The Caligiuri laboratory at The Ohio State University Comprehensive Cancer Center pursues basic science discovery with the immediate intent of creating impact in clinical medicine. Our laboratory is especially suited for the physician-scientist in training or the postdoctoral researcher interested in discovery for the sake of clinical application. Our research focuses on natural killer cell biology, the Epstein-Barr virus (EBV), lymphoma and leukemia. Since 1990, more than 100 students have trained in the Caligiuri laboratory and have received more than 70 awards for their research.

About the Lab

The laboratory of Michael A. Caligiuri, MD, began in 1990 at Roswell Park Cancer Institute (RPCI) when Dr. Caligiuri was a newly appointed assistant professor in internal medicine (oncology) and microbiology/immunology at RPCI and the State University of New York (SUNY) at Buffalo.

The Caligiuri laboratory moved to The Ohio State University (OSU) in July 1997. Fifteen members of Dr. Caligiuri's team at RPCI joined him at OSU, and since that time he has recruited additional members into the laboratory. The laboratory, which is supervised by Donna Bucci, consists of investigators at the technical, undergraduate, graduate, postgraduate and assistant professor level. The laboratory is also the home for one of the world's largest leukemia tissue banks: the Alliance Hematologic Malignancy Biorepository (HEME). The laboratory also houses the OSU Leukemia Tissue Bank Shared Resource, which serves the Leukemia and hematologic malignancy research community both at OSU and at large.

Dr. Caligiuri's laboratory has evolved to investigate three main scientific areas:

  • The development and normal role of the body's large granular lymphocytes called natural killer cells, and to exploit their properties in order to develop effective therapies against cancer and immune deficiency;
  • The development of a vaccine to prevent lymphoma associated with the Epstein-Barr virus;
  • Why we get acute leukemia and how we should treat it. The lab has mouse models of acute leukemia as well as the world's largest bank of human leukemia cells to study the causes of acute leukemia and to develop novel immune therapies to treat acute leukemia. 

Lab Research

Acute Myeloid Leukemia:

In the era of personalized medicine, we are developing targeted drug combinations for acute myeloid leukemia (AML) patients harboring mutations in the H3K4 methyltransferase, MLL (myeloid/lymphoid or mixed lineage leukemia) and the receptor tyrosine kinase FLT3 (FMS-like tyrosine kinase 3). Preclinical studies utilize a mouse model of acute myeloid leukemia that harbors these two genetic mutations. We are targeting the downstream effects of both mutations by testing the efficacy of epigenetic modifiers as well as tyrosine kinase inhibitors in drug trials. We hope to find a combinatorial effect that gives MLL-PTD (partial tandem duplication); FLT3-ITD patients a potentially better therapeutic outcome. Future experiments will address epigenetic changes that occur in response to the drugs with the goal of finding yet more therapeutic targets to help these patients survive longer and eventually be cured of cancer.

Additional areas of research in AML include studing of the role of the Axl/Gas6 pathway in the pathogenesis of this disease. The Axl/Gas6 pathway is a receptor tyrosine kinase (RTK) known to be involved in a variety of biological functions. As it was previously published, the Axl/Gas6 pathway is crucial for signaling of another RTK c-Kit, which is highly homologous to RTK FLT3. As FLT3 is the most well-known prognostic marker for AML, my work has been to test the hypothesis that the Axl/Gas6 pathway may contribute to AML through regulating FLT3 and its biological functions. Current data has demonstrated that the Axl/Gas6 pathway promotes the growth and survival of leukemic cells and blocks myeloid differentiation. Furthermore, the Axl/Gas6 pathway is crucial for FLT3 signaling. Ongoing and future studies will test whether inhibiting the Axl/Gas6 pathway can suppress the occurrence of AML in vivo in a mouse leukemia model.

Natural Killer Cell Biology:

Research efforts are directed to define the molecular mechanisms regulating the immunoregulatory and cytotoxicity functions of natural killer (NK) cells and their subsets. To achieve this, we are currently the activatory and inhibitory pathways that regulate NK cell activity. We’ve discovered that the inositol-phosphatase SHIP-1 and the PP2A inhibitor SET gene are, respectively, a negative and a positive regulator of interferon gamma production, which is induced in NK cells by different monokines. We also have evidence that SET regulates NK cell cytotoxicity by effecting expression of granule components like the Granzyme B. In addition, we also investigated the role of anti-inflammatory cytokines TGF-β in regulating Fc receptor functions. We reported that the anti-inflammatory cytokine TGF-β utilizes SMAD3 to inhibit CD16-mediated IFN-γ production, antibody dependent cytotoxicity, granzyme B and perforin expression in NK cells. Based on these findings we are also investigating the role of microRNAs in the regulation of NK cell activation and/or development. The goal of our studies is to identify activatory and inhibitory molecules that can be used to enhance NK cell anti tumor activity.

