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LRF's Newest Grantees Winter 2012 – The Future of Lymphoma Research

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The Lymphoma Research Foundation (LRF) is pleased to introduce our seven newest grantees. In the fall of 2011, LRF's Scientific Advisory Board (SAB) reviewed applications for two different grant programs: the Clinical Investigator Career Development Award (CDA) and the Post-Doctoral Fellowship.

Paul M. Barr, MD from the University of Rochester Medical Center and Christian Grommes, MD from Memorial Sloan-Kettering Cancer Center each received three-year $225,000 CDAs.

In addition, Fuliang Chu, PhD from the University of Texas MD Anderson Cancer Center, Hua-Xin Gao, PhD from the University of California, San Francisco, Goldi A. Kozloski, PhD from the Miller School of Medicine of the University of Miami, Chia-Jui Ku, PhD from The Regents of the University of Michigan, and Julia Pagan, PhD from New York University School of Medicine each received fellowships for $105,000 over two years. These CDAs and fellowships are supported by Genentech BioOncology, Millennium: The Takeda Oncology Company, and the Caccomo Family Foundation.

Clinical Investigator Career Development Awards (CDAs)

This three-year program funds training of clinicians who will participate in developing new therapeutics and diagnostic tools for lymphoma. The focus of the training is to prepare physician investigators to design and administer clinical research studies and to take on the primary responsibilities for clinical research, protocol writing, Institutional Review Board (IRB) submission and publication.

Paul M. Barr, MDPaul M. Barr, MD
University of Rochester Medical Center; Rochester, NY
Targeting B cell receptor signaling in non-Hodgkin lymphoma

 

Dr. Barr is an Assistant Professor of Medicine and Oncology at the University of Rochester Medical Center. He earned his Medical Degree from Northeastern Ohio Universities College of Medicine. His current research focuses on understanding signaling through the B-cell receptor, "a cell surface protein present on most B-cell NHL subtypes," as it relates to lymphoma biology. This "has led to an improved understanding of critical molecules, including syk, phosphoinositide 3-kinase and Bruton's tyrosine kinase, for which several therapeutics now exist," Dr. Barr said. "The preliminary efficacy of these agents as well as their limited side effect profile will likely change how we treat NHL."

With Dr. Barr's CDA funding, he will evaluate novel agent combinations targeting BCR signaling as rational therapy for NHL. "The LRF grant will help provide the resources and time needed in order to ultimately become an independently funded investigator," Dr. Barr said. "The award provides critical support to gain additional practical experience in translational research, strengthen collaborations, and build my research program."

Samuel Katz, MD, PhD

Christian Grommes, MD
Memorial Sloan-Kettering Cancer Center; New York, NY
Molecular determinants of treatment outcome in central nervous system (CNS) lymphoma

Dr. Grommes is a neuro-oncologist at Memorial Sloan-Kettering Cancer Center in New York, NY, specializing in adult primary brain tumors and primary central nervous system lymphoma (PCNSL). He earned his Medical Degree from RWTH Aachen Medical School in Germany.

With his CDA funding, Dr. Grommes will be able to commit the majority of his time to basic and translational research. "The LRF CDA enables me to focus on basic scientific research to establish myself as an independent investigator," he said. Dr. Grommes' funded research project will "establish animal models derived from human PCNSL tumors and a model mimicking CNS metastasis from systemic lymphoma," he said. "Additionally, we will identify genes that are associated with poor clinical outcome in two separate, large PCNSL patient populations. Both approaches will enable us to generate data that can be used to predict patient risk and serve to help develop more effective treatment approaches with fewer side effects."

Post-Doctoral Fellowships

These two-year fellowships help attract the nation's best scientific talent to careers in lymphoma and allow them to pursue promising research leads. The purpose of this fellowship is to support research, which may be laboratory or clinic based, with results and conclusions that must be clearly relevant to the treatment, diagnosis or prevention of Hodgkin lymphoma (HL) and/or NHL. Areas of research may include, but are not limited to, etiology, immunology, genetics, therapies and transplantation.

Samuel Katz, MD, PhD

Fuliang Chu, PhD
University of Texas MD Anderson Cancer Center; Houston, TX
Pro- and anti-tumor effects of regulatory T-cells in human follicular lymphoma (FL)

Dr. Chu is a postdoctoral fellow at the University of Texas MD Anderson Cancer Center in Houston, TX. He received his PhD in Viral and Structural Immunology from the Institute of Microbiology, Chinese Academy of Sciences in Beijing, China. His current research focuses on studying interactions between tumor and stromal (connective tissue) cells in FL in order to ultimately develop novel therapies.

Dr. Chu's fellowship-funded project will identify the subtypes of regulatory T-cells that have either harmful or beneficial effects with the goal of developing strategies to inhibit their harmful effects while preserving or enhancing their beneficial effects against FL tumors. "By understanding the differential effects of Treg subsets, we will be able to design novel immunotherapeutic strategies to selectively exploit the antitumor effects of Tregs while suppressing their pro-tumor effects in FL and other lymphomas," he said. "Development of novel immunotherapies is especially appealing for patients with FL and other lymphomas as unlike with chemotherapy they are generally well-tolerated and have minimal side effects."

