The focus of my research is on understanding how cancer impacts host immune responses in patients, with the goal of developing novel treatments to restore/enhance immune function in cancer patients. My group utilizes state-of-the-art technologies – such as high-dimensional flow cytometry, quantitative spatial image analysis, and next-generation genomics – to dissect the complex interplay between immune/stromal cells and cancer cells within tumors, tumor-draining lymph nodes (TDLNs), and blood. Through image analysis of breast tumors and TDLNs, we have found that immune cell populations as well as their spatial distributions and clustering patterns have strong correlation with clinical outcome.
My group has also shown that lymphocytes from patients with breast cancer, melanoma, and colorectal cancer develop immune signaling defects that blunt their proliferation and function in vivo. We are currently extending these findings in multiple directions, including to other human cancers such as prostate cancer and leukemia.
A unique focus of my work is on the impact of heterogeneity within tumors and tumor cell populations, including subpopulations commonly referred to as ‘cancer stem cells’, on the immune response. We utilize computational modeling and network analysis to understand the population dynamics of cancer and immune responses, as well as control theory to find novel interventions. As such, my group is highly interdisciplinary, combining immunology, pathology, genomics, bioinformatics, mathematical modeling, computer science, engineering, network analysis, and control systems.
Diana received her B.S. in Microbiology from San Jose State University. Prior to working at City of Hope, she worked as a research associate in Dr. Peter Lee's lab at Stanford University since 2006 and facilitated in investigating mechanisms causing immune dysfunction in melanoma and breast cancer patients' peripheral blood, lymph node and tumor specimens utilizing techniques including microarray analysis, RT-PCR, Phospho-flow cytometry, histoloogy, and functional FACS studies. In addition she recruited patients into research studies, and procured and processed tissue specimens for study purposes. Diana joined City of Hope in the department of Cancer Immunotherapeutics and Tumor Immunology in November 2011 where she continues to elucidate mechanisms of immune dysfuction in breast cancer patients as well as aid in identifying antigens recognized by anti-tumor T cells. Additionally her roles in the lab are senior lab manager and regulatory administrator. Diana is interested in learning more about immune-tumor-stromal cell intereactions in the setting of breast cancer and how the information learned can be harnessed to develop therapeutic strategies for breast cancer.
Colt received his B.S. from the University of Illinois, Urbana-Champaign in 2006 and his Ph.D. from Rush University in Chicago in 2011. Prior to obtaining his B.S., Colt also held an internship at an NCI Vaccine Branch in 2005. Colt's current main project hopes to identify immunologically validated T cell antigens in the context of breast cancer. In other words, we are attempting to identify the antigens that breast cancer patient T cells naturally react to. With this information we hope to design a therapy that will boost a breast cancer patient's natural immune response instead of trying to induce one de novo. This ambitious project involves the screening of breast cancer patient T cells for antigen specifically and reactivity, high throughput sequencing, and bioinformatics. We look forward to the results along with our collaborators at UC Denver/National Jewish Health and Oregon Health Sciences University.
His second projects involve studying the phenotype and function of tumor infiltrating T cells, which have been shown to be functionally defective. Whether these defects are due to improper T cell activation by dysfunctional antigen presenting cells, suppression by the tumor microenvironment, or by improper homing of the 'correct' T cells to the tumor is not known. Through the analysis of breast cancer patient blood, lymph node, and tumor samples by high-dimensional flow cytometry and in vitro functional assays we hope to unravel some of the answers to these questions.
Dr. Sailesh G-Pillai received his Ph.D. in Molecular Biology and Biotechnology from G.B. Pant university of Agriculture and Technology, India and Project Management Education from CALTECH, USA. Dr. Pillai joined City of Hope as Postdoctoral Fellow in the Department of Molecular and Cellular Bilolgy, where he developed novel genomic methods to regulate alternative splicing using artificial riboswitch. Dr. Pillai later joined Department of Neurosciences, where he developed novel tools and reagents for charactization of pluripotent stem cells and cancer initiating cells. Dr. Pillai comes from multidisciplinary research background including molecular biology, biochemistry, stem cell biology and genomics. Recently, he joined Dr. Peter P. Lee's Laboratory in the Department of Cancer Immunotherapeutics and Tumor Immunology (CITI). Using expertise in genomics and cell biology, Dr. Pillai is looking forward to expanding his research in the field of Tumor Immunology, with focus on Breast Cancer. His research includes, uncovering the complex transcriptional network that exists in the tumor microenvironment roles of cancer initiating cells in immune suppresion, understanding the mechanism of T cell anergy and molecular analysis of T cell repertoire of patients with breast cancer. Findings from his research will be invaluable towards the development of systems immunotherapy for breast cancer.