EBV-Associated Disease:

EBV-associated post-transplant lymphoproliferative disorder (PTLD) is a common and often fatal malignancy in organ transplant patients. The incidence of PTLD has been shown to be directly related to a low frequency of EBV-specific cytotoxic T lymphocytes (CTLs) in patients receiving immunosuppressive therapy to prevent organ rejection. Using a chimeric mouse-human model of human PTLD and subsequently in PTLD patients, we have identified that the expression of an EBV lytic gene, BZLF1, plays an important role in controlling the development of PTLD. We hypothesize that at least one component of the increased incidence of PTLD in this patient population is a cellular immune deficiency against EBV lytic and latent antigens. A corollary to this hypothesis is that vaccine-enhanced, EBV-specific immunity will restore the protection from this malignancy. We recently reported a novel strategy for vaccination against the EBV-associated PTLD using a chimeric rAdF35/BZLF1 viral vector or a highly purified EBV BZLF1 protein. Approximately 75 percent of normal human donor cells show a moderate to strong immune response to rAdF35/BZLF1 viral vector stimulation assayed by an IFN- ELISpot. Moreover, rAdF35BZLF1 viral vector-transduced dendritic cell vaccination greatly improves survival rates in a Hu-PBL-SCID animal model. We have cloned the lytic EBV BZLF1 protein into a prokaryotic vector expression cassette name pET26b+ system, expressed in E. Coli BL26 cells. From this system, large quantities of highly purified and endotoxin-free BZLF1 protein (>95 percent by SDS-PAGE) have been obtained by ion exchange and subsequent size column chromatography. We’ve shown that the highly purified BZLF1-loaded human antigen-presenting cells (APCs) can promote the expansion of the EBV BZLF1 specific memory CD8+ CTLs in vitro. We are evaluating the efficacy of highly purified BZLF1 protein-mediated vaccination in a chimeric mouse-human model of human PTLD.

Lab Mentoring

The Caligiuri lab is strongly committed to the mentoring of MD, MD-PhD and PhD students interested in basic discovery and translation into the clinic. We believe this theme of basic discovery and "translational" research is our strength, and we seek students and postdoctoral fellows interested in the career track.

Mentoring is at the heart of the Caligiuri laboratory. We judge our success by the quality and quantity of student publications, the success with grant applications, and the subsequent training and job opportunities that we are able to create for our students. We have worked very hard to place our students in the best clinical training programs. Students train in the laboratory for at least one year, and no graduate or postdoctoral student leaves our laboratory without having competed for a peer-reviewed federal grant. Many of these students are continuing their training at highly reputable institutions, while others are assistant or associate professors at institutions throughout the world. 

We gratefully acknowledge the kind and generous support of Mr. and Mrs. Richard Wells. Each summer since 1998, the Wells family has provided support for student research positions in our lab. The interns are undergraduate students, from universities across the United States, with a strong interest in pursuing graduate study in medicine or the biomedical sciences.

CCC Members

Michael Caligiuri, MD

Michael A. Caligiuri, MD, is director of The Ohio State University Comprehensive Cancer Center, chief executive officer of Ohio State’s James Cancer Hospital and Solove Research Institute, and holder of the John L.

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Don Benson, MD, PhD

Our laboratory and clinical research programs seek to develop novel treatments for cancer that harness and enhance the immune system’s ability to detect and kill cancer cells. Natural killer cells, one type of immune cell in the body, are capable of killing cancer cells and much of the research.

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Anjali Mishra, PhD

Dr. Mishra's research has shown stage-related ‘interleukin-15 (IL-15)’ mRNA and protein over-expression in lesional skin and circulating tumor cells of CTCL patients. Using IL-15 transgenic (tg) mice, Dr. Mishra's lab has characterized an animal model of spontaneous epidermotropic T-cell lymphoma.

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Jianhua Yu, PhD

Dr. Yu's research interests include Immuno-cellular therapy, blood and marrow transplantation, NK cell biology, gene regulation and cell signaling in immune response and malignant transformation

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Adrienne Dorrance, PhD

Dr. Dorrance's research focuses on the identification of pathways important for the regulation of normal and leukemic stem cell functions.

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Researchers and Lab Staff

Donna Bucci, BS

Donna serves as Manager of the Caligiuri Research Lab, HEME Biorepositories and OSU Leukemia Tissue Bank Shared Resource.

Wing Chan, PhD

Wing recently joined the Caligiuri Lab as a Post-Doctoral Researcher. He came to the lab from St. Jude’s Research Center. Wing works with the NK Cell Development and Oncolytic Virus Research Teams.

Li Chen, MB

Li is a Research Associate in the Caligiuri Lab. Li works with the NK Cell Development team.

HongSheng Dai, PhD

HongSheng is a Post-Doctoral Fellow and recipient of a Pelotonia Fellowship for 2014-2016. HongSheng works with the NK Cell Development and Oncolytic Virus Research Teams.

