Contact Information
Peter P. Lee, M.D.
  • Billy and Audrey L. Wilder Professorship in Cancer Immunotherapeutics
  • Chair, Cancer Immunotherapeutics & Tumor Immunology

Research

 
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.

Lab Personnel


Kim Blenman  kblenman@coh.org
Lymph node metastasis is well established as one of the strongest prognostic indicators of clinical outcome for patients with breast cancer.  Sentinel lymph node (SLN) biopsy accurately predicts non-sentinel axillary lymph node metastasis and clinical outcome. This level of accuracy has led to the recommendation to not perform ALND on T1-T2 tumors or node negative SLN.  Among patients with tumor-invaded SLNs relapse rates are highly variable, 4% to 68%, and dependent on other clinical factors such as tumor size, number of tumor-invaded NSALNs, and adjuvant therapy.  Breast cancer metastases not seen with routine pathological or clinical examination can be identified by immunohistochemistry staining.  However, recent studies suggest that in women receiving breast-conserving therapy and SLN dissection, immunohistochemistry confirmation of SLN metastasis was not associated with overall survival. In essence, the mere presence of metastasis does not predict disease-free or overall survival in breast cancer patients.  What may be a better predictor of clinical outcome is the state of the microenvironment, specifically immune cells, within the tumor region and the tumor draining lymph nodes.  Advances in pathological analysis of primary breast tumors have found infiltrating immune cells of prognostic significance.

She proposes that immune profile analysis of tumor microenvironment and TDLNs can add substantially to prognosis and understanding mechanisms of metastasis of breast cancer.  Her goal is to utilize immune profile analysis to further to help stratify risk of disease recurrence using both TDLN and tumors (primary and metastatic).  Ultimately, we seek to combine immune profile of tumor and TDLN into a comprehensive predictor of recurrence for breast cancer patients.  This may lead to a new, more efficient approach to the work-up of breast cancer patients.  A comprehensive immune profile analysis could also yield biological insights that could lead to novel therapeutic strategies aimed at modulating tumor-immune system interactions.
 

Diana Simons  dsimons@coh.org
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, histology, 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 dysfunction 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 interactions in the setting of breast cancer and how the information learned can be harnessed to develop therapeutic strategies for breast cancer.

Colt Egelston  cegelston@coh.org
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 natural 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 specificity 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 secondary 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.

John Murad  jmurad@coh.org
John received his B.S. in Chemistry from Cal Poly Pomona and his M.S. in Pharmaceutical Sciences from Western University of Health Science, Pomona CA.  Prior to working at City of Hope; he was an undergraduate research aid at Cal Poly Pomona for 2 years where he improved isoelectric focusing techniques to quantify HbA1c in whole blood.  For 2 years at Western University, he was also a research associate, where his main research focus was understanding platelet biology and determining and analyzing the anti-platelet and anti-thrombotic potential of an thromboxane receptor antibody therapeutic in vitro, ex vivo, and in vivo.  John joined City of Hope in October of 2012 and has had the great pleasure of working with Dr. Peter Lee's lab in the department of Cancer Immunotherapeutics Tumor Immunology (CITI).  His main focus is to aid research staff in identifying novel characteristics of the tumor micro-environment and tumor associated stroma and the combined effect on immune response/signaling events by utilizing multiple techniques including RT-PCR, 3D cell culturing and imaging, and RNA micro-array and RNAseq analyses.  He is interested in learning more about the unique cell-cell interactions that take place in the immune system and how they may be manipulated in our favor for battling cancers with our own immune system more efficiently.

Sailesh Pillai  spillai@coh.org
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 a Postdoctoral Fellow in the department of Molecular and Cellular Biology, 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 characterization of pluripotent stem cells and cancer initiating cells.  Dr.Pillai comes from a 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 expand 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, role of cancer initiating cells in immune suppression, 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.

Emily Anderson  eandersen@coh.org
Since joining City of Hope in 2011, Emily's research has focused on elucidating important prognostic factors that may help determine clinical outcome for breast cancer patients.  Using multiplex immunohistochemistry and immunofluorescence staining, she has sought to determine whether the presence, quantity, and spatial distribution of certain immune cell populations in a patient's breast tumor and lymph node correlate with their survival rate.  Her unique staining technique and analysis software allows her to stain up to 8 unique cell populations on a single glass slide, scan high resolution images of the entire tissue, and quantify each population depending on its spectral distribution.

The tumor microenvironment has been shown as a significant factor in cancer progression, and my research has also sought to create and study an in vitro tumor model using three dimensional cell culture techniques.  Hydrogel serves as an artificial microenvironment and allows us to grow cancer cells, stromal cells, and immune cells together in a single petri dish.  Using confocal microscopy and fluorescence labeling, we can image and analyze in 3D how each cell type interacts with one another.
Prior to arriving at City of Hope, Emily attended the University of Pennsylvania where she completed her undergraduate studies in biology.

Dobrin Draganov  ddraganov@coh.org
Dobrin received his B.S. degree in Biology from MIT 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 carcinogenesis in the lab of Dr. Jianzhu Chen, MIT 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 form 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 prevention.
 
He is currently working on the design of an integrated cancer immunotherapy based on synergistic drug combinations inducing immunogenic cell death.  Surgical removal of primary tumors often drives the outgrowth of distant metastases, 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 immunopotentiating properties are currently being explored in the lab include the iRGD peptide, CpG nano-particles and others.
He would like to expand his research towards some novel and extremely promising strategies for the induction of immunogenic cell death in cancer patients, including thermal ablation using lasers or high intensity focused ultrasound as well as oncolytic viruses.  These innovative strategies likely represent optimal platforms for future integrated cancer immunotherapies.

Daryl Mar  damar@coh.org
Daryl completed his undergraduate studies in biological sciences at the University of California, Irvine.  Prior to joining Peter P. Lee's lab, Daryl also researched in a lab that primarily focused on using molecular genetics to better understand Huntington's disease for 2 years.  His previous project attempted to elucidate the lethality of a mutation in a gene known as CG42389 which was believed to be related to neuromuscular junctions in drosophila melanogaster.  Since joining City of Hope during the summer of 2013, Daryl has worked on a project that aims to selectively isolate various subsets of macrophages from peripheral blood mononucleated cells.  In the future, he would like to better understand what effect these various subsets of macrophages have on the microenvironment of tumors and the tumor stroma in a 3D cell culture model.
 

Locations

  • City of Hope - Main Campus (Duarte)
    1500 East Duarte Road
    Duarte, CA 91010