AML). Despite our best standard of care for AML, long term survival rates range from 50-60% with an unacceptably high relapse rate of 40%. The urgent need for novel treatments inspired me to pursue a research project in adoptive immunotherapy, genetically modifying Tcells to express artificial T cell receptors, termed chimeric antigen receptors (CARs), that target AML specific antigens. In parallel to my clinical training, I constructed an AML specific CAR and demonstrated its ability to redirect T cell function mediating eradication of AML cells. As the field of CAR therapy rapidly advances, novel methods to optimize this therapeutic modality are imperative. To this end, supported by research demonstrating superior antitumor function of naïve derived effector T cells compared to central memory derived effector T cells, I am investigating whether preferential modification of naïve T cells to express CARs will generate a T cell subpopulation with increased efficacy. Consolidating my clinical and research experiences within highly academic institutes allows me to synthesize my pursuit of scientific rigor and commitment to the field of oncology, with a mission to achieve productive research and translatable results.

Clinical Focus


  • Pediatric Hematology-Oncology

Academic Appointments


Honors & Awards


  • Faculty of Pure and Applied Science Scholarship, York University (2000, 2001, 2002)
  • Ivan H. Smith Memorial Studentship Award, Cancer Care Ontario and Hospital for Sick Children (2005)
  • Kurdyak International Health Elective Award, Center for International Health and University of Toronto (2006)
  • Betty Lee Fellowship, New York Presbyterian Hospital, Weill Cornell (2010)

Boards, Advisory Committees, Professional Organizations


  • Board Certification in General Pediatrics, American Board of Pediatrics (2010 - Present)
  • Member, American Society of Hematology (2012 - Present)
  • Member, American Society of Pediatric Hematology Oncology (2012 - Present)
  • Member, American Society of Clinical Oncology (2012 - Present)
  • Member, American Academy of Pediatrics (2007 - Present)

Professional Education


  • Board Certification: Pediatrics, American Board of Pediatrics (2010)
  • Board Certification: Pediatric Hematology-Oncology, American Board of Pediatrics (2015)
  • Medical Education:University of Toronto (2007) Canada
  • Internship:New York Presbyterian Hospital- Weill CornellNY
  • Residency:New York Presbyterian Hospital- Weill CornellNY
  • Fellowship:Memorial Sloan Kettering Cancer CenterNY
  • Fellow, Memorial Sloan-Kettering Cancer Center, Pediatric Hematology Oncology (2013)
  • Resident, New York Presbyterian Hospital- Weill Cornell, Pediatrics (2010)

Publications

All Publications


  • Driving CAR T cell translation forward. Science translational medicine Schultz, L., Mackall, C. 2019; 11 (481)

    Abstract

    Successes in CAR T cell translation have propelled their commercial launch, but expanding the impact of cancer immunotherapies remains challenging.

    View details for PubMedID 30814337

  • Acute myeloid leukemia immunopeptidome reveals HLA presentation of mutated nucleophosmin. PloS one Narayan, R., Olsson, N., Wagar, L. E., Medeiros, B. C., Meyer, E., Czerwinski, D., Khodadoust, M. S., Zhang, L., Schultz, L., Davis, M. M., Elias, J. E., Levy, R. 2019; 14 (7): e0219547

    Abstract

    Somatic mutations in cancer are a potential source of cancer specific neoantigens. Acute myeloid leukemia (AML) has common recurrent mutations shared between patients in addition to private mutations specific to individuals. We hypothesized that neoantigens derived from recurrent shared mutations would be attractive targets for future immunotherapeutic approaches. Here we sought to study the HLA Class I and II immunopeptidome of thirteen primary AML tumor samples and two AML cell lines (OCI-AML3 and MV4-11) using mass spectrometry to evaluate for endogenous mutation-bearing HLA ligands from common shared AML mutations. We identified two endogenous, mutation-bearing HLA Class I ligands from nucleophosmin (NPM1). The ligands, AVEEVSLRK from two patient samples and C(cys)LAVEEVSL from OCI-AML3, are predicted to bind the common HLA haplotypes, HLA-A*03:01 and HLA-A*02:01 respectively. Since NPM1 is mutated in approximately one-third of patients with AML, the finding of endogenous HLA ligands from mutated NPM1 supports future studies evaluating immunotherapeutic approaches against this shared target, for this subset of patients with AML.

    View details for DOI 10.1371/journal.pone.0219547

    View details for PubMedID 31291378

  • Organoid Modeling of the Tumor Immune Microenvironment. Cell Neal, J. T., Li, X., Zhu, J., Giangarra, V., Grzeskowiak, C. L., Ju, J., Liu, I. H., Chiou, S., Salahudeen, A. A., Smith, A. R., Deutsch, B. C., Liao, L., Zemek, A. J., Zhao, F., Karlsson, K., Schultz, L. M., Metzner, T. J., Nadauld, L. D., Tseng, Y., Alkhairy, S., Oh, C., Keskula, P., Mendoza-Villanueva, D., De La Vega, F. M., Kunz, P. L., Liao, J. C., Leppert, J. T., Sunwoo, J. B., Sabatti, C., Boehm, J. S., Hahn, W. C., Zheng, G. X., Davis, M. M., Kuo, C. J. 2018; 175 (7): 1972