Dobrin received his B.S. degree in Biology from MT and Ph.D. degree in immunology from Harvard University. His main fields of interest are basic cancer and immunology research with a particular emphasis on the area of cancer immunology and immunotherapy. He has previously worked on the link between VDJ re-arrangement and carcinogensis in the lab of Dr. Jianzhu Chen, MT Cancer Center. His graduate studies were done in the lab of Dr. Glenn Dranoff, Dana-Farber Cancer Institute, Harvard Medical School, where he worked on evaluating the potential of a RGE dominant - negative mutant for of MFG-E8 to improve GM-CSF-secreting whole tumor cell-based vaccines. His research interests and work are strongly motivated by the current challenges and unmet clinical needs for the development of novel and effective therapies for cancer. His ultimate goal is to pursue a career in the field of drug design and development leading to the implementation of novel immune-based approaches to cancer treatment and pervention.
He is currently working on the design of an integrated cancer immunotherapy based on synergistic drug combinations inducing immunogenic cells death. Surgical removal of primary tumors often drives the outgrowth of distant metastasis, while induction of immunogenic cell death in situ takes advantage of tumors as natural reservoirs of tumor antigens and achieves endogenous vaccination effect. Using metastatic mouse breast cancer models, he intends to demonstrate that proper immunomodulation can substantially improve the therapeutic results of standard chemotherapies in patients with advanced and metastatic disease. The goal is to identify synergistic drug combinations that are immunostimulatory and lower the effective dose of standard chemotherapeutic agents. Additional compounds whose immunostimulatory lower the effective dose of standard chemotherapeutic agents iRGD peptide, CpG nano-particles and others.
He would like to expand hs research towards some novel and extremely promising strategies for the induction of immunogenic cell death in cancer patients, including thermal ablation using lasers of high intensity focused ultrasound as well as oncolytic viruses. These innovative strategies likely represent optimal platforms for future integrated cancer immunotherpies.
Allison received her bachelor’s degree from the University of Pittsburgh, where she majored in molecular biology on the biochemistry track. As an undergraduate, she worked in the lab of Dr. James Pipas, where she studied the interactions between SV40 large T antigen and RB/E2F complexes. The goal of the project was to better understand how T antigen could disrupt normal cell cycle regulation to cause cancer. After graduation, she worked for Dr. Harry Blair at the University of Pittsburgh Medical School. Allison contributed to several projects in the lab, but her primary focus was studying how death receptor ligands disrupted gap junctions in osteoblasts. She received her doctorate degree from the Pathobiology program at Johns Hopkins Medical School. Dr. Richard Jones served as her thesis mentor, and her thesis project identified and characterized ovarian cancer stem cells. She is currently interested in studying the role of cancer stem cells in treatment failure with the goal of improving patient outcomes. In addition to this, she will be working on the Artemis Project, which seeks to design a preventative breast cancer vaccine.
Lei received his B.S and M.S degree in Biochemistry from Hong Kong University of Science and Technology in China. He came to the US in 2008 and received his Ph.D. degree in Biochemistry from UC Riverside in 2013. He has been in the field of cancer research for approximately 7 years. The major two focuses of his Ph.D. study were to study the cellular and molecular mechanisms of prostate cancer metastasis and to study the effects of pomegranate derived natural products on prostate and breast cancer progression. Cancer hijacks the immune system by various cellular and molecular mechanisms and dysfunction of immune system arises during the early stages of cancer and throughout progression to later aggressive stages. The current immunotherapies are subject to the immunosuppressive effects of cancer, which likely contribute to their lack of success. Different types of immune cells use cytokine/chemokine as the language for communication. We aim to investigate the cytokine/chemokine signaling network of the immune system to efficiently and accurately monitor and evaluate the overall status of the immune system.
Grecia received her B.S in Biology with a concentration in molecular and biotechnology, from California State University, Fullerton. Grecia joined City of Hope in 2012 where she is currently working as a research associate. Her research consist of investigating cancer immunology; focusing on breast cancer. This is done by looking at breast cancer patients and isolating immune cells from specimens, for example lymph node, blood and tumor. Grecia is currently working on a project that consist of finding breast cancer patient's T cells; that are reacting to antigen along with identifying these antigens. Techniques such as flow cytometry, genomics and multiple cell culture techniques can help determine T-cells reactivity to antigen as well as help find unknown antigens. Grecia wants to continue growing as a scientist and keep on learning about cancer and the immune system. She is also interested in knowing more about cancer-fighting foods and how they contribute to cancer prevention.
In previous labs, Brile Chung, Ph.D., has worked on both murine and human lymphoid differentiation. The tumor microenvironment is comprised of heterogeneous populations of cells including cancer, immune and tumor associated stromal cells. Clinical data and experimental models have shown that the extent and nature of immune infiltrations into tumors is an important independent prognostic factor. Recent findings suggest that tumor associated stroma is another important regulator of tumor growth and progression which may also modulate the recruitment, activation status and retention of immune cells in the tumor microenvironment. Therefore, the main focal point of his research is to target both tumor associated stroma and cancer cells for halting the progression of tumor and metastasis.
March 16, 2014
August 20, 2013
February 09, 2012
Information listed here is obtained from Pubmed, a public database; City of Hope is not responsible for its accuracy.