Samuel Katz, MD, PhD

Hua-Xin Gao, PhD
University of California, San Francisco; San Francisco, CA
Macrophage polarization and central nervous system (CNS) progression of non-Hodgkin lymphoma (NHL)

Dr. Gao, who received her Doctoral Degree from the Albert Einstein College of Medicine, is currently a postdoctoral scholar in the Department of Medicine, Division of Hematology/Oncology, at the University of California, San Francisco. Her current research involves the immune microenvironment of primary central nervous system lymphoma (PCNSL), and especially the role of tumor macrophages in the progression of PCNSL.

Dr. Gao's fellowship will enable her to establish herself as an independent investigator in the field of lymphoma. With this funding, she will examine how tumor-associated macrophages are important in the progression of PCNSL. "How was the immune system hijacked by the tumor?" she said. "How should we reverse this process? My study can potentially identify the important tumor-helper cells in PCNSL progression and thus provide clues to develop cancer therapies for this aggressive disease."

Samuel Katz, MD, PhD

Goldi A. Kozloski, PhD
Miller School of Medicine of the University of Miami; Miami, FL
Regulation of NF-kB Signaling Pathway in DLBCL by MicroRNAs

Dr. Kozloski obtained her BS in pre-med from Eckerd College and her PhD in biochemistry and molecular biology from the University of Miami School of Medicine. Dr. Kozloski is a postdoctoral associate at the Sylvester Cancer Center of the University of Miami working in the laboratory of Izidore S. Lossos, MD. Her current research focuses on the mechanistic role of microRNAs as master regulators of disease pathogenesis.

According to her abstract, "One factor in the pathogenesis of Diffuse Large B-Cell Lymphoma (DLBCL) and other lymphomas is aberrant NF-kB signaling activity. While several regulators of NF-kB have been characterized, a key factor that suppresses this pathway was not identified. We identified a small non-coding RNA that suppresses NF-kB and kills DLBCL cells that are dependent on NF-kB. We hypothesize that a small non-coding RNA can be used for DLBCL therapy, and this award will allow us to test this hypothesis. We will characterize its molecular mechanism in NF-kB regulation, determine its biological consequences, and test its effect in a mouse model."

Samuel Katz, MD, PhD

Chia-Jui Ku, PhD
The Regents of the University of Michigan; Ann Arbor, MI
Transcription network controlled by GATA-3 protein during T-cell specification and commitment

Dr. Ku is a postdoctoral research fellow in the Cell and Developmental Biology department at the University of Michigan. She received her BS in Chemistry from the National Tsing Hua University in Taiwan and her PhD in Chemistry from Michigan State University.

Her research project abstract states, "Multiple kinds of immune cells are in the human immune system (e.g. macrophages, B-lymphocytes and T-lymphocytes, or T-cells). A nuclear regulatory protein named GATA-3, discovered in our lab, is vital for T-cell development at multiple stages; from the early T-cell progenitor (ETP) stage to peripheral helper type2 (Th2) cells: the timing and abundance of GATA-3 must be precisely controlled throughout normal T-cell development, or disastrous consequences (e.g. immunodeficiency, lymphoma or leukemia) can result from production of either too little or too much GATA-3."

"The goal of this project is to identify functional target genes that are directly or indirectly controlled by GATA-3 protein through whole-genome transcriptome approach, and to validate its function by transgenic mouse rescue experiments," Dr. Ku said. "Contribution of our understanding to GATA-3 regulation in thymopoiesis may be critical for eventually deciphering the etiology and progression of T-cell leukemia/lymphoma and Hodgkin's lymphoma, since aberrant GATA-3 expression has been implicated as a causal agent in a subset of these diseases."

Samuel Katz, MD, PhD

Julia Pagan, PhD
New York University School of Medicine; New York, NY
Regulation of BCL6 levels by phosphorylation and ubiquitination in diffuse large B-cell lymphoma (DLBCL)

Dr. Pagan is a postdoctoral fellow at the New York University (NYU) Medical Center in New York, NY, in the Department of Pathology. She received her PhD in molecular and cellular biology from the Queensland Institute of Medical Research in Australia. Dr. Pagan focuses her research on mechanisms involved in the targeted degradation of key regulatory proteins in cancer. She is currently interested in mechanisms leading to the degradation of the BCL6 oncogene. "Since high levels of BCL6 lead to the development of DLBCL, understanding more about the pathways leading to BCL6 degradation could provide important insight into future diagnostics or therapies for DLBCL," she said.

The LRF fellowship will enable Dr. Pagan to further understand the mechanisms of lymphoma development. "I believe the successful completion of this project will give valuable insight into DLBCL development in a significant proportion of DLBCL cases," she said.