    Abstract

    Invitro cancer cultures, including three-dimensional organoids, typically contain exclusively neoplastic epithelium but require artificial reconstitution to recapitulate the tumor microenvironment (TME). The co-culture of primary tumor epithelia with endogenous, syngeneic tumor-infiltrating lymphocytes (TILs) as a cohesive unit has been particularly elusive. Here, an air-liquid interface (ALI) method propagated patient-derived organoids (PDOs) from >100 human biopsies or mouse tumors in syngeneic immunocompetent hosts as tumor epithelia with native embedded immune cells (T, B, NK, macrophages). Robust droplet-based, single-cell simultaneous determination of gene expression and immune repertoire indicated that PDO TILs accurately preserved the original tumor Tcell receptor (TCR) spectrum. Crucially, human and murine PDOs successfully modeled immune checkpoint blockade (ICB) with anti-PD-1- and/or anti-PD-L1 expanding and activating tumor antigen-specific TILs and eliciting tumor cytotoxicity. Organoid-based propagation of primary tumor epithelium en bloc with endogenous immune stroma should enable immuno-oncology investigations within the TME and facilitate personalized immunotherapy testing.

    View details for PubMedID 30550791

  • 1 Study of CD19/CD22 Bispecific Chimeric Antigen Receptor (CAR) Therapy in Children and Young Adults with B Cell Acute Lymphoblastic Leukemia (ALL) Schultz, L. M., Davis, K. L., Baggott, C., Chaudry, C., Marcy, A., Mavroukakis, S., Sahaf, B., Kong, K. A., Muffly, L. S., Kim, S., Meyer, E. H., Fry, T. J., Qin, H., Miklos, D. B., Mackall, C. L. AMER SOC HEMATOLOGY. 2018
  • T-cell immunopeptidomes reveal cell subtype surface markers derived from intracellular proteins. Proteomics Olsson, N., Schultz, L. M., Zhang, L., Khodadoust, M. S., Narayan, R., Czerwinski, D. K., Levy, R., Elias, J. E. 2018

    Abstract

    Immunopeptidomes promise novel surface markers as ideal immunotherapy targets, but their characterization by mass spectrometry (MS) remains challenging. Until recently, cell numbers exceeding 109were needed to survey thousands of HLA ligands. Such limited analytical sensitivity has historically constrained the types of clinical specimens that can be evaluated to cell cultures or bulk tissues. Measuring immunopeptidomes from purified cell subpopulations would be preferable for many applications, particularly those evaluating rare, primary hematopoietic cell lineages. Here, we test the feasibility of immunopeptidome profiling from limited numbers of primary purified human regulatory T cells (TReg), conventional T cells (Tconv) and activated T cells. The combined T-cell immunopeptide dataset reported here contains 13,804 unique HLA ligands derived from 5,049 proteins. Of these, more than 700 HLA ligands were derived from 82 proteins that we exclusively identified from TReg-enriched cells. This study 1) demonstrates that primary, lineage-enriched T cell supbopulations recovered from single donors are compatible with immunopeptidome analysis; 2) presents new TReg-biased ligand candidates; and 3) supports immunopeptidome surveys value for revealing T cell biology that may not be apparent from expression data alone. Taken together, these findings open up new avenues for targeting TRegand abrogating their suppressive functions to treat cancer. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1002/pmic.201700410

    View details for PubMedID 29493099

  • New developments in immunotherapy for pediatric solid tumors. Current opinion in pediatrics Schultz, L. M., Majzner, R., Davis, K. L., Mackall, C. 2017

    Abstract

    Building upon preclinical advances, we are uncovering immunotherapy strategies that are translating into improved outcomes in tumor subsets. Advanced pediatric solid tumors carry poor prognoses and resultant robust efforts to apply immunotherapy advances to pediatric solid tumors are in progress. Here, we discuss recent developments in the field using mAb and mAb-based therapies including checkpoint blockade and chimeric antigen receptors (CARs).The pediatric solid tumor mAb experience targeting the diganglioside, GD2, for patients with neuroblastoma has been the most compelling to date. GD2 and alternative antigen-specific mAbs are now being incorporated into antibody-drug conjugates, bispecific antibodies and CARs for treatment of solid tumors. CARs in pediatric solid tumors have not yet achieved comparative responses to the hematologic CAR experience; however, novel strategies such as bispecific targeting, intratumoral administration and improved understanding of T-cell biology may yield enhanced CAR-efficacy. Therapeutic effect using single-agent checkpoint blocking antibodies in pediatric solid tumors also remains limited to date. Combinatorial strategies continue to hold promise and the clinical effect in tumor subsets with high antigenic burden is being explored.Pediatric immunotherapy remains at early stages of translation, yet we anticipate that with advanced technology, we will achieve widespread, efficacious use of immunotherapy for pediatric solid tumors.

    View details for DOI 10.1097/MOP.0000000000000564

    View details for PubMedID 29189429

  • T-cell-based Immunotherapy: Adoptive Cell Transfer and Checkpoint Inhibition. Cancer immunology research Houot, R., Schultz, L. M., Marabelle, A., Kohrt, H. 2015; 3 (10): 1115-1122

    View details for DOI 10.1158/2326-6066.CIR-15-0190

    View details for PubMedID 26438444