Bio

Bio


Kara Davis, D.O. is an Assistant Professor of Pediatrics in the Division of Hematology and Oncology. Dr. Davis obtained her B.A. from Pennsylvania State University and her D.O. from the Philadelphia College of Osteopathic Medicine. Clinically, she completed her training in Pediatrics at Thomas Jefferson University/A.I. DuPont Children’s Hospital and her Heme/Onc fellowship at Lucile Packard Children’s Hospital at Stanford. During her fellowship training, Kara worked in the laboratory of Garry Nolan, Ph.D. where she utilized single-cell, high-dimensional analysis platforms to study healthy human B cell development and B cell leukemia. Her research focuses on using single-cell analysis to organize tumor heterogeneity in pediatric cancers, especially blood cancers, as means to determine cell populations associated with clinical risks such as relapse. Clinically, Dr. Davis sees patients with leukemia and is involved with the Cancer Cellular Therapies program with experience in treating children with chimeric antigen receptor (CAR) T-cells and other immunotherapies including checkpoint inhibitors.

Clinical Focus


  • Pediatric Hematology-Oncology

Academic Appointments


Administrative Appointments


  • Vice Chair, COG Study ADVL1412, Children's Oncology Group (2016 - Present)

Professional Education


  • Fellowship:Lucile Packard Children's Hospital (2010) CA
  • Residency:Thomas Jefferson University/AI duPont Hospital (2007) DE
  • Medical Education:Philadelphia College of Osteopathic Medicine (2004) PA
  • Board Certification: Pediatric Hematology-Oncology, American Board of Pediatrics (2011)
  • Board Certification: Pediatrics, American Board of Pediatrics (2007)

Research & Scholarship

Current Research and Scholarly Interests


To address the intrinsic heterogeneity of primary cancers, we have taken a single-cell approach to the study of cancer, particularly childhood leukemia. To organize the tremendous data generated from single-cell studies, we also seek to understand the healthy structure of the tissue of origin.

Using single-cell, high-parameter analysis platforms, especially mass cytometry, to examine primary patient samples, we seek to identify how childhood cancers diverge from their healthy tissue of origin and how cancer cells may exploit developmental states for their benefit. Further, what populations or features of tumor cells are associated with clinical outcomes of interest, such as site of disease, relapse, or drug resistance? Using this knowledge, we can further investigate new approaches to treatment for children with cancer and mechanisms of drug resistance, and with a particular interest in how this relates to immunotherapeutic approaches to cancer treatment.

Clinical Trials


  • Genome, Proteome and Tissue Microarray in Childhood Acute Leukemia Not Recruiting

    We will study gene and protein expression in leukemia cells of children diagnosed with acute leukemia. We hope to identify genes or proteins which can help us grade leukemia at diagnosis in order to: (a) develop better means of diagnosis and (b) more accurately choose the best therapy for each patient.

    Stanford is currently not accepting patients for this trial. For more information, please contact Norman J Lacayo, 650-723-5535.

    View full details

  • Determine Efficacy and Safety of CTL019 in Pediatric Patients With Relapsed and Refractory B-cell ALL Not Recruiting

    This is a single arm, open-label, multi-center, phase II study to determine the efficacy and safety of CTL019 in pediatric patients with r/r B-cell ALL.

    Stanford is currently not accepting patients for this trial. For more information, please contact Christina Baggott, 650-497-7659.

    View full details

  • Open Label, Phase II Study to Evaluate Efficacy and Safety of Oral Nilotinib in Philadelphia Positive (Ph+) Chronic Myelogenous Leukemia (CML) Pediatric Patients. Not Recruiting

    To evaluate the safety, efficacy and concentration of nilotinib over time in the Ph+ chronic myelogenous leukemia (CML) in pediatric patients (from 1 to <18 years).

    Stanford is currently not accepting patients for this trial. For more information, please contact Contact, 650-723-5117.

    View full details

  • Nivolumab With or Without Ipilimumab in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Sarcomas Recruiting

    This phase I/II trial studies the side effects and best dose of nivolumab when given with or without ipilimumab to see how well they work in treating younger patients with solid tumors or sarcomas that have come back (recurrent) or do not respond to treatment (refractory). Monoclonal antibodies, such as nivolumab and ipilimumab, may block tumor growth in different ways by targeting certain cells. It is not yet known whether nivolumab works better alone or with ipilimumab in treating patients with recurrent or refractory solid tumors or sarcomas.

    View full details

  • CD19/CD22 Chimeric Antigen Receptor T Cells and Chemotherapy in Treating Children or Young Adults With Recurrent or Refractory CD19 Positive B Acute Lymphoblastic Leukemia Recruiting

    This phase I trial studies the best dose and side effects of CD19/CD22 chimeric antigen receptor (CAR) T cells when given together with chemotherapy, and to see how well they work in treating children or young adults with CD19 positive B acute lymphoblastic leukemia that has come back or does not respond to treatment. A CAR is a genetically-engineered receptor made so that immune cells (T cells) can attack cancer cells by recognizing and responding to the CD19/CD22 proteins. These proteins are commonly found on B acute lymphoblastic leukemia. Drugs used in chemotherapy, such as fludarabine phosphate and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving CD19/CD22-CAR T cells and chemotherapy may work better in treating children or young adults with B acute lymphoblastic leukemia.