Christopher Manring, BA

Chris is the Research Data Manager for the HEME Biorepository and OSU Leukemia Tissue Bank Shared Resource.

Charlene Mao, MS

Charlene serves as Research Associate and Flow Cytometry Specialist in the Caligiuri Lab. Charlene plays a key role in the lab providing training and support for all research teams.

Kathleen McConnell, BS

Kathleen serves as Research Assistant and Research Animal Colony Specialist in the Caligiuri Lab. Kathleen plays a key role in the lab providing training and support for all research teams.

Bethany Mundy-Bosse, PhD

Bethany studies Natural Killer (NK) cell development related to Acute Myeloid Leukemia and is a recipient of the prestigious T32 Post-Doctoral Fellowship award for training in Oncology. Bethany presented a poster at the Society for Natural Immunity Meeting in Montreal, May 2015.

Il-Kyoo Park, PhD

Il-Kyoo studies NK cell development related to Acute Myeloid Leukemia and is a recipient of the prestigious T32 Post-Doctoral Fellowship award for training in Oncology.

Victoria Sellers, BS

Victoria serves as Research Assistant and Research Animal Colony Specialist in the Caligiuri Lab. Victoria primarily supports NK Cell Development projects.

Robin Taxier, BS

Robin is Research Technologist for the OSU Leukemia Tissue Bank Shared Resource and Alliance HEME Biorepository.

Wacharaphon Vonchucherd, BS

Wacharaphon is the Senior Research Technologist for the OSU Leukemia Tissue Bank Shared Resource and Alliance HEME Biorepository.

Jing Wen, MB

Jing is a Research Associate with the Mishra Lab research team.

Max Yano, AB

Max is Research Aide with the Mishra Lab research team. Max has been accepted to the OSU School of Medicine.

Students

Elshafa Ahmed , CVM, MPH

Elshafa is currently pursuing a PhD in Veterinary Biosciences; Dr. Caligiuri is her Doctoral Advisor. She is studying the development of vaccine for a specific type of tumor relevant to post organ transplant disease.

Stephen Bergin, BS

Stephen is enrolled in the MD/PhD program, OSU School of Medicine. Stephen works with the NK Cell Development and Oncolytic Virus Research Teams.

Daniel Brook

Daniel is an undergraduate student at OSU and Research Volunteer in the Caligiuri lab.

Billy Carson

Billy is an undergraduate student at OSU and a Wells Family Scholar for 2014.

Taylor Fisher

Taylor is an undergraduate student at OSU and a Student Clinical Data Assistant for the OSU Leukemia Tissue Bank Shared Resource.

Erin Glankler

Erin is an undergraduate student at OSU and a Research Volunteer working in the Wing Chan lab.

Nathaniel Griffin

Nathaniel is an OSU Undergraduate Research Volunteer working with Hongsheng Dai.

Evan Gutter

Evan is an undergraduate student at OSU and a Research Volunteer working in the Biorepository Central Processing Lab.

Sonya Kwiatkowski

Sonya is an Undergraduate Research Assistant. Sonya works with the Mishra Lab research team. Sonya has been accepted to the OSU School of Medicine.

Ayako McGregor

Ayako is an undergraduate student at OSU and a Student Research Assistant working in the Biorepository Central Processing Lab.

Mary Nemer

Mary is an OSU Undergraduate Research Volunteer working with Aaron Victor. She has been awarded a summer research fellowship by Ohio State's Undergraduate Research Office.

Steven Scoville, BS

Steven is enrolled in the MD/PhD program, OSU School of Medicine, and part of the Medical Scientist Training Program. Steven works with the NK Cell Development team. Recipient of F30 Ruth L. Kirschstein National Research Service Award from the NIH. Steven also presented a poster and the ASCI/AAP meeting in Paris in April 2015. Steven presented a poster at the Society for Natural Immunity Meeting in Montreal, May 2015.

Kevin Stephenoff

Kevin is an undergraduate student at OSU and Student Research Assistant working in the Biorepository Central Processing Lab.

Aaron Victor, BS

Aaron is enrolled MD/PhD program, OSU School of Medicine. Aaron works with the NK Development team.

Michael Zhang

Michael is an undergraduate research volunteer working with Steven Scoville. He has been awarded a summer research fellowship by Ohio State's Undergraduate Research Office.

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Michael Caligiuri, MD

Michael Caligiuri

 

Michael A. Caligiuri, MD, is director of The Ohio State University Comprehensive Cancer Center, chief executive officer of Ohio State’s James Cancer Hospital and Solove Research Institute, and holder of the John L. Marakas Nationwide Insurance Enterprise Foundation Chair in Cancer Research. He also is a professor in the Department of Internal Medicine and in the Department of Molecular Virology, Immunology and Medical Genetics in Ohio State’s College of Medicine.

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