Dr. Jacob’s research program focuses on three areas:

  1. Epigenetic silencing of tumor suppressors at different stages of tumorigenesis using cells in culture and animal models with emphasis on mechanisms and therapeutic interventions in human cancer;
  2. Delineating the role of microRNAs in the initiation and progression of hepatocellular carcinoma and breast cancer; and in resistance to potent anticancer drugs; and
  3. Applications in therapy.

Epigenetic Silencing of Tumor Suppressor Genes

The majority of the tumor-suppressor genes are silenced by epigenetic mechanisms that include promoter methylation, specific histone modifications and chromatin remodeling. These mechanisms provide an alternate approach to treat cancer by reactivating the silenced tumor suppressor genes via agents that restore normal cellular phenotype-epigenetic therapy. We have shown that the gene encoding a membrane-bound (receptor-type) protein tyrosine phosphatase (PTPRO) is silenced by promoter methylation in hepatocellular carcinoma (HCC), breast and lung cancer, as well as chronic lymphocytic leukemia (CLL). We have identified substrates of PTPRO that exhibit altered phosphorylation states in cancer, resulting in aberrations in signaling pathways leading to enhanced tumorigenesis. We have demonstrated that PTPRO can be re-expressed in tumors by established and novel DNA hypomethylating agents. We are exploring other PTPRO substrates, their phosphorylation states in cancer and the therapeutic advantages of re-activating this gene as well as other epigenetically silenced novel tumor-suppressor genes in CLL and HCC using tumor-specific animal models. We have also generated B-cell specific PTPRO Tg mice to study the gene’s role in chronic lymphocytic leukemia in vivo.

Delineating the Role of microRNAs (miRs) in Tumorigenesis and Applications in Therapy

We are studying the differential expression of microRNAs (miRs) at early stages of hepatocarcinogenesis using two mouse models – one that mimics non-alcoholic steatohepatitis (NASH)-induced HCC that has shown increased incidence in Western countries, and another model that induces HCC upon exposure to DEN (diethyl nitrosamine). miR microarray analysis followed by real time RT-PCR showed that a few miRs that  target mRNAs for specific tumor suppressors and oncoproteins are  upregulated and downregulated, respectively, weeks before preneoplastic nodule formation. We are exploring the possibility of reversing the tumorigenic process by altering specific miR expression using anti-miRs (for upregulated miRs) or miR mimetics (for downregulated miRs) targeted to liver using nanoparticle-mediated delivery systems. We are also exploring the role of miRs in altered glucose metabolism in liver cancer, and using miR-based therapeutic approaches to restore the energy metabolism and normal cellular phenotype. We have made significant progress in these areas.

Contact Us

646A Tzagournis Medical Research Facility (TMRF)
420 W. 12th Avenue
Columbus, OH 43210

Phone: 614-688-5494

Members

Research Scientist

Tasneem Motiwala, PhD

Research Associate

Huban Kutay, PhD

Graduate Students

Ryan Reyes

Kun-Yu Teng (co-adviser)

Vivek Chowdhary (co-adviser)

Collaborator

Kalpana Ghoshal, PhD
Associate Professor of Pathology

CCC Members

Michael Caligiuri, MD

Michael A. Caligiuri, MD, is director of The Ohio State University Comprehensive Cancer Center (OSUCCC), where he is also a member of the Leukemia Research Program.

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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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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.

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.

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.

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. Steven works with the NK Cell Development team.

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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