    View full details

  • Study of Efficacy and Safety of CTL019 in Pediatric ALL Patients Not Recruiting

    This is a single arm, open-label, multi-center, phase II study to determine the efficacy and safety of an experimental therapy called CTL019 T-cells in pediatric patients with B-cell acute lymphoblastic leukemia, who are refractory to standard chemotherapy regimen or relapsed after allogeneic stem cell transplant

    Stanford is currently not accepting patients for this trial.

    View full details

Teaching

2017-18 Courses


Stanford Advisees


Publications

All Publications


  • Data-Driven Phenotypic Dissection of AML Reveals Progenitor-like Cells that Correlate with Prognosis CELL Levine, J. H., Simonds, E. F., Bendall, S. C., Davis, K. L., Amir, E. D., Tadmor, M. D., Litvin, O., Fienberg, H. G., Jager, A., Zunder, E. R., Finck, R., Gedman, A. L., Radtke, I., Downing, J. R., Pe'er, D., Nolan, G. P. 2015; 162 (1): 184-197

    Abstract

    Acute myeloid leukemia (AML) manifests as phenotypically and functionally diverse cells, often within the same patient. Intratumor phenotypic and functional heterogeneity have been linked primarily by physical sorting experiments, which assume that functionally distinct subpopulations can be prospectively isolated by surface phenotypes. This assumption has proven problematic, and we therefore developed a data-driven approach. Using mass cytometry, we profiled surface and intracellular signaling proteins simultaneously in millions of healthy and leukemic cells. We developed PhenoGraph, which algorithmically defines phenotypes in high-dimensional single-cell data. PhenoGraph revealed that the surface phenotypes of leukemic blasts do not necessarily reflect their intracellular state. Using hematopoietic progenitors, we defined a signaling-based measure of cellular phenotype, which led to isolation of a gene expression signature that was predictive of survival in independent cohorts. This study presents new methods for large-scale analysis of single-cell heterogeneity and demonstrates their utility, yielding insights into AML pathophysiology.

    View details for DOI 10.1016/j.cell.2015.05.047

    View details for Web of Science ID 000357542300019

    View details for PubMedID 26095251

  • Single-Cell Trajectory Detection Uncovers Progression and Regulatory Coordination in Human B Cell Development CELL Bendall, S. C., Davis, K. L., Amir, E. D., Tadmor, M. D., Simonds, E. F., Chen, T. J., Shenfeld, D. K., Nolan, G. P., Pe'er, D. 2014; 157 (3): 714-725

    Abstract

    Tissue regeneration is an orchestrated progression of cells from an immature state to a mature one, conventionally represented as distinctive cell subsets. A continuum of transitional cell states exists between these discrete stages. We combine the depth of single-cell mass cytometry and an algorithm developed to leverage this continuum by aligning single cells of a given lineage onto a unified trajectory that accurately predicts the developmental path de novo. Applied to human B cell lymphopoiesis, the algorithm (termed Wanderlust) constructed trajectories spanning from hematopoietic stem cells through to naive B cells. This trajectory revealed nascent fractions of B cell progenitors and aligned them with developmentally cued regulatory signaling including IL-7/STAT5 and cellular events such as immunoglobulin rearrangement, highlighting checkpoints across which regulatory signals are rewired paralleling changes in cellular state. This study provides a comprehensive analysis of human B lymphopoiesis, laying a foundation to apply this approach to other tissues and "corrupted" developmental processes including cancer.

    View details for DOI 10.1016/j.cell.2014.04.005

    View details for Web of Science ID 000335392100019

    View details for PubMedID 24766814

    View details for PubMedCentralID PMC4045247

  • viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia. Nature biotechnology Amir, E. D., Davis, K. L., Tadmor, M. D., Simonds, E. F., Levine, J. H., Bendall, S. C., Shenfeld, D. K., Krishnaswamy, S., Nolan, G. P., Pe'er, D. 2013; 31 (6): 545-552

    Abstract

    New high-dimensional, single-cell technologies offer unprecedented resolution in the analysis of heterogeneous tissues. However, because these technologies can measure dozens of parameters simultaneously in individual cells, data interpretation can be challenging. Here we present viSNE, a tool that allows one to map high-dimensional cytometry data onto two dimensions, yet conserve the high-dimensional structure of the data. viSNE plots individual cells in a visual similar to a scatter plot, while using all pairwise distances in high dimension to determine each cell's location in the plot. We integrated mass cytometry with viSNE to map healthy and cancerous bone marrow samples. Healthy bone marrow automatically maps into a consistent shape, whereas leukemia samples map into malformed shapes that are distinct from healthy bone marrow and from each other. We also use viSNE and mass cytometry to compare leukemia diagnosis and relapse samples, and to identify a rare leukemia population reminiscent of minimal residual disease. viSNE can be applied to any multi-dimensional single-cell technology.

    View details for DOI 10.1038/nbt.2594

    View details for PubMedID 23685480

  • Pediatric Acute Myeloid Leukemia as Classified Using 2008 WHO Criteria: A Single-Center Experience. American journal of clinical pathology Davis, K. L., Marina, N., Arber, D. A., Ma, L., Cherry, A., Dahl, G. V., Heerema-McKenney, A. 2013; 139 (6): 818-825

    Abstract

    The classification of acute myeloid leukemia (AML) has evolved to the most recent World Health Organization (WHO) schema, which integrates genetic, morphologic, and prognostic data into a single system. However, this system was devised using adult data and how this system applies to a pediatric cohort is unknown. Performing a retrospective chart review, we examined our single-center experience with AML in 115 children and classified their leukemia using the WHO 2008 schema. We examined patient samples for mutations of FLT3, NPM1, and CEBPA. Overall survival was calculated within categories. In our pediatric population, most cases of AML had recurrent genetic abnormalities of favorable prognosis. More than 10% of patients in our series were categorized as AML, with myelodysplasia-related changes, an entity not well-described in pediatric patients. In addition, a large proportion of patients were categorized with secondary, therapy-related AML. To our knowledge, this is the first application of the WHO 2008 classification to a pediatric cohort. In comparison to adult studies, AML in the pediatric population shows a distinct distribution within the WHO 2008 classification.

    View details for DOI 10.1309/AJCP59WKRZVNHETN

    View details for PubMedID 23690127

  • Ikaros: master of hematopoiesis, agent of leukemia. Therapeutic advances in hematology Davis, K. L. 2011; 2 (6): 359-368

    Abstract

    Ikaros is the founding member of a family of zinc finger transcription factors whose function during early hematopoietic development is required for differentiation into the three major hematopoietic lineages. Ikaros deletions have been described in human malignancies, particularly precursor B-cell leukemia. Deletions of this transcription factor appear to mediate leukemogenesis, although the exact mechanism is unclear. This article reviews the structure and function of Ikaros proteins in chromatin remodeling and gene expression as well as the current knowledge of Ikaros deletions in human malignancies. A new proteomic platform, mass cytometry, is introduced which allows measurements of greater than 30 parameters at the single-cell level and should thus provide a greater level of detail to unravel the mechanistic consequences of Ikaros dysfunction in leukemia.

    View details for DOI 10.1177/2040620711412419

    View details for PubMedID 23556102

  • Speeding the Flow Toward Personalized Therapy in Childhood Acute Leukemia PEDIATRIC BLOOD & CANCER Simonds, E. F., Davis, K. L., Lacayo, N. J. 2009; 53 (4): 525-526

    View details for DOI 10.1002/pbc.22180

    View details for Web of Science ID 000269295500001

    View details for PubMedID 19642213

  • Why Are Young Infants Tested for Herpes Simplex Virus? PEDIATRIC EMERGENCY CARE Davis, K. L., Shah, S. S., Frank, G., Eppes, S. C. 2008; 24 (10): 673-678

    Abstract

    The polymerase chain reaction (PCR)-based test to detect herpes simplex virus (HSV) genome in cerebrospinal fluid (CSF) has become the test of choice for diagnosing this infection. The utility of this test in young infants undergoing sepsis evaluations is unknown.We sought to identify the factors that prompted physicians to include HSV PCR in their evaluation of young infants undergoing lumbar puncture. In addition, the impact of ordering this test on patient management was assessed.This case-control study included infants 0 to 60 days who were evaluated by lumbar puncture at the Alfred I. duPont Hospital for Children over a 5-year period. Case patients had CSF HSV PCR ordered as part of their evaluation and control patients did not.Eighty-eight case patients and 83 control patients were identified. The median patient age was 12 days and most patients (55%) were male. Both groups were similar in demographics. Herpes simplex virus infection was diagnosed by PCR in 3.4% of cases. The occurrence of a seizure (adjusted odds ratio [OR], 8.3; 95% confidence interval [CI], 1.7-41.0), the performance of CSF enteroviral PCR testing (adjusted OR, 4.7; 95% CI, 1.4-15.8), and the decision to obtain hepatic transaminases (adjusted OR, 5.6; 95% CI, 2.7-11.8) were associated with the decision to perform CSF HSV PCR testing. Use of health care resources associated with PCR testing was considerable.The occurrence of a seizure, the performance of CSF enteroviral PCR testing, and the decision to obtain hepatic transaminases were independently associated with the decision to perform CSF HSV PCR testing. Features traditionally associated with neonatal HSV infection, such as elevated numbers of CSF white blood cells or red blood cells, did not appear to influence the decision to perform CSF HSV PCR testing. The yield of testing in this population was low. Clinicians should weigh the benefits of early diagnosis in a few patients against the consequences of excessive testing in this population.

    View details for Web of Science ID 000260157500006

    View details for PubMedID 